Highly efficient enantioselective synthesis of optically active carboxylic acids by Ru(OCOCH3)(2)[(S)-H-8-BINAP]

In the presence of a catalytic amount of Ru(OCOCH3)(2)[(S)-H-8-BINAP] [HB-BINAP = 2,2'-bis(diphenylphosphino)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphtyl], the asymmetric hydrogenation of alpha,beta- and beta,gamma-unsaturated carboxylic acids afforded the corresponding saturated carboxylic acids in higher enantiomeric excesses and at faster reaction rates than those using the Ru(OCOCH3)(2)[(R)-BINAP] catalyst [BINAP = 2,2'-bis(diphenylphosphino)-1, 1'-binaphthyl]. The hydrogenation of (E)-2-alkyl-2-alkenoic acids by the H-8-BINAP catalyst system produced saturated acids in 95-97% ee. 2-Methylcinnamic acid was treated with H-8-BINAP-Ru(II) complex as a catalyst to yield a hydrogenated product in much higher ee than that produced by BINAP-Ru(II) (89 and 30% ee, respectively). This homogeneous catalysis using H-8-BINAP-Ru(II) established a promising synthetic route to (S)-ibuprofen in up to 97% ee. Asymmetric hydrogenation of beta-disubstituted acrylic acids also proceeded smoothly with good enantioselectivities (70-93% ee). In addition, the hydrogenation of trisubstituted acrylic acids (up to 88% ee) was investigated. Hydrogen pressure effect on the sense and level of enantioselection was shown to be substrate dependent. The difference between the H-8-BINAP- and BINAP-Ru(II) complexes was also discussed.