Synthesis of Novel (P,S) Ligands Based on Chiral Nonracemic Episulfides. Use in Asymmetric Hydrogenation

A strategy for the synthesis of new chiral (P,S) ligands is described. It is based on the opening of chiral nonracemic episulfides using phosphorus nucleophiles. Chiral episulfides, 4, are derived either from the reaction of thiourea with the corresponding epoxide ( 4a, R = CH 3 ) or from the stepwise conversion of chiral diols to the episulfide via the thiocarbonate ( 4b, R = cyclohexyl). The reaction of lithium salts of phosphines, R 2 ‘PLi (R = Ph, cyclohexyl), with episulfides is regioselective and gives the ring-opened products 5 − 8, PR 2 CH 2 CH(R‘)SLi. Upon treatment with electrophiles, R‘ ‘Cl (R‘ ‘ = −CH 2 Ph, −CH 2 (C 5 (CH 3 ) 5 ), −CH 2 (C 14 H 9 ), −CH(C 14 H 12 )), they give novel chiral (P,S) ligands, PR‘ 2 CH 2 CH(R‘)SR‘ ‘, 9 − 17 in 31−93% yield. Reactions of PCy 2 CH 2 CH(CH 3 )SCH 2 (C 6 (CH 3 ) 5 ), 11, with LMCl 2 (LM = (DME)Ni, (COD)Pd, and (NBD)Pt; DME = dimethoxyethane, COD = 1,5-cyclooctadiene, NBD = 2,5-norbornadiene) yields the corresponding metal complexes, ( 11 )MCl 2, 18 . Variable-temperature 1 H NMR spectroscopy indicates that in these complexes sulfur inversion occurs on the NMR time scale. Compound 18b (M = Pd) was characterized by single-crystal X-ray analysis. Reaction of PCy 2 CH 2 CH(CH 3 )SCH(C 14 H 12 ), 13, with (COD)PdCl 2 results in C−S bond cleavage and produces a dinuclear thiolato-bridged complex, dichlorobis{μ-[2-(dicyclohexylphosphino)-1-(methyl)ethanethiolato]-P,μ-S}-dipalladium(II), 19 . Complex 19 was characterized by single-crystal X-ray analysis. Reactions of ligands 9 − 17 with Rh(COD) 2 + OTf - (COD = cyclooctadiene, OTf - = CF 3 SO 3 - ) yields rhodium complexes that have been tested in the asymmetric hydrogenation of α-enamide methyl esters, providing enantioselectivities of up to 51%. The rhodium complex obtained with ligand 11, ( 11 )Rh(COD)OTf, 22, was characterized by single-crystal X-ray analysis.