Highly Efficient Enantioselective Synthesis of Optically Active Carboxylic Acids by Ru(OCOCH₃)₂[(<i>S</i>)-H₈-BINAP]

Abstract

In the presence of a catalytic amount of Ru(OCOCH3)2[(S)-H8-BINAP] [H8-BINAP = 2,2‘-bis(diphenylphosphino)-5,5‘,6,6‘,7,7‘,8,8‘-octahydro-1,1‘-binaphthyl], the asymmetric hydrogenation of α,β- and β,γ-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 H8-BINAP catalyst system produced saturated acids in 95−97% ee. 2-Methylcinnamic acid was treated with H8-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 H8-BINAP−Ru(II) established a promising synthetic route to (S)-ibuprofen in up to 97% ee. Asymmetric hydrogenation of β-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 H8-BINAP− and BINAP−Ru(II) complexes was also discussed.