Novel bis (1,3,2-diazaphospholidine) ligands for asymmetric catalysis

1 No el Bis-1,3,2-diazaphospholidine Ligands o Asymme ic Ca alysis Inmaculada A ibas, Eleu e io Ál a ez and An onio Pizzano* Ins i u o de In es igaciones Químicas (IIQ), Consejo Supe io de In es igaciones Cien í icas and Uni e sidad de Se illa. A da Amé ico Vespucio nº 49, Isla de la Ca uja. 41092 Se illa, Spain. *Co esponding au ho . E-mail: [email p o ec ed] ABSTRACT: A amily o modula ly designed chi al bis-1,3,2-diazaphospholidines wi h N-a yl subs i uen s (NP-PN) is epo ed. These compounds ha e been p epa ed in wo s eps om eadily a ailable (R,R)-1,2-diaminocyclohexane and e achlo odiphosphines. Examples in he se di e in he backbone and he a yl subs i uen s aiming a hei applica ion in asymme ic ca alysis. Thus, [Rh(NBD)(NP-PN)]BF 4 complexes lead o ac i e ca alys s in he hyd ogena ion 2 o me hyl α-ace amidoac yla e, which p o ide enan ioselec i i ies up o 96 % ee. In addi ion, NP-PN ligands also gene a e ac i e ca alys s in he hyd o o myla ion o inyl ace a e, leading o high egioselec i i ies (iso:n a io highe han 99:1) and enan ioselec i i ies up o 65 % ee. 3 C 2 symme ic bis-phospholanes (Figu e 1, A) cons i u e a p ominen class o ligands in asymme ic ca alysis. 1-2 The ou s anding pe o mance o hese compounds is due o he p oximi y o he s e eogenic cen e s o he me al and, as well, o he abili y o inely une he R g oup. Howe e , he ange o hese subs i uen s is la gely limi ed o alkyl ones, while examples bea ing a yl subs i uen s a e es ic ed o he 2,5-diphenylphospholane moie y, 3 due o he highly di icul syn hesis o hese de i a i es. 4 No ewo hy, he p esence o a yl subs i uen s in posi ions 2 and 5 may ha e a p o ound in luence on a ca aly ic p ocess, as i has been obse ed in asymme ic hyd o o myla ion eac ions. 5 Figu e 1. Gene ic s uc u es o R subs i u ed phospholanes (A) and 1,3,2-diazaphospholidines (B). ESPHOS ligand (C). A seemingly ela ed s uc u e o bis-phospholanes A is p o ided by bis-1,3,2- diazaphospholidines (B). The la e compounds a e a ac i e ligands o syn he ic easons due o he easy o ma ion o P-N bonds om app op ia e amines and phospho us chlo ides. Some alkyl examples (R = Me, CH 2 - -Bu, CH 2 Ph) ha e al eady been desc ibed in he li e a u e, al hough he e iciency o compounds B as ligands o asymme ic ca alysis has no been subs an ia ed ye . 6 4 A his espec , a p oblem a ises om he poo ly de ined posi ion o R subs i uen s in B, due o he expec edly easy ni ogen in e sion. This aspec has success ully been ci cum en ed by he use o b idgehead N a oms in ESPHOS (C) 7 and ela ed diaminophosphi e ligands. 8 In con as , an a es ed N in e sion in B could ely on an s e ic in e ac ion be ween app op ia e R and R’ g oups. Some p eceden s sugges he easibili y o his app oach. Fo ins ance, he g oup o Tsuji has desc ibed an e icien Pd ca alys based on seconda y a yl diamines wi h chi al backbones. 9 On he o he hand, P al z and cowo ke s ha e desc ibed highly enan ioselec i e I phosphine- oxazoline ca alys s con aining N-a yl diazaphospholidine agmen s. 10 In his con ibu ion we desc ibe he syn hesis o he i s bis-1,3,2-diazaphospholidine ligands bea ing N-a yl subs i uen s, along wi h p elimina y ca aly ic esul s which include a highly enan ioselec i e hyd ogena ion eac ion. As he s a ing diamine sca old, ans-1,2-cyclohexanediamine was chosen because i is eadily a ailable in bo h enan iome s and can easily be a yla ed o p o ide a wide a ie y o chi al seconda y amines. 9-11 Among he la e phenyl (1a) and p- olyl (1b) diamines, we e selec ed as ep esen a i e examples and eac ed wi h comme cially a ailable e achlo odiphosphines, in he p esence o an excess o NE 3 (Scheme 1). These eac ions p o ide a amily o bis-1,3,2-diazaphospholidines 2-4, which di e in he na u e o he backbone. In con as wi h he eac ion be ween seconda y alipha ic amines wi h 1,2- bis(dichlo ophosphino)e hane, 6b he gene a ion o he p esen bis-diazaphospholidines is slow a oom empe a u e and a p olonged hea ing is needed o each a good con e sion. Fo ins ance, eac ion be ween 1a and 1,2-bis(dichlo ophosphino)benzene shows a oom empe a u e he o ma ion o he in e media e mono diazaphospholidine compound (P-P’, Figu e 2), cha ac e ized by wo double s cen e ed a 104 and 154 ppm wi h a J PP coupling cons an o 151 5 Hz, along wi h some s a ing ma e ial a 150 ppm. These signals disappea ed upon hea ing and he single o desi ed compound 3a s a ed o g ow as he e y p edominan p oduc . In e es ingly, his eac ion is a he clean and shows a high con e sion. Howe e , in o de o gua an ee he elimina ion o eac i e phospho us chlo ide impu i ies, he esul ing mix u e was pu i ied h ough neu al alumina wi h some dec ease in he yield o isola ed 3a. Scheme 1. P epa a ion o bis(diazaphospholidines) 2-4. Compounds 2-4 ha e been cha ac e ized by NMR and he da a collec ed a e in acco d wi h he s uc u e p oposed o hem. Thus, hey show ela i ely simple 1 H and 13 C{ 1 H} NMR spec a due o he C 2 -symme y o hese compounds. In addi ion, he wo 31 P nuclei a e equi alen and 6 appea as a single in he 31 P{ 1 H} NMR spec a. The la e signals appea a ca. 110 ppm o ligands 2 and 4, and a ca. 130 ppm o compounds 3. Figu e 2. 31 P{ 1 H} NMR (162 MHz, oluene) moni o ing o he o ma ion o 3a. In o de o es ima e he dono p ope ies o his amily o ligands, he eac ion be ween 3a and Se has been pe o med. This eac ion p oduces he co esponding diselenophosphine 5a which appea s as a single a 73.1 ppm in he 31 P{ 1 H} NMR spec um. Measu emen o he 1 J SeP coupling cons an in he sa elli es co esponding o he 77 Se iso opome indica es a coupling o 868 Hz. This alue shows, as expec ed, an in e media e dono abili y be ween phosphines and phosphi es. 12 Howe e , he N-a yl agmen s in 3a educe he σ-dono abili y o 2a, compa ed 7 wi h N-alkyl 1,3,2-diazaphospholidines, 13 and make i compa able wi h ha p o ided by s uc u ally ela ed diaminophosphi es. 14 To p o ide in o ma ion abou he s uc u al ea u es o he diazaphospholidine agmen in compounds 2-4, a ep esen a i e example (4b) has been cha ac e ized by X- ay c ys allog aphy (Figu e 4). The s uc u e o his compound clea ly shows he p esence o he wo phospho us he e ocycles, each used wi h a cyclohexane ing in a chai con o ma ion. Mos in e es ing aspec ega ds he an i posi ion o he N-a yl subs i uen s, de ined by C(7) and C(14), ela i e o he cyclohexane ca bons C(6) and C(3), espec i ely. On he o he hand, he sum o he bond angles in ol ing he ni ogen a oms amoun 342.1º [ΣN(1)] and 350.9º [ΣN(2)], indica i e o an in e media e geome y be ween e ahed al and igonal plana o hese a oms. The impo an in luence o he chi al cyclohexane agmen on ni ogen geome y in 4b is e iden upon compa ison wi h he s uc u e o 2-phenyl-1,3-di(-p- olyl)-1,3,2-diazaphospholidine, 15 which shows wo plana ni ogens wi h a ΣN alue o 359.1º. I should inally be men ioned ha he N- C(a yl) dis ances in 4b (1.416 and 1.425 Å), a e signi ican ly sho e han he exocyclic N-C bond leng hs obse ed in ela ed N-alkyl de i a i es (1.72-1.75 Å). 6b We ha e nex examined he coo dina ion o ligands 2 and 3 in ca ionic hodium complexes. Thus, hese bis-(diazaphospholidines) cleanly eac wi h [Rh(NBD) 2 ]BF 4 o gi e he co esponding complexes [Rh(NBD)(NP-PN)]BF 4 (6, 7, Scheme 2). These compounds appea in he 31 P{ 1 H} NMR spec a as a double cen e ed be ween 120 and 140 ppm, wi h 1 J RhP coupling cons an s be ween 208 and 215 Hz. In addi ion, he 1 H and 13 C{ 1 H} NMR spec a show he equi alence be ween g oups acco ding o he p esence o a C 2 symme y axis. 8 Figu e 4. ORTEP iew o complex 4b a he 50 % p obabili y le el (H a oms ha e been omi ed o cla i y). Selec ed bond leng hs [Å] and angles [deg]: P(1)-C(21) = 1.8191(13); P(1)-N(1) = 1.7474(10); P(1)-N(2) = 1.7225(11); N(1)-C(7) = 1.4250(16); N(2)-P(1)-N(1) = 91.40(5); C(7)- N(1)-P(1) = 114.96(8); C(14)-N(2)-P(1) = 120.88(9); C(14)-N(2)-C(2)-C(3) = 76.63(15); C(7)- N(1)-C(1)-C(6) = 64.09(15). 9 Scheme 2. P epa a ion o Rh complexes 6-7. I is impo an o no e ha upon coo dina ion o ligands 2-4, di e en s uc u es o complexes 6 and 7 a e possible due o ni ogen in e sion (a-c, Figu e 3). In e es ingly, hese s uc u es di e on he s e ic in e ac ion be ween he A subs i uen s and he cyclohexane agmen and in he p oximi y o he a yl ings o he NBD ole inic p o ons. A his espec , an inspec ion o he 1 H NMR spec a o complexes 6 and 7, indica es ha one o he ole in signals appea be ween 5.62 and 5.97 ppm, in he ange ound o o he NBD complexes wi h diphosphine ligands. 16 In con as , he second ole inic signal o 6 and 7 appea s signi ican ly shi ed up ield, be ween 4.36 and 5.10 ppm. The shi o he la e signal can be a ibu ed o he shielding caused by a close a yl ing (d). As a con i ma ion, an analysis o complex 7b by a 2D NOESY expe imen has allowed us o assign signals co esponding o olyl g oups poin ing o he NBD ligand. No ably, he o ho hyd ogens o he la e a yl ings exhibi s a NOE signal wi h he high ield ole in p o ons. Mo eo e , an examina ion o he NOE signals obse ed be ween hese a oma ic p o ons and he p o ons o he close CHN and CH 2 agmen s o he cyclohexane ing do no show e idence o in e sion o N con igu a ion in solu ion (see supplemen a y ma e ial), in acco d wi h a p e e ed C 2 symme ic an i-an i s uc u e in solu ion o his complex.