Rhodium-catalyzed heterogeneous enantioselective hydrogenation of 3,5-di-(trifluoromethyl)-acetophenone

Abstract

Asymmetric hydrogenation of 3,5-di-(trifluoromethyl)-acetophenone (1) to 1-[3,5-di-(trifluoromethyl)-phenyl]ethanol (2) was studied over 5 wt.% Rh/Al2O3 modified by cinchonidine (CD) and its O-methyl, O-ethyl, O-phenyl, O-trimethylsilyl, N-methyl, and N-benzyl derivatives. Replacement of CD by the ether derivatives resulted in the inversion of enantioselectivity from (S)-2 to (R)-2, and an improvement in chemoselectivity up to 100%. Interestingly, O-phenyl-CD (36% enantiomeric excess (ee)) is a more effective chiral modifier for the reaction than CD (27% ee). CD and its ether derivatives induced a small rate acceleration compared to the unmodified reaction. The basic quinuclidine N of CD seems to be a necessary prerequisite for enantioselection, whereas the role of the OH group is not clear yet. Blocking of the OH group changes the absolute configuration of the major enantiomer.