Understanding the ligand influence in the multistep reaction of diazoalkanes with palladium complexes leading to carbene-aryl coupling

Understanding the Ligand Influence in the Multistep Reaction of Diazoalkanes with Palladium Complexes Leading to Carbene-Aryl Coupling Francisco Villalba and Ana C. Albéniz* Cite This: Organometallics 2025, 44, 394−402 Read Online ACCESS Metrics & More Article Recommendations * sı Supporting Information ABSTRACT: The reaction of diphosphino aryl complexes [Pd- (C6F5)(L-L)(NCMe)](BF4) (L-L = dppe, dppp, dppb) with diazoalkanes N2CHR (R=−CH�CHPh, Ph) leads to η3-allyl or η3-benzyl palladium derivatives that are the organometallic products resulting from carbene-aryl coupling. The experimental trend shows that the reaction is favored for dppe > dppp > dppb. It involves several consecutive steps, i.e., diazoalkane coordination, nitrogen extrusion to give a Pd-carbene, and migratory insertion, which are experimentally inseparable, but they can be studied with the help of DFT calculations. The bulkiness and bite angle of the ligand exert a large influence in the relative rate of the steps involved in the reaction, and we have found that carbene formation by N2extrusion is the step with the largest barrier for dppe. In contrast, the coordination of the diazoalkane is the most energy-demanding step for the larger dppp and dppb diphosphines. Thus, ligand substitution controls the rate, an important elemental step rarely considered in mechanistic studies of carbene cross coupling reactions. Since diazoalkanes are the most common carbene precursors, either directly or generated from hydrazones, the choice of ligand can be very important to facilitate the entrance of the carbene precursor in the catalytic cycle. ■INTRODUCTION Palladium-catalyzed cross coupling reactions that use carbene precursors as reagents are important processes in the C−C bond forming reaction toolbox. The carbene fragment is amenable to double functionalization and cascade reactions lead to the formation of two C−C or C-X bonds, which builds up molecular complexity in a fewer number of synthetic steps. 1,2 The key step in these transformations is the 1,1insertion (or migratory insertion) of a carbene fragment into a Pd−C bond in a metal carbene intermediate (B) formed by reaction of the carbene precursor and a palladium hydrocarbyl complex A. The detailed experimental study of this specific step (Bto C,Scheme 1) is not easy because the preceding carbene complex is usually difficult to detect or isolate. Therefore, it is not possible to collect experimental data pertaining the rate of the migratory insertion step or the factors that favor it alone, since the observed outcome will be a combination of several consecutive steps. Very few isolated carbenes Bhave been shown to undergo a migratory insertion reaction and they are stabilized monoamino carbenes (R1= NR2, R2= alkyl, aryl, Scheme 1), 3 and N-heterocyclic carbenes (NHCs). 4 For carbenes with hydrocarbyl substituents or alkoxo groups the carbene is too unstable to be isolated and only the transformation Ato Ccan be observed (Scheme 1). 3a,c,5−7 The most common carbene precursors used in Pd-catalyzed coupling processes are diazoalkanes N2R1R2, where R1, R2= H, hydrocarbyl. They can be directly used as reagents or generated in situ via the decomposition of tosylhydrazones. Using these precursors the carbene intermediates Bare too unstable to be detected but suitable substituents in the diazoalkane have allowed isolation of the alkyl complex right after the migratory insertion (C,Scheme 1). Thus, we have Received: October 14, 2024 Revised: December 3, 2024 Accepted: December 27, 2024 Published: January 10, 2025 Scheme 1. Intermediates in the Carbene-Hydrocarbyl Coupling from Carbene Precursors Article pubs.acs.org/Organometallics © 2025 The Authors. Published by American Chemical Society 394 https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 This article is licensed under CC-BY 4.0 Downloaded via UNIVERSIDAD DE VALLADOLID on February 17, 2025 at 08:57:40 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. reported that using [Pd(C6F5)(dppe)(NCMe)](BF4) as precursor complex Ait is possible to isolate derivatives of type Cwhere the alkyl group is stabilized by coordination of a C−C double bond (η3-allylic complex) or a phenyl ring (η3benzylic complex). 8 With this system at hand, we decided to study the influence of the ligands in the formation of the migratory insertion product. In particular, we looked at the cis−trans stereochemistry of the complexes and the ligand bite angle for analogous chelating phosphines. The influence of the ligand bulk and bite angle on C−C bond formation reactions can be used to modulate a catalyst reactivity. For example, the increase of the reductive elimination rate upon introducing bulky ligands is known and has proved to be one of the most successful strategies to achieve efficient cross-coupling reactions in milder conditions or those of reluctant substrates (i.e fluorinated substates). 9,10 1,1-Migratory insertion reactions of carbon monoxide are also favored by bulky ligands with large bite angles and this has been shown for the insertion of CO into a Pd-alkyl bond. A series of well-defined methyl Pd(II)-complexes with bidentate phosphines, were examined by Brookhart et al. They observed that the kinetic barriers for the migratory insertion of CO into the Pd-methyl bond decrease with increasing the P−Pd−P bond angle of the complex and the steric bulk of the ligand. 11 A large bite angle of the auxiliary ligand, brings the groups that have to couple close together (CO and Me in this case) and the barrier to reach the three membered transition state in the migratory insertion decreases. Although the migratory insertion of CO and carbenes have many analogies (both are isolobal), 12 no study of the influence of the ligands on the coupling of a carbene fragment and a PdR moiety has been reported. We have examined the reactivity of palladium aryl complexes with different monodentate and bidentate phosphine ligands and diazoalkanes, leading to C−C coupling complexes C. Because of the impossibility of isolating the relevant palladium carbene complex Band separating the migratory insertion step from the reaction of Awith the diazo compound, both experimental and computational work is reported here. The combined experimental and computational data give information on the influence of the different steps in controlling the rate of the overall carbene-aryl coupling. ■RESULTS AND DISCUSSION Preparation of the Palladium Phosphino Precursors. Complexes [PdBr(C6F5)(L-L)] (1-3), [Pd(C6F5)(L-L)- (NCMe)](BF4) (4-6; L-L = dppe, dppp, dppb) (Scheme 2) and [Pd(C6F5)(NCMe)(PPh3)2](BF4) (7) were used as models to evaluate the ligand-dependent reactivity with diazoalkanes N2CH−CH�CHPh (8) and N2CHPh (9). These diazoalkanes have already proved to be suitable for stabilizing the expected alkyl intermediate after the migratory insertion step (C,Scheme1), by coordination of the unsaturated double bond or aryl group to the metal. 8 The chosen phosphine ligands belong to the same family of diphosphines. Their electronic properties are very similar, but the tether between the phosphorus atoms and therefore the bite angle (P-M-P) is different in each phosphine. The use of pentafluorophenyl as a model aryl moiety is convenient since it allows the very informative follow up of the reactions by 19F NMR (see below), while showing analogous behavior to less fluorinated aryls in palladium-mediated C−C coupling processes. 13 The syntheses of complexes 1-3were carried out using the same dimeric precursor (NBu4)2[Pd(μBr)2Br2(C6F5)2] in the presence of the stoichiometric amount of the chelating ligand. Complex 1has been reported before, 14 and the molecular structure of the dppp derivative 2was determined by X-ray diffraction. It shows a palladium squareplanar geometry and a cis arrangement of the C6F5and Br ligands (Figure S5, Supporting Information). The P−Pd−P and C−Pd−Br angles are 93.44°and 88.28°respectively, being in the expected range for other similar molecular structures of [PdAr(dppp)(X)] complexes reported in the literature. 15 The cis arrangement is also present in solution as clearly shown by the appearance of two inequivalent 31P NMR resonances (see Experimental section). A different behavior was observed for dppb and the isolated complex 3is a trans-species as shown by the appearance of only one 31P NMR resonance at 18.92 ppm. In chloroform solution at room temperature, 3isomerizes to give a trans:cis mixture in a 0.8:1 mol ratio after 48 h (cf. Figures S14−S17, Supporting Information). When the isolated complex trans-3is treated with AgBF4to remove the Br ligand in acetonitrile at room temperature, complex 6was obtained as a mixture of isomers trans:cis = 1:0.8 mol ratio (Scheme 2). This was observed by 19F and 31P NMR (Figures S22, S23, Supporting Information). This behavior is only observed for the dppb ligand because of its inherent wide P−Pd−P angle in comparison to the dppe or dppp ligands. For the complexes bearing the latter ligands (1and 2) their reaction with AgBF4 affords the corresponding cis-solvento acetonitrile derivatives 4 and 5(Scheme 2). Complex trans-[Pd(C6F5)(NCMe)- (PPh3)2](BF4) (7) was prepared in the same way from the known trans-[PdBr(C6F5)(PPh3)2] complex. 14 The diphosphine 1,1-bis(diphenylphosphino)methane (dppm), with the smallest bite angle, was excluded from the study since the parent palladium complex of composition “PdBr(C6F5)dppm” was obtained as a mixture of the binuclear [Pd(μ-dppm)Br(C6F5)]2(58%) with a bridging dppm and the monomeric [PdBr(C6F5)dppm] (42%). The percentages given were obtained from the crude reaction mixture by 19F and 31P NMR integration. This behavior of dppm has been observed before, 16 and the presence of the bridging phosphine does not allow to evaluate the influence of the bite angle properly. Scheme 2. Synthesis of the Precursor Model Complexes Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 395 Reactions of the Solvento Palladium Complexes with Diazo Compounds. The solvento acetonitrile complexes readily react with diazoalkanes 8and 9giving organometallic η3-allylic complexes or η3-benzylic complexes respectively (Scheme 3). They are the result of the aryl-carbene coupling and correspond to the stabilized alkyl derivative Cin Scheme 1. The reactions were carried out under the same conditions for all the complexes and the amounts of coupling products were determined by integration of the corresponding 19F signals in the NMR spectra of the reaction mixtures at a fixed reaction time (Scheme 3). We have reported the formation of complexes 10 and 11 by reaction the dppe derivative 4with the diazoderivatives in full conversion after 5 min at room temperature (Scheme 3a) as well as their structural characterization. 8 The characteristic 19F NMR signals of the starting solvento complex 4(Pd−C6F5, Fortho about −120 ppm) disappear and are replaced by the characteristic C−C6F5resonances (Fortho about −140 ppm) of the organometallic complexes obtained after the migratory insertion (Figure S1, Supporting Information). The reaction of the analogous dppp solvento complex 5with an equimolar amount of diazoalkane 8afforded 46% of the η3-allylic Pd complex 12. An additional portion of diazoalkane was added to the same sample, and the reaction proceeded to reach 83% of 12 and a 17% of the starting 5which remains unreacted (Scheme 3b). Characteristic signals for the migration of the C6F5group to the carbene fragment were observed in the 19F NMR (Fortho c.a −142 ppm, Figure 1, b). The Fortho signals are broad showing a restricted rotation of the C−C6F5bond at room temperature, presumably caused by the large bite angle and increased steric hindrance of the dppp ligand. The molecular structure of the η3-allyl complex 12 was determined by X-ray diffraction and it shows that both aryl-substituents of the η3-allylic fragment are in a syn arrangement (Figure 2). The reaction of 5with the diazoalkane 9(Pd:9= 1:1.5 mol ratio) leads to the η3-benzylic palladium complex 13, as a mixture of the syn pentafluorophenyl complex and a small amount of a tentatively assigned anti-C6F5complex as collected in Scheme 3b and shown in Figure 1c. As it was mentioned above the freshly prepared complex 6is a mixture of trans:cis isomers (Scheme 2). This introduces a new factor that can distort the observed experimental results since the migratory insertion requires a cis arrangement of the carbene and hydrocarbyl fragments. The reaction of 6with diazoalkane 8afforded only 8% of the η3-allyl-palladium complex 14 (Scheme 3c). The remaining starting complex 6is a mixture of the trans:cis isomers in a different ratio to that observed minutes before its in situ preparation (Figure S3, Supporting Information). This means that the cis-trans equilibrium, presumably slow, was not established at the beginning of the reaction. The analysis of the final reaction mixture indicates that the cis-6isomer is the major one, so the poor formation of the η3-allyl-palladium complex 14 is not governed by the lack of cis-6, although it can certainly be influenced by the lower concentration of this isomer in the starting mixture of complexes. Scheme 3. Complexes Formed upon Reaction of 4-6 with the Diazoalkanes Figure 1. 19F NMR spectra (470.17 MHz, CH3CN, (CD3)2SO capillary) of: a) complex 5; b) the reaction of 5with diazoalkane 8, to give complex 12 (Pd:8= 1:2 mol ratio); c) the reaction of 5with diazoalkane 9to give 13 as a mixture of syn (depicted) and anti isomers. Figure 2. X-ray molecular structure of 12. Solvent molecules (CHCl3) and the BF4 −anion are omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd1−P2, 2.3035(17); Pd1−P1, 2.3057(16); Pd1− C9, 2.229(6); Pd1−C8, 2.196(6), Pd1−C7, 2.226(7); C7−C8, 1.406(10); C8−C9, 1.397(10). Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 396 The reaction of 6and the diazoalkane 9leads to two new organometallic species (30% of the total amount of C6F5in 19F NMR) which have been tentatively assigned to the anti:syn isomers of the η3-benzyl-organometallic product 15, in an almost equimolar ratio (Figures S4, S39 and S40, Supporting Information). The syn-isomer shows characteristic chemical shifts in the 19F NMR analogous to the data for complex 11 (syn) that has been unequivocally characterized (Fortho resonances at about −137 ppm (syn) vs −140 ppm (anti)). 8 As can be seen in Scheme 3, the syn arrangement in the η3benzylic complexes is preferred to the anti arrangement but the latter gains importance as the bulkiness of the ligands increase. This is confirmed by DFT calculations which show that the syn isomer is more stable for the dppe derivative by 1.62 kcal mol−1, but the energy difference is almost the same for both isomers in the case of the more sterically demanding dppp and dppb, in agreement with the experimental observations (Figure S41, Supporting Information). Trans-[Pd(C6F5)(NCMe)(PPh3)2](BF4) (7) reacts with the diazoalkanes to give almost no aryl migration species (eq 1). When a mixture of 7and the diazoderivative 8was analyzed, we could not identify any organometallic product from the migratory insertion of a transient palladium carbene complex into the Pd−C6F5bond and just small amounts of C6F5containing organic products (5%) were detected by 19F NMR. Only decomposition products of the diazo compound were observed by 1H NMR: 5-Ph-1H-pyrazole, formed by cyclization of the diazoalkane 8, and 1,6-diphenylhexa-1,3,5triene, as result of the dimerization of the carbene fragment. Similar results were obtained in the reaction of 7and diazoalkane 9where no organometallic migratory insertion products could be detected by 19F NMR. Benzaldehyde, cis/ trans stilbene and the azine Ph−CH = N−N = CH-Ph were detected by NMR as decomposition products of the diazoalkane 9. For the monodentate phosphine precursor, the putative palladium carbene generated would be a transient trans-[Pd(C6F5)(PPh3)2(carbene)]+and in this arrangement the migratory insertion cannot occur. Thus, the results obtained are consistent with a scenario where the isomerization process to afford a cis complex is slower than the decomposition of both the free diazoalkane and the metal carbene. DFT Calculations on the Carbene Formation and Migratory Insertion Steps. The nature of the auxiliary ligand and the different number of carbons in the backbone of the diphosphine ligands exert a relevant influence in the outcome of the reaction with diazoalkanes. For the chelating diphosphines the reactivity order that can be extracted from Scheme 3 roughly follows the trend: dppe > dppp > dppb. In a simplified way, the steps involved in the reactions of solvento acetonitrile Pd(II) complexes with diazoalkane 8are depicted in Scheme 4. Only the η3-allylic products after migratory insertion were detected, so the coordination of the diazoalkane, the formation of the intermediate palladium carbene and the migratory insertion reaction cannot be experimentally studied separately. Attempts at detecting intermediate species at low temperature (−90 °C) were reported before for the dppe precursor with no success.8For this reason, DFT calculations were employed to gain insight into the steps that are responsible for the differences observed. We modeled and compared the energy profiles for the reactions of dppe, dppp and dppb with diazoalkane 8using the M06 functional and including solvation (MeCN) through the SMD implicit solvent method (see computational details in the Experimental part). First, we analyzed the nitrogen extrusion and migratory insertion steps. Figure 3 shows a general profile for the three phosphines and the energy values for the intermediates and transition states (for full specific energy profiles for each phosphine, see the Supporting Information, section 4). The activation barriers for the migratory insertion step, i.e. ΔGTS‑MI−ΔGI2‑carb, follow the trend: dppe (6.1 kcal mol−1) > dppp (5 kcal mol−1)≥dppb (4.6 kcal mol−1). As the bite angle of the phosphine increases the barrier slightly decreases. This is more noticeable on going from dppe to dppp and it is the same trend observed for the migratory insertion reaction of CO. 11 Scheme 4. Reaction Pathway Leading to Aryl-Carbene Coupling Products Figure 3. Gibbs energy profile for the N2extrusion and migratory insertion steps (energies in kcal mol−1). Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 397 The angle C(C6F5)−Pd−C(carbene) in the carbene intermediate (I2-carb) is indeed smaller as the bite angle of the phosphine increases and this geometrical parameter is closer to the small angle required in the transition state (see Table S5, Supporting Information). The barriers for nitrogen extrusion are higher than those for the migratory insertion step, as has also been found for a few other calculated systems. 17 As shown in Figure 3, the ease of carbene formation (I2-carb) from the coordinated diazo compound (I1-κ1-C) for the three diphosphines follow the same trend found for the migratory insertion step, i.e. ΔGTS−I1‑I2−ΔGI1‑κ 1−C: dppe (11 kcal mol−1) > dppp (10.2 kcal mol−1) > dppb (8.9 kcal mol−1). These results do not fit with those observed experimentally. The efficiency in the formation of the migratory insertion products, i.e. dppe > dppp > dppb follows the opposite trend to that expected from the barriers in Figure 3. Therefore, we decided to explore the other step that is also involved in the reaction, i.e. the coordination of the diazoalkane to the palladium center to give intermediate I1-κ1-C. Diazoalkane Coordination. Diazoalkanes are ambidentate ligands that can coordinate to the metal using the terminal N (κ1-N) or the C (κ1-C) as donor atoms. Both intermediates were calculated for dppe and dppp, and they are close in energy although only the κ1-C coordinated diazoalkane evolves to the formation of the carbene complex (Figures S42−S43, Supporting Information). Both an associative substitution, where the transition state is a pentacoordinated trigonal-bipyramidal species, or a dissociative pathway, via a three-coordinated intermediate by dissociation of acetonitrile, could be possible (see the Supporting Information, section 4.3, for the dppe complexes). However, the reaction of the dppp complex 5with diazoalkane 8is informative and favors one of these pathways. Scheme 3 shows that the formation of the migratory insertion product 12 was not complete when the reaction was carried out with a Pd:8= 1:1 mol ratio for 5 min. However, the addition of another portion of diazoalkane 8to the same sample increased the amount of 12. To test the diazoalkane concentration dependence, three separate reactions with the same initial concentration of the solvento acetonitrile complex 5([5] = 28.4 mM) and different Pd:8mol ratios were carried out. Figure 4 shows the formation of 12 (%) when diazoalkane 8 was added in a Pd:8= 1, 2, and 3 mol ratio after 5 min at room temperature. The values depicted in the plot show an increase of the reaction rate upon diazoalkane concentration and this points to an associative pathway, which was the one modeled for the system. Figure 5 shows the energy profiles for the diazoalkane coordination to palladium as well as the N2-extrusion step to generate the palladium carbene. The coordination of the diazoalkane becomes more energy demanding on going from dppe to the bulkier dppp and dppb. This effect is important and in fact, Figure 5 shows that the rate-controlling step for the overall carbene-aryl coupling in the dppe complex is the N2 extrusion to form the palladium carbene (energy barrier 14 kcal mol−1). In contrast, the process for the bulkier phosphines is controlled by the coordination of the diazoalkane to give intermediate I1-κ1-C (energy barrier around 16−17 kcal mol−1). According to this, the expected reactivity trend wouldbe dppe (N2-extrussion) > dppp ≥dppb (diazoalkane coordination), consistent with the experimental trend. These results show the importance of the diazoalkane coordination and how this step can be easily affected by the steric bulk of the ligand, therefore controlling the overall reaction rate. Many catalytic cross-coupling reactions use hydrazones that slowly decompose to diazoalkanes providing a usually low concentration of the latter in the reaction medium. Under these conditions, the choice of ligands and the study of the ligand substitution step can be crucial to avoid a too demanding diazoalkane coordination and to ensure an efficient catalysis. For example, Dingwall et al. carried out an experimental mechanistic study on the Pd-catalyzed cross coupling of a diazoalkane with benzyl bromide and determined that the palladium carbene formation, i.e. the overall reaction of the diazoalkane with a palladium benzyl complex, is turnover limiting in a Pd-phosphine system. The diazo coordination could be responsible for this, but the ligand substitution step was not calculated separately. 18 Figure 4. Amount of complex 12 formed by reaction of 5([5]0= 28.4 mM) and different Pd:8mol ratios after 5 min at room temperature. Figure 5. Gibbs energy profile for the diazoalkane coordination and N2extrusion steps (energies in kcal mol−1). Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 398 ■CONCLUSIONS The reaction of diazoalkanes and palladium-hydrocarbyl complexes is involved in many catalytic processes that lead to carbene-hydrocarbyl cross-coupling products. The reaction is a multistep process that involves several elemental reactions (diazoalkane coordination, nitrogen extrusion to give a Pdcarbene, and migratory insertion) whose rates can be influenced by the auxiliary ligands. The experimental trend for the ease of formation of carbenearyl coupling products in the reaction of the solvento complexes [Pd(C6F5)(P−P)(NCMe)]BF4with diazoalkanes for different ancillary diphosphine ligands is P−P = dppe > dppp > dppb. Since the electronic features of these phosphines are similar, the observed differences in the formation of the migratory insertion organometallic complexes can be attributed primarily to the ligand backbone. DFT calculations show that the trend in energy barriers for nitrogen extrusion and migratory insertion do not mirror the experimental outcome, since the bulkier phosphines show lower reaction barriers. The experimental differences can be explained considering the rates of coordination of the diazoalkane to palladium. We have found that the coordination of the diazoalkane 8to the palladium complex bearing a dppe ligand has a low activation energy and the nitrogen extrusion in a κ1-C coordinated diazoalkane is the rate controlling step of the reaction. In contrast, the dppp and dppb complexes show a higher activation barrier for the coordination of the diazoalkane, via an associative pathway. Therefore, the coordination of the diazoalkane is controlling the overall reaction rate for large bite angle phosphines. The coordination of the diazoalkane is often overlooked in mechanistic studies on carbene-hydrocarbyl couplings catalyzed by palladium complexes, which usually concentrate on the carbene formation by N2extrusion and migratory insertion to explain either rate or selectivity, or both. The importance of ligand substitution reactions in catalysis cannot be underestimated and the results here show that this is also the case in carbene-hydrocarbyl couplings. The reaction of trans-[Pd(C6F5)(NCMe)(PPh3)2]BF4with diazoalkanes does not lead to carbene-aryl coupling. This fact clearly evidence that the trans arrangement hampers the migratory insertion process and that the required isomerization to a cis complex can be slower than the decomposition pathways of the diazoalkane and the trans-palladium carbene species. ■EXPERIMENTAL SECTION General Methods. 1H, 13C{1H} 31P{1H} and 19F NMR spectra were recorded on an Agilent MR-500 spectrometer at the Laboratorio de Tecnicas Instrumentales (LTI) of the UVa. Chemical shifts (in δ units, ppm) were referenced to SiMe4(1H and 13C), CFCl3(19F) and H3PO4(85%, 31P). The spectral data were recorded at 298 K unless otherwise noted. Homonuclear (1H−COSY) and heteronuclear (1H−13C HSQC and HMBC) NMR experiments were used to help with the signal assignments. Elemental analyses were carried out in a Carlo Erba 1108 microanalyzer (at the Vigo University, Spain). All reactions were conducted under a N2atmosphere. Solvents were dried using a solvent purification system SPS PS-MD-5 (ether, hexane, THF and CH2Cl2) or distilled from appropriate drying agents under nitrogen prior to use and stored over 3 or 4 Å molecular sieves (acetonitrile and acetonitrile-d3). All commercial reagents and solvents were used as received unless otherwise indicated. Complexes (NBu4)2[Pd(μ-Br)2Br2(C6F5)2],14 [PdBr(C6F5)(dppe)] (1),14 [Pd- (C6F5)(dppe)(NCMe]BF4(4),8and [PdBr(C6F5)(PPh3)2]14 were prepared according to the literature methods. Complexes 10 and 11 have been reported and characterized before. 8 The syntheses of the diazo compounds were carried out according to the literature methods. 19 The diazoalkanes were prepared and kept as dichloromethane solutions for no longer than 10 days under a nitrogen atmosphere at −28 °C in the dark. The concentrations of these solutions were determined by 1H NMR using CF3CH2I as internal standard. Synthesis of [PdBr(C6F5)(dppp)] (2). 1,3-Bis- (diphenylphosphino)propane (dppp) (110.87 mg, 0.268 mmol) was added to a solution of (NBu4)2[Pd(μ-Br)2Br2(C6F5)2] (176.5 mg, 0.130 mmol) in acetone (30 mL). The mixture was stirred at room temperature for 1 h. During this time the orange solution became pale-yellow. The solvent was evaporated to dryness and the yellow oil was triturated with cold EtOH until the formation of a pale-yellow solid that was filtered, washed with cold EtOH and air-dried. Yield: 165 mg (83%). Crystals suitable for X-ray analyses were obtained by slow evaporation of a solution of 2in CHCl3.1H NMR (499.73 MHz, δ, CDCl3): 7.78−7.73 (m, 4H, Harom), 7.50−7.42 (m, 6H, Harom), 7.41−7.33 (m, 6H, Harom), 7.17 (td, J = 5.5 Hz, 2.4 Hz, 4H, Harom), 2.66 (m, 2H, CH2), 2.33 (m, 2H, CH2), 2.03 (m, 2H, CH2). 13C{1H} NMR (125.67 MHz, δ, CDCl3): 138.3 (d, JC−P= 11.2 Hz, Carom), 133.4 (d, JC−P= 10.6 Hz, Carom), 132.7 (d, JC−P= 11.0 Hz, Carom), 131.1 (d, JC−P= 2.6 Hz, Cpara), 130.8 (d, JC−P= 2.5 Hz, Cpara), 130.4 (d, J1C−P= 45.7 Hz, Cipso), 130.1 (d, J1C−P= 54.7 Hz, Cipso), 128.7 (d, JC−P= 10.3 Hz, Carom), 25.8 (dd, J = 29.2, 7.3 Hz, CH2), 25.4 (dd, J = 25.2, 7.4 Hz, CH2), 18.9 (s, CH2).*19F NMR (470.17 MHz, δ, CDCl3): −116.92 (m, 2F, Fortho), −161.77 (t, J= 20.1 Hz, 1F, Fpara), −162.85 (m, 2F, Fmeta). 31P{1H} NMR (202.31 MHz, δ, CDCl3): 13.60 (dt, J = 42.4 Hz, 6.4 Hz, 1P), −5.82 (m, 1P). Anal. Calcd for C33H26BrF5P2Pd: C, 51.76%; H, 3.42%. Found: C, 51.60%; H, 3.26%. *The 13C signals for the C6F5group, heavily coupled to 19F, could not be observed. Synthesis of trans-[PdBr(C6F5)(dppb)] (trans-3). 1,4-Bis- (diphenylphosphino)butane (dppb) (111.55 mg, 0.256 mmol) was added to a solution of (NBu4)2[Pd(μ-Br)2Br2(C6F5)2] (173.0 mg, 0.128 mmol) in acetone (30 mL). The mixture was stirred at room temperature for 1 h. During this time the orange solution became pale-yellow. The solvent was evaporated to dryness and the yellow oil was triturated with cold EtOH until the formation of a pale-yellow solid that was filtered, washed with cold EtOH and air-dried. Yield: 175 mg (88%). 1H NMR (499.72 MHz, δ, CDCl3): 7.43 (m, 9H, Harom), 7.27 (t, J = 7.2 Hz, 4H, Harom), 7.21 (m, 7H, Harom), 2.63 (m, 4H, CH2), 2.01 (m, 4H, CH2). 13C{1H} NMR (125.67 MHz, δ, CDCl3): 132.9 (br, Carom), 131.4 (d, J1C−P= 47.1 Hz, Carom), 130.2 (br, Carom), 128.1 (br, Carom), 27.5 (m, 4C, CH2). 19F NMR (470.17 MHz, δ, CDCl3): −116.19 (m, 2F, Fortho), −161.59 (t, J= 19.7 Hz, 1F, Fpara), −162.22 (m, 2F, Fmeta). 31P{1H} NMR (202.31 MHz, δ, CDCl3): 18.92 (s, 2P). Anal. Calcd for C34H28BrF5P2Pd: C, 52.36%; H, 3.62%. Found: C, 52.56%; H, 3.68%. When a solution of complex trans-3was kept at room temperature for 48 h in CDCl3a mixture of isomers (trans:cis = 0.8:1) was formed. cis-3:19F NMR (470.17 MHz, δ, CDCl3): −117.15 (m, 2F, Fortho), −161.99 (t, J= 19.9 Hz, 1F, Fpara), −162.83 (m, 2F, Fmeta). 31P{1H} NMR (202.31 MHz, δ, CDCl3): 40.72 (d, J = 32.5 Hz, 1P), −1.40 (m, 1P). Characterization of [Pd(C6F5)(dppp)(NCMe)](BF4) (5). [PdBr- (C6F5)(dppp)] (13.4 mg, 0.017 mmol) and AgBF4(3.4 mg, 0.017 mmol) were mixed in dry MeCN (0.6 mL) and stirred for 15 min at room temperature under nitrogen. The suspension was filtered through Kieselguhr to remove the AgBr and the resulting colorless solution was characterized by NMR. Upon isolation attempts some reorganization of the aryl groups occurs by transmetalation and the solids obtained were inevitably contaminated by small amounts of “Pd(C6F5)2” derivatives. Therefore, the complexes were usually synthesized in situ and used in solution. 1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 7.94− 7.83 (m, 10H, Harom), 7.71−7.64 (m, 6H, Harom), 7.52 (m, 4H, Harom), 3.18 (m, 2H, CH2), 2.98 (m, 2H, C’H2).*19F NMR (470.17 MHz, δ, CH3CN,(CD3)2SO capillary): −117.87 (m 2F, Fortho), −151.42 (BF4), −161.10 (t, J = 19.2 Hz, 1F, Fpara), −162.99 (m, 2F, Fmeta). Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 399 31P{1H} NMR (202.31 MHz, δ, CH3CN, (CD3)2SO capillary): 16.50 (dt, J = 39.7, 7.2 Hz, 1P), −4.39 (m, 1P). *One CH2from dppp is overlapped with the NCCH3signal. Characterization of [Pd(C6F5)(dppb)(NCMe)](BF4) (6). [PdBr- (C6F5)(dppb)] (52.0 mg, 0.066 mmol) and AgBF4(13.0 mg, 0.066 mmol) were mixed in dry MeCN (0.6 mL) and stirred for 15 min at room temperature under nitrogen. The suspension was filtered through Kieselguhr to remove the AgBr and the resulting colorless solution was characterized by NMR. The resulting complex is a mixture of trans:cis = 1:0.8 isomers. 1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary; cis-6 + trans-6): 7.92 (m, 1H, Harom), 7.85 (m, 3H, Harom), 7.80 (m, 2H, Harom), 7.77−7.69 (m, 10H, Harom), 7.66 (m, 2H, Harom), 7.57 (td = J = 7.8, 2.9 Hz, 2H, Harom). The CH2 signals of the dppb ligand are overlapped with the NCCH3signal. cis6:19F NMR (470.17 MHz, δ, CH3CN,(CD3)2SO capillary): −118.58 (m 2F, Fortho), −151.11 (BF4), −161.04 (t, J = 19.2 Hz, 1F, Fpara), −162.78 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN, (CD3)2SO capillary): 40.60 (dt, J = 30.8, 7.2 Hz, 1P), 7.26 (m, 1P). trans-6:19F NMR (470.17 MHz, δ, CH3CN,(CD3)2SO capillary): −116.85 (m 2F, Fortho), −151.11 (BF4), −160.18 (t, J = 19.6 Hz, 1F, Fpara), −161.98 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN,(CD3)2SO capillary): 17.60 (s). Synthesis of [Pd(C6F5)(NCMe)(PPh3)2](BF4) (7). Equimolar amounts of [PdBr(C6F5)(PPh3)2] (184.3 mg, 0.210 mmol) and AgBF4(41 mg, 0.210 mmol) were mixed in dried CH3CN (10 mL) and stirred for 15 min at room temperature under nitrogen. The suspension was filtered through Kieselguhr and the filtrate was evaporated to dryness. The resulting yellow oil was triturated with nhexane until the formation of a pale-yellow solid that was filtered, washed with n-hexane and air-dried. Yield: 118 mg, (60%). 1H NMR (499.73 MHz, δ, CD3CN): 7.62 (m, 6H, Hpara PPh3) 7.60−7.50 (m, 24H, Hmeta,ortho PPh3). 13C{1H} NMR (125.67 MHz, δ, CD3CN): 144.3 (m, 1JC−F= 230.5 Hz, Cortho, C6F5), 138.2 (m, 1JC−F= 250 Hz, Cpara, C6F5), 136.3 (m, 1JC−F= 248 Hz, Cmeta, C6F5), 133.7 (t, JC−P= 6.5 Hz, Cortho PPh3), 131.9 (Cpara PPh3), 129.2 (t, JC−P= 5.3 Hz, Cmeta PPh3), 127.5 (t, JC−P= 25.5 Hz, Cipso PPh3). 19F NMR (470.17 MHz, δ, CD3CN): −118.40 (m, 2F, Fortho), −151.70 (BF4), −161.63 (tt, J = 19.0, 2.4 Hz, 1F, Fpara), −162.34 (m, 2F, Fmeta). 31P{1H} NMR (202.29, MHz, δ, CD3CN): 23.12 (td, J = 6.8, 2.2 Hz). Anal. Calcd for C44H33BF9NP2Pd: C, 57.08%; H, 3.59%; N, 1.51%. Found: C, 56.68%; H, 3.44%; N, 1.40%. *The 13C signals for the Cmeta and Cipso (C6F5group) could not be observed. Characterization of [Pd(dppp)(η3-Ph−CH−CH−CH-C6F5)]- (BF4) (12). [Pd(Br)(C6F5)(dppp)] (13.4 mg, 0.017 mmol) and AgBF4(3.4 mg, 0.017 mmol) were mixed in dry MeCN (0.6 mL) and stirred for 15 min at room temperature under nitrogen. The suspension was filtered through Kieselguhr to remove the AgBr. Addition of a dichloromethane solution of the diazo compound N2CH−CH�CHPh (2-fold molar amount in two portions, 87 μL, 0.4 M, total of 0.046 mmol) afforded an intense yellow solution, which was stirred at room temperature for 5 min. Then, the solution was characterized by NMR. The crude yield was determined by integration of the 19F NMR signals in the mixture, (83%). Crystals suitable for X-ray analyses were obtained by slow diffusion of nhexane layered onto a solution of the complex 12 in CHCl3at −28 °C. 1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 7.72− 7.36 (m, 25H, Harom), 6.86 (t, J = 12.7 Hz, 1H, Hallyl), 5.36 (t, J = 11.2 Hz, 1H, Hallyl), 4.87 (t, J = 11.2 Hz, 1H, Hallyl).*19F NMR (470.17 MHz, δ, CH3CN, (CD3)2SO capillary): −141.99 (br, 2F, Fortho), −151.53 (BF4), −158.04 (t, J = 20.5 Hz, 1F, Fpara), −164.00 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN, (CD3)2SO capillary): AB system. νA: 8.50 (d, J = 83.2 Hz, 1P), νB: 7.06 (d, J = 83.2 Hz, 1P). *The CH2signals of the dppp ligand are overlapped with the NCCH3signal. The analogous reactions for the dppb and PPh3derivatives were carried out in the same way using an equimolar amount of the diazocompound. The formation of [Pd(dppb)(η3-Ph−CH−CH− CH-C6F5)](BF4) (14) was observed in 8% yield. 1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 6.59 (t, J = 12.6 Hz, 1H, Hallyl), 5.52 (t, J = 11.5 Hz, 1H, Hallyl), 4.91 (t, J = 11.5 Hz, 1H, Hallyl).*19F NMR (470.17 MHz, δ, CH3CN, (CD3)2SO capillary): −140.31 (br, 1F, Fortho), −143.12 (br, 1F, Fortho), −151.64 (BF4). The Fpara and Fmeta as well as the 31P NMR signals have not been assigned due to the very low concentration of η3-allyl-complex in the reaction medium. Characterization of [Pd(dppp)(η3-Ph−CH-C6F5)](BF4) (13). [Pd(Br)(C6F5)(dppp)] (17.7 mg, 0.023 mmol) and AgBF4(4.5 mg, 0.023 mmol) were mixed in dry MeCN (0.6 mL) and stirred for 15 min at room temperature under nitrogen. The suspension was filtered through Kieselguhr to remove the AgBr. The addition of a dichloromethane solution of the diazo compound N2CHPh (0.0345 mmol, 128 μL, 0.27 M) afforded an intense yellow solution, which was stirred at room temperature for 5 min. Then, the solution was characterized by NMR. Two isomers were observed, syn:anti = 89:11, The crude yield was determined by integration of the 19F NMR signals in the crude mixture (85%). syn-13:1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 6.97 (m, 2H, H2, H6), 4.28 (d, JH−P= 4.28 Hz, 1H, Hα).*19F NMR (470.17 MHz, δ, CH3CN, (CD3)2SO capillary): −137.02 (m 2F, Fortho), −151.72 (BF4), −158.84 (m, 1F, Fpara), −164.04 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN, (CD3)2SO capillary): 17.29 (dt, J = 81.2, 8.2 Hz, 1P), 4.94 (d, J = 81.2 Hz, 1P). anti-13:19F NMR (470.17 MHz, δ, CH3CN, (CD3)2SO capillary): −140.16 (m 2F, Fortho), −150.59 (m, 1F, Fpara), −151.72 (BF4), −162.87 (m, 2F, Fmeta). *The remaining signals could not be assigned. The reaction for the dppb and PPh3derivatives were carried out in the same way. Complex 15 (dppb) was observed in 30% crude yield. syn-15:1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 6.96 (m, 2H, H2, H6), 4.17 (d, J = 11.9 Hz, 1H, Hα).*19F NMR (470.17 MHz, δ, CH3CN,(CD3)2SO capillary): −137.02 (m 2F, Fortho), −151.66 (BF4), −158.02 (m, 1F, Fpara), −163.94 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN,(CD3)2SO capillary): 36.55 (dt, J = 64.0 Hz, 1P), 11.31 (d, J = 64.0 Hz, 1P). anti-15:1H NMR (499.73 MHz, δ, CH3CN/(CD3)2SO capillary): 6.64 (m, 2H, H2, H6), 4.72 (m, 1H, Hα).*19F NMR (470.17 MHz, δ, CH3CN, (CD3)2SO capillary): −140.02 (m 2F, Fortho), −151.14 (m, 1F, Fpara), −151.66 (BF4), −160.67 (m, 2F, Fmeta). 31P{1H} NMR (202.31, MHz, δ, CH3CN,(CD3)2SO capillary): 28.35 (d, J = 44.9 Hz, 1P), 14.95 (d, J = 44.9 Hz, 1P). *The remaining signals could not be assigned. Experiments for the Formation of Complex 12 at Different Diazoalkane Concentrations. [Pd(C6F5)(dppp)(NCMe)]BF4 (0.028 mmol) and 0.5 mL of dry CH3CN ([Pd]0= 56 mM) were added into an NMR tube along with a sealed glass capillary filled with (CD3)2SO as NMR lock signal under a nitrogen atmosphere. Addition of a dichloromethane solution of the diazo compound N2CH−CH�CHPh (8) (Pd:8= 1:1, 1:2 and 1:3 mol ratio for each of the three experiments) afforded an intense yellow solution, which was stirred at room temperature for 5 min. Then, the solution was checked by 19F NMR. The crude yield of 12 was determined by integration of the 19F NMR signals in the mixture: Pd:8= 1:1; 30%. Pd:8= 1:2; 64%. Pd:8= 1:3; 80%. See Figure 4. Computational Methods. All calculations were performed using the DFT approach with the meta-hybrid GGA M06 functional, 20,21 using Gaussian09 as program package. 22 The selected basis set was 631+G(d) for C, N, F and H, 23,24 and LANL2TZ(f) for Pd 25,26 (Basis set I). Solvation was introduced in all the optimizations, frequency calculations and potential energy refinement through the SMD model, where we applied the experimental solvent, acetonitrile (ε= 37.5, at 25 °C). All geometry optimizations were carried out in solution with no symmetry restrictions. Free energy corrections were calculated at 298.15 K and 105Pa pressure, including zero-point energy corrections (ZPE), and the energies were converted to 1 M standard state in solution (adding/subtracting 1.89 kcal/mol for nonunimolecular processes). Vibrational frequency calculations were performed to establish the stationary points were minima (without imaginary frequencies) or transition states (with one imaginary frequency). Connectivity of the transition state structures were confirmed by relaxing the transition state geometry toward both the reactant and the product. Final potential energies were refined by performing Organometallics pubs.acs.org/Organometallics Article https://doi.org/10.1021/acs.organomet.4c00439 Organometallics 2025, 44, 394−402 400 additional single-point energy calculations (also in solution), Pd was still described with LANL2TZ(f) basis set, and the remaining atoms were treated with 6311++G(d,p) basis set (Basis set II). All reported energies in the manuscript correspond to Gibbs energies in solution, obtained from potential energies (including solvation) with basis set II plus Gibbs energy corrections with basis set I and are given in kcal mol−1. ■ASSOCIATED CONTENT * sı Supporting Information The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.organomet.4c00439. Additional experimental data, selected spectra, computational data including calculated potential energies (PDF) Coordinates for the calculated structures (XYZ) Accession Codes Deposition Numbers 2390734 and 2390743 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via the joint Cambridge Crystallographic Data Centre (CCDC) and Fachinformationszentrum Karlsruhe Access Structures service. ■AUTHOR INFORMATION Corresponding Author Ana C. Albéniz −IU CINQUIMA/Química Inorgánica, Universidad de Valladolid, Valladolid 47071, Spain; orcid.org/0000-0002-4134-1333; Email: [email protected] Author Francisco Villalba −IU CINQUIMA/Química Inorgánica, Universidad de Valladolid, Valladolid 47071, Spain Complete contact information is available at: https://pubs.acs.org/10.1021/acs.organomet.4c00439 Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interest. ■ACKNOWLEDGMENTS We acknowledge the financial support of the Spanish MICIU (AEI, grant PID2022-142100NB-I00), the joint support of the EU/MICINN/JCyL (C17.I01.P01.S21, H2MetAmo), and the MEC (FPU-17/04559 fellowship to F. V.). ■REFERENCES (1) (a) Greenman, K. L.; Carter, D. S.; Van Vranken, D. L. Palladium-catalyzed insertion reactions of trimethylsilyldiazomethane. Tetrahedron 2001,57, 5219−5225. (b) Greenman, K. L.; Van Vranken, D. L. Palladium-catalyzed carbene insertion into benzyl bromides. Tetrahedron 2005,61, 6438−6441. (2) Selected reviews: (a) Xia, Y.; Qiu, D.; Wang, J. Transition-MetalCatalyzed Cross-Couplings through Carbene Migratory Insertion. Chem. Rev. 2017,117, 13810−13889. (b) Barroso, R.; Cabal, M. P.; Valdés, C. Pd-catalyzed Auto-Tandem Cascades Based on NSulfonylhydrazones: Heteroand Carbocyclization Processes. 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