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: ZnEt 2 + 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 ZnMe 2 ·( 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 structure and exhibit the same catalytic properties and the same ee's for the reduction of acetophenone as the in situ prepared catalytic system. The complex ZnEt 2 ·( S, S )-ebpe) ( A ‘) reacts with benzaldehyde to give the seven-membered ring dimer complex La in which benzaldehyde inserts into the Zn−N bond of complex A ‘. Acetophenone also reacts with A ‘ to give a similar seven-membered ring dimer complex Lb . Both La and Lb are catalysts for the enantioselective reduction of acetophenone by PMHS and gave activities and ee's similar to those of A ‘. Synthetic and mechanistic aspects of this new economical method are discussed in this paper.
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Mimoun et al. (1999) studied this question.