Enantioselective Reduction of Ketones by Polymethylhydrosiloxane in the Presence of Chiral Zinc Catalysts

Abstract

Enantioselective reduction of ketones, particularly acetophenones, by polymethylhydrosiloxane (PMHS) to the corresponding secondary alcohols can be achieved with high yields and enantiomeric excesses (ee's) up to 88% in the presence of chiral zinc catalysts (eq 1). Two catalytic systems have been developed giving similar ee's: (i) System A: ZnEt2 + chiral diimine or diamine 1−10. (ii) System B: Zn(carboxylate)2 + chiral diamine activated by Vitride. System B is inexpensive, stable, and ready to use in toluene, providing either (R) or (S) chiral secondary alcohols with 70−80% ee in the presence of (S,S)- or (R,R)-N,N‘-ethylenebis(1-phenylethylamine) (ebpe, 6). The reduction has been carried out at the 1 kg scale without scale-up problems. The ligand is cheap and is recovered at the end of reaction by simple distillation from residues of the organic phase. Both precursors ZnMe2·(S,S)-ebpe (A) and Zn(dea)2·(S,S)-ebpe (B) for systems A and B, respectively, have been isolated and characterized by X-ray stru...