Synthesis, reactivity and catalytic applications of Ir and Ru complexes based on lutidine-derived pincer ligands

INSTITUTO DE INVESTIGACIONES QUÍMICAS Tesis Doctoral Synthesis, reactivity and catalytic applications of Ir and Ru complexes based on lutidine-derived pincer ligands Práxedes Sánchez Mellado Sevilla, 2019 Synthesis, reactivity and catalytic applications of Ir and Ru complexes based on lutidine-derived pincer ligands por Práxedes Sánchez Mellado Memoria presentada para optar al Título de Doctor en Química Fdo. Práxedes Sánchez Mellado Directores Andrés Suárez Escobar Científico Titular del CSIC Nuria Rendón Márquez Profesora Titular de la Universidad de Sevilla A mis padres Victoria y Práxedes. Y a mis abuelos Juanita y Luis, Carmen y Juan José. ! VII Consideraciones generales ................................................................................ XI Summary of Compounds ................................................................................ XV Abbreviations ................................................................................................. XIX General Introduction ................................................................................... 01 Bibliography ................................................................................................. 17 I. Synthesis, reactivity and catalytic applications of M-CNP (M = Pd, Ir) complexes .................................................................................. 25 1. Introduction ......................................................................................... 27 1.1. H2 activation by iridium pincer complexes ................................... 30 1.2. Iridium catalysts based on proton-responsive pincer ligands for hydrogenation reactions ............................................................... 38 1.3. Hydroboration of CO2 catalyzed by transition metal complexes . 45 2. Results and discussion .......................................................................... 53 2.1. General considerations ................................................................. 55 2.2. Synthesis, reactivity and catalytic applications of M-CNPPh (M = Pd, Ir) complexes .......................................................................... 56 2.2.1. Synthesis of precursors of CNPPh ligands ............................ 56 2.2.2. Synthesis and reactivity of Pd-CNPPh complexes ............... 59 2.2.3. Synthesis, reactivity and catalytic applications of olefin Ir- CNPPh complexes ................................................................ 64 2.2.3.a. Synthesis and structural features of olefin Ir-CNPPh complexes .............................................................. 64 2.2.3.b. Reactivity with bases and H2 of olefin Ir-CNPPh complexes .............................................................. 73 2.2.3.c. Hydrogenation of ketones catalyzed by Ir-CNPPh complexes .............................................................. 81 ! VIII 2.2.4. Synthesis, reactivity and catalytic applications of carbonyl Ir-CNPPh complexes ............................................................ 85 2.2.4.a. Synthesis and reactivity of carbonyl Ir-CNPPh complexes .............................................................. 85 2.2.4.b. Hydroboration of CO2 catalyzed by carbonyl Ir- CNPPh complexes ................................................... 94 2.2.4.c. Metal species formed under catalytic conditions . 101 2.3. Synthesis of Ir-CNPtBu complexes and catalytic applications in the hydrogenation of aldehydes ................................................. 114 2.3.a. Synthesis of CNPtBu ligands precursors .............................. 114 2.3.b. Synthesis and reactivity of Ir-CNPtBu complexes .............. 115 2.3.c. Hydrogenation of aldehydes catalyzed by Ir-CNPtBu complexes ...................................................................... 126 2.3.d. Mechanistic studies of the hydrogenation of aldehydes ... 130 3. Experimental procedures ................................................................... 141 3.1. General considerations ............................................................... 143 3.2. Synthesis of imidazolium salts .................................................... 145 3.3. Synthesis of Pd-CNPPh complexes .............................................. 161 3.4. Synthesis of olefin Ir-CNPPh complexes ...................................... 168 3.5. Reactivity of complexes 7 towards KOtBu and H2 .................... 176 3.6. Synthesis of carbonyl Ir-CNPPh complexes ................................. 184 3.7. Synthesis of Ir-CNPtBu complexes ............................................... 201 3.8. Catalytic reactions ...................................................................... 218 3.8.1. Hydrogenation reactions .................................................. 218 3.8.2. Hydroboration of CO2 ..................................................... 219 4. Bibliography ....................................................................................... 221 ! IX II. Synthesis of Ru-CNN(H) complexes. Catalytic applications in hydrogenation and dehydrogenation of N-heterocycles ........... 235 1. Introduction ....................................................................................... 237 1.1. Catalytic applications of metal complexes based on multimodal proton-responsive ligands ........................................................... 240 1.1.a. Ruthenium complexes ................................................. 240 1.1.b. First-row metal complexes ........................................... 247 1.2. Acceptorless dehydrogenation of N-heterocycles ........................ 252 1.2.a. Dehydrogenation of N-heterocycles with ruthenium catalysts ....................................................................... 254 1.2.b. Reversible dehydrogenation of N-heterocycles catalyzed by transition metal complexes ................. 260 2. Results and discussion ........................................................................ 271 2.1. General considerations ............................................................... 273 2.2. Synthesis of CNN(H) ligand-type precursors and Ag-CNN(H) complexes ................................................................................... 274 2.3. Synthesis of Ru-CNN(H) complexes .......................................... 275 2.4. Hydrogenation and dehydrogenation of N-heterocycles ............ 282 2.4.a. Hydrogenation of N-heterocycles ..................................... 282 2.4.b. Dehydrogenation of N-heterocycles ................................. 286 2.5. Reactivity of Ru-CNN(H) complexes towards bases and H2. Mechanistic implications in the hydrogenation of N-heterocycles ............................................................................. 290 3. Experimental procedures ................................................................... 299 3.1. General considerations ............................................................... 301 3.2. Synthesis of imidazolium salts .................................................... 303 3.3. Synthesis of Ag-CNN(H) complexes .......................................... 310 3.4. Synthesis of Ru-CNN(H) complexes .......................................... 314 3.5. Catalytic reactions ...................................................................... 325 Summary of Compounds ! XVI !! 7a(Cl): Ar = Mes, X = Cl 7b(Cl): Ar = 3,5-Xyl, X = Cl 7b(Br): Ar = 3,5-Xyl, X = Br 7b(BArF): Ar = 3,5-Xyl, X = BArF X Ir N N N Ar P Ph2 Ir N N N Xyl P Ph2 89 N N PPh2 NXyl Ir H H H 10a: Ar = Mes 10b: Ar = 3,5-Xyl N N PPh2 NAr Ir H Cl H 13(Cl): X = Cl 13(Bcat2): X = Bcat2 13(BArF): X = BArF 14 N N PPh2 NMes Ir CO X N N PPh2 NMes Ir CO Cl CO N PPh2 NNMes Ir CO N PPh2 NNMes Ir CO 15a 15b 16 N N PPh2 NMes Ir H H CO 17 N N PPh2 NMes Ir H H CO Cl 18(Bcat2): R2 = catecholate 19(BArF): R2 = pinacolate N N PPh2 NMes Ir BR2 H CO X Summary of Compounds ! XVII N NPtBu2 N Ar Cl 20a: Ar = Mes 20b: Ar = 3,5-Xyl N N N PtBu2 Ir Cl H 21 22a 25a N N PtBu2 NMes Ir H Cl H N N PtBu2 NMes Ir H H H 23 Cl Ir N N N Xyl P tBu2 N N PtBu2 NXyl Ir H Cl H 22b N N PtBu2 NXyl Ir H Cl H 24 N N PtBu2 NXyl Ir H H H 25b N N PtBu2 NXyl Ir H H H 26 29 N N PtBu2 NMes Ir H H Ir N N Mes N H P tBu H Ar H O 30am: Ar = Ph 30bm: Ar = p-Br-Ph 2 Ir N N Mes N H P tBu H H Ar O 30aM: Ar = Ph 30bM: Ar = p-Br-Ph 2 Summary of Compounds ! XVIII Chapter II. Ru-CNN(H) Br 2a: R = tBu 2b: R = CH2Ph 2c: R = Ph H 3a: R = tBu 3b: R = CH2Ph 3c: R = Ph N NNR N Mes H AgBr N NBr N Mes Br N NNR N Mes 1a(Br) 4a: R = tBu 4b: R = CH2Ph 4c: R = Ph N N N Ru NtBu Mes L H H CO BF4 L = PPh3 N N N Ru NtBu Mes L H H CO 8: L = PPh3 N N N Ru NtBu Mes LCO 10: L = PPh3 K N N N Ru NtBu Mes H CO 9 ! XIX ABBREVIATIONS ν infrared stretching frequency of a bond (cm-1) acac acetylacetonate COD cycloocta-1,5-diene DFT Density Functional Theory ESI Electrospray Ionization (technique for mass spectrometry) HRMS High Resolution Mass Spectrometry IR infrared KHMDS potassium bis(trimethylsilyl)amide 2-MeTHF 2-methyltetrahydrofuran MLC metal-ligand cooperation Mes mesityl (2,4,6-Me3C6H2) NHC N-heterocyclic carbene ORTEP Oak Ridge Thermal Ellipsoid Program (crystallographic representation) r.t. room temperature S/C substrate/catalyst ratio THF tetrahydrofuran, C4H8O Tol toluene Xyl 3,5-xylyl (3,5-Me2C6H3) XNX lutidine-derived pincer ligand with X donor flanking groups (X = phosphine, amine, NHC) XNX* deprotonated lutidine-derived pincer ligand Abbreviations ! XX NMR Abbreviations δ chemical shift COSY correlation spectroscopy Cq quaternary carbon EXSY Exchange Spectroscopy HSQC 1H-13C correlation spectroscopy (Heteronuclear Single Quantum Coherence) HMBC 1H-13C correlation spectroscopy (Heteronuclear Multiple Bond Correlation) NMR Nuclear Magnetic Resonance NOESY nuclear Overhauser enhancement spectroscopy ppm parts per million T1 relaxation time s singlet d doublet t triplet q quartet m multiplet br broad nJAB coupling constant (Hz) between A and B nuclei separated by n bonds General Introduction General Introduction ! 3 Transition metal catalysis has been largely associated to metalcentered processes, such as oxidative addition, reductive elimination and insertion of unsaturated molecules, in which the ancillary ligands plays merely a spectator role modifying the steric and electronic properties of the metal to improve its reactivity.1 At variance with most transition metal catalysts, metalloenzymes possess functional groups as part of the first and second coordination spheres around the metal center that participate in the recognition and activation of substrates and in the stabilization of reaction intermediates, providing an efficient acceleration of the biological transformations.2 For example, the [FeFe]-hydrogenase active site contains a secondary amino function that directly participates in the heterolytic splitting of the H2 molecule coordinated to the Fe(II) center by accepting a proton (H+) (Figure 1). The overall process takes place without an overall change of the metal oxidation states. ! Figure 1. H2 heterolysis by the [FeFe]-hydrogenase. Inspired by Nature, metal complexes incorporating ligands containing Brønsted acidic/basic sites, which facilitate substrate binding and activation !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 1 (a) P. W. N. M. van Leeuwen, Homogeneous Catalysis: Understanding the Art, Kluwer Academic, 2004; (b) J. Hartwig, Organotransition Metal Chemistry, University Science Book, 2010. 2 M. D. Wodrich, X. Hu, Nat. Rev. Chem. 2017, 2, 0099; (b) D. Schilter, J. M. Camara, M. T. Huynh, S. Hammes-Schiffer, T. B. Rauchfuss, Chem. Rev. 2016, 116, 8693; (c) W. Lubitz, H. Ogata, O. Rüdiger, E. Reijerse, Chem. Rev. 2014, 114, 4081. FeII FeI S HN S NC CO CO CN C O S[Fe4S4]2+ Cys H H FeII FeI S H N S NC CO CO CN C O HS[Fe4S4]2+ Cys H General Introduction! ! 4 as in metalloenzymes, have also been explored, and their use has become a fundamental approach to the development of improved catalytic systems and novel reactions.3 In these artificial catalysts, the ligand cooperates with the metal in the activation of a substrate, usually undergoing a reversible chemical transformation. A prevailing metal-ligand cooperation (MLC) mode is based on the reversible metal-amine/metal-amide interconversion (Figure 2).4 This approach was pioneered by the group of Noyori allowing for the development of hydrogenation, transfer hydrogenation and dehydrogenation catalysts that furnish unrivaled levels of catalytic activity and selectivity.5 For example, RuCl2(P-P)(N-N) complexes (P-P = chiral diphosphine, N-N = chiral primary diamine), in the presence of a base, catalyzes the hydrogenation of ketones with enantioselectivities of up to 99% ee using low catalyst loadings under mild reaction conditions (8 bar H2, 28 oC, S/C up to 105).6 The commonly accepted catalytic species is a dihydride complex, RuH2(P-P)(N-N), generated by reaction of RuCl2(P-P)(N-N) with H2 and base (Figure 3).7 This species transfers a hydride bound to Ru and a proton of the !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 3 (a) H. Grützmacher, Angew. Chem. Int. Ed. 2008, 47, 1814; (b) J. R. Khusnutdinova, D. Milstein, Angew. Chem. Int. Ed. 2015, 54, 12236; (c) B. Askevold, H. W. Roesky, S. Schneider, ChemCatChem 2012, 4, 307. 4 P. A. Dub, J. C. Gordon, Nat. Rev. Chem. 2018, 2, 396. 5 B. Zhao, Z. Han, K. Ding, Angew. Chem. Int. Ed. 2013, 52, 4744. 6 (a) T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. Muñiz, R. Noyori, J. Am. Chem. Soc. 2005, 8288; (b) T. Ohkuma, H. Ooka, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995, 10417; (c) T. Ohkuma, H. Doucet, T. Pham, K. Mikami, T. Korenaga, M. Terada, R. Noyori, J. Am. Chem. Soc. 1998, 1086; (d) H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E. Katayama, A. F. England, T. Ikariya, R. Noyori, Angew. Chem. Int. Ed. 1998, 1703; (e) N. Arai, K. Suzuki, S. Sugizaki, H. Sorimachi, T. Ohkuma, Angew. Chem. Int. Ed. 2008, 47, 1770. 7 (a) S. E. Clapham, A. Hadzovic, R. H. Morris, Coord. Chem. Rev. 2004, 248, 2201; (b) C. A. Sandoval, T. Ohkuma, K. Muñiz, R. Noyori, J. Am. Chem. Soc. 2003, 125, 13490; (c) K. Abdur-Rashid, S. E. Clapham, A. Hadzovic, J. N. Harvey, A. J. Lough, R. H. Morris, J. Am. Chem. Soc. 2002, 15104; (d) R. Noyori, M. Yamakawa, S. Hashiguchi, J. Org. Chem. 2001, 7931. General Introduction ! 5 diamine ligand to the ketone through an outer-sphere mechanism.8,9 Subsequent heterolytic splitting of H2 assisted by the amido ligand leads to the initial dihydride Ru complex. Figure 2. Metal-ligand cooperation based on metal-amine/metal-amide interconversion, and examples of catalysts based on this MLC mode. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 8 O. Eisenstein, R. H. Crabtree, New J. Chem. 2013, 37, 21. 9 Proton-transfer from the amine ligand to the ketone has been recently questioned: ref. 4. M X NR2 HBase MNR2M H NR2 H H2 Cl Ru Cl P iPr P iPr H2 N H2 N 2 2 H Ru Cl CO P Ph2 PPh2 N Ir Cl NNH2 Ts Ru Cl NNH2 Ts H X = halogen General Introduction! ! 12 ! Figure 7. Catalytic applications of lutidine-derived Ru-CNN complexes. Also of note, ruthenium complexes furnishing lutidine-derived CNC ligands have received a considerable attention in catalysis (Figure 8). While these derivatives exhibit a moderate activity in the dehydrogenation of alcohols33 and in the hydrogenation of ethylene carbonate,34 they are active !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 34 X. Wu, L. Ji, Y. Ji, E. H. M. Elageed, G. Gao, Catal. Commun. 2016, 85, 57. R O OR’ ROH + R’OH H2 (5 bar) [Ru] 1 mol% KOtBu 8 mol% Toluene, 105 ºC, 2 h R O OR’ ROH + R’OH H2 (5 bar) [Ru] 1 mol% KOtBu 10 mol% Toluene, 135 ºC, 2 h N N NEt2 NAr Ru CO H Br N N N Ar Ru CO H PPh3 N Cl O O O O H2 (10 bar) [Ru] 1 mol% KOtBu 1 mol% THF, 110 ºC, 48 h HO OH Song (2011) Milstein (2011) N N N NMes Ru CO H Sanchez (2011) R O OR 2 ROH [Ru] 1 mol% KOH 10 mol% Toluene, 110 ºC, 3 h R O R’ [Ru] 1 mol% KOH 1 mol% iPrOH, 82 ºC, 1 h R OH R’ + 2 H2 Cl General Introduction ! 13 catalysts for ester hydrogenation providing to higher efficiencies than their Ru-PNP counterparts.35 Conversely, PNP-derived ruthenium complexes have been shown to be significantly more active in the hydrogenation of CO2 to formates than the Ru-CNC derivatives.24d,36 Mechanistic studies indicate that, as a consequence of the six-membered chelating ring, heterolytic H2 cleavage by the deprotonated Ru-CNC* intermediates, that leads to catalytically active dihydride Ru-CNC species, takes place with much lower barriers than in the case of Ru-PNP*. However, catalysts deactivation by CO2 addition to Ru- CNC* is also thermodynamically more favorable and occurs with only a slightly higher free energy barrier than the reaction with H2.36 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 35 G. A. Filonenko, E. Cosimi, L. Lefort, M. P. Conley, C. Copéret, M. Lutz, E. J. M. Hensen, E. A. Pidko, ACS Catal. 2014, 4, 2667. 36 G. A. Filonenko, D. Smykowski, B. M. Szyja, G. Li, J. Szczygieł, E. J. M. Hensen, E. A. Pidko, ACS Catal. 2015, 5, 1145. General Introduction! ! 14 ! Figure 8. Catalytic applications of lutidine-derived Ru-CNC complexes. Finally, our group has also previously synthesized Ru-CNC complexes that are active catalysts in the hydrogenation of imines.37 The CNC ligands in these complexes adopt facial or meridional coordination modes depending on the size of the substituent of the NHC fragment due to the enlarge chelate rings in comparison to those of the PNP ligands. Aiming to study new ligand architectures that may lead to improved catalytic systems, this PhD Thesis has focused on the synthesis of metal complexes containing lutidine-derived ligands with two non-equivalent donor groups,38 a NHC and an additional flanking group such as phosphine or amine. Thus, in Chapter I, iridium and palladium complexes incorporating !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 37 (a) M. Hernández-Juárez, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Dalton Trans. 2013, 42, 351; (b) M. Hernández-Juárez, J. López-Serrano, P. Lara, J. P. Morales-Cerón, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Chem. Eur. J. 2015, 21, 7540. 38 M. Asay, D. Morales-Morales, Dalton Trans. 2015, 44, 17432. N Ru NN NN CO H L RR Br N N N NR N R Ru Cl P Ph3 CO H R O OR’ ROH + R’OH H2 (50 bar) [Ru] 0.5 mol% KOMe 10 mol% THF, 70 ºC, 4 h H2 (40 bar) [Ru] 2.5 · 10-5 mol% DBU DMF, 33-84 ºC, 1.5 h H2 (5 bar) [Ru] 0.1 mol% KOtBu 10 mol% 2-MeTHF, 70 ºC, 6 h CO2[HCOO][DBUH] (1 bar) RR’ N R’’ R’ = H, Me RR’ HN R’’ L = PPh3 Pidko (2013) Suárez (2013) General Introduction ! 15 CNP tridentate ligands with NHC and phosphine flanking donors are described. These derivatives have been examined in different reduction reactions including the hydrogenation of aldehydes and ketones, and the hydroboration of CO2. In Chapter II, ruthenium complexes incorporating CNN(H) (C = NHC; N(H) = secondary amine) ligands that combine two potential metalligand cooperation modes, metal-amine/metal-amido interconversion and lutidine deprotonation, have been prepared and their catalytic performances in the hydrogenation and acceptorless dehydrogenation of N-heterocycles explored. Bibliography ! 17 1) (a) P. W. N. 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Gunanathan, D. Milstein, Science 2013, 341, 1229712; (b) A. Kumar, N. A. Espinosa‐Jalapa, G. Leitus, Y. Diskin‐Posner, L. Avram, D. Milstein, Angew. Chem. Int. Ed. 2017, 56, 14992; (c) C. Gunanathan, L. J. W. Shimon, D. Milstein, J. Am. Chem. Soc. 2009, 131, 3146; (d) C. Gunanathan, D. Milstein, Angew. Chem. Int. Ed. 2008, 47, 8661; (e) J. Zhang, M. Gandelman, L. J. W. Shimon, H. Rozenberg, D. Milstein, Organometallics 2004, 23, 4026; (f) B. Gnanaprakasam, J. Zhang, D. Milstein, Angew. Chem. Int. Ed. 2010, 49, 1468; (g) M. Nielsen, A. Kammer, D. Cozzula, H. Junge, S. Gladiali, M. Beller, Angew. Chem. Int. Ed. 2011, 50, 9593; (h) B. Gnanaprakasam, E. Balaraman, Y. Ben‐David, D. Milstein, Angew. Bibliography ! 21 Chem. Int. Ed. 2011, 50, 12240; (i) M. Nielsen, H. Junge, A. Kammer, M. Beller, Angew. Chem. Int. Ed. 2012, 51, 5711; (j) A. Mukherjee, A. Nerush, G. Leitus, L. J. W. Shimon, Y. Ben-David, N. A. Espinosa- Jalapa, D. Milstein, J. Am. Chem. Soc. 2016, 138, 4298; (k) J. O. Bauer, G. Leitus, Y. Ben-David, D. Milstein, ACS Catal. 2016, 6, 8415; (l) C. Gunanathan, Y. Ben-David, D. Milstein, Science 2007, 317, 790; (m) H. Zeng, Z. Guan, J. Am. Chem. Soc. 2011, 133, 1159; (n) B. Gnanaprakasam, D. Milstein, J. Am. Chem. Soc. 2011, 133, 1682; (o) D. Srimani, E. Balaraman, B. Gnanaprakasam, Y. Ben‐David, D. Milstein, Adv. Synth. Catal. 2012, 354, 2403; (p) P. Hu, Y. Diskin- Posner, Y. Ben-David, D. Milstein, ACS Catal. 2014, 4, 2649; (q) E. Balaraman, E. Khaskin, G. Leitus, D. Milstein, Nat. Chem. 2013, 5, 122; (r) D. Srimani, Y. Ben‐David, D. Milstein, Angew. Chem. Int. Ed. 2013, 52, 4012; (s) D. Srimani, Y. Ben-David, D. Milstein, Chem. Commun. 2013, 49, 6632; (t) P. Daw, S. Chakraborty, J. Anand Garg, Y. Ben‐David, D. Milstein, Angew. Chem. Int. Ed. 2016, 55, 14373; (u) U. K. Das, Y. Ben‐David, Y. Diskin‐Posner, D. Milstein, Angew. Chem. Int. Ed. 2018, 57, 2179; (v) U. K. Das, Y. Ben-David, G. Leitus, Y. Diskin-Posner, D. Milstein, ACS Catal. 2019, 9, 479. 26) (a) M. Vogt, M. Gargir, M. A. Iron, Y. Diskin‐Posner, Y. Ben‐David, D. Milstein, Chem. Eur. J. 2012, 18, 9194; (b) C. A. Huff, J. W. Kampf, M. S. Sanford, Organometallics 2012, 31, 4643. 27) (a) M. Montag, J. Zhang, D. Milstein, J. Am. Chem. Soc. 2012, 134, 10325; (b) C. A. Huff, J. W. Kampf, M. S. Sanford, Chem. Commun. 2013, 49, 7147. 28) (a) M. Vogt, A. Nerush, M. A. Iron, G. Leitus, Y. Diskin-Posner, L. J. W. Shimon, Y. Ben-David, D. Milstein, J. Am. Chem. Soc. 2013, 135, Introduction ! 29 In the first Chapter of this PhD Thesis, the synthesis of a series of Pd and Ir complexes stabilized with new lutidine-derived pincer ligands incorporating non-equivalent phosphino and N-heterocyclic carbene flanking donor groups is described. Besides, the reactivity of the Ir complexes towards bases and H2 has been investigated, as well as the catalytic performance in different processes such as the hydrogenation of ketones and aldehydes, and the hydroboration of CO2. Chapter I. Ir-CNP complexes 30 I.1.1. H2 activation by iridium pincer complexes Dihydrogen activation is a key step in many catalytic reactions mediated by transition metal complexes, such as hydrogenation and hydroformylation.1 The hydrogen atoms in the H2 molecule are bound by a rather strong covalent bond (103 kcal/mol);2 however, metal complexes are able to oxidatively add the H2 molecule since the formation of two M-H bonds suffices for the breaking of the H-H bond (Scheme 1).3 This process involves donation of the σ-bonding electrons of the hydrogen molecule on a vacant metal d orbital, and transfer of electrons from an occupied d orbital of the metal to the antibonding (σ*) orbital of dihydrogen (Figure 1). Moreover, if the latter interaction is not particularly strong, formation of a σ-dihydrogen intermediate complex can be expected.4 ! Figure 1. Orbital interactions in the H2 activation by transition metal complexes. In a (transient) σ-H2 complex, heterolytic H-H activation may also occur. Due to the nonpolar and remarkably strong H-H bond, hydrogen gas !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 1 J. F. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, University Science Books, 2010. 2 E. S. Wiedner, M. B. Chambers, C. L. Pitman, R. M. Bullock, A. J. M. Miller, A. M. Appel, Chem. Rev. 2016, 116, 8655. 3 (a) G. J. Kubas, D. M. Heinekey, Physical Inorganic Chemistry: Reactions, Processes, and Applications, ed. A. Bakac, John Wiley & Sons, 2010, Ch. 5; (b) M. A. Esteruelas, A. M. López, M. Oliván, Chem. Rev. 2016, 116, 8770. 4 (a) G. J. Kubas, Metal Dihydrogen and σ-Bond Complexes: Structure, Theory and Reactivity; Kluwer, 2001; (b) M. A. Esteruelas, L. A. Oro, Chem. Rev. 1998, 98, 577; (c) R. H. Crabtree, Chem. Rev. 2016, 116, 8750. H H H H σ(H2)σ*(H2) Introduction ! 31 is a very weak acid (pKa = 35, in H2O). However, binding of H2 to form a σ complex makes it a much better acid (pKa < 20), facilitating deprotonation of the η 2-H2 ligand by base and leading to the heterolytic cleavage of dihydrogen.5 This deprotonation can be effected either by an external base or a basic moiety contained within a ligand of the complex in a ligand-assisted process (Scheme 1). ! Scheme 1. Activation of H2 by transition metal complexes. Addition of H2 to square-planar iridium complexes has been extensively studied, particularly with the Vaska’s complex. Activation of H2 by this derivative takes place by initial H2 coordination to form a side-on bound σ-complex that undergoes a concerted oxidative addition to afford a cis-dihydride species (Scheme 2).6 Similar steps have also been proposed for H2 splitting by iridium pincer complexes. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 5 (a) P. G. Jessop, R. H. Morris, Coord. Chem. Rev. 1992, 121, 155; (b) D. M. Heinekey, W. J. Jr. Oldham, Chem. Rev. 1993, 93, 913. 6 (a) P. P. Deutsch, R. Eisenberg, Chem. Rev. 1988, 88, 1147; (b) L. Vaska, Acc. Chem. Res. 1968, 1, 335. LnM+H2LnM H H LnM H H σ-H2 complex oxidative addition LnMH+ [HBase]+ base assisted heterolytic cleavage ligand-assisted heterolytic cleavage base LnMH LH Chapter I. Ir-CNP complexes 32 Scheme 2. H2 activation by the Vaska´s complex. For example, carbonyl iridium complexes containing anionic PCP and POCOP ligands reversibly add H2 leading to cis-dihydride derivatives (Scheme 3).7,8 The reversibility of this process has been attributed to the rigid square-planar geometry imposed by the pincer ligand since, as shown by theoretical calculations, electron density donation from the metal filled d orbital into the empty σ*(H-H) orbital is increased in square-planar d8 complexes upon deviation from the ideal geometry.9 Similarly, favorable H- H reductive elimination from cationic cis-dihydride iridium complexes incorporating a lutidine-derived PNP ligand has also been observed (Scheme 4).10 Furthermore, H-H addition to Ir(POCOP)(CO) and Ir(PCP)(CO) complexes is significantly affected by the steric and electronic properties of the PR2 groups. Thus, concerted oxidative addition of H2 to sterically impeded Ir(POCOPtBu)(CO) and Ir(PCPtBu)(CO) complexes does not take place;8,11 whereas the use of electron-withdrawing substituents affords the formation of cis-hydrides with both meridional and facially coordinated PCP ligands (Scheme 5).12 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 7 B. Rybtchinski, Y. Ben-David, D. Milstein, Organometallics 1997, 16, 3786. 8 J. M. Goldberg, S. D. T. Cherry, L. M. Guard, W. Kaminsky, K. I. Goldberg, D. M. Heinekey, Organometallics 2016, 35, 3546. 9 (a) A. Dedieu, A. Strich, Inorg. Chem. 1979, 18, 2940; (b) J.-Y. Saillard, R. Hoffmann, J. Am. Chem. Soc. 1984, 106, 2006. 10 S. M. Kloek, D. M. Heinekey, K. I. Goldberg, Organometallics 2006, 25, 3007. 11 F. Liu, A. S. Goldman, Chem. Commun. 1999, 655. 12 J. J. Adams, N. Arulsamy, D. M. Roddick, Organometallics 2011, 30, 697. Ir CO Cl Ph3P PPh3H2Ir CO Cl Ph3P PPh3 H H Ir CO H Ph3P PPh3 Cl H Introduction ! 33 ! Scheme 3. H2 activation by carbonyl Ir pincer complexes containing anionic PCP and POCOP ligands. ! Scheme 4. H-H reductive elimination in a cis-[IrH2(PNP)(CO)]PF6 complex. ! Scheme 5. H2 addition to the Ir(PCPCF3)(CO) complex. Interestingly, upon heating, cis-IrH2(POCOP)(CO) and cis- IrH2(PCP)(CO) complexes isomerize to the thermodynamically more stable XPiPr2 XPiPr2 Ir H H CO XPiPr2 XPiPr2 Ir CO H2 - H2 XPiPr2 XPiPr2 Ir CO H H X = CH2, O Δ N PiPr2 PiPr2 Ir H H CO CO PF6 - H2N PiPr2 PiPr2 Ir CO PF6 N PiPr2 PiPr2 Ir H H PF6 P(CF3)2 P(CF3)2 Ir CO H2, fast H2, medium P P(CF3)2 Ir H H CO (CF3)2 slow P H Ir H P(CF3)2 CO (CF3)2 P H Ir H P(CF3)2 (CF3)2 CO Chapter I. Ir-CNP complexes 34 trans derivatives (Scheme 3). While the higher stability of the trans-dihydride complexes in comparison to the cis-dihydrides is difficult to explain considering the high trans influence of the hydride ligands, the observed relative stability can be rationalized considering both steric and electronic factors. An axially coordinated CO ligand is sterically disfavored, whereas coordination of a hydride trans to the PCP aryl is more destabilizing than a carbonyl. Furthermore, different mechanisms have been proposed for this cistrans isomerization, including: i) a non-dissociative trigonal twist of the pincer ligand in which the complex passes through a distorted octahedral intermediate (Scheme 6a),13 and ii) a CO migratory insertion pathway involving a formyl derivative (Scheme 6b).14 ! Scheme 6. Mechanisms for the cis/trans isomerization of dihydride Ir complexes. Brookhart and coworkers observed that, while an Ir(I) methyl complex based on a bulky PONOP ligand did not activate H2, addition of catalytic amounts of a weak acid, such as water, yielded a trans-dihydride species !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 13 S. Li, M. B. Hall, Organometallics 1999, 18, 5682. 14 T. T. Lekich, J. B. Gary, S. M. Bellows, T. R. Cundari, L. M. Guarda, D. M. Heinekey, Dalton Trans. 2018, 47, 16119 PH2 PH2 Ir H CO H PH2 PH2 Ir H CO H PH2 PH2 Ir CO H H PMe2 PMe2 Ir H H CO PMe2 PMe2 Ir CO H H PMe2 PMe2 Ir H O H a) b) Introduction ! 35 (Scheme 7).15 Mechanistic studies revealed an acid-catalyzed pathway resulting in a dihydrogen-hydride complex that is deprotonated by the conjugate base in solution to give the trans-dihydride product. Protoncatalyzed H2 activation leading to trans-dihydride complexes has also been shown for Ir(POCOP)(CO) and Ir(PCP)(CO) complexes, even in the case of ligands containing bulky PtBu2 groups that were not capable of oxidatively activate H2.8 ! Scheme 7. Proton-catalyzed H2 activation by PONOP-Ir complex. Ligand-assisted heterolytic splitting of H2 was first observed by Fryzuk and coworkers (Scheme 8).16 The Ir(COE)[N(SiMe2CH2PPh2)2] complex under H2 generates an iridium(III) trihydride, fac- IrH3[HN(SiMe2CH2PPh2)2], that isomerizes to the mer isomer. Both isomers were found to be only stable in the presence of H2, since H2 elimination to yield the dihydrideamido complex IrH2[N(SiMe2CH2PPh2)2] is favored. A related H2 addition to Ir(III) methyl halide derivatives was also observed. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 15 M. Findlater, W. H. Bernskoetter, M. Brookhart, J. Am. Chem. Soc. 2010, 132, 4534. 16 (a) M. D. Fryzuk, P. A. MacNeil, Organometallics 1983, 2, 682; (b) M. D. Fryzuk, P. A. MacNeil, S. J. Rettig, Organometallics 1985, 4, 1145; (c) M. D. Fryzuk, P. A. MacNeil, S. J. Rettig, J. Am. Chem. Soc. 1987, 109, 2803. N OPtBu2 OPtBu2 Ir CH3 H2O N OPtBu2 OPtBu2 Ir CH3 H H N OPtBu2 OP Ir CH3 H H H tBu2 N OPtBu2 OPtBu2 Ir CH3 H OH H2 OH - H2O Chapter I. Ir-CNP complexes 36 ! Scheme 8. Ligand-assisted heterolytic splitting of H2 by an amido Ir complex. Milstein et al. reported the generation of trans-dihydride complexes after exposure to H2 of aryl and acetonyl Ir(I) complexes containing lutidinederived PNP ligands (Scheme 9).17,18 The proposed mechanism for the formation of these species accounts for the existence of an equilibrium of the initial Ir(I) complexes with their corresponding deprotonated hydride Ir(III)- PNP* species, formed by a water-assisted proton transfer from a methylene arm of the pincer to the Ir center. Subsequent binding of H2 to the vacant position trans to the hydrido ligand followed by transfer of hydrogen from the η2-H2 to the methyne carbon of the pincer bridge yields the trans-dihydride derivative.19 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 17 E. Ben-Ari, G. Leitus, L. J. M. Shimon, D. Milstein, J. Am. Chem. Soc. 2006, 128, 15390. 18 L. Schwartsburd, M. A. Iron, L. Konstantinovski, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon, D. Milstein, Organometallics 2010, 29, 3817. 19 M. A. Iron, E. Ben-Ari, R. Cohen, D. Milstein, Dalton Trans. 2009, 9433. Ir N PPh2 PPh2 Me2Si Me2Si Ir N P P Me2Si Me2Si Ph2 H H H Ph2 H Ir N PPh2 PPh2 Me2Si Me2Si H HH2 - H2 Ir N PPh2 PPh2 Me2Si Me2Si H H HH - H2 H2 H2 Introduction ! 37 ! Scheme 9. Hydrogen activation by Ir-PNP pincer complexes. Finally, a seemingly related ligand-assisted H2 activation was reported for a dihydride Ir(III) complex containing a deprotonated lutidine-derived PNP* ligand. Exposure of this complex to hydrogen gas resulted in the formation of a trihydride IrH3(PNP) species (Scheme 10).20 ! Scheme 10. Dihydrogen activation by an Ir-PNP* pincer complex. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 20 (a) R. Tanaka, M. Yamashita, K. Nozaki, J. Am. Chem. Soc. 2009, 131, 14168; (b) R. Tanaka, M. Yamashita, L. W. Chung, K. Morokuma, K. Nozaki, Organometallics 2011, 30, 6742. N PtBu2 PtBu2 Ir R N PtBu2 PtBu2 Ir R H H H N PtBu2 PtBu2 Ir H R N PtBu2 P Ir H R H2 (1 atm) H2 R = Ph, CH2C(O)CH3 25 ºC H H tBu2 (16 equiv) THF N PiPr2 PiPr2 Ir H H Cl r.t. 1.5 h N PiPr2 PiPr2 Ir H H H2 (1 atm) THF r.t. 4 days N PiPr2 PiPr2 Ir H H H CsOH · H2O Chapter I. Ir-CNP complexes 44 ! Figure 8. Examples of hydrogenation reactions performed with a chiral lutidinederived Ir-PNP complex. N P P Ir H X H X = Cl, H tBu Me Me tBu Ph OH2 (50 bar) [Ir] 1 mol% KOH 10 mol% EtOH/MeOH, 25 ºC, 24 h Ph OH 38-95% conv. 6-17% ee Ph H2 (50 bar) [Ir] 1 mol% KOH 10 mol% EtOH, 25 ºC, 24 h >99% conv. 0-7% ee R XPh R X Ph COOH H2 (50 bar) [Ir] 1 mol% KOH 10 mol%, MeI EtOH/MeOH, 25 ºC, 24 h 54% conv. 5% ee Ph COOMe X = CN, NO2; R = Ph, Me H2 (50 bar) [Ir] 1 mol% KOH 10 mol%, MeI EtOH/MeOH, 25 ºC, 24 h 11% conv. 4% ee NN H O OH O OO H2 (50 bar) [Ir] 1 mol% KOH 10 mol% EtOH/MeOH, 25 ºC, 24 h 60% conv. 14% ee * * * * Introduction ! 45 I.1.3. Hydroboration of CO2 catalyzed by transition metal complexes Carbon dioxide is the most convenient C1 carbon source for the synthesis of value added bulk and fine chemicals due to its renewable, economical, abundant and non-toxic nature.33 Reactions involving the CO2 molecule can be categorized into two main classes: i) non-redox processes, such as the synthesis of carbamates, carbonates, and urethanes,33,34 and ii) reduction reactions to C1 products such as formic acid derivatives and MeOH equivalents.35 While the former addition reactions are wellestablished processes, as exemplified by the industrial production of urea (Bosch−Meiser process),36 efficient reduction of CO2 still represents a formidable challenge due to the high thermodynamic and kinetic stability of this molecule.37 Catalytic hydrogenation is by far the most atom-economical alternative for the reduction of CO2 to formates and methanol; however, it usually requires the use of harsh reaction conditions (high temperatures and H2/CO2 pressures).37 Therefore, unsurprisingly, reactions of CO2 with other reductants, such as hydrosilanes38 and hydroboranes,39 have also been widely !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 33 (a) M. Aresta, Carbon Dioxide as Chemical Feedstock, Wiley-VCH, 2010; (b) Q. Liu, L. P. Wu, R. Jackstell, M. Beller, Nat. Commun. 2015, 6, 5933; (c) A. M. Appel, J. E. Bercaw, A. B. Bocarsly, H. Dobbek, D. L. DuBois, M. Dupuis, J. G. Ferry, E. Fujita, R. Hille, P. J. A. Kenis, C. A. Kerfeld, R. H. Morris, C. H. F. Peden, A. R. Portis, S. W. Ragsdale, T. B. Rauchfuss, J. N. H. Reek, L. C. Seefeldt, R. K. Thauer, G. L. Waldrop, Chem. Rev. 2013, 113, 6621; (d) Y. Li, X. Cui, K. Dong, K. Junge, M. Beller, ACS Catal. 2017, 7, 1077. 34 (a) J. Klankermayer, S. Wesselbaum, K. Beydoun, W. Leitner, Angew. Chem. Int. Ed. 2016, 55, 7296; (b) M. Aresta, A. Dibenedetto, A. Angelini, Chem. Rev. 2014, 114, 1709. 35 C. Chauvier, T. Cantat, ACS Catal. 2017, 7, 2107. 36 M. A. Benvenuto, Industrial Chemistry, De Gruyter, 2013. 37 (a) Y.-N. Li, R. Ma, L.-N. He, Z.-F. Diao, Catal. Sci. Technol. 2014, 4, 1498; (b) W.-H. Wang, Y. Himeda, J. T. Muckerman, G. F. Manbeck, E. Fujita, Chem. Rev. 2015, 115, 12936; (c) W. Wang, S. Wang, X. Ma, J. Gong, Chem. Soc. Rev. 2011, 40, 3703. 38 F. J. Fernández-Álvarez, A. M. Aitani, L. A. Oro, Catal. Sci. Technol. 2014, 4, 611. Chapter I. Ir-CNP complexes 46 investigated since they allow for the use of milder reaction conditions. In addition, the reactivity of these reducing agents can be tuned by varying the silane or borane substituents, facilitating access to different C1 products including CO, MeOH and CH4, as well as synthetically valuable formate and acetal derivatives.40 Hydroboration of CO2 is promoted by diverse species including nonmetal,41 main group metal,42 and transition metal catalysts,43,44,45-59 which mediate the reduction of CO2 to the formate, acetal or methoxide oxidation levels (Scheme 11). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 39 (a) C. C. Chong, R. Kinjo, ACS Catal. 2015, 5, 3238; (b) S. Bontemps, Coord. Chem. Rev. 2016, 308, 117. 40 A. Tlili, E. Blondiaux, X. Frogneux, T. Cantat, Green Chem. 2015, 17, 157. 41 (a) M.-A. Courtemanche, M.-A. Légaré, L. Maron, F.-G. Fontaine, J. Am. Chem. Soc. 2013, 135, 9326; (b) T. Wang, D. W. Stephan, Chem. Eur. J. 2014, 20, 3036; (c) Y. Yang, M. Xu, D. Song, Chem. Commun. 2015, 51, 11293; (d) A. Ramos, A. Antiñolo, F. Carrillo-Hermosilla, R. Fernández-Galán, A. Rodríguez-Diéguez, D. García-Vivó, Chem. Commun. 2018, 54, 4700; (e) S. C. Sau, R. Bhattacharjee, P. K. Vardhanapu, G. Vijaykumar, A. Datta, S. K. Mandal, Angew. Chem. Int. Ed. 2016, 55, 15147; (f) R. Declercq, G. Bouhadir, D. Bourissou, M.-A. Légaré, M.-A. Courtemanche, K. S. Nahi, N. Bouchard, F.-G. Fontaine, L. Maron, ACS Catal. 2015, 5, 2513; (g) M.-A. Courtemanche, M.-A. Légaré, L. Maron, F.-G. Fontaine, J. Am. Chem. Soc. 2014, 136, 10708; (h) C. Das Neves Gomes, E. Blondiaux, P. Thuéry, T. Cantat, Chem. Eur. J. 2014, 20, 7098; (i) T. Wang, D. W. Stephan, Chem. Commun. 2014, 50, 7007; (j) A. Tlili, A. Voituriez, A. Marinetti, P. Thuéry, T. Cantat, Chem. Commun. 2016, 52, 7553; (k) N. von Wolff, G. Lefèvre, J.-C. Berthet, P. Thuéry, T. Cantat, ACS Catal. 2016, 6, 4526; (l) G. Tuci, A. Rossin, L. Luconi, C. Pham-Huu, S. Cicchi, H. Ba, G. Giambastiani, Catal. Sci. Technol. 2017, 7, 5833. 42 (a) M. D. Anker, M. Arrowsmith, P. Bellham, M. S. Hill, G. Kociok-Köhn, D. J. Liptrot, M. F. Mahon, C. Weetman, Chem. Sci. 2014, 5, 2826; (b) D. Mukherjee, S. Shirase, T. P. Spaniol, K. Mashima, J. Okuda, Chem. Commun. 2016, 52, 13155; (c) D. Mukherjee, H. Osseili, T. P. Spaniol, J. Okuda, J. Am. Chem. Soc. 2016, 138, 10790; (d) T. J. Hadlington, C. E. Kefalidis, L. Maron, C. Jones, ACS Catal. 2017, 7, 1853; (e) J. A. B. Abdalla, I. M. Riddlestone, R. Tirfoin, S. Aldridge, Angew. Chem. Int. Ed. 2015, 54, 5098. 43 M. J. Sgro, D. W. Stephan, Angew. Chem. Int. Ed. 2012, 51, 11343. 44 S. Bontemps, L. Vendier, S. Sabo-Etienne, Angew. Chem. Int. Ed. 2012, 51, 1671. 45 R. Pal, T. L. Groy, R. J. Trovitch, Inorg. Chem. 2015, 54, 7506. Introduction ! 47 ! Scheme 11. Hydroboration of CO2 to the formate, acetal and methoxide oxidation levels. The accepted mechanism for the metal catalyzed hydroboration of CO2 assumes the formation of metal-H species and involves three sequential catalytic cycles (Figure 9).46 In the first cycle, CO2 insertion into the catalyst M–H bond forms a metal-formate intermediate that upon interaction with a borane molecule yields borylformate, HCO2BR2. The subsequent reduction of formoxyborane implies the insertion into the catalyst M–H bond to produce formaldehyde47 and, after interaction of the resulting M-OBR2 intermediate with a new borane molecule, bis(boryl)oxide as by-product, R2BOBR2 (cycle II). Finally, formaldehyde can be reduced to CH3OBR2 by a third molecule of hydroborane (cycle III). In cycle II, the bis(boryl)acetal product can also be formed if β -alkoxy elimination from the M-OCH2OBR2 intermediate and reaction with HBR2 occur. Therefore, as expected of a tandem catalytic process, a significant influence on the selectivity of both the catalyst and the nature of the borane, among other factors, is usually observed.46c !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 46 (a) F. Huang, C. Zhang, J. Jiang, Z.-X. Wang, H. Guan, Inorg. Chem. 2011, 50, 3816; (b) F. Huang, Q. Wang, J. Guo, M. Wenb, Z.-X. Wang, Dalton Trans. 2018, 47, 4804; (c) M. R. Espinosa, D. J. Charboneau, A. Garcia de Oliveira, N. Hazari, ACS Catal. 2019, 9, 301. 47 S. Bontemps, L. Vendier, S. Sabo-Etienne, J. Am. Chem. Soc. 2014, 136, 4419. CO2HOBR2 OR2BO OBR2 CH3OBR2 + R2BOBR2 [Cat] H H R2BH [Cat] R2BH [Cat] R2BH Chapter I. Ir-CNP complexes 48 ! Figure 9. Mechanism for the metal-catalyzed hydroboration of CO2.! MO H O MH HBR2 R2BO H O MO MH C H2 OBR2 Transmetallation Insertion CO2 Borylformate Cycle I Cycle II HBR2 MOCH3 MH Transmetallation Bis(boryl)oxide Cycle III H C H O HBR2 Transmetallation Methoxyborane R2BOCH3 MOBR2 R2BOBR2 Insertion Insertion β -Alkoxy Elimination R2BO C H2 OBHR2MH + HBR2 Transmetallation Bis(boryl)acetal Introduction ! 49 Hydroboration of CO2 with catecholborane catalyzed by transitionmetal complexes usually proceeds to the methoxide reduction level (Figure 10). Among the different catalysts reported for this transformation, nickel and palladium pincer complexes have provided the highest catalytic activities, with TOF values of up to 1,780-2,400 h-1.48, 49, 50, 51, 52 ! Figure 10. Ni and Pd pincer complexes employed in the hydroboration of CO2 with HBcat.! !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 48 T. Liu, W. Meng, Q.-Q. Ma, J. Zhang, H. Li, S. Li, Q. Zhao, X. Chen, Dalton Trans. 2017, 46, 4504. 49 Q.-Q. Ma, T. Liu, S. Li, J. Zhang, X. Chen, H. Guan, Chem. Commun. 2016, 52, 14262. 50 (a) S. Chakraborty, J. Zhang, J. A. Krause, H. Guan, J. Am. Chem. Soc. 2010, 132, 8872; (b) S. Chakraborty, J. Zhang, Y. J. Patel, J. A. Krause, H. Guan, Inorg. Chem. 2013, 52, 37; (c) S. Chakraborty, Y. J. Patel, J. A. Krause, H. Guan, Polyhedron 2012, 32, 30. 51 N. N. Wellala, H. T. Dong, J. A. Krause, H. Guan, Organometallics 2018, 37, 4031. 52 J. Zhang, J. Chang, T. Liu, B. Cao, Y. Ding, X. Chen, Catalysts 2018, 8, 508. CO2CH3OBcat +catBOBcat OPtBu2 OPtBu2 Ni H OPR2 OPR2 Pd SR’ R = iPr, tBu, Ph R’ = Ph, CH2Ph OPR2 OPR2 Ni SR’ R = iPr, tBu R’ = Ar, CH2Ar OPiPr2 OPiPr2 Ni H O O P P Ni H iPr2 iPr2 + 3 HBcat [Cat] 0.2 mol% C6H6, r.t. TON up to 495 TOF up to 495 h-1 TON up to 490 TOF up to 2400 h-1 TON up to 449 TOF up to 1780 h-1 TON up to 75 TOF up to 10.7 h-1 (1 bar) Chapter I. Ir-CNP complexes 50 Although CO2 can also be reduced to methanol equivalents with less reactive boranes such as HBpin (pinacolborane) or 9-BBN (9- borabicyclo[3.3.1]nonane), selective reduction of CO2 to the formate and acetal oxidation levels can be achieved by a proper selection of the catalyst. For example, Cu-NHC complexes have been found to be efficient catalysts for the selective hydroboration of CO2 with HBpin to formoxyborane, which has been proven to serve as a formate source for synthetic purposes (Figure 11).53,54,55 Similarly, ruthenium complexes based on lutidine-derived CNC ligands56 and a Pd-PSiP pincer complex57 provided high catalytic activities in the selective reduction of CO2 to the formate level (Figure 11). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 53 R. Shintani, K. Nozaki, Organometallics 2013, 32, 2459. 54 A. Burgun, R. S. Crees, M. L. Cole, C. J. Doonan, C. J. Sumby, Chem. Commun. 2014, 50, 11760. 55 S. Bagherzadeh, N. P. Mankad, J. Am. Chem. Soc. 2015, 137, 10898. 56 C. Koon Ng, J. Wu, T. S. Andy Hor, H.-K. Luo, Chem. Commun. 2016, 52, 11842. 57 H.-W. Suh, L. M. Guard, N. Hazari, Chem. Sci. 2014, 5, 3859. Introduction ! 51 ! Figure 11. Examples of metal complexes for the hydroboration of CO2 with HBpin, and synthetic applications of the resulting formoxyborane. Acetal derivatives resulting from the partial reduction of CO2 have been employed as methylene transfer reagents giving rise to the formation of new E-C bonds (E = N, C, O, P). At this respect, selective hydroboration of carbon dioxide to bis(boryl)acetal was carried out with HBpin using [RuH2(H2)2(PCyp3)2]47 and nickel-PSiP58 complexes as catalyst, and with 9- BBN catalyzed by the [Fe(H)2(dmpe)2] complex (dmpe = Me2PCH2CH2PMe2) (Figure 12).59 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 58 L. J. Murphy, H. Hollenhorst, R. McDonald, M. Ferguson, M. D. Lumsden, L. Turculet, Organometallics 2017, 36, 3709. 59 G. Jin, C. G. Werncke, Y. Escudié, S. Sabo-Etienne, S. Bontemps, J. Am. Chem. Soc. 2015, 137, 9563.! N N Ar Ar Cu OtBu CO2+ HBpin [Cu] 10 mol% THF, 24 h, 35 ºC HOBpin O Et3N, THF 65 ºC, 45 h HNHR O RNH2 Si Pd Me PCy2 PCy2 H N NN N R N R Ru CO H CO PF6 CO2+ HBpin [Pd] 1-0.001 mol% C6D6, r.t. 10 min - 5 days HOBpin O (1 bar) CO2+ HBpin [Ru] 1 mol% KOtBu 2.5 mol% CD2Cl2, r.t. 30 min HOBpin O (1 bar) + pinBOBpin (1 bar) Ar = 2,6-iPr-Ph Chapter I. Ir-CNP complexes 52 ! Figure 12. Catalysts used in the selective hydroboration of CO2 with HBpin and 9-BBN to bis(boryl)acetal, and synthetic applications. Ru H H H2 H2 PCyp3 PCyp3 N Si N Ni Me PiPr2 PiPr2 H 1 bar CO2, HBpin [Ru] 1-10 mol% C6D6, 1 h, r.t. 1 bar CO2, HBpin [Ru] 0.2 mol% C6D6, 1-4 h, r.t. Fe Me2P Me2P H H PMe2 PMe2 1 bar CO2, 9-BBN [Fe] 5 mol% THF-d8, 47 min, r.t. (R2BO)2CH2 AriPrNH2N iPr iPr CH2 2 HMeNPh PhMeN H2 CNMePh Ph3P=CHPh Ph CH2 R = OH, NHMe X N Me R H NMe OH tBu tBu 2 OH tBu tBu OH tBu tBu CO2 (1 bar) + HBR2 [Cat.] I.2. Results and discussion Chapter I. Ir-CNP complexes 60 ! Scheme 2. Synthesis and reactivity of palladium complexes 3-6. Table 1. Selected NMR data for palladium complexes 3-6.a [Pd] δ (31P) δ (1H) δ (13C) CH2N CH2P / CHP C-2 NHC CO MeCN 3 34.8 6.05 4.32 (d) (JHP = 11.3) 166.4 (d) (JCP = 183) - - 4 43.7 5.81 4.59 (d) (JHP = 12.3) 163.1 (d) (JCP = 161) - 118.8 (br) 5 48.2 5.91 4.83 (d) (JHP = 13.2) 164.8 (d) (JCP = 142) 169.7 (d) (JCP = 11) - 6b 25.3 4.87 3.41 (s) 175.1 (d) (JCP = 166) - - a NMR spectra registered in CD2Cl2, unless otherwise noted. Chemical shifts (δ) are given in ppm. Coupling constants (J) are given in Hz. b NMR spectra registered in THF-d8. 2a(Cl) i) Ag2O ii) PdCl2(COD) CH2Cl2THF KHMDS CO 2 AgBF4 MeCN/CH2Cl2 36 45 N N PPh2 NMes Pd Cl AgCl2 N N PPh2 NMes Pd Cl N N PPh2 NMes Pd NCMe (BF4)2 N N PPh2 NMes Pd CO (BF4)2 Results and Discussion ! 61 NMR data for complex 3 support the formation of a square-planar complex in which the CNP ligand is coordinated to the metal center as a pincer. A single crystal X-ray diffraction study of 3 confirmed the proposed structure (Figure 3). As anticipated, in the solid state the Pd atom shows a planar-square coordination sphere, as reflected in the values of the angles C(1)–Pd(1)–P(1) and N(3)–Pd(1)–Cl(1) of 168.65o and 175.03o, respectively. Moreover, the NHC–Pd–Py chelate ring presents a boat conformation as determined by the torsion angle C(14)–N(3)–Pd(1)–C(1) of 32.4o, whereas the 5-membered ring involving the phosphine donor has an envelope conformation with a C(18)–N(3)–Pd(1)–P(1) dihedral angle of 28.4o. Chapter I. Ir-CNP complexes 62 ! Bond lenghts (Å) Angles (º) C(1)–Pd(1)–P(1) 168.65(16) Pd(1)–C(1) 2.038(6) N(3)–Pd(1)–Cl(1) 175.03(14) Pd(1)–N(3) 2.071(4) P(1)–Pd(1)–Cl(1) 93.97(5) Pd(1)–P(1) 2.2623(15) P(1)–Pd(1)–N(3) 81.34(14) Pd(1)–Cl(1) 2.2758(14) C(1)–Pd(1)–Cl(1) 95.93(16) C(1)–Pd(1)–N(3) 88.6(2) Figure 3. ORTEP drawing at 30% ellipsoid probability, and selected bond lengths (Å) and angles (o), of the cationic component of complex 3. Hydrogen atoms and solvent molecules (CH2Cl2) have been omitted for clarity. Results and Discussion ! 63 Halide abstraction from 3 with AgBF4 in a CH2Cl2/MeCN solution mixture provided complex 4 (Scheme 2). This derivative was only stable in the presence of small amounts of MeCN, and therefore could not be isolated with analytical purity. Since the NMR data for this complex are similar to those of 3 (Table 1), with the exception of the presence of signals attributable to the MeCN ligand, an analogous structure can be anticipated. Upon submitting the acetonitrile complex 4 to 1 bar of CO, ligand exchange occurred and partial transformation of 4 to the carbonyl complex 5 was observed. Interestingly, complexes 4 and 5 were in equilibrium, and CO removal produced the complete regeneration of 4. In the 13C{1H} NMR spectrum of 5, doublet signals at 169.7 (JCP = 11 Hz) and 164.8 ppm (JCP = 142 Hz) appear, which are assignable to the CO ligand and the C2-NHC carbon, respectively. To determine the acid/base reactivity of the Pd-CNPPh complexes, deprotonation of 3 was investigated.66 Addition of KHMDS (1.1 equiv) to a suspension in THF-d8 of 3 produced the selective deprotonation of the CNPPh ligand at the CH2P arm yielding complex 6 as the sole observable product. In the 1H NMR spectrum of 6, the =CHP fragment appears as a singlet resonance at 3.41 ppm (integrating to 1H), whereas the methylene CH2N produces a singlet at 4.87 ppm (integrating to 2H). Moreover, a significant upfield shift for the signals of the pyridine protons appearing in the range 5.55–6.46 ppm is observed, in accordance with the expected dearomatization of the ring. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 66 (a) J. I. van der Vlugt, M. A. Siegler, M. Janssen, D. Vogt, A. L. Spek, Organometallics 2009, 28, 7025; (b) M. Feller, E. Ben-Ari, M. A. Iron, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon, L. Konstantinovski, D. Milstein, Inorg. Chem. 2010, 49, 1615; (c) W. D. Bailey, W. Kaminsky, R. A. Kemp, K. I. Goldberg, Organometallics 2014, 33, 2503. Chapter I. Ir-CNP complexes 64 I.2.2.3. Synthesis, reactivity and catalytic applications of olefin Ir- CNPPh complexes I.2.2.3.a) Synthesis and structural features of olefin Ir-CNPPh complexes Reactions of imidazolium salts 2 with [Ir(acac)(COD)] in CH2Cl2 yielded the cationic complexes 7 (Scheme 3). These olefin derivatives were isolated as yellow to orange solids that were stable in the solid state to the atmospheric conditions. Complexes 7 present very similar features in their NMR spectra. As exemplified with 7a(Cl), in the 1H NMR spectrum (Figure 4) the CH2P protons are non-equivalent and appear as an overlapped resonance at δ 3.45 and a doublet of doublets at 3.97 ppm (2JHH = 14.8 Hz, 2JHP = 11.5 Hz); whereas the CH2N bridge hydrogens produce two doublets at δ 5.56 and 7.12 (2JHH = 14.0 Hz) (Figure 4). The olefinic protons cause two broad signals at 2.93 and 3.45 ppm, integrating for two protons each. In the 13C{1H} NMR spectrum, the C2-NHC carbon originates a doublet at 164.5 ppm with a small JCP coupling constant of 8 Hz, evidencing a cis arrangement of the phosphine and NHC donors, and therefore a fac coordination of the CNPPh ligand. Results and Discussion ! 65 ! Scheme 3. Synthesis of cationic iridium complexes 7.! ! Figure 4. Region of the 1H NMR spectrum (400 MHz, CD2Cl2) of complex 7a(Cl) (* denotes residual CH2Cl2). Since attempted crystallization of the above complexes did not yield X-ray quality crystals, anion exchange in complex 7b(Br) was carried out by reaction with NaBArF in CH2Cl2 (Scheme 3). The obtained complex 7b(BArF) shows similar NMR data to those of 7b(Br), and its structure has been studied by single crystal X-ray diffraction (Figure 5). In the solid state, complex 7b(BArF) is conveniently described as adopting a distorted trigonal bipyramidal geometry, despite the acute P–Ir–N(Py) bond angle of 75.98(8)o. Ir(acac)(COD) 7a(Cl): Ar = Mes 7b(Cl): Ar = Xyl 7b(Br): Ar = Xyl X Ir N N N Ar P Ph2 2 CH2Cl2CH2Cl2 NaBArF BArF Ir N N N Xyl P Ph2 7b(BArF) Chapter I. Ir-CNP complexes 66 As anticipated, the CNPPh ligand coordinates in a facial mode; the NHC moiety ocuppies the apical position (P–Ir–C(NHC) = 95.61(10)o), and the pyridine and phosphine fragments are bound to the metal in the equatorial plane. In addition, the chelate ring involving the phosphine and pyridine fragments exhibits an envelope conformation (C(17)–N(3)–Ir(1)–P(1) = 29.5o), while the six-membered chelate ring containing the NHC donor adopts a boat-like conformation (C(13)–N(3)–Ir(1)–C(1) = −50.6o). The facial coordination of the CNPPh ligand, at variance with the mer arrangement showed by lutidine-derived PNP ligands, may be attributed to the larger flexibility of the six-membered Py–M–NHC chelate ring.67 Moreover, this C(NHC)ax–N(Py)eq–Peq coordination of the ligand differs significantly from previously reported pentacoordinated d8 pincer complexes that usually exhibit an equatorial–axial–equatorial distribution of the ligand donors.68,69,12 Finally, as observed with other pentacoordinated diolefin Ir complexes,69 slightly longer distances from the metal to the C=C bond centroids for the alkene coordinated trans to the NHC than for the olefin placed in the meridional plane (Δd(Ir-centroid C=C) = 0.14 Å) are observed. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 67 (a) M. Hernández-Juárez, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Dalton Trans. 2013, 42, 351; (b) M. Hernández-Juárez, J. López-Serrano, P. Lara, J. P. Morales-Cerón, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Chem. Eur. J. 2015, 21, 7540. 68 G. A. Silantyev, O. A. Filippov, S. Musa, D. Gelman, N. V. Belkova, K. Weisz, L. M. Epstein, E. S. Shubina, Organometallics 2014, 33, 5964. 69 (a) D. M. Roddick, D. Zargarian, Inorg. Chim. Acta 2014, 422, 251; (b) G. Mancano, M. J. Page, M. Bhadbhade, B. A. Messerle, Inorg. Chem. 2014, 53, 10159; (c) P. D. Newman, K. J. Cavell, A. J. Hallett, B. M. Kariuki, Dalton Trans. 2011, 40, 8807; (d) B. M. Kariuki, J. A. Platts, P. D. Newman, Dalton Trans. 2014, 43, 2971; (e) M. Iglesias, A. Iturmendi, P. J. Sanz Miguel, V. Polo, J. J. Pérez-Torrente, L. A. Oro, Chem. Commun. 2015, 51, 12431. Results and Discussion ! 67 Bond lenghts (Å) Angles (º) Ir(1)–C(1) 2.029(4) Ir(1)–N(3) 2.253(3) Ir(1)–P(1) 2.3412(9) C(1)-Ir(1)-P(1) 95.61(10) Ir(1)–C(31) 2.263(4) N(3)–Ir(1)–P(1) 75.98(8) Ir(1)–C(32) 2.217(4) N(3)–Ir(1)–C(1) 81.07(13) Ir(1)–C(35) 2.140(3) Ir(1)–C(36) 2.101(4) Figure 5. ORTEP drawing at 30% ellipsoid probability, and selected bond lengths (Å) and angles (o), of the cationic component of complex 7b(BArF). Hydrogen atoms and solvent molecules (CH2Cl2) have been omitted for clarity.! Chapter I. Ir-CNP complexes 68 As mentioned above, the olefinic protons of the COD ligand in complexes 7 produce two broad signals (integrating for 2H each) in the 1H NMR spectrum recorded at 25 oC, suggesting the existence of a dynamic behavior involving the cyclooctadiene rings. Moreover, 1H–1H COSY and 1H–1H NOESY experiments indicate that each signal is produced by protons of different olefinic moieties; i.e. the same resonance is produced by the H1b and H2b protons, while the H1a and H2a hydrogens originate another resonance (Figure 4). Therefore, the solution dynamics of the diolefin complexes 7 were studied by registering 1H NMR spectra of complex 7a(Cl) in the temperature range between 50 and −80 ºC (Figure 6). The olefinic signals, appearing at 2.98 and 3.49 ppm at 25 oC, broaden upon lowering the temperature and eventually split at temperatures below −25 oC into two sets of two signals each, appearing at δ 2.23 (H2b) and 3.39 (H1b), and 2.86 (H2a) and 3.90 (H1a), respectively. A value of ΔG‡ = 10.9 kcal mol−1 at the coalescence temperature (244 K) was estimated for the fluxional process.70 The observed dynamic process can be attributed to olefin site exchange involving the decoordination of the C=C bond trans to the NHC fragment leading to a distorted tetrahedral intermediate A, followed by re-coordination of the free olefin moiety to the opposite side without lost of the fac coordination mode of the CNP ligand (Figure 7). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 70 J. Sandström, Dynamic NMR Spectroscopy, Academic Press, 1982. Chap. 6. Results and Discussion ! 69 ! Figure 6. VT-1H NMR spectra of 7a(Cl) (400 MHz, CD2Cl2).! Chapter I. Ir-CNP complexes 76 ! Scheme 6. Synthesis of the chlorodihydride complexes 10, and reaction of 10b with H2 in the presence of KOtBu. ! Figure 11. Regions of the 1H NMR spectrum (CD2Cl2, 400 MHz) of complex 10a (* denotes CH2Cl2). Crystals of the complexes 10a and 10b adequate for X-ray diffraction studies were obtained from saturated CH2Cl2/hexane or THF solutions, respectively (Figures 12 and 13). In the solid state, these complexes are isostructural and show an octahedral geometry with a cis arrangement of the two hydrido ligands and the CNPPh pincer adopting a meridional H2 (5 bar) THF-d8 H2 (5 bar) THF-d8 9 7(Cl) 10a: Ar = Mes 10b: Ar = 3,5-Xyl N N PPh2 NAr Ir H Cl HKOtBu N N PPh2 NXyl Ir H H H Results and Discussion ! 77 coordination, as defined in the structure of 10a by the C(1)–Ir(1)–P(1) angle value of 166.5(3)o. In this complex, the torsion angle of −26.5(9)o for C(14)– N(3)–Ir(1)–C(1) denotes a boat-like conformation for the chelate ring incorporating the NHC arm, while the C(18)–N(3)–Ir(1)–P(1) dihedral angle of −14.9(8)o evidences an envelope conformation for the five membered chelate ring. Moreover, there exist short contacts (2.76 Å (10a) and 2.74 Å (10b)) between the axial hydrogens of the CH2N arms and the chloride ligands suggestive of the existence of a weak hydrogen bond (sum of van der Waals radii of H and Cl: 2.9-3.0 Å).63,72 This interaction is also manifested in the 1H NMR spectra of 10a and 10b in the significant deshielding of the doublet resonances corresponding to the axial CHHN hydrogens (10a: δH = 6.70 ppm, 2JHH = 14.6 Hz; 10b: δH = 6.53 ppm, 2JHH = 14.4 Hz) !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 72 J. Reedijk, Chem. Soc. Rev. 2013, 42, 1776. Chapter I. Ir-CNP complexes 78 ! Bond lenghts (Å) Angles (º) Ir(1)–C(1) 2.037(10) C(1)–Ir(1)–P(1) 166.5(3) Ir(1)–N(3) 2.192(9) N(3)–Ir(1)– H(1)Ir 173.9 Ir(1)–P(1) 2.262(3) P(1)–Ir(1)–H(1)Ir 92.7 Ir(1)–H(1)Ir 1.600 P(1)–Ir(1)–N(3) 82.2(3) Ir(1)–H(2)Ir 1.599 C(1)–Ir(1)–H(1)Ir 95.4 Ir(1)–Cl(1) 2.509(3) C(1)–Ir(1)–N(3) 89.0(4) Figure 12. ORTEP drawing at 30% ellipsoid probability, and selected bond lengths (Å) and angles (o), of complex 10a. Hydrogen atoms, except hydrido ligands, and solvent molecules (CH2Cl2) have been omitted for clarity. ! Results and Discussion ! 79 Bond lenghts (Å) Angles (º) Ir(1)–C(1) 2.018(3) C(1)–Ir(1)–P(1) 165.20(8) Ir(1)–N(3) 2.186(2) N(3)–Ir(1)– H(1)Ir 178.7(10) Ir(1)–P(1) 2.2521(7) P(1)–Ir(1)–H(1)Ir 97.8(11) Ir(1)–H(1)Ir 1.591(17) P(1)–Ir(1)–N(3) 81.92(6) Ir(1)–H(2)Ir 1.574(17) C(1)–Ir(1)–H(1)Ir 91.6(10) Ir(1)–Cl(1) 2.5022(8) C(1)–Ir(1)–N(3) 88.89(9) Figure 13. ORTEP drawing at 30% ellipsoid probability, and selected bond lengths (Å) and angles (o), of complex 10b. Hydrogen atoms, except hydrido ligands, and solvent molecules (THF) have been omitted for clarity. Chapter I. Ir-CNP complexes 80 ! Reversible H/D exchange of the hydrido ligands, albeit no deuteration of the methylene bridges of the CNPPh ligand, rapidly took place after exposure of a sample of 10a in CD2Cl2 to deuterium gas (2 bar) at 45 oC (Scheme 7). Similarly, the same outcome was observed upon treating a sample of 10a with CD3OD for 24 h. ! Scheme 7. Reactions with D2 and CD3OD of 10a. Finally, reaction of the chlorodihydride complex 10b with H2 (5 bar) in the presence of KOtBu (1 equiv) in THF-d8 produced the quantitative formation of the trihydride derivative 9. This transformation likely involves a ligand-assisted H—H splitting (Scheme 6). 10a-d N N PPh2 NMes Ir H/D Cl H/D 10a N N PPh2 NMes Ir H Cl H 99% D 99% D i) or ii) i) D2 (2 bar), CD2Cl2, 45 ºC, 6 h ii) CD3OD, 24 h Results and Discussion ! 81 I.2.2.3.c) Hydrogenation of ketones catalyzed by Ir-CNPPh complexes Iridium trihydride complexes analogous to derivative 9 based on lutidine-derived PNP ligands are active catalysts in hydrogenation reactions.20 Therefore, since the trihydride complex 9 is readily obtained by reaction of 7b(Br) with H2 in the presence of base, the Ir–CNPPh complexes 7 were examined as catalyst precursors in the hydrogenation of ketones (Table 2).24,73 In the presence of 15 mol% of KOtBu, complex 7a(Cl) catalyzed the hydrogenation of acetophenone (11a) under 4 bar of H2 at 30 ºC in 2- methyltetrahydrofuran using 1.0 mol% of catalyst with 95% conversion after 16 h (entry 1). Catalyst loading could be decreased to 0.4 mol% by heating the reaction to 60 ºC without a significant influence on the reaction rate (entry 2). Moreover, at this temperature, the pressure of H2 could be reduced to 1 bar leading to full conversion of 11a (entry 3). Finally, under the latter conditions, complex 7b(Cl) was found to be slightly less active than its mesityl counterpart (entry 4). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 73 For selected examples of ketone hydrogenation catalyzed by Ir complexes with protonresponsive ligands: (a) L. Dahlenburg, R. Götz, Eur. J. Inorg. Chem. 2004, 888; (b) C. S. Letko, Z. M. Heiden, T. B. Rauchfuss, Eur. J. Inorg. Chem. 2009, 4927; (c) J. E. D. Martins, M. Wills, Tetrahedron 2009, 65, 5782; (d) J.-H. Xie, X.-Y. Liu, J.-B. Xie, L.-X. Wang, Q.-L. Zhou, Angew. Chem. Int. Ed. 2011, 50, 7329; (e) W. W. N. O, A. J. Lough, R. H. Morris, Organometallics 2012, 31, 2152. Chapter I. Ir-CNP complexes 82 Table 2. Hydrogenation of ketones catalyzed by Ir-CNPPh complexes.a Entry Ketone Ir-CNPPh T (ºC) Conv. (%) 1b Acetophenone (11a) 7a(Cl) 30 95 2b,c 60 93 3 60 >99 4 7b(Cl) 60 98 5 4’-Methoxyacetophenone (11b) 7a(Cl) 80 96 6 4’-Chloroacetophenone (11c) >99 7 2’-Bromoacetophenone (11d) 99 8 2’-Fluoroacetophenone (11e) 82 9 (11f) 89 a Reaction conditions, unless otherwise noted: 1 bar of H2, 2-methyltetrahydrofuran, 1.0 mol% [Ir], 15 mol% KOtBu, 16 h. [S] = 0.1 M. Conversion was determined by 1H NMR spectroscopy. b 4 bar of H2. c 0.4 mol% [Ir]. O H2 11 12 [Ir], KOtBu 2-MeTHF R OH R O Results and Discussion ! 83 Next, the hydrogenation of a series of substituted acetophenones was also studied using complex 7a(Cl). At 80 oC and under 1 bar of H2, using 1.0 mol% of catalyst, p-methoxy-, p-chloro- and o-bromoacetophenone (11b- 11d) were reduced with high conversions to their corresponding secondary alcohols 12b-12d (entries 5-7). However, the hydrogenation of ofluoroacetophenone (11e) was sluggisher (entry 8). Finally, under the same conditions, the reduction of α -tetralone (11f), a cyclic ketone, also proceeded with high conversion (entry 9). The catalytic activity of complex 7a(Cl) was also tested in the reduction of ketones using isopropanol as the hydrogen source (Table 3).23,25! In these reactions, a small catalyst loading of 0.1 mol% was employed. Thus, acetophenone was reduced at 80 ºC in 16 hours with 98% conversion (entry 1). The reduction of other acetophenones was also assayed and high conversions were achieved for the p-chloro and o-fluoro derivatives, whereas the p-methoxy- and o-bromoacetophenone were reduced with lower rates (entries 2-5). Finally, a low catalytic activity of 7a(Cl) in the hydrogenation of α -tetralone with iPrOH was observed (entry 6). Chapter I. Ir-CNP complexes 84 Table 3. Transfer hydrogenation of ketones catalyzed by complex 7a(Cl).a ! Entry Ketone Conv. (%) 1 b Acetophenone (11a) 98 2 4’-Methoxyacetophenone (11b) 70 3 4’-Chloroacetophenone (11c) 95 4 2’-Bromoacetophenone (11d) 55 5 2’-Fluoroacetophenone (11e) 99 6 (11f) 6 a Reaction conditions, unless otherwise noted: iPrOH, 80 ºC, 0.1 mol% 7a(Cl), 15 mol% KOtBu, [S] = 0.8 M. Reaction time: 16 h. Conversion was determined by 1H NMR spectroscopy. b [S] = 1.2 M. O iPrOH 11 12 [Ir], KOtBu R OH R O Results and Discussion ! 85 I.2.2.4. Synthesis, reactivity and catalytic applications of carbonyl Ir-CNPPh complexes I.2.2.4.a) Synthesis and reactivity of carbonyl Ir-CNPPh complexes The cyclooctadiene ligand in complexes 7 is readily displaced by carbon monoxide, as inferred from the reaction of 7a(Cl) with CO in CH2Cl2 (Scheme 8). The 1H NMR spectrum of the carbonyl complex 13(Cl) evidences a planar coordination of the CNPPh since the methylene bridge of the phosphine arm appears as a doublet at 4.18 ppm (2JHP = 10.0 Hz) and the CH2N hydrogens produce a singlet at 6.11 ppm. Moreover, in the 13C{1H} NMR spectrum, the CO ligand appears at 177.2 ppm (d, 2JCP = 10 Hz), while the resonance for the C-2 NHC carbon is found at 178.1 ppm as a doublet signal with a large coupling constant of 2JCP = 99 Hz, further supporting the proposed mutually trans arragement of the carbene and the phosphino donor groups. Complex 13(Cl) allowed us to evaluate the donating properties of the new CNPPh ligands. The carbonyl ligand of 13(Cl) absorbs in the IR spectrum at 1985 cm−1, which is a higher frequency than that corresponding to the [Ir(PNPtBu)(CO)]PF6 analogue complex (1964 cm−1),10,74 suggesting a lower electron density at the metal center in the Ir–CNPPh system. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 74 E. Ben-Ari, R. Cohen, M. Gandelman, L. J. W. Shimon, J. M. L. Martin, D. Milstein, Organometallics 2006, 25, 3190. Chapter I. Ir-CNP complexes 92 Bond lenghts (Å) Angles (º) Ir(1)-C(1) 2.034(8) C(1)-Ir(1)-P(1) 168.3(2) Ir(1)-N(3) 2.127(5) C(1)-Ir(1)-C(32) 97.2(3) Ir(1)-P(1) 2.285(2) C(32)-Ir(1)-N(3) 172.9(3) Ir(1)-C(32) 1.818(8) C(1)-Ir(1)-N(3) 89.7(2) C(18)-C(19) 1.370(10) P(1)-Ir(1)-N(3) 82.64(16) P(1)-C(19) 1.743(7) C(32)-Ir(1)-P(1) 90.3(2) Figure 18. ORTEP drawing at 30% ellipsoid probability, and selected bond lengths (Å) and angles (º), of complex 15a. All hydrogen atoms except the methyne proton and solvent molecule (THF) have been omitted for clarity. N N N Ir PPh2 Mes 1.74 1.37 1.46 1.34 1.40 1.38 1.36 1.40 CO Results and Discussion ! 93 As mentioned above, the ratio of complexes 15a and 15b in solution depends on the solvent, in strong agreement with the existence of an equilibrium between the tautomers. Further support for the proposed equilibrium was obtained from the 1H-1H EXSY spectrum of 15a/15b in wet THF-d8 registered at 25 ºC (Figure 19). Intense exchange cross-peaks were observed between the signals of the methyne and methylene fragments of 15a and 15b with those of water (red squares). Moreover, cross-peaks due to exchange between the hydrogens of the CHP and CH2N bridges of 15a (blue square), and the protons of the CHP and CH2N moieties of 15a with those of the CH2P and CHN moieties of 15b, respectively, were also detected (green squares). These observations indicate that interconversion between the tautomeric species 15a and 15b should take place both intra- and intermolecularly throught reversible protonation/deprotonation mediated by water acting as proton shuttle.79 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 79 T. Cheisson, A. Auffrant, Dalton Trans. 2016, 45, 2069. Chapter I. Ir-CNP complexes 94 Figure 19. Region of the 1H-1H EXSY spectrum of 15a/15b in wet THF-d8 (500 MHz, 25 ºC). I.2.2.4.b) Hydroboration of CO2 catalyzed by carbonyl Ir-CNPPh complexes The catalytic performance of complexes 15a/15b in the hydroboration of CO2 with catecholborane (HBcat) was explored. Reactions were carried out under 2 bar of CO2 using 1.0 mol% of 15a/15b in THF-d8 at 30 ºC. Selective reduction of CO2 to the methoxyborane derivative (CH3OBcat) was confirmed by the appearance of a singlet at 3.81 ppm in the 1H{11B} NMR spectra of the catalytic reactions, and a broad signal in the 11B NMR spectra at 22.5 ppm (Figures 20 and 21). Also, the concomitant formation of diboroxane, catBOBcat, was established by the precipitation of Results and Discussion ! 95 a white solid after removal of THF-d8 under vacuum and addition of C6H6. This precipitate produces in the 1H NMR spectrum (THF-d8) two multiplets centered at δ 6.83 and 6.93, and in the 11B NMR experiment a broad signal at δ 16.5, which coincide with the literature spectroscopic data for catBOBcat.80 ! Figure 20. 1H{11B} NMR spectrum (400 MHz, THF-d8) of the hydroboration of CO2 with HBcat catalyzed by 15a/15b (Table 4, entry 2). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 80 A. Lang, J. Knizek, H. Nöth, S. Schur, M. Thomann, Z . Anorg. Allg. Chem. 1997, 623, 901. Chapter I. Ir-CNP complexes 96 ! Figure 21. 11B NMR spectrum (128 MHz, THF-d8) of the hydroboration of CO2 with HBcat catalyzed by 15a/15b (Table 4, entry 2) (*, B5H9 and other boron species from commercial HBcat). Initial catalytic reactions were found difficult to reproduce. Consequently, a detailed screening of the reaction parameters was carried out, evidencing that the presence of water has a significant influence on the reaction rate. Table 4 collects the results of the hydroboration of CO2 with HBcat catalyzed by complexes 15a/15b in the presence of variable amounts of water. While all the reactions proceeded to completion after prolongued reaction times, for a meaningful comparison of the catalytic activity, TON values were determined after 1.5 h. Results and Discussion ! 97 Table 4. Hydroboration of CO2 with HBcat catalyzed by carbonyl Ir-CNPPh complexes.a Entry Catalyst H2O (mol%) Yield (%) TON 1 15a/15b 1 18 54 2 3 24 72 3 5 28 84 4 6 25 75 5b 13(Cl) 3 26 78 a Reaction conditions: 1.0 mol% [Ir], 2 bar CO2, 30 ºC, THF-d8, [HBcat] = 0.5 M. Reaction time: 1.5 h, unless otherwise noted. Conversions were determined by 1H{11B} NMR spectroscopy using hexamethylbenzene as internal standard. TON values based on moles of B-H bonds reacted per mole catalyst: (mmol methoxyborane × 3)/(mmol Ir). b Reaction time: 16 h. In the presence of 1 mol% of H2O, formation of 18% of methoxyborane was observed (TON = 54; TOF = 36 h-1) (entry 1). A gradual increase of the water content up to 5 mol% produced a faster transformation of CO2 to methoxyborane, reaching up to 28% conversion (TON = 84; TOF = 56 h-1) (entries 2 and 3). However, a further increase of the amount of water to 6 mol% led to a slight erosion in the catalytic activity (entry 4). It is interesting to note that complex 13(Cl) was a poorer catalyst than 15a/15b providing 78 turnovers after 16 h (entry 5). CO2+ 3 HBcat [Ir] cat. THF-d8 CH3OBcat + catBOBcat Chapter I. Ir-CNP complexes 98 Since a significant dependence on the hydroborane nature in the reaction rate and selectivity can be expected, the catalytic hydroboration of CO2 with pinacolborane (HBpin) was also investigated. As in the case of the reactions with HBcat, a marked influence of the presence of water was noticed. Catalytic reactions were carried out with low catalyst loadings of 0.2 mol% of 15a/15b and using 1 bar of CO2 at 30 ºC (Table 5). Although, the use of pinacolborane in the hydroboration of CO2 may proceed to the formate (HCO2Bpin), acetal (H2C(OBpin)2) or methoxy (CH3OBpin) derivatives, or mixtures thereof, formation of formoxyborane was found kinetically limiting (Figure 22 and 23). ! Figure 22. 1H{11B} NMR spectrum (400 MHz, THF-d8) of the hydroboration of CO2 with HBpin catalyzed by 15a/15b (Table 5, entry 3) (reaction time: 10 min). (* solvent residual signals). Results and Discussion ! 99 ! Figure 23. 11B (top) and 11B{1H} (bottom) NMR spectra (128 MHz, THF-d8) of the hydroboration of CO2 with HBpin catalyzed by 15a/15b (Table 5, entry 3) (reaction time: 10 min). ! Chapter I. Ir-CNP complexes 100 Table 5. Hydroboration of CO2 with HBpin catalyzed by 15a/15b.a Entry H2O (mol%) Yield (%) TON 1 1 30 150 2 2 72 360 3 3 79 395 4 6 80 400 5 7 83 415 6b 3 74 740 a Reaction conditions, unless otherwise noted: 0.2 mol% 15a/15b, 1 bar CO2, 30 ºC, THF-d8, [HBpin] = 0.4 M. Reaction time: 20 min. Conversions were determined by 1H{11B} NMR spectroscopy using hexamethylbenzene as internal standard. TON values as determined from (mmol HCO2Bpin)/(mmol Ir). b 0.1 mol% 15a/15b. Reaction time: 1.0 h. All the reactions proceeded to conversions of HBpin higher than 90%, although TON values were compared after a reaction time of 20 min. In the presence of 1 mol% of water, the formoxyborane derivative was obtained in 30% yield (TOF = 450 h-1, entry 1), whereas upon sucessive additions of water up to 7 mol% a ca. three-fold rise of the catalytic activity was observed (TOF = 1,245 h-1) (entries 2-5). It should be pointed out that in the presence of 7 mol% of water, the maximum theoretical yield of formoxyborane is 86% after taking into account the hydrolysis of pinacolborane to pinBOBpin. CO2+HBpin THF-d8 O OBpin H 15a/15b Results and Discussion ! 101 Moreover, lower catalyst loadings were tested for this reaction. With 0.1 mol% of 15a/15b, a 74% NMR yield of HCO2Bpin after 1 h was obtained, which represents a notable TOF value of 740 h-1 (entry 6). Among the few catalysts that selectively perform the hydroboration of CO2 to formoxyborane,42c,53,54,56,57 only a palladium pincer complex reported by Hazari et al. provides faster reaction rates with low catalyst loadings (TOF >8,500 h-1 with 0.01 mol% Pd).57 I.2.2.4.c) Metal species formed under catalytic conditions In an attempt to study the metal species formed under catalytic conditions, the hydroboration of CO2 with HBcat in THF-d8 using 20 mol% of 15a/15b was investigated by NMR spectroscopy. After reaction completion, a single peak at 16.9 ppm was observed in the 31P{1H} NMR spectrum; whereas the 1H NMR experiment showed the formation of a dihydride compound as deduced from the appearance of two doublets of doublets signals at −17.5 (2JHP = 12 Hz, 2JHH = 2 Hz) and −8.3 ppm (2JHP = 22 Hz, 2JHH = 2 Hz). To unequivocally identify this newly formed species, a solution of 15a/15b in THF-d8 was exposed to H2 (5 bar) (Scheme 10), leading to the quantitative formation of a species, 16, characterized in the 1H NMR spectrum by two doublets of doublets appearing at δ −8.64 (2JHP = 20.8 Hz, 2JHH = 1.5 Hz) and δ −16.59 (2JHP = 11.3 Hz, 2JHP = 1.5 Hz). Derivative 16 contains a deprotonated CNPPh ligand as inferred from the appareance of a doublet at 3.93 ppm (2JHP = 2.7 Hz), attributable to the =CHP linker, and an AX system composed of two doublets appearing at 5.01 and 4.70 ppm (2JHH = 14.3 Hz) due to the CH2N arm hydrogens. The Chapter I. Ir-CNP complexes 108 ! ! ! Figure 26. 11B{1H} (bottom) and 11B NMR (top) spectra (160 MHz, THF-d8) of the reaction of 13(Bcat2) with HBcat (1.2 equiv) to yield 18(Bcat2). While the above spectroscopic data support the proposed formulation for 18(Bcat2) as [Ir(mer-CNPPh)(CO)H(Bcat)][(Bcat2)], the two possible isomers resulting from the oxidative addition of HBcat to 13(Bcat2), i.e. trans (18-I) or cis (18-II) coordination of the boryl ligand to the pyridine fragment, cannot be directly distinguished. However, from the comparison of the chemical shift of the resonance of the hydrido ligand of this compound with those of complex 17(Bcat2), cis coordination of the Bcat moiety to the carbonyl ligand is suggested. Moreover, this ligand arrangement should be favored since the trans coordination of the two potentially π-accepting boryl and carbonyl ligands is prevented.87 DFT calculations (B3LYP-D3, 6- 31g(d,p)/SDD) of both complexes indicated that the proposed cationic species 18-I is more stable by 3.2 kcal mol−1 than 18-II (Figure 27). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 87 (a) H. Braunschweig, M. Colling, Coord. Chem. Rev. 2001, 223, 1; (b) J. Zhu, Z. Lin, T. B. Marder, Inorg. Chem. 2005, 44, 9384. Results and Discussion ! 109 ! Figure 27. Optimized structures and relative thermodynamic stability of the cationic fragments of 18-I and 18-II, and 19-I and 19-II. Data in parentheses are ΔG in THF (kcal mol-1). + N P NNMes Ir BR2 CO H Ph2+ N P NNMes Ir H CO R2B Ph2 18-I (0.0) 19-I (3.5) 18-II (3.2) 19-II (0.0) R2 = catechol R2 = pinacol 18-I 18-II 19-I 19-II Chapter I. Ir-CNP complexes 110 In the 1H-1H EXSY spectrum of the reaction mixture of 13(Bcat2) and HBcat in THF-d8 registered at 25 ºC, exchange cross peaks were observed between the signals of the aromatic hydrogens corresponding to the [Bcat2]− anion and those of free HBcat, indicative of the existence of a boron substituent scrambling process (Scheme 13). Upon registering the same experiment at 50 oC, a cross-peak signal caused by the exchange between free HBcat and the hydrido ligand was also observed, further manifesting the reversibility of B–H oxidative addition by complex 13(Bcat2) (Figure 28). ! Scheme 13. Scrambling of boron substituents between HBcat and [Bcat2]−. ! Figure 28. 1H-1H EXSY spectrum (400 MHz, THF-d8, 328 K) of the reaction of 13(Bcat2) with HBcat (1.2 equiv) to yield 18(Bcat2) (mixing time = 800 ms). O O B O O - O O BH + O O B O O - O O BH + Results and Discussion ! 111 Formation of analogous species to 18(Bcat2) with HBpin was examined by reacting complex 13(BArF), previously synthetized by treatment of 13(Cl) with NaBArF, with an excess of HBpin (2.4 equiv) (Scheme 12). NMR data of the hydridoboryl iridium complex 19(BArF) resemblance those of 18(Bcat2), with the logical differences of the signals due to the boryl ligand and [BArF]−, evincing the cis arrangement of the boryl and CO ligands. However, DFT calculations (B3LYP-D3, 6-31g(d,p)/SDD) showed a lower stability for 19-I in comparison to 19-II by 3.5 kcal mol−1. Inspection of the optimized structure of 19-I allow ascribing the reduced stability to the presence of non-stabilizing interactions between the more sterically demanding pinacol moiety with the substituents of the NHC and phosphine fragments (Figure 27). In addition, exchange cross-peaks between the resonances of the hydrido ligand of 19(BArF) and those of the free borane were observed in the 1H-1H EXSY spectrum. A likely mechanism for the hydroboration of CO2 catalyzed by complexes 18(Bcat2) and 19(BArF) would involve the insertion of CO2 into the metal-H bond to yield formate species. However, no changes were noticed in the NMR spectra of solutions in THF-d8 of 18(Bcat2) and 19(BArF) upon exposure to CO2 (2 bar). Therefore, in order to corroborate whether 18(Bcat2) and 19(BArF) could participate in the reduction of CO2 with boranes, the catalytic performance of complexes 13(Bcat2) and 13(BArF) was examined. Under the reaction conditions of Table 4, entry 5, 13(Bcat2) provided in the hydroboration of CO2 with HBcat a significantly low TOF of 6.8 h-1 (89% conv. after 13 h). Similarly, complex 13(BArF) was also found to be an inefficient catalyst in the reduction of CO2 with HBpin since negligible formation of the expected formoxyborane was observed (<5% conv. after 21 h). These observations support that 18(Bcat2) and 19(BArF) are not significantly involved in the hydroboration of CO2 using Chapter I. Ir-CNP complexes 112 15a/15b as catalytic precursors. Similar results have been previously observed in other metal catalyzed hydroborations. For instance, while [IrCl(COE)2]2/PPh3 mixtures are active in the addition of HBcat to olefins, the isolated boryl iridium complexes generated from the reaction of this catalytic system and hydroboranes are poor catalysts.82c Also, while thiolate Ni and Pd pincer complexes have been shown to provide very active catalysts for the hydroboration of CO2 to CH3OBcat, the hydride species observed under catalytic conditions does not seem to be involved in the catalytic process.48,49 The level of reduction of CO2 with HBpin can be controlled to some extent by an appropriate choice of the catalyst, leading to the formation of formate, acetal and methoxide derivatives.39,47,53-54,56-59 The metal-catalyzed hydroboration of CO2 to CH3OBR2 occurs in three successive steps.46 The first one involves CO2 insertion into the metal–H bond to yield a formate intermediate that upon interaction with a molecule of HBR2 produces the formoxyborane derivative. Subsequent insertion of HCO2BR2 into the catalyst M–H bond produces formaldehyde, which is finally reduced to CH3OBR2 by a third molecule of HBR2. Based on this mechanism, Hazari et al. have assumed that the high selectivity observed for a pincer Pd complex in the hydroboration of CO2 with HBpin to formoxyborane is determined by the larger size of the pinacol fragment that prevents further reduction of HCO2Bpin.57 Furthermore, selective reduction of CO2 to the formate level with HBpin has only been accomplished with metal based catalysts.54,56-57 Therefore, since a highly selective CO2 hydroboration with HBpin to formoxyborane takes place using 15a/15b, it can be expected that metal species should be involved in the catalytic reactions. Furthermore, considering the degradation of the hydroboranes as well as the observed influence of water, it can be proposed that the catalytically active species are Results and Discussion ! 113 iridium derivatives formed in low concentrations by reaction of 15a/15b with hydroborane and water. Chapter I. Ir-CNP complexes 114 I.2.3. Synthesis of Ir-CNPtBu complexes and catalytic applications in the hydrogenation of aldehydes I.2.3.a) Synthesis of CNPtBu ligand precursors Di-tert-butylphosphino substituted imidazolium salts 20 were prepared by alkylation of di-tert-butylphosphine with 1(Cl) in CH2Cl2, followed by the deprotonation of the resulting phosphonium salts 20·HCl with phenethyldiethylamine ScavengePore resin (Scheme 14). Derivatives 20a and 20b·HCl were isolated with moderate purity (65-77% as determined by NMR), and used without further purification for the preparation of Ir-CNPtBu complexes, as described in the following section. ! Scheme 14. Synthesis of CNPtBu ligands precursors 20. Salts 20 were characterized by NMR spectroscopy and HRMS. In the 31P{1H} NMR spectrum, the imidazolium salt 20a produces a broad resonance at 37.1 ppm. Meanwhile, in the 1H NMR experiment, the methylene protons of the CH2P and CH2N arms appear as singlets at 3.04 (br) and 6.02 ppm, respectively, and the H-2 hydrogen of the imidazolium ring produces a broad resonance at 10.84 ppm. On the other hand, 20b·HCl shows in the 1H NMR spectrum a doublet signal at 4.01 ppm (JHP = 12.1 Hz) and a singlet resonance at 6.06 ppm, corresponding to the methylene CH2P N NCl N Ar Cl N NPtBu2 N Ar (Cl)2 20· HCl 1a(Cl); Ar = Mes 1b(Cl); Ar = 3,5-Xyl N NPtBu2 N Ar Cl 20 CH2Cl2 70ºC PtBu2H H NEt2 CH2Cl2 Results and Discussion ! 115 and CH2N hydrogens; whereas a singlet is observed at 11.90 ppm caused by the H-2 hydrogen of the imidazolium moiety. Protonation of the phosphino group of 20b·HCl is evidenced by the presence of a doublet resonance at 8.93 ppm with a large 1H-31P coupling of 495 Hz. This coupling value is also manifested in the 31P NMR spectrum, where a doublet signal at 32.5 ppm (1JPH = 490 Hz) is observed. I.2.3.b) Synthesis and reactivity of Ir-CNPtBu complexes As shown with the carbene precursors 2 in Section I.2.2.3.a, the synthesis of Ir complexes containing CNPtBu ligands was initially assayed by reaction of the imidazolium salt 20a with Ir(acac)(COD), leading to the formation of the fully characterized complex 21 (Scheme 15). In the 1H NMR spectrum, this derivative exhibits the resonances corresponding to the CH2N methylene protons as a set of two mutually coupled doublets appearing at 7.03 and 4.86 ppm (2JHH = 14.5 Hz), and the signals of the CH2P hydrogens as two doublets of doublets at 3.54 (2JHH = 16.5 Hz, 2JHP = 8.7 Hz) and 2.66 ppm (2JHH = 16.5 Hz, 2JHP = 7.1 Hz) (Figure 29). More interestingly, there is a doublet signal in the hydride region at −24.5 ppm (JHP = 17 Hz), and only two singlets (integrating for 3 H each) in the region expected for the methyl substitutents of the mesityl group. Meanwhile, two other resonances are observed at 3.92 (d, 2JHH = 11.6 Hz, 1H) and 2.88 ppm (dd, 2JHH = 11.6 Hz, 3JHP = 9.1 Hz, 1H) that exhibit cross-peak signals in the 1H-13C HSQC experiment with a broad resonance appearing at δC −9.6 ppm, suggestive of the presence of an Ir-C bond (Figure 30). Overall, these Chapter I. Ir-CNP complexes 116 data point to the metalation of one of the CH3 groups of the mesityl fragment.88 Scheme 15. Synthesis of Ir-CNPtBu complexes 21 and 22a. ! Figure 29. Selected regions of the 1H NMR spectrum (300 MHz, CD2Cl2) of complex 21. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 88 M. Albrecht, Chem. Rev. 2010, 110, 576. Ir(acac)(COD) 22a CH2Cl2 N N N PtBu2 Ir Cl H 21 H2 20a(Cl) CH2Cl2 N N PtBu2 NMes Ir H Cl H Results and Discussion ! 117 ! Figure 30. Region of the 1H-13C HSQC spectrum (400 MHz, CD2Cl2) of 21. The proposed structure of 21 was further confirmed by an X-ray diffraction study of the complex (Figure 31). In the solid state, this complex has a slightly distorted octahedral geometry with the metalated CNPtBu ligand adopting a tetracoordinated planar coordination as indicated by the value of the angles C(1)–Ir(1)–P(1)=166.79(16)º and C(10)–Ir(1)–N(3)=172.79(16)º. Moreover, the existence of a hydrogen bond between the axial hydrogen of the CH2N arm and the chloro ligand is evident from the value of the H···Cl distance of 2.6 Å, which is shorter than the sum of van der Waals radii of H and Cl (2.9-3.0 Å).63,72 This interaction is also manifested in the significant deshielding of the doublet resonance corresponding to the CHHN axial hydrogen in the 1H NMR spectrum (δH 7.07, 2JHH = 14.5 Hz) (Figure 29). Chapter I. Ir-CNP complexes 124 ! ! Figure 32. Representation of T1 values of the Ir-H hydrogens vs temperature. Deuteration studies were also performed with derivatives 25. The trihydride derivative 25a in toluene-d8 underwent partial H/D exchange of the hydrido ligands and the methylene bridges in the presence of D2 (5 bar; 20 h), suggestive of the reversible exchange of free D2 with a η 2-H2 ligand resulting from the intramolecular protonation of Ir-H by protons of the CNPtBu methylene moieties (Figure 33).93 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 93 (a) X. Yang, M. B. Hall, J. Am. Chem. Soc. 2010, 132, 120; (b) J. Li, Y. Shiota, K. Yoshizawa, J. Am. Chem. Soc. 2009, 131, 13584. Results and Discussion ! 125 ! ! Figure 33. Deuteration of complex 25a in toluene-d8 with D2 (5 bar), and proposed mechanism for H/D exchange (formation of a σ-H2 complex after protonation by the CH2-P bridge is also possible). D2 (4 bar) THF-d8 25a-d N N PtBu2 NMes Ir H/D H/D H/D 25a N N PtBu2 NMes Ir H H H 60 ºC, 20 h 68% D 58% D 70% D 61% D N N PtBu2 NMes Ir H H H2 N N PtBu2 NMes Ir H H D2 D2 Chapter I. Ir-CNP complexes 126 I.2.3.c) Hydrogenation of aldehydes catalyzed by Ir–CNPtBu complexes Trihydride complexes 25 and 26 were explored as catalysts in the chemoselective hydrogenation of aldehydes (Table 7).94 Firstly, the catalytic performances in the hydrogenation of benzaldehyde (27a) (4 bar H2, 25 oC) of complex 25a and the mixture of 25b and 26 were compared using catalyst loadings of 0.5 mol% (entries 1 and 2). Similar catalytic activities were observed for both systems. Using lower catalyst loadings (0.1 mol%) of 25a and higher concentrations of substrate, benzaldehyde was hydrogenated with 96% conversion with a TOF of 40 h-1 (entry 3). Under these reaction conditions, the hydrogenation of a range of substituted aromatic aldehydes was investigated in order to assess the chemoselectivity and functional group tolerance of the catalyst. The reduction of substrates bearing p-bromo (27b) and p-fluoro (27c) substituents was accomplished with high conversions, and hydrogenolysis of the C-X bonds was not detected (entries 4 and 5). Also, 4- nitrobenzaldehyde (27d) was selectively hydrogenated to the corresponding alcohol without observable reduction of the nitro group (entry 6). Finally, ptrifluoromethyl-substituted benzaldehyde (27e) and vanillin (27f) were hydrogenated with 76% and >99% conversion, respectively (entries 7 and 8). The selective hydrogenation of an aldehyde function in the presence of a C=C bond is an important step in the production of fragances, fine chemicals and pharmaceutical compounds.95 Therefore, the reduction of a series of α , β - !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 94 For selected examples of aldehyde hydrogenation catalyzed by Ir complexes: (a) I. Cano, L. M. Martínez-Prieto, L. Vendier, P. W. N. M. van Leeuwen, Catal. Sci. Technol. 2018, 8, 221; (b) X. Wu, C. Corcoran, S. Yang, J. Xiao, ChemSusChem 2008, 1, 71; (c) M. G. Manas, J. Graeupner, L. J. Allen, G. E. Dobereiner, K. C. Rippy, N. Hazari, R. H. Crabtree, Organometallics 2013, 32, 4501. 95 (a) P. Gallezot, D. Richard, Catal. Rev.: Sci. Eng. 1998, 40, 81; (b) P. Mäki-Arvela, J. Hájek, T. Salmi, D. Y. Murzin, Appl. Catal. A 2005, 292, 1.! Results and Discussion ! 127 unsaturated aldehydes was examined using catalyst 25a. High conversion and selectivity towards C=O hydrogenation was observed in the reduction with H2 of trans-cinnamaldehyde (27g) under the previous optimized conditions (entry 9). Conversely, the hydrogenation of trans-2-hexenal (27h) was sluggish and required a higher catalyst loading (0.5 mol%) to achieve 88% conversion with a notable selectivity to the unsaturated alcohol (entry 10). The reduction of citronellal (27i), having a non-conjugated C=C bond, was also examined (entry 11). Alcohol (28i) was quantitatively obtained with a selectivity of 99%. Finally, citral, a 1:0.6 mixture of geranial (cis-27j) and neral (trans-27j), was reduced under the standard conditions to geraniol (cis-28j) and nerol (trans-28j) with no observable isomerization of the conjugated C=C bond and a selectivity of 96% (entry 12). Chapter I. Ir-CNP complexes 128 Table 7. Hydrogenation of aldehydes catalyzed by Ir-CNPtBu complexes.a ! Entry Aldehyde [Ir] Conv. (%) Ratio unsaturated/saturated alcohol (%) 1b 25a 70 - 2b 25b/26 72 - 3 25a 96 - 4 25a >99 - 5 96 - 6c >99 - 7 76 - R O HROH H2 27 28 [Ir], 2-MeTHF Ph H O 27a H O Br 27b H O F27c H O O2N27d H O F3C27e Results and Discussion ! 129 Table 7(cont). Hydrogenation of aldehydes catalyzed by Ir-CNPtBu complexes.a Entry Aldehyde [Ir] Conv. (%) Ratio unsaturated/saturated alcohol (%) 8 25a >99 - 9 >99 99:1 10c,d 84 88:12 11 >99 99:1 12e cis/trans = 1:0.6 >99e 96:4 a Reaction conditions, unless otherwise noted: 4 bar of H2, 2-methyltetrahydrofuran, 0.1 mol% Ir-CNPtBu, 25 ºC, 24 h. [S] = 2.0 M. Conversion and selectivity towards the unsaturated alcohol were determined by 1H NMR spectroscopy using mesitylene as internal standard. b 0.5 mol% Ir-CNPtBu, [S] = 0.3 M, 6 h. c [S] = 1.0 M. d 0.5 mol% Ir- CNPtBu. e Geranial/neral ratio = 1:0.6. H O HO OCH3 27f Ph H O 27g H O 27h H O 27i H O 27j Chapter I. Ir-CNP complexes 130 I.2.3.d) Mechanistic studies of the hydrogenation of aldehydes The acid–base properties of the methylene bridges of lutidine derived ligands are relevant to the development of ligand-assisted reactions.96 Hence, as previously studied with the Ir-CNPPh complexes, the reactivity of 22a towards bases was investigated. Reaction of 22a with KHMDS or KOtBu (1.5 equiv) in THF-d8 resulted in the selective deprotonation of the CH2N arm with formation of the pyridine dearomatized species 29 (Scheme 19). The 1H NMR spectrum of 29 features a singlet resonance for the proton of the methyne CHN bridge at 6.44 ppm, and a doublet at 2.78 ppm (2JHP = 8.9 Hz) caused by the CH2P arm. Moreover, the expected dearomatization of the pyridine ring is reflected in the significant upfield shift of the resonances of the central ring hydrogens appearing in the range 6.2-4.9 ppm. In the 13C{1H} NMR spectrum, the carbenic carbon appears at 179.6 ppm as a doublet with a large JCP coupling constant of 110 Hz, evincing a meridional coordination of the CNPtBu ligand. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 96 (a) C. Gunanathan, D. Milstein, Acc. Chem. Res. 2011, 44, 588; (b) R. Khusnutdinova, D. Milstein, Angew. Chem. Int. Ed. 2015, 54, 12236. Results and Discussion ! 131 ! Scheme 19. Formation of complex 29, and reactions with H2 and aldehydes. Interestingly, in the 1H NMR spectrum of 29 the hydrido ligands are equivalent at temperatures above –50 oC producing a sharp doublet at –23.77 ppm (2JHP = 11.3 Hz), indicative of a trigonal bipyramidal geometry of the complex, as previously observed for Ir(PCP)H2 derivatives,77,97 or a square pyramidal structure,98 in which the pincer occupies the pyramid base and the hydrido ligands are rapidly exchanging. Furthermore, T1 determinations in THF-d8 shows a T1,min value of approximately 150 ms, in agreement with a IrH2(CNP*) formulation for complex 29 (Figure 34, Table 8). !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 97 (a) J.-F. Riehl, Y. Jean, O. Eisenstein, M. Pélissier, Organometallics 1992, 11, 729; (b) M. Gupta, C. Hagen, W. C. Kaska, R. E. Cramer, C. M. Jensen, J. Am. Chem. Soc. 1997, 119, 840; (c) K. Krogh-Jespersen, M. Czerw, M. Kanzelberger, A. S. Goldman, J. Chem. Inf. Comput. Sci. 2001, 41, 56; (d) S. Niu, M. B. Hall, J. Am. Chem. Soc. 1999, 121, 3992. 98 A. V. Polukeev, R. Marcos, M. S. G. Ahlquist, O. F. Wendt, Chem. Eur. J. 2016, 22, 4078. 22a 29 KOtBu THF H2 (1.5 bar) 25a Ar H O 27 Ir N N Mes N H P tBu H Ar H O 30m 2 N N PtBu2 NMes Ir H Cl H N N PtBu2 NMes Ir H H H Ir N N Mes N H P tBu H H Ar O 30M 2 + N N PtBu2 NMes Ir H H 30a: Ar = Ph 30b: Ar = p-Br-Ph (9.4:0.6) Chapter I. Ir-CNP complexes 132 Table 8. T1 values for Ir-H hydrogens of complex 29 in THF-d8.! Temperature (K) T1 (ms) 298.15 385 273.15 260 263.15 213 253.15 160 243.15 157 233.15 163 ! ! Figure 34. Representation of T1 values of the Ir-H hydrogens of 29 vs temperature. The ability of the deprotonated complex 29 to participate in ligandassisted H-H activation was established after the observed formation of the trihydride derivative 25a upon exposure of a solution of 29 in THF-d8 to an atmosphere of H2 (1.5 bar) (Scheme 19). Results and Discussion ! 133 Complexes based on deprotonated lutidine-derived pincer ligands have been shown to exhibit FLP-type reactivity towards electrophiles such as CO2, carbonyl compounds, nitriles and imines.99,67b Hence, formation of analogous species with aldehydes was investigated by addition of KHMDS to a 1:2 solution of 22a and benzaldehyde in THF-d8 (Scheme 19). In the hydride region, the 1H NMR spectrum of the resulting solution demonstrates the formation of two new dihydride species, 30aM and 30am, in a 9.4:0.6 ratio (Table 9). This ratio did not change further after prolonged standing of the solution at room temperature, suggesting that it represents the equilibrium product mixture (see below). The major complex, 30aM, produces two doublets of doublets at –19.39 (2JHP = 14.2 Hz, 2JHH = 7.8 Hz) and –24.33 ppm (2JHP = 18.2 Hz, 2JHH = 7.8 Hz); whereas the minor derivative also shows two doublet of doublets appearing at –20.06 (2JHP = 13.7 Hz, 2JHH = 7.4 Hz) and –24.11 ppm (2JHP = 18.5 Hz, 2JHH = 7.4 Hz). Moreover, the CHN methyne bridge of 30aM appears at 5.64 ppm as a singlet, and the resonances for the diasterotopic protons of the methylene CH2P are shown as two doublet of doublets at 3.61 (2JHH = 15.5 Hz, 2JHP = 8.9 Hz) and 2.95 (2JHH = 15.5 Hz, 2JHP = 6.7 Hz) ppm. The presence of a intense cross-peak signal in the 1H-1H NOESY spectrum between one of the resonances corresponding to the CH2P arm (δ 2.95 ppm) and one of the !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 99 (a) M. Vogt, M. Gargir, M. A. Iron, Y. Diskin-Posner, Y. Ben-David, D. Milstein, Chem. Eur. J. 2012, 18, 9194; (b) C. A. Huff, J. W. Kampf, M. S. Sanford, Organometallics 2012, 31, 4643; (c) M. Montag, J. Zhang, D. Milstein, J. Am. Chem. Soc. 2012, 134, 10325; (d) C. A. Huff, J. W. Kampf, M. S. Sanford, Chem. Commun. 2013, 49, 7147; (e) C. A. Huff, M. S. Sanford, ACS Catal. 2013, 3, 2412; (f) G. A. Filonenko, M. P. Conley, C. Copéret, M. Lutz, E. J. M. Hensen, E. A. Pidko, ACS Catal. 2013, 3, 2522; (g) M. Vogt, A. Nerush, M. A. Iron, G. Leitus, Y. Diskin-Posner, L. J. W. Shimon, Y. Ben-David, D. Milstein, J. Am. Chem. Soc. 2013, 135, 17004; (h) M. Vogt, A. Nerush, Y. Diskin-Posner, Y. Ben-David, D. Milstein, Chem. Sci. 2014, 5, 2043; (i) G. A. Filonenko, E. Cosimi, L. Lefort, M. P. Conley, C. Copéret, M. Lutz, E. J. M. Hensen, E. A. Pidko, ACS Catal. 2014, 4, 2667. II.1. Introduction Introduction ! 239 Hydrogenation and acceptorless dehydrogenation are low environmental impact processes for the reduction of aromatic N-heterocycles to their corresponding saturated derivatives, and the oxidation of the latter products to the parent N-heteroarenes. These transformations are not only of synthetic interest but may also serve for the development of H2-storage systems based on N-heteroarenes as organic hydrogen carriers. In Chapter II, a series of Ru complexes stabilized with lutidinederived pincer ligands incorporating a secondary amino group has been synthetized. As a consequence of the presence of two acidic functionalities, i.e. the lutidine methylenes and the NH moieties, it could be expected that these complexes might exhibit two modes of metal-ligand cooperation: pyridine aromatization/dearomatization and amine/amido interconversion. Additionally, the catalytic activity of these complexes for the reversible (de)hydrogenation of N-heterocycles has been examined, and preliminary mechanistic studies have been performed. Chapter II. Ru-CNN(H) complexes 240 II.1.1. Catalytic applications of metal complexes based on multimodal proton-responsive ligands Among the considerable diversity of ligands containing Brønsted acid/base functionalities, those incorporating amine1 and lutidine donors2 have provided highly active and selective catalysts for a broad variety of hydrogenation and dehydrogenation reactions. Since both metal-ligand cooperation (MLC) strategies, amine/amido interconversion and pyridine aromatization/dearomatization, have been proven successful, a further approach for the development of efficient catalysts might consist of the use of ligands containing two different proton-responsive modes. The underlying idea of this strategy is to allow the catalyst to choose the lowest energetically accessible MLC mode for each step of the catalytic cycle. While this approach has led in some cases to more efficient catalysts, mechanistic information regarding the action modes of these catalytic systems still remains scarce. II.1.1.a. Ruthenium complexes The Milstein group has synthetized ruthenium complexes incorporating lutidine-based tridentate PNN(H) ligands containing secondary amines as side donors (Figure 1).3 These derivatives are active ester !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 1 (a) B. Zhao, Z. Han, K. Ding, Angew. Chem. Int. Ed. 2013, 52, 4744; (b) T. Ikariya, Bull. Chem. Soc. Jpn. 2011, 84, 1. 2 (a) J. L. van der Vlugt, J. N. H. Reek, Angew. Chem. Int. Ed. 2009, 48, 8832; (b) C. Gunanathan, D. Milstein, Acc. Chem. Res. 2011, 44, 588; (c) D. Milstein, Phil. Trans. R. Soc. A 2015, 373, 20140189. 3 E. Fogler, J. A. Garg, P. Hu, G. Leitus, L. J. W. Shimon, D. Milstein, Chem. Eur. J. 2014, 20, 15727. Introduction ! 241 hydrogenation catalysts under very mild conditions (room temperature, 5 bar of H2), and catalyze the dehydrogenative coupling of alcohols to esters at low temperatures (35 oC). Interestingly, reaction of a Ru-PNN(H) complex with 2.5 equiv of KH produced the formation of an enamino anionic Ru(II) species (Scheme 1). DFT calculations supported that the latter species is able to catalyze the dehydrogenative coupling of alcohols only involving the amine/amido metal-ligand cooperation mode.4 The origin of this preference for amine/amido interconversion has been attributed to the conjugation effect of the amido group that stabilizes the dearomatized complex and diminishes the driving force of the aromatization/dearomatization mode. ! Figure 1. Hydrogenation of esters and dehydrogenation of alcohols catalyzed by Ru-PNN(H) complexes. ! Scheme 1. Reactivity of a Ru-PNN(H) complex towards base. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 4 C. Hou, J. Jiang, Y. Li, C. Zhao, Z. Ke, ACS Catal. 2017, 7, 786. N NHR PtBu2 Ru CO Cl H R = tBu, iPr, CH2Ph ROR’ O ROH +R’OH H2 (5 bar) 0.5 mol% [Ru] NaOtBu 1.1-5 mol% THF, r.t., 24-48 h 2ROH RO+ 0.1 mol% [Ru] KOtBu 0.22 mol% Et2O, reflux R O 2 H2 N NHR PtBu2 Ru CO Cl H KH (2.5 equiv) THF-d8 N NR PtBu2 Ru CO H K Chapter II. Ru-CNN(H) complexes 242 Aiming to develop H2-storage systems, Milstein and co-workers have investigated the reversible dehydrogenation of 2-aminoethanol (AE) to a cyclic dipeptide (glycine anhydride, GA) and linear polypeptides using ruthenium catalysts containing lutidine-derived PNN ligands, in which the N- arm is either a hemilabile diethylamino group or a proton-responsive NH functionality (Figure 2).5 Mixtures of glycine anhydride and linear polypeptides were hydrogenated to 2-aminoethanol and 2-amino-N-(2- hydroxyethyl)acetamide (AA) with similar catalytic activities by both complexes in the presence of base. On the contrary, slightly higher conversions were achieved in the dehydrogenation reaction upon using the Ru-PNN(H) precursor. More importantly, repetitive cycles of H2 release/recharge were conducted using the Ru-PNN(H) complex without adding new catalyst loadings. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 5 P. Hu, E. Fogler, Y. Diskin-Posner, M. A. Iron, D. Milstein, Nat. Commun. 2015, 6, 6859. Introduction ! 243 ! Figure 2. Hydrogenation of GA and dehydrogenation of AE with Ru-PNN complexes. Furthermore, the same group has examined the hydrogenation of a variety of cyclic imides to diols and amines using ruthenium catalysts bearing lutidine-containing ligands (Figure 3).6 The higher catalytic activities observed with a Ru-PNN(H) complex in comparison to catalysts based on other PNN ligands have been ascribed to the ability of the former derivative to exhibit both N(H)-M/N=M and lutidine aromatization/dearomatization MLC modes. Moreover, the high selectivity achieved for succinimide hydrogenation led to testing a hydrogen storage system based on the reversible hydrogenation of a bis-cyclic imide formed by the dehydrogenative coupling of 1,4-butanediol and ethylenediamine. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 6 A. Kumar, T. Janes , N. A. Espinosa-Jalapa, D. Milstein, J. Am. Chem. Soc. 2018, 140, 7453. N NEt2 PtBu2 Ru CO Cl H HO + H2 (50-70 bar) [Ru] up to 0.5 mol% KOtBu 2.4 mol% Dioxane, 110 ºC N NHtBu PtBu2 Ru CO Cl H N H H N O O NH2 HO H N O NH2 GA AE AA HO + [Ru] 0.5 mol% KOtBu 1.2-6 mol% Dioxane, 110 ºC N H H N O O NH2HO H N O NH2 GA AE + H2 n +HO H N O NH2 n Chapter II. Ru-CNN(H) complexes 244 ! Figure 3. Hydrogenation of cyclic imides and dehydrogenation of diols in the presence of amines. A ruthenium complex based on a tetradentate PN(H)NP ligand containing amine and lutidine fragments has been investigated by Zhang and coworkers (Figure 4).7 This Ru-PN(H)NP complex in the presence of an alkoxide base was found particularly effective for the hydrogenation of esters at very low metal loadings (S/C = 104–105). For example, the hydrogenation of ethyl acetate was achieved under 50 bar of H2 at 80 ºC under solventless conditions with a TON of 80,000 and a TOF of 2,600 h-1. This catalytic system has also exhibited a high activity in the hydrogenation of amides !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 7 (a) X. Tan, Y. Wang, Y. Liu, F. Wang, L. Shi, K-H. Lee, Z. Lin, H. Lv, X. Zhang, Org. Lett. 2015, 17, 454; (b) F. Wang, X. Tan, H. Lv, X. Zhang, Chem. Asian J. 2016, 11, 2103. NR O O n OH OH n+ RNH2 H2NNH2 HO OH + 2 N N O O O O + 8 H2 N NEt2 PtBu2 Ru CO Cl H N NHtBu PR2 Ru CO Cl H N PtBu2 Ru CO Cl H N H2 (20-40 bar) [Ru] 1 mol% KOtBu 3 mol%, THF 110-135 ºC, 24-40 h [Ru] 1 mol%, KH/KOtBu 1-2 mol% Dioxane/Toluene, 24 h, 120-135 ºC [Ru] 1 mol%, H2 (40 bar) KOtBu 1-3 mol% Dioxane, 40 h, 135 ºC R = tBu2, Ph2 Introduction ! 245 under 50 bar of H2 at 100 ºC in the presence of KOtBu as base (Figure 4).8 The reduction of challenging secondary and tertiary amides was achieved with wide functional group tolerance and TONs of up to 19,600. ! Figure 4. Hydrogenation of esters and amides using Ru-PN(H)NP complex. Gao and coworkers have examined a series of Ru complexes with lutidine-derived pincer ligands incorporating NHC flanking groups in the hydrogenation of ethylene carbonate (Figure 5).9 A Ru-CNN(H) complex provided very similar catalytic activities to that of structurally related Ru- CNC derivatives. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 8 L. Shi, X. Tan, J. Long, X. Xiong, S. Yang, P. Xue, H. Lv, X. Zhang, Chem. Eur. J. 2017, 23, 546. 9 X. Wu, L. Ji, Y. Ji, E. H. M. Elageed, G. Gao, Catal. Commun. 2016, 85, 57. R O OR’ ROH R’OH H2 (50 bar) [Ru] 0.005-0.001 mol% KOtBu 2.5 mol% THF, 80 ºC, 5-30 h N P Ph2 Ru NH P Ph2 Cl Cl R O NHR’ H2 (50 bar) [Ru] 0.01-0.005 mol% KOtBu 1-2 mol% THF, 100 ºC, 20 h + ROH R’NH2 + Chapter II. Ru-CNN(H) complexes 252 II.1.2. Acceptorless dehydrogenation of N-heterocycles Saturated and unsaturated N-heterocycles are important building blocks for the synthesis of dyes, biologically active molecules, and ligands with applications in homogeneous catalysis.19 At this respect, hydrogenation of N- heteroarenes is of paramount importance in industry,20 where heterogeneous catalysts are usually preferred. However, significant efforts have been made for the development of efficient catalysts based on transition metal complexes,21 mainly due to the higher selectivity, milder reaction conditions and easiness of mechanistic understanding usually associated to the homogeneous catalysts. Likewise, oxidation of saturated N-heterocycles to their unsaturated counterparts is also of synthetic interest. From the perspective of Green Chemistry, the most efficient process for this transformation is the direct dehydrogenation of the substrate in the absence of a hydrogen acceptor. Since in these reactions free H2 is released, these transformations are not only synthetically appealing but can also be potentially applied for the development of hydrogen storage systems based on the realization of cycles of hydrogenation and dehydrogenation of N-heterocycles.22 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 19 L. D. Quin, J. Tyrell, Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals, Wiley, 2010. 20 (a) B. Chen, U. Dingerdissen, J. G. E. Krauter, H. G. J. Lansink-Rotgerink, K. Möbus, D. J. Ostgard, P. Panster, T. H. Riermeier, S. Seebald, T. Tacke, H. Trauthwein, Appl. Catal. A: General 2005, 280, 17; (b) H.-U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer, Adv. Synth. Catal. 2003, 345, 103. 21 (a) Z. X. Giustra, J. S. Ishibashi, S. Y. Liu, Coord. Chem. Rev. 2016, 314, 134; (b) C. Bianchini, A. Meli, F. Vizza, “Hydrogenation of Arenes and Heteroaromatics” in The Handbook of Homogeneous Hydrogenation (J. G. de Vries, C. J. Elsevier, Eds.), Vol. 1, Chap. 16. Wiley-VCH, 2007. 22 (a) D. L. J. Broere, Phys. Sci. Rev. 2018, 3, 9; (b) R. H. Crabtree, ACS Sustainable Chem. Eng. 2017, 5, 4491; (c) P. Preuster, C. Papp, P. Wasserscheid, Acc. Chem. Res. 2017, 50, 74. Introduction ! 253 Dehydrogenation of cyclic hydrocarbons is highly endothermic; however, isolobal replacement of a CH2 unit by NH have been shown to significantly reduce the endothermicity of H2 release because of the weakening effect caused to a C—H bond by an adjacent nitrogen and the presence of a slightly weaker N—H bond in comparison to a C—H bond (Figure 11).23 Consequently, in the presence of a catalyst, it can be expected that acceptorless dehydrogenation of N-heterocycles can be carried out under relatively mild heating. ! Figure 11. Effect of the replacement of CH2 units by NH in the endothermicity of H2 release (adapted from ref. 22a). Although the principle of microscopic reversibility dictates that species able to catalyze the hydrogenation of a substrate should also be active for the reverse dehydrogenation process, the number of catalytic systems that !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 23 (a) A. Moores, M. Poyatos, Y. Luo, R. H. Crabtree, New J. Chem. 2006, 30, 1675; (b) E. Clot, O. Eisenstein, R. H. Crabtree, Chem. Commun. 2007, 22, 2231; (c) R. H. Crabtree, Energy Environ. Sci. 2008, 1, 134. + 3 H2ΔH = +53 kcal/mol N HN + 3 H2ΔH = +48 kcal/mol N H NH N N+ 3 H2ΔH = +43 kcal/mol HN N H NH N N N + 3 H2ΔH = +39 kcal/mol Chapter II. Ru-CNN(H) complexes 254 promote both hydrogenation of N-heterocycles and acceptorless dehydrogenation of their reduced counterparts is scarce. A likely explanation to this resides in the still high endothermicity of the dehydrogenation process that requires robust catalysts that could operate under relatively harsh conditions. In fact, although the dehydrogenation of N-heterocycles has been reported using different homogeneous24,25 as well as heterogeneous catalysts,26 only very few catalytic systems are able to catalyze both processes. Aiming to place the results of Section II.2. in context, ruthenium catalysts for the dehydrogenation of N-heterocycles, and systems based on transition metals for the reversible (de)hydrogenation of N-heteroarenes will be next reviewed. II.1.2.a. Dehydrogenation of N-heterocycles with ruthenium catalysts While ruthenium complexes have been examined in the dehydrogenation of nitrogen-containing heterocycles, their efficiency in the hydrogenation of the resulting unsaturated derivatives have usually not been explored. For example, some “classical” Ru hydrogenation catalysts, such as !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 24 (a) M. A. Esteruelas, V. Lezaun, A. Martínez, M. Oliván, E. Oñate, Organometallics 2017, 36, 2996; (b) M. L. Buil, M. A. Esteruelas, M. P. Gay, M. Gómez-Gallego, A. I. Nicasio, E. Oñate, A. Santiago, M. A. Sierra, Organometallics 2018, 37, 603. 25 (a) D. F. Brayton, C. M. Jensen, Chem. Commun. 2014, 50, 5987; (b) Z. Wang, I. Tonks, J. Belli, C. M. Jensen, J. Organomet. Chem. 2009, 694, 2854. 26 For selected examples of heterogeneous catalysts for the reversible dehydrogenation of N- heterocycles: (a) C. Deraedt, R. Ye, W. T. Ralston, F. D. Toste, G. A. Somorjai, J. Am. Chem. Soc. 2017, 139, 18084; (b) S. K. Moromi, S. M. A. H. Siddiki, K. Kon, T. Toyao, K. Shimizu, Catal. Today 2017, 281, 507; (c) Y. Han, Z. Wang, R. Xu, W. Zhang, W. Chen, L. Zheng, J. Zhang, J. Luo, K. Wu, Y. Zhu, C. Chen, Q. Peng, Q. Liu, P. Hu, D. Wang, Y. Li, Angew. Chem. Int. Ed. 2018, 57, 11262; (d) J.-W. Zhang, D.-D. Li, G.-P. Lu, T. Deng, C. Cai, ChemCatChem 2018, 10, 4966. Introduction ! 255 RuCl2(PPh3)3,27 RuH2(CO)(PPh3)3,27c-d,28 RuH2(PPh3)4,27c-d,29 and the Shvo´s complex30 have been found to promote the acceptorless dehydrogenation of 1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydroquinoline and indoline (Figure 12).31,32 However, the catalytic performance of these catalysts in the hydrogenation of the corresponding N-heteroarenes has not been reported. Figure 12. Dehydrogenation of N-heterocycles using Ru classical complexes. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 27 (a) Y. Takagi, S. Teratani, S. Takahashi, K. Tanaka, J. Mol. Catal. 1977, 2, 321; (b) S. R. Patil, R. V. Chaudhari, D. N. Sen, J. Mol. Catal. 1984, 23, 51; (c) R. A. Sánchez-Delgado, O. L. de Ochoa, J. Organomet. Chem. 1980, 202, 427; (d) R. A. Sánchez-Delgado, A. Andriollo, O. L. de Ochoa, T. Suárez, N. Valencia, J. Organomet. Chem. 1981, 209, 77; (e) J. F. Knifton, Tetrahedron Lett. 1975, 26, 2163; (f) J. F. Knifton, J. Org. Chem. 1975, 40, 519; (g) Y. Sasson, J. Blum, J. Org. Chem. 1975, 40, 1887; (h) J. Tsuji, H. Suzuki, Chem. Lett. 1977, 6, 1085. 28 Z. Broucková, M. Czaková, M. Capka, J. Mol. Catal. 1985, 30, 241. 29 (a) A. Toti, P. Frediani, A. Salvini, L. Rosi, C. Giolli, J. Organomet. Chem. 2005, 690, 3641; (b) A. Toti, P. Frediani, A. Salvini, L. Rosi, C. Giolli, C. Giannelli, C. R. Chimie 2004, 7, 769; (c) P. Frediani, V. Pistolesi, M. Frediani, L. Rosi, Inorg. Chim. Acta 2006, 359, 917; (d) S. Komiya, A. Yamamoto, J. Organomet. Chem. 1979, 5, 279. 30 B. L. Conley, M. K. Pennington-Boggio, E. Boz, T. J. Williams, Chem. Rev. 2010, 110, 2294. 31 Y. Tsuji, S. Kotachi,K. T. Huh, Y. Watanabe, J. Org. Chem. 1990, 55, 580. 32 S. Muthaiah, S. H. Hong, Adv. Synth. Catal. 2012, 354, 3045. NH N N HN N HN H - RuCl2(PPh3)3 aRuH2(CO)(PPh3)3 bRuH2(PPh3)4 bShvo’s complexb 73% 78% 99% -48% 32% 98% 99% 95% 89% 98% a conditions: 2 mol% [Ru], toluene, reflux, 6 h. b conditions: 5 mol% [Ru], mesitylene, reflux, 24-48 h. H Ru Ru CO CO CO CO O Ph Ph Ph Ph O H Ph Ph Ph Ph Shvo’s complex cat. cat. cat. Chapter II. Ru-CNN(H) complexes 256 The Blacquiere group compared the catalytic performance of [Ru(Cp)(P2N2)(MeCN)]PF6 (Cp = cyclopentadienyl), containing a protonresponsive P2N2 ligand, and [Ru(Cp)(dppp)(MeCN)]PF6 (dppp = Ph2PCH2CH2CH2PPh2) in the dehydrogenation of five- and six-membered heterocycles (Figure 13).33 Under the optimized catalytic conditions (3 mol% Ru, anisole at 110 oC), both catalysts dehydrogenated indoline with similar rates, although the Ru complex incorporating the proton-responsive P2N2 ligand significantly outperformed [Ru(Cp)(dppp)(MeCN)]PF6 in the reaction of 2-methylindoline. On the contrary, both catalysts showed poor performances (<27% conv.) in the dehydrogenation of 1,2,3,4- tetrahydroquinoline. Figure 13. Dehydrogenation of N-heterocycles using [Ru(Cp)(P2N2)(MeCN)]PF6 and [Ru(Cp)(dppp)(MeCN)]PF6 complexes. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 33 J. M. Stubbs, R. J. Hazlehurst, P. D. Boyle, J. M. Blacquiere, Organometallics 2017, 36, 1692. Ru P PNCMe PF6 N N Bn Bn Ph Ph Ru P PNCMe PF6 Ph Ph Ph Ph N HN H 94% Ru-P2N2Ru-dppp 91% 93% 68% conditions: 3 mol% [Ru], anisole, 110 ºC, 48 h. R = H R = Me RR Introduction ! 257 Recently, Yu and coworkers tested ruthenium complexes based on pyrazolyl-(2-indol-1-yl)-pyridine ligands for the oxidation of substituted tetrahydroquinolines, tetrahydroisoquinolines, terahydroquinoxalines and indolines (Figure 14).34 These complexes provided high conversions in the dehydrogenation of a series of derivatives using 2.0 mol% catalyst loadings at 140 oC (o-xylene). Furthermore, this catalytic system was employed for the synthesis of β -carbolines that are derivatives of pharmaceutical interest. ! Figure 14. Dehydrogenation of N-heterocycles, and synthesis of β -carbolines, using the Ru complex reported by Yu and coworkers. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 34 Q. Wang, H. Chai, Z. Yu, Organometallics 2018, 37, 584. N NN NN Ru H L L OMe L = PPh3 N H [Ru] 2 mol% o-xylene 140 ºC, 48 h R R’ N R R’ N H NH2 RCHO TFA, reflux N H NH R [Ru] 2 mol% o-xylene 140 ºC, 48 h N H N R β -carboline Chapter II. Ru-CNN(H) complexes 258 Acceptorless dehydrogenation of indoline has also been investigated by the groups of Szymczak35 and Mata36 using Ru-NNN and arene Ru complexes incorporating NHC ligands, respectively (Figure 15). These catalysts quantitatively catalyzed the formation of indole under relatively mild conditions (100 oC, toluene) using catalyst loadings between 1-2 mol%. ! Figure 15. Dehydrogenation of indoline using the Ru complexes reported by the groups of Mata and Szymczak. Finally, our group has reported the dehydrogenation of dihydrophenantridine using Ru complexes with facially coordinated CNC ligands as catalytic precursors. Upon using 1.0 mol% of a Ru-CNC complex in the presence of KOtBu (10 mol%), dihydrophenantridine was oxidized to phenanthridine in 24 h with 94% conversion (Figure 16).37 Besides, the same catalytic system was capable of hydrogenating phenantridine under 10 bar of !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 35 K.-N. T. Tseng, A. M. Rizzi, N. K. Szymczak, J. Am. Chem. Soc. 2013, 135, 16352. 36 D. Ventura-Espinosa, A. Marzá-Beltrán, J. A. Mata, Chem. Eur. J. 2016, 22, 17758. 37 M. Hernández-Juárez, J. López-Serrano, P. Lara, J. P. Morales-Cerón, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Chem. Eur. J. 2015, 21, 7540. Ru N N N N N H PPh3 PPh3 Ru Cl Cl Szymczak et al. N N Cl Cl nBu nBu Ru Cl Cl Mata et al. N N N H [Ru] 1-2 mol% Toluene 100-110 ºC, 24 h N H + H2 Introduction ! 259 H2 at 80 ºC. Although the catalyst hydrogenated other N-heterocycles under similar reaction conditions, including quinoline, quinoxaline, acridine, 4,7- phenanthroline and benzo[h]quinoline, it showed a negligible catalytic activity in the dehydrogenation of their saturated N-heterocyclic counterparts.38 ! Figure 16. Reversible dehydrogenation of dihydrophenantridine using a Ru-CNC complex. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 38 J. Morales-Cerón, V. Salazar, A. Suárez. Unpublished results. N [Ru] 1 mol% KOtBu 10 mol% Dioxane, reflux NH H2 (10 bar) H2 [Ru] 0.4 mol% KOtBu 10 mol % 2-MeTHF, 80 ºC N N N NR N R Ru Cl P Ph3 CO H R = Hexyl Chapter II. Ru-CNN(H) complexes 260 II.1.2.b. Reversible dehydrogenation of N-heterocycles catalyzed by transition metal complexes In a seminal report, Fujita, Yamaguchi et al. reported the use of iridium complexes with pentamethylcyclopentadienyl (Cp*) and 2-pyridonate ligands for the dehydrogenation of 1,2,3,4-tetrahydroquinolines (Figure 17).39 Hydrogen release from these substrates took place using 2 mol% catalyst in refluxing p-xylene. Furthermore, the same catalytic systems promoted the hydrogenation of quinolines under 1 bar of H2 at 110 oC. Based on these results, the repetitive hydrogenation-dehydrogenation of 2-methylquinoline (H2 gravimetric capacity: 2.7 wt%) was assayed with 5 mol% of catalyst. Up to five hydrogen storage/release cycles were performed with only a low erosion in the catalytic activity (100 to 98% conv.). Interestingly, although experimental studies and DFT calculations have supported a ligand-assisted dehydrogenation process, the [Cp*Ir(Cl)(μ-H)]2 complex, resulting from the protonation of the pyridonate ligand to 2-hydroxypyridine and subsequent decoordination, has been shown to be the active intermediate in the reduction reaction.40 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 39 R. Yamaguchi, C. Ikeda, T. Takahashi, K. Fujita, J. Am. Chem. Soc. 2009, 131, 8410. 40 (a) X. B. Zhang, Z. Xi, Phys. Chem. Chem. Phys. 2011, 13, 3997; (b) H. Li, J. Jiang, G. Lu, F. Huang, Z.-X. Wang, Organometallics 2011, 30, 3131. Introduction ! 261 ! Figure 17. Dehydrogenation of 1,2,3,4-tetrahydroquinolines and hydrogenation of quinolines with the Cp*Ir complex reported by Fujita, Yamaguchi et al. The same group has also carried out the perdehydrogenation of 2,6- dimethyldecahydro-1,5-naphthyridine, a fused saturated bicyclic compound, with release of five equivalents of H2 per molecule catalyzed by Cp*Ir complexes with bipyridonate or 1,10-phenanthroline-2,6-dione ligands (Figure 18).41 Using 5 mol% of catalyst, a mixture of the stereoisomers of 2,6- dimethyldecahydro-1,5-naphthyridine was dehydrogenatively oxidized with almost complete conversion in 20 h. These catalysts were also active in the perhydrogenation of 2,6-dimethyl-1,5-naphthyridine under 70 bar of H2 at 130 oC. Sucessive hydrogenation of 2,6-dimethyl-1,5-naphthyridine and hydrogen release from the resulting hydrogen-rich products were accomplished under the optimized reaction conditions for the individual steps. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 41 K. Fujita, Y. Tanaka, M. Kobayashi, R. Yamaguchi, J. Am. Chem. Soc. 2014, 136, 4829. N H [Ir] 5 mol%, p-xylene, 20 h N H2 (1 bar) H2 Ir O N Cl F3C Chapter II. Ru-CNN(H) complexes 268 hydrogenation of N-heterocycles (5-10 bar H2, 80 oC, 3 mol% Fe, 10 mol% base). Mechanistic studies revealed that a pentacoordinated iron hydride species, containing a deprotonated PNP ligand, and a trans-dihydride intermediate were common intermediates for both processes.50 ! ! Figure 25. Dehydrogenation of N-heterocycles using Fe-PN(H)P complexes. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 50 (a) S. M. Bellows, S. Chakraborty, J. B. Gary, W. D. Jones, T. R. Cundari, Inorg. Chem. 2017, 56, 5519; (b) B. Sawatlon, P. Surawatanawong, Dalton Trans. 2016, 45, 14965. Fe N PiPr2 PiPr2 H CO FeN P PiPr2 CO H BH3 H iPr2 FeN P PiPr2 CO Br H iPr2 N H [Fe] 3 mol% xylene reflux, 30 h R R’ N R R’ N H2 (5-10 bar) [Fe] 3 mol% THF 80 ºC, 24 h R R’ N H R R’ HHFeN P PiPr2 CO H H iPr2 H Introduction ! 269 Similarly, a cobalt complex based on a PN(H)P ligand was examined in the acceptorless dehydrogenation of N-heterocycles (Figure 26). 51 By using 10 mol% of catalyst in p-xylene at 150 ºC, a series of N-heterocycles, including six-membered tetrahydroquinoline and five-membered 2- methylindoline, were successfully dehydrogenated to produce the corresponding aromatic products with high conversions. Interestingly, a related complex based on a PN(Me)P ligand was inefficient in the oxidation of the N-heterocycles, pointing out to the participation of the ligand NH moiety in the catalytic process. On the other hand, the Co-PN(H)P complex was also found to efficiently catalyze the hydrogenation of N-heterocycles. However, in these reactions replacement of the NH function by a NMe group did not affect the hydrogenation activity. ! Figure 26. Dehydrogenation of N-heterocycles using the Co-PN(H)P complex. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 51 R. Xu, S. Chakraborty, H. Yuan, W. D. Jones, ACS Catal. 2015, 5, 6350.! N H [Co] 10 mol% p-xylene 150 ºC, 3-4 days R’’ R’ N R’’ R’ N H2 (10 bar) [Co] 5 mol% THF 120 ºC, 48 h R’’ R’ N H R’’ R’ Co N CH2SiMe3 PCy2 Cy2P RBArF R = H, Me II.2. Results and discussion Results and Discussion ! 273 II.2.1. General considerations As previously mentioned, two of the most representative types of proton-responsive pincer ligands are those based on M-amine/M-amido interconversion and lutidine reversible deprotonation. In Chapter II, we have aimed to combine both metal-ligand cooperation modes to develop efficient catalysts for the reversible hydrogenation of N-heterocycles. Particularly, new Ru complexes incorporating lutidine-derived pincer CNN(H) ligands containing a secondary amino side group have been synthetized (Figure 1). Moreover, these Ru-CNN(H) complexes have been examined in the hydrogenation and dehydrogenation of a series of N-heterocycles, and initial mechanistic studies have been performed. ! Figure 1. General structure of lutidine-derived CNN(H) ligands. N NNR N Mes H Chapter II. Ru-CNN(H) complexes ! 274 II.2.2. Synthesis of CNN(H) ligand-type precursors and Ag- CNN(H) complexes Synthesis of imidazolium salts 2a-c was effected by reaction of derivative 1a(Br) with the corresponding primary amine RNH2 (R = tBu, CH2Ph, Ph) (Scheme 1).9 These compounds were obtained with moderate to good yields (60-90%) as white solids, and were characterized by NMR spectroscopy and high-resolution mass spectrometry. The 1H NMR spectrum of 2a presents the distinctive downfield signal appearing at 10.45 ppm expected for the imidazolium H-2 proton; whereas the resonances of the methylene CH2-NHC and CH2-NH bridges appear as singlets at 5.97 and 4.07 ppm, respectively, and that of the amine proton is exhibited at 5.22 ppm as a broad singlet. Similar NMR spectroscopic data were obtained for derivatives 2b and 2c. Scheme 1. Synthesis of CNN(H) ligand precursors 2, and silver complexes 3. ! ! ! ! Br 2a: R = tBu 2b: R = CH2Ph 2c: R = Ph RNH2 H Ag2O 3a: R = tBu 3b: R = CH2Ph 3c: R = Ph N NNR N Mes H AgBr CH2Cl2 N NBr N Mes Br CH3CN N NNR N Mes 1a(Br) 63-93% 40-93% Results and Discussion ! 275 Treatment of the imidazolium salts 2a-c with Ag2O in CH2Cl2 allowed the isolation of the corresponding silver-carbene complexes 3a-c, as inferred from the disappearance of the downfield signal of the imidazolium H-2 protons in the 1H NMR spectra (Scheme 1). The silver complexes were characterized by NMR spectroscopy and elemental analysis. Their most relevant spectroscopic feature resides in the presence of a singlet resonance in the 13C{1H} NMR experiments at ca. 183 ppm attributable to the C-2 carbons of the NHC moieties. II.2.3. Synthesis of Ru-CNN(H) complexes Since the use of silver complexes as NHC transfer reagents for the synthesis of metal-NHC derivatives is well precedented52 and have permitted the preparation of different ruthenium complexes incorporating pincer ligands with NHC donors,37,53 the synthesis of Ru-CNN(H) complexes was sought by reaction of the silver derivatives 3 with an appropiate ruthenium precursor (Scheme 2). Addition of RuHCl(CO)(PPh3)3 to 3a in THF at 55 ºC gave rise in the hydride region of the 1H NMR spectrum of the reaction mixture to several resonances, which have been tentatively assigned to [RuH(CNN(H))(CO)(PPh3)]+ and RuHX(CNN(H))(CO) (X = Br, Cl) complexes (Figure 2). Aiming to obtain a single species, the mixture of complexes was treated with NaBF4 and PPh3 in CH3CN, affording the isolation of complex 4a in high yield (88%).9 The ruthenium complexes 4b and 4c were prepared and isolated similarly. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 52 (a) H. M. J. Wang, I. J. B. Lin, Organometallics 1998, 17, 972; (b) J. C. Garrison, W. J. Youngs, Chem. Rev. 2005, 105, 3978; (c) I. J. B. Lin, C. S. Vasam, Coord. Chem. Rev. 2007, 251, 642.! 53 M. Hernández-Juárez, M. Vaquero, E. Álvarez, V. Salazar, A. Suárez, Dalton Trans. 2013, 42, 351. Chapter II. Ru-CNN(H) complexes ! 276 ! Scheme 2. Synthesis of ruthenium complexes 4a-c.! ! Figure 2. Hydride region of the 1H NMR spectrum (300 MHz, CD2Cl2) of the reaction of RuHCl(CO)(PPh3)3 and 3a. Spectroscopic data of compounds 4 are in good agreement with their proposed structures, which have been further confirmed by X-ray diffraction studies carried out for complexes 4a and 4b. For example, in the hydride region, the 1H NMR spectrum of 4a shows a doublet resonance at −7.79 ppm with a large coupling constant of 2JHP = 114.0 Hz, evincing the trans arrangement of the hydrido and PPh3 ligands (Figure 3, Table 1). In the same experiment, the resonance of the amine hydrogen appears at 2.71 ppm as a i) RuHCl(CO)(PPh3)3 4a: R = tBu 4b: R = CH2Ph 4c: R = Ph ii) PPh3, NaBF4 CH3CN THF, 55 ºC 3a: R = tBu 3b: R = CH2Ph 3c: R = Ph N NNR N Mes H AgBr N N N Ru NtBu Mes L H H CO BF4 L = PPh335-88% Results and Discussion ! 277 broad doublet of doublet of doublet due to the coupling with the diastereotopic CH2-N protons and the phosphorus atom (3JHH = 12.2 Hz, 3JHH = 3.4 Hz, 3JHP = 3.4 Hz); whereas the methylene protons give rise to four different signals, two doublets appearing at 5.00 and 4.21 ppm (2JHH = 15.6 Hz) corresponding to the CH2-NHC bridge, and two doublets of doublets at 4.18 (2JHH = 14.7 Hz, 3JHH = 3.7 Hz) and 3.95 (2JHH = 14.2 Hz, 3JHH = 13.6 Hz) ppm caused by the CH2N arm. Moreover, in the 13C{1H} NMR spectrum of 4a, the presence of the coordinated CO was confirmed by the existence of a doublet resonance at 208.3 ppm (JCP = 6 Hz), while the C-2 carbon atom of the NHC fragment causes a doublet at 185.2 ppm (JCP = 5 Hz) (Table 2). Figure 3. 1H NMR spectrum (400 MHz, CD2Cl2) of complex 4a. Chapter II. Ru-CNN(H) complexes ! 284 Table 3 (cont.). Hydrogenation of N-heterocycles catalyzed by Ru-CNN(H) complexes.a Entry Substrate Product [Ru] (mol%) T (oC) Conv. (%) (time, h) 12 4a (1.0) 95 97 (48) 13 4a (1.0) 95 >99 (24) 14b 4a (1.0) 95 93 (72) (+ 7% 6j) 15 4a (1.0) 85 0 (24) 16b 4a (1.0) 95 74 (24) 17b 4a (1.0) 95 0 (24) a Reaction conditions, unless otherwise noted: 4 bar of H2, 2-methyltetrahydrofuran, KOtBu (10 mol%). [S] = 0.24 M. Conversions were determined by 1H NMR spectroscopy using mesitylene as internal standard. b 10 bar of H2. N 5i HN 6i N N 5j NNH 6j N N 5j HN NH 6j’ N N 5k NH HN 6k N 5l NH 6l N 5m NH 6m Results and Discussion ! 285 ! Figure 6. Complex 7. Based on these results, the hydrogenation of 2-substituted quinoxalines 5b and 5c was examined using complex 4a (entries 5 and 6). These derivatives were reduced under the previous conditions with high conversions after 24 h. Under the same reaction conditions, acridine (5d) and phenanthridine (5e) were hydrogenated with conversions higher than 92% in 19 h (entries 7 and 8). However, the reduction of other N-heterocycles, including quinazoline (5f), quinoline (5g), quinaldine (5h) and benzo[h]quinoline (5i), required higher catalyst loadings (1.0 mol%) and harsher reaction conditions (95 oC, 48 h) (entries 9-12). Next, the reduction of 4,7-phenanthroline (5j), having two N- heterocyclic rings, was studied (entries 13 and 14). Under 4 bar of H2, full hydrogenation of one of the N-containing rings was observed. Moreover, the hydrogenation of both N-heterocyclic rings was accomplished by increasing the H2 pressure to 10 bar after a reaction time of 3 days. On the contrary, hydrogenation of the chelating 1,10-phenanthroline (5k) was not achieved (entry 15). Hydrogenation of isoquinoline (5l) was also assayed, requiring 10 bar of H2 to get acceptable conversions (entry 16). Alternatively, the reduction of 2-methylisoquinoline (5m) was not effected even under 10 bar of H2 at 95 ºC (entry 17). N N N Ru NEt2 Mes Br H CO Chapter II. Ru-CNN(H) complexes ! 286 II.2.4.b. Dehydrogenation of N-heterocycles Taking into consideration the efficiency of complex 4a in the hydrogenation of a series of N-heterocycles (Table 3), the catalytic performance of this derivative was tested in the reverse reactions, namely the dehydrogenation of the resulting hydrogenated heterocycles (Table 4). Initially, dehydrogenation of tetrahydroquinoxaline (6a) was performed using 4.0 mol% of 4a and 15 mol% of KOtBu in 2-methyltetrahydrofuran at 85 ºC, leading to complete formation of quinoxaline (5a) after 24 h (entry 1). However, these conditions were not appropriate for the dehydrogenation of 6b, and more energetic reaction conditions (160 oC, o-xylene) and the influence of different bases were examined (entries 2-4). Using KHMDS as base did not improve the conversion in comparison to the the reaction with KOtBu, whereas NaH had a deleterious effect on the catalyst activity. Moreover, the oxidation of the 2-substituted tetrahydroquinoxaline 6c using KOtBu as base was sluggish (entry 5). Results and Discussion ! 287 Table 4. Dehydrogenation of N-heterocycles catalyzed by complex 4a.a Entry Substrate Product Base Conv. (%) (time, h) 1b KOtBu >99 (24) 2 KOtBu 85 (24) 3 KHMDS 84 (24) 4 NaH 6 (24) 5 KOtBu 8 (24) 6 50 (48) 7 94 (24) 8 >99 (24) N H H N 6a N N 5a N H H N 6b N N 5b N H H N 6c Br N N 5c Br N H 6d N 5d N H 6e N 5e N H NH 6f N N 5f Chapter II. Ru-CNN(H) complexes ! 288 Table 4(cont.). Dehydrogenation of N-heterocycles catalyzed by complex 4a.a Entry Substrate Product Base Conv. (%) (time, h) 9 47 (24) 50 (48) 10 16 (24) 27 (48) 11 84 (24) 12 51 (24) 74 (48) 13 27 (48) a Reaction conditions, unless otherwise noted: o-xylene, 4.0 mol% 4a, 160 ºC, 15 mol% base. [S] = 0.12 M. Conversions were determined by 1H NMR spectroscopy using mesitylene as internal standard. b 2-methyltetrahydrofuran, 85 ºC. [S] = 0.06 M. N H 6g N 5g N H 6h N 5h HN 6i N 5i NNH 6j N N 5j NH 6l N 5l Results and Discussion ! 289 In addition to hydroquinoxalines, dehydrogenation of other classes of N-heterocycles was also tested. Dihydroacridine (6d) was oxidized under the conditions of Table 4, entry 2 with moderate catalytic activity (50% conversion after 48 h) (entry 6). Alternatively, the reactions of dihydrophenanthridine (6e) and tetrahydroquinazoline (6f) took place with conversions higher than 94% after 24 h (entries 7 and 8). Under the latter conditions, the dehydrogenation of tetrahydroquinoline (6g) and tetrahydroquinaldine (6h) proceeded with only low to moderate conversions, even increasing the reaction time from 24 to 48 h (entries 9 and 10). In contrast, hydrogen release from tetrahydrobenzoquinoline (6i) took place with 84% conversion after 24 h (entry 11). The oxidation of tetrahydro-4,7- phenanthroline (6j) yielded the corresponding dehydrogenated N-heterocycle with 51% conversion in 24 h, which was increased to 74% after 48 h (entry 12). Finally, the reaction of tetrahydroisoquinoline (6l) proceeded with low conversion even after 48 h (entry 13). ! Chapter II. Ru-CNN(H) complexes ! 290 II.2.5. Reactivity of Ru-CNN(H) complexes towards bases and H2. Mechanistic implications in the hydrogenation of N-heterocycles In order to determine the ability of the CNN(H) ligands to participate in ligand-assisted processes, and to provide information regarding the species involved in the Ru-CNN(H) catalyzed reactions, deprotonation of the ruthenium complex 4a was explored. Addition of 1.3 equiv of KOtBu to a clear solution of 4a in THF-d8 led to the instantaneous formation of a dark red solution of the deprotonated complex 8 (Scheme 3).54 In the 1H NMR spectrum, the hydrido ligand of 8 produces a slightly broad doublet at −7.64 ppm having a large coupling constant 2JHP of 140 Hz, indicative of the relative trans disposition of the phosphine and hydrido ligands (Figure 7). Moreover, selective deprotonation of the CH2-NHC arm of 4a was evident from the observation of a singlet signal at 4.38 ppm (integrating to 1H), corresponding to the methyne =CH-NHC bridge, and two doublets of doublets at 3.43 (2JHH = 12.0 Hz, 3JHH = 12.0 Hz) and 3.09 (2JHH = 11.3 Hz, 3JHH = 1.9 Hz) ppm, attributable to the methylene CH2-NH moiety. Furthermore, the dearomatization of the pyridine fragment is manifested by the high-field shifted signals of the ring protons (5.08–6.09 ppm); whereas the proton of the NH donor group appears at 1.76 ppm overlapped with the solvent signal. The 13C{1H} NMR spectrum of 8 exhibits a singlet at 210.2 ppm for the CO ligand, while the resonance of the C-2 of the NHC moiety appears at 177.3 ppm. Finally, the coordination of the PPh3 ligand is further manifested by the presence of a broad singlet at 16.0 ppm in the 31P{1H} NMR spectrum. Results and Discussion ! 291 ! ! ! ! Scheme 3. Reactions of complex 4a with bases yielding complexes 8, 9 and 10. ! KOtBu (1.3 equiv) THF-d8 60 ºC THF-d8 KHMDS (3 equiv) THF-d8 N N N Ru NtBu Mes L H H CO BF4 4a, L = PPh3 N N N Ru NtBu Mes L H H CO 8, L = PPh3 + tBuOH N N N Ru NtBu Mes LCO 10, L = PPh3 K N N N Ru NtBu Mes H CO 9 + PPh360 ºC THF-d8 THF-d8 KOtBu (10 equiv) + HMDS or tBuOH Chapter II. Ru-CNN(H) complexes ! 292 ! Figure 7.!1H NMR spectrum (400 MHz) of the reaction of 4a with KOtBu (1.3 equiv) in THF-d8 to yield complex 8 (* denotes residual THF).! Subsequent treatment of solutions in THF-d8 of the in situ generated complex 8 with an excess of KOtBu (10 equiv), or of derivative 4a with KHMDS (3.0 equiv), produced after 24 h a dark violet solution. NMR analysis of the sample indicated the formation of the anionic amido complex 9 (Scheme 3). In the 1H NMR experiment of 9, the enamino =CH-NtBu proton of the pincer ligand resonates at 6.69 ppm as a singlet, while the inequivalent methylene protons of the CH2-NHC bridge appear as mutually coupled doublets at 4.83 and 4.56 ppm (2JHH = 12.7 Hz) (Figure 8). As for complex 8, the dearomatized central N-heterocycle produces upfield shifted resonances appearing in the range between 5.33 and 6.54 ppm. Moreover, the presence of the hydrido ligand is deduced by the existence of a singlet at Results and Discussion ! 293 −17.09 ppm. Diagnostic signals in the 13C{1H} NMR spectrum of 9 include the resonances appearing at 213.7 ppm, corresponding to the CO ligand, and at 195.6 ppm due to the carbene carbon. In support of the proposed structure for complex 9, it is worth mentioning a previous report of Milstein et al. on an analogous Ru(II) complex based on a deprotonated lutidine-derived PNN(H) ligand.3 ! Figure 8. 1H NMR spectrum (400 MHz, THF-d8) of the reaction of 4a with KHMDS (3.0 equiv) to yield complex 9 (* denotes residual THF). Prolonged heating to 60 ºC of solutions of the in situ formed complexes 8 or 9, or mixtures thereof, produced the clean formation of a new species that has been spectroscopically characterized as the Ru(0) complex 10 (Scheme 3). 1H NMR analysis of the resulting dark blue solution indicates the Experimental Procedures! ! 301 II.3.1. General considerations All reactions and manipulations were performed under nitrogen or argon atmosphere, either in a MBraun Unilab Pro glovebox or using standard Schlenk-type techniques.60 All solvents were dried and distilled under nitrogen, using the following desiccants: sodium-benzophenone-ketyl for diethyl ether (Et2O), tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF); sodium for hexane, pentane, toluene and o-xylene; CaH2 for dichloromethane (CH2Cl2) and acetonitrile (CH3CN); and NaOMe for methanol (MeOH). 61 Microanalyses were performed by the Analytical Service of the Instituto de Investigaciones Químicas, using a Leco TruSpec Micro elemental analyzer. The NMR experiments were carried out on Bruker DPX-300, DRX-400, DRX-500 and AdvanceIII-400/R apparatus. The 1H and 13C spectra were referenced to external SiMe4 using the residual proton peaks of the deuterated solvent as internal standards, while 31P was referenced to external 85% H3PO4. Spectral assignments were made by routine one- and two-dimensional experiments, including 1H-1H COSY, 1H- 1H NOESY, 1H-13C HSQC, 1H-13C HMBC and 31P NMR spectroscopies. All NMR measurements were carried out at 25 °C. High resolution mass spectrometry (HRMS) data were obtained using a ThermoFisher QExactive mass spectrometer at the Analytical Services of the Universidad de Sevilla (CITIUS). ESI-MS experiments were carried out in a Bruker Esquire 6000 apparatus by the Mass Spectrometry Service of the Instituto de Investigaciones Químicas. Infrared spectra were recorded on a Bruker Tensor 27 spectrometer. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 60 D. F. Shriver, M. A. Dredzon, The Manipulation of Air-Sensitive Compounds, 2nd Edition; Wiley-Interscience, 1986.!! 61 D. D. Perrin, W. L. F. Armarego, Purification of Laboratory Chemicals, 2nd Edition; Pergamon Press, 1980.! Chapter II. Ru-CNN(H) complexes 302 The following compounds were synthetized according to previously reported methods: 1-(2,4,6-trimethylphenyl)-1H-imidazole,62 RuHCl(CO)(PPh3)3,63 and RuHBr(CNNEt)(CO) (7).54a All other reagents were purchased from commercial suppliers and used as received. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 62 M. C. Perry, X. Cui, M. T. Powell, D.-R. Hou, J. H. Reibenspies, K. Burgess, J. Am. Chem. Soc. 2003, 125, 113. 63 N. Ahmad, J. J. Levison, S. D. Robinson, M. F. Uttley, E. R. Wonchoba, G. W. Parshall, Inorg. Synth. 1974, 15, 45. Experimental Procedures! ! 303 II.3.2. Synthesis of imidazolium salts 1-[(6-(Bromomethyl)pyridin-2-yl)methyl]-3-mesityl-1H-imidazol- 2-ium bromide, 1a(Br) A solution of 1-mesityl-1H-imidazole (1.24 g, 6.6 mmol) and 2,6- bis(bromomethyl)pyridine (3.00 g, 11.3 mmol) in THF (30 mL) was stirred for 7 days. The resulting precipitate was filtered, washed with cold THF (2 × 10 mL) and hexane (2 × 10 mL) and dried under vacuum to yield a light brown solid (2.00 g, 67%). NMR spectra of the imidazolium salt 1a(Br) are analogous to previously reported data.54a,64 1H NMR (300 MHz, CDCl3): δ 10.20 (s, 1H, H arom Imid), 8.20 (s, 1H, H arom Imid), 7.99 (d, 3JHH = 7.7 Hz, 1H, H arom Py), 7.80 (dd, 3JHH = 7.7 Hz, 3JHH = 7.7 Hz, 1H, H arom Py), 7.48 (d, 3JHH = 7.7 Hz, 1H, H arom Py), 7.20 (s, 1H, H arom Imid), 7.02 (s, 2H, H arom Mes), 6.25 (s, 2H, CH2- Imid), 4.50 (s, 2H, CH2Br), 2.42 (s, 3H, CH3), 2.11 (s, 6H, 2 CH3) ppm. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 64 C. del Pozo, M. Iglesias, F. Sanchez, Organometallics 2011, 30, 2180. N NBr N Br Chapter II. Ru-CNN(H) complexes 304 1-[(6-(N-tert-Butylaminomethyl)pyridin-2-yl)methyl]-3-mesityl- 1H-imidazol-2-ium bromide, 2a tBuNH2 (0.656 g, 8.98 mmol) was added to a solution of the imidazolium salt 1a(Br) (0.810 g, 1.80 mmol) in CH3CN (25 mL), and the resulting mixture was stirred overnight. The resulting mixture was filtered, and the solvent was evaporated under reduced pressure. The residue was washed with Et2O (3 × 10 mL), dissolved in CH2Cl2 (10 mL), and treated with ScavengePore phenethyl diethylamine resin (3.50 g; 0.66 mmol/g loading). The solution was separated from the resin by filtration, brought to dryness and washed with Et2O (3 × 10 mL). The treatment with the resin was repeated twice following the same steps. White solid (0.742 g, 93%). 1H NMR (500 MHz, CD2Cl2): δ 10.45 (s, 1H, H arom Imid), 8.27 (s, 1H, H arom Imid), 7.77 (dd, 3JHH = 7.5 Hz, 3JHH = 7.5 Hz, 1H, H arom Py), 7.70 (d, 3JHH = 7.5 Hz, 1H, H arom Py), 7.53 (d, 3JHH = 7.5 Hz, 1H, H arom Py), 7.20 (s, 1H, H arom Imid), 7.08 (s, 2H, 2 H arom Mes), 5.97 (s, 2H, CH2- Imid), 5.22 (br s, 1H, NH), 4.07 (s, 2H, CH2NH), 2.39 (s, 3H, CH3), 2.13 (s, 6H, 2 CH3), 1.41 (s, 9H, C(CH3)3) ppm. 13C{1H} NMR (126 MHz, CD2Cl2): δ 156.3 (Cq arom), 152.0 (Cq arom), N N N N Br H Experimental Procedures! ! 305 141.2 (Cq arom), 138.5 (CH arom), 138.1 (CH arom), 134.4 (2 Cq arom), 130.9 (Cq arom), 129.7 (2 CH arom), 124.1 (CH arom), 123.3 (CH arom), 122.6 (CH arom), 122.6 (CH arom), 54.9 (C(CH3)3), 53.5 (overlapped with deuterated solvent signal, CH2-Imid), 46.9 (CH2NH), 27.1 (C(CH3)3), 20.8 (CH3), 17.6 (2 CH3) ppm. HRMS (ESI): m/z calcd for C23H31N4 [(M−Br)+]: 363.2543; found: 363.2540. Chapter II. Ru-CNN(H) complexes 306 1-[(6-(N-Benzylaminomethyl)pyridin-2-yl)methyl]-3-mesityl-1H- imidazol-2-ium bromide, 2b Benzylamine (0.143 g, 1.33 mmol) was added to a solution of the imidazolium salt 1a(Br) (0.200 g, 0.44 mmol) in CH3CN (12 mL), and the mixture was stirred overnight. The solvent was evaporated, and the residue was extracted with CH2Cl2 (2 × 10 mL). The solution was brought to dryness, and the residue was washed with Et2O (2 × 10 mL) and pentane (2 × 10 mL) giving a white solid (0.133 g, 63%).65 1H NMR (300 MHz, CD2Cl2): δ 10.30 (s, 1H, H arom Imid), 8.04 (s, 1H, H arom Imid), 7.76 (dd, 3JHH = 7.5 Hz, 3JHH = 7.5 Hz, 1H, H arom Py), 7.69 (d, 3JHH = 7.5 Hz, 1H, H arom Py), 7.41 (d, 3JHH = 7.2 Hz, 2H, 2 H arom CH2Ph), 7.37 (d, 3JHH = 7.5 Hz, 1H, H arom Py), 7.30 (m, 3H, 3 H arom CH2Ph), 7.13 (s, 1H, H arom Imid), 7.04 (s, 2H, 2 H arom Mes), 5.99 (s, 2H, CH2-Imid), 3.92 (s, 2H, CH2NH), 3.89 (s, 2H, CH2NH), 2.64 (br s, 1H, NH), 2.36 (s, 3H, CH3), 2.05 (s, 6H, 2 CH3) ppm. 13C{1H} NMR (101 MHz, CD2Cl2): δ 159.4 (Cq arom), 152.4 (Cq arom), 141.7 (Cq arom), 138.9 (Cq arom), 138.7 (CH arom), 138.4 (CH arom), 134.8 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 65 José Mª Gordón Pidal, Trabajo Fin de Grado. Universidad de Sevilla, 2017. N N N N Br H Experimental Procedures! ! 307 (2 Cq arom), 131.2 (Cq arom), 130.1 (2 CH arom), 129.1 (2 CH arom), 128.8 (2 CH arom), 127.7 (CH arom), 124.1 (CH arom), 123.0 (CH arom), 122.9 (CH arom), 122.4 (CH arom), 54.2 (CH2-Imid), 53.6 (CH2NH), 53.1 (CH2NH), 21.2 (CH3), 17.8 (2 CH3) ppm. HRMS (ESI): m/z calcd for C26H29N4 [(M−Br)+]: 397.2392; found: 397.2387. Chapter II. Ru-CNN(H) complexes 308 1-[(6-(N-Phenylaminomethyl)pyridin-2-yl)methyl]-3-mesityl-1H- imidazol-2-ium bromide, 2c Aniline (0.433 g, 4.65 mmol) was added to a solution of the imidazolium salt 1a(Br) (0.700 g, 1.55 mmol) in CH3CN (15 mL), and the resulting mixture was stirred overnight. The mixture was filtered, and brought to dryness. The resulting residue was extracted with CH2Cl2 (2 × 10 mL), the solvent was evaporated under reduced pressure, and the solid was washed with Et2O (2 × 10 mL) and pentane (2 × 10 mL). White solid (0.650 g, 90%). 1H NMR (400 MHz, CD2Cl2): δ 10.29 (s, 1H, H arom Imid), 8.02 (s, 1H, H arom Imid), 7.73 (m, 2H, 2 H arom), 7.38 (d, 3JHH = 6.7 Hz, 1H, H arom Py), 7.14 (m, 3H, 3 H arom), 7.06 (s, 2H, 2 H arom Mes), 6.71 (m, 3H, 3 H arom), 6.07 (s, 2H, CH2-Imid), 4.85 (br, 1H, NH), 4.44 (s, 2H, CH2NH), 2.39 (s, 3H, CH3), 2.09 (s, 6H, 2 CH3) ppm. 13C{1H} NMR (101 MHz, CD2Cl2): δ 159.0 (Cq arom), 152.2 (Cq arom), 147.4 (Cq arom), 141.3 (Cq arom), 138.3 (CH arom), 138.1 (CH arom), 134.4 (2 Cq arom), 130.8 (Cq arom), 129.7 (2 CH arom), 129.1 (2 CH arom), 123.8 (CH arom), 122.6 (CH arom), 122.0 (CH arom), 121.9 (CH arom), 117.9 N N N N Br H Experimental Procedures! ! 309 (CH arom), 113.4 (2 CH arom), 53.4 (overlapped with deuterated solvent signal, CH2-Imid), 49.3 (CH2NH), 20.8 (CH3), 17.4 (2 CH3) ppm. HRMS (ESI): m/z calcd for C25H27N4 [(M−Br)+]: 383.2230; found: 383.2224. Chapter II. Ru-CNN(H) complexes 316 [RuH(CNN(H)Bn)(CO)(PPh3)]BF4 (4b) A suspension of 3b (0.207 g, 0.35 mmol) and RuHCl(CO)(PPh3)3 (0.337 g, 0.35 mmol) in THF (15 mL) was heated to 55 ºC for 24 h. The solution was filtered, and the solvent was evaporated under reduced pressure. The resulting residue was extracted with MeOH (2 × 10 mL), and the solvent was evaporated under vacuum. To the resulting solid, PPh3 (0.102 g, 0.39 mmol), NaBF4 (0.046 g, 0.43 mmol) and CH3CN (8 mL) were added, and the mixture was stirred overnight. The solvent was evaporated, and the residue was extracted with CH2Cl2 (2 × 10 mL) and precipitated by addition of toluene. Crystallization from MeOH and subsequent washing with Et2O (2 × 10 mL) of the complex yielded 4b as a light brown solid (0.121 g, 39%). Crystals of 4b suitable for X-ray diffraction analysis were grown from a saturated solution of the complex in MeOH. Anal. calcd (%) for C45H44BF4N4OPRu: C 61.7, H 5.1, N 6.4; found: C 61.8, H 4.9, N 6.4. 1H NMR (400 MHz, CD2Cl2): δ 7.83 (dd, 3JHH = 7.7 Hz, 3JHH = 7.7 Hz, 1H, H arom Py), 7.50 (d, 3JHH = 2.0 Hz, 1H, H arom NHC), 7.46 (m, 2H, 2 H arom), 7.40 (d, 3JHH = 7.7 Hz, 1H, H arom Py), 7.32 (m, 10 H, 10 H arom), 7.02 (s, 1H, H arom Mes), 6.92 (m, 7 H, 7 H arom), 6.88 (s, 1H, H arom Mes), 6.86 (d, 3JHH = 2.0 Hz, 1H, H arom NHC), 6.62 (m, 2H, 2 H N N N Ru N Mes L H H CO BF4 L = PPh3 Ph Experimental Procedures! ! 317 arom), 5.20 (d, 2JHH = 16.0 Hz, 1H, CHH-NHC), 4.34 (d, 2JHH = 16.0 Hz, 1H, CHH-NHC), 4.00 (m, 2H, Py-CHHNH + NCHHPh), 3.83 (m, 2H, Py- CHHNH + NCHHPh), 2.87 (br dd, 3JHH = 11.0 Hz, 3JHH = 11.0 Hz, 1H, NH), 2.33 (s, 3H, CH3), 1.97 (s, 3H, CH3), 1.85 (s, 3H, CH3), −7.30 (d, 2JHP = 109.9 Hz, 1H, RuH) ppm. 31P{1H} NMR (162 MHz, CD2Cl2): δ 24.5 ppm. 13C{1H} NMR (101 MHz, CD2Cl2): δ 206.8 (d, JCP = 7 Hz, CO), 186.2 (d, JCP = 5 Hz, C-2 NHC), 159.9 (Cq arom), 154.9 (Cq arom), 139.5 (Cq arom), 139.1 (CH arom), 137.1 (Cq arom), 136.7 (2 Cq arom), 136.4 (Cq arom), 134.0 (d, JCP = 28 Hz, 3 Cq arom), 132.9 (d, JCP = 11 Hz, 6 CH arom), 130.8 (3 CH arom), 129.6 (m, 9 CH arom), 129.2 (CH arom), 129.1 (CH arom), 128.8 (2 CH arom), 124.9 (CH arom), 123.2 (CH arom), 123.0 (CH arom), 121.6 (CH arom), 63.0 (CH2NH), 59.9 (CH2NH), 54.5 (CH2-NHC), 21.2 (CH3), 19.2 (CH3), 18.9 (CH3) ppm. IR (Nujol): 1936 cm−1 (νCO). Chapter II. Ru-CNN(H) complexes 318 [RuH(CNN(H)Ph)(CO)(PPh3)]BF4 (4c) A suspension of 3c (0.195 g, 0.34 mmol) and RuHCl(CO)(PPh3)3 (0.326 g, 0.34 mmol) in THF (12 mL) was heated to 55 ºC for 24 h. The solution was filtered, and the solvent was evaporated under reduced pressure. The resulting residue was extracted with MeOH (2 × 10 mL), solvent was removed and the obtained solid was dried under vacuum. To this solid PPh3 (0.098 g, 0.38 mmol), NaBF4 (0.045 g, 0.41 mmol) and CH3CN (8 mL) were added, and the mixture was stirred overnight. The solvent was evaporated, and the residue was extracted with CH2Cl2 (2 × 10 mL) and precipitated with toluene (2 × 10 mL). Crystallization from MeOH and subsequent washing with Et2O (2 × 10 mL) of the complex yielded 4c as a light brown solid (0.104 g, 35%). 1H NMR (400 MHz, CD2Cl2): δ 7.92 (dd, 3JHH = 7.7 Hz, 3JHH = 7.7 Hz, 1H, H arom Py), 7.50 (m, 2H, 2 H arom), 7.42 (m, 4H, 4 H arom), 7.24 (m, 8H, 8 H arom), 7.02 (s, 1H, H arom), 6.82 (m, 10H, 10 H arom), 6.76 (s, 1H, H arom), 5.15 (d, 2JHH = 15.6 Hz, 1H, CHH-NHC), 4.54 (m, 3H, 2 CHHNH + NH), 4.40 (d, 2JHH = 15.6 Hz, 1H, CHH-NHC), 2.29 (s, 3H, CH3), 2.03 (s, 3H, CH3), 1.78 (s, 3H, CH3), −7.05 (d, 2JHP = 110.7 Hz, 1H, RuH) ppm. 31P{1H} NMR (162 MHz, CD2Cl2): δ 23.6 ppm. N N N Ru NPh Mes L H H CO BF4 L = PPh3 Experimental Procedures! ! 319 13C{1H} NMR (101 MHz, CD2Cl2): δ 205.6 (d, JCP = 7 Hz, CO), 185.8 (d, JCP = 4 Hz, C-2 NHC), 159.6 (Cq arom), 154.7 (Cq arom), 147.1 (Cq arom), 139.6 (Cq arom), 139.2 (CH arom), 137.0 (Cq arom), 136.6 (Cq arom), 136.4 (Cq arom), 133.6 (d, JCP = 29 Hz, 3 Cq arom), 133.3 (d, JCP = 11 Hz, 6 CH arom), 130.7 (3 CH arom), 129.5 (m, 9 CH arom), 129.1 (CH arom), 126.7 (CH arom), 124.7 (CH arom), 123.3 (CH arom), 123.1 (CH arom), 122.8 (2 CH arom), 122.0 (CH arom), 65.6 (CH2NH), 54.6 (CH2-NHC), 21.1 (CH3), 19.1 (CH3), 18.8 (CH3) ppm. IR (Nujol): 1958 cm−1 (νCO). HRMS (ESI): m/z calcd for C44H42N4OPRu [(M−BF4)+]: 775.2140; found: 775.2133. Chapter II. Ru-CNN(H) complexes 320 Complex 8 In a J.Young valved NMR tube, THF-d8 (0.5 mL) was added to a mixture of 4a (0.023 g, 0.027 mmol) and KOtBu (0.004 g, 0.035 mmol), giving rise to the immediate formation of a dark red solution. The resulting sample was analyzed by NMR spectroscopy. Attempted isolation of complex 8 was unsuccessful due to significant decomposition during work-up. 1H NMR (400 MHz, THF-d8): δ 7.32 (m, 15H, 15 H arom Ph), 6.94 (s, 1H, H arom Mes), 6.81 (s, 1H, H arom Mes), 6.75 (d, 3JHH = 1.9 Hz, 1H, H arom NHC), 6.65 (d, 3JHH = 1.9 Hz, 1H, H arom NHC), 6.09 (dd, 3JHH = 9.0 Hz, 3JHH = 6.1 Hz, 1H, Hc), 5.14 (d, 3JHH = 6.0 Hz, 1H, Hd), 5.08 (d, 3JHH = 9.0 Hz, 1H, Hb), 4.38 (s, 1H, Ha), 3.43 (dd, 2JHH = 12.0 Hz, 3JHH = 12.0 Hz, 1H, CHHNH), 3.09 (dd, 2JHH = 11.3 Hz, 3JHH = 1.9 Hz, 1H, CHHNH), 2.31 (s, 3H, CH3), 2.12 (s, 3H, CH3), 1.76 (overlapped with solvent signal, NH), 1.73 (s, 3H, CH3), 0.93 (s, 9H, C(CH3)3), −7.64 (d, 2JHP = 140.2 Hz, 1H, RuH) ppm. 31P{1H} NMR (121 MHz, THF-d8): δ 16.0 (br) ppm. 13C{1H} NMR (101 MHz, THF-d8): δ 210.2 (CO), 177.3 (C-2 NHC), 155.7 (Cq arom), 143.0 (Cq arom), 137.9 (Cq arom), 137.7 (Cq arom), 137.6 (Cq arom), 137.4 (Cq arom), 133.6 (d, JCP = 16 Hz, 6 CH arom PPh3), 129.0 (m, N N N Ru NtBu Mes L H H CO L = PPh3 a b c d Experimental Procedures! ! 321 Cc + 10 CH arom + 3 Cq arom PPh3), 120.8 (2 CH arom), 120.0 (CH arom), 111.8 (Cb), 96.8 (Cd), 90.9 (Ca), 55.6 (C(CH3)3), 54.7 (CH2NH), 28.4 (C(CH3)3), 21.1 (CH3), 19.2 (CH3), 18.7 (CH3) ppm. Chapter II. Ru-CNN(H) complexes 322 Complex 9 ! In a J.Young valved NMR tube, THF-d8 (0.5 mL) was added to a mixture of 4a (0.025 g, 0.030 mmol) and KHMDS (0.018 g, 0.090 mmol) giving rise initially to a dark red solution that gradually evolves to dark violet. The resulting solution was analyzed by NMR spectroscopy after 24 h. Attempted isolation of complex 9 was unsuccessful due to significant decomposition during work-up. 1H NMR (400 MHz, THF-d8): δ 7.05 (d, 3JHH = 2.0 Hz, 1H, H arom NHC), 6.80 (s, 1H, H arom Mes), 6.74 (s, 1H, H arom Mes), 6.69 (s, 1H, He), 6.59 (d, 3JHH = 2.0 Hz, 1H, H arom NHC), 6.54 (d, 3JHH = 8.9 Hz, 1H, Hb), 5.83 (dd, 3JHH = 8.9 Hz, 3JHH = 5.7 Hz, 1H, Hc), 5.33 (d, 3JHH = 5.7 Hz, 1H, Hd), 4.83 (d, 2JHH = 12.7 Hz, 1H, CHH-NHC), 4.56 (d, 2JHH = 12.7 Hz, 1H, CHH-NHC), 2.26 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.57 (s, 3H, CH3), 1.50 (s, 9H, C(CH3)3), −17.09 (s, 1H, RuH) ppm. 13C{1H} NMR (101 MHz, THF-d8): δ 213.7 (CO), 195.6 (C-2 NHC), 150.2 (Cq arom), 138.7 (Cq arom), 137.3 (Cq arom), 137.2 (Cq arom), 137.0 (Cq arom), 135.0 (Cq arom), 128.7 (2 CH arom), 120.4 (2 CH arom), 119.3 (Cb), 117.6 (Ce), 116.7 (Cc), 95.9 (Cd), 59.6 (C(CH3)3), 57.6 (CH2-NHC), 35.9 (C(CH3)3), 21.1 (CH3), 20.5 (CH3), 18.4 (CH3) ppm. e K N N N Ru NtBu Mes H CO b c d Experimental Procedures! ! 323 Complex 10 ! In a J.Young valved NMR tube, THF-d8 (0.5 mL) was added to a mixture of 4a (0.022 g, 0.026 mmol) and KOtBu (0.0038 g, 0.034 mmol) forming a dark red solution. Heating the resulting mixture to 60 ºC for 24 h produced a dark blue solution that was analyzed by NMR spectroscopy. Attempted isolation of 10 was unsuccessful due to decomposition of the complex during work-up. 1H NMR (400 MHz, THF-d8): δ 7.92 (d, 4JHP = 3.7 Hz, 1H, CH=NtBu), 7.30 (d, 3JHH = 2.0 Hz, 1H, H arom NHC), 7.12 (d, 3JHH = 8.5 Hz, 1H, Hd), 7.07 (m, 3H, 3 H arom PPh3), 7.00 (m, 7H, 6 H arom PPh3 + H arom NHC), 6.91 (s, 1H, H arom Mes), 6.75 (m, 7H, 6 H arom PPh3 + H arom Mes), 6.37 (ddd, 3JHH = 8.5 Hz, 3JHH = 6.4 Hz, 6JHP = 4.3 Hz, 1H, Hc), 5.79 (dd, 3JHH = 6.4 Hz, 5JHP = 3.1 Hz, 1H, Hb), 4.74 (d, 2JHH = 14.0 Hz, 1H, CHH-NHC), 3.91 (d, 2JHH = 13.9 Hz, 1H, CHH-NHC), 2.28 (s, 6H, 2 CH3), 1.30 (s, 3H, CH3), 1.23 (s, 9H, C(CH3)3) ppm. 31P{1H} NMR (162 MHz, THF-d8): δ 50.5 ppm. 13C{1H} NMR (101 MHz, THF-d8): δ 216.1 (d, JCP = 10 Hz, CO), 191.3 (d, JCP = 7 Hz, C-2 NHC), 148.1 (Cq arom), 143.1 (Cq arom), 139.8 (d, JCP = 34 Hz, 3 Cq arom), 138.6 (Cq arom), 138.3 (Cq arom), 137.0 (Cq arom), 136.7 N N N Ru NtBu Mes LCO b c d L = PPh3 Chapter II. Ru-CNN(H) complexes 324 (Cq arom), 132.9 (d, JCP = 11 Hz, 6 CH arom PPh3), 131.8 (d, JCP = 3 Hz, CH=NtBu), 129.4 (CH arom), 129.3 (CH arom), 128.1 (3 CH arom PPh3), 127.8 (d, JCP = 9 Hz, 6 CH arom PPh3), 123.5 (CH arom), 122.8 (d, JCP = 5 Hz, Cd), 121.6 (CH arom), 119.6 (d, JCP = 4 Hz, Cc), 107.5 (Cb), 63.1 (d, JCP = 4 Hz, C(CH3)3), 56.4 (CH2-NHC), 33.9 (d, JCP = 3 Hz, C(CH3)3), 21.0 (CH3), 20.3 (CH3), 19.0 (CH3) ppm. Experimental Procedures! ! 325 II.3.5. Catalytic reactions Representative procedure for the hydrogenation of N- heterocycles In a glovebox, a Fischer–Porter vessel was charged with a solution of complex 4a (1.0 mg, 1.2 μmol), KOtBu (1.3 mg, 12 μmol) and quinoxaline (0.031 g, 0.24 mmol) in 2-methyltetrahydrofuran (1.0 mL). The reactor was purged three times with H2, and finally pressurized to 4 bar and heated to 80 oC. After 6 h, the reactor was slowly cooled down to room temperature and depressurized. The reaction solution was evaporated, and conversion was determined by 1H NMR spectroscopy using mesitylene as internal standard. Representative procedure for the dehydrogenation of N- heterocycles In a glovebox, a Schlenk tube was charged with a solution of complex 4a (4.0 mg, 4.7 μmol), KOtBu (8.0 mg, 71 μmol) and tetrahydroquinoxaline (17.6 mg, 119 μmol) in 2-MeTHF (1.0 mL). A reflux condenser was adapted to the Schlenk tube, and the solution was heated to 85 ºC under N2. After 24 h, the reaction solution was evaporated, and conversion was determined by 1H NMR spectroscopy using mesitylene as internal standard. Chapter II. Ru-CNN(H) complexes! ! 332 28) Z. Broucková, M. Czaková, M. Capka, J. Mol. Catal. 1985, 30, 241. 29) (a) A. Toti, P. Frediani, A. Salvini, L. Rosi, C. Giolli, J. Organomet. Chem. 2005, 690, 3641; (b) A. Toti, P. Frediani, A. Salvini, L. Rosi, C. Giolli, C. Giannelli, C. R. Chimie 2004, 7, 769; (c) P. Frediani, V. Pistolesi, M. Frediani, L. Rosi, Inorg. Chim. 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A series of lutidine-derived CNP (C = N-heterocyclic carbene, P = phosphine) pincer-type ligand precursors has been prepared, and used in the synthesis of Pd and Ir complexes. Structural studies of these complexes have shown a considerable ability of the CNP ligands to adopt different coordination modes as a consequence of the flexibility of the six-membered Py–M–NHC chelate ring. Thus, both fac and mer coordination of the pincer ligand in five- and six-coordinated Ir–CNP complexes have been observed. 2. The M-CNP (M = Pd, Ir) complexes react with bases leading to the deprotonation of either the CH2-NHC or the CH2-P methylene bridge that is accompanied of the dearomatization of the pyridine central ring of the CNP ligand. Deprotonated Ir-CNP* derivatives are able to activate H2 in a ligandassisted process providing hydride species that are catalytically active in the (transfer) hydrogenation of ketones in the presence of base (Ir-CNPPh complexes), and in the chemoselective reduction of aldehydes with H2 (Ir- CNPtBu complexes). 3. The deprotonated carbonyl Ir-CNP* complexes 15a and 15b are efficient catalytic precursors for the selective hydroboration of CO2 to methoxy- (with catecholborane) and formoxyborane (with pinacolborane). In these processes, a significant influence of the presence of small amounts of water on the rate of the catalytic reactions has been observed. Thus, TOF values of up to 58 h-1 in the reduction of CO2 to methoxyborane with HBcat, and up to 1245 h-1 in the hydroboration to the formate level using HBpin have been achieved after optimization of the water content of the reactions. Moreover, NMR spectroscopy and MS analyses of the catalytic reactions have shown the formation, as the sole observable species, of Ir-CNP derivatives resulting from the oxidative addition of the hydroborane to [Ir(CNP)(CO)][B(R2)2] (R2 = Conclusions ! 340 catechol, pinacol) complexes. Control experiments, however, have ruled out a significant participation of these species in the hydroboration reactions. 4. The synthesis of Ru complexes 4 incorporating lutidine-derived CNN(H) pincer ligands (C = N-heterocyclic carbene, N(H) = secondary amine) that have two potentially metal-ligand cooperation modes have been accomplished using Ag-CNN(H) complexes (3) as carbene transfer reagents. Use of Ru- CNN(H) complexes 4 in the presence of base lead to catalytically active species in the hydrogenation of a series of diverse N-heteroarenes and in the acceptorless dehydrogenation of the corresponding saturated N-heterocycles. 5. The acid-base reactivity of the Ru-CNN(H) complex 4a has been explored. Addition of base (KHMDS or KOtBu) to solutions of 4a produces the deprotonation of the methylene bridges as well as of the amino donor group, leading to the formation of mono- (complex 8) and di-deprotonated (complex 9) ruthenium species. Moreover, heating of these solutions provides the formal Ru(0) complex 10. Control experiments suggest that this Ru(0) species is directly involved in the catalytic hydrogenation of N-heterocycles.