Achiral phenolic N-oxides as additives: an alternative strategy for asymmetric cyanosilylation of ketones

The activation of chiral titanium(IV) complexes with additives, phenolic N-oxides, is found to provide an alternative strategy for asymmetric cyanosilylation of ketones in excellent yield with up to 82% ee. 2004 Elsevier Ltd. All rights reserved. Recent years, there are a number of important observations made in regarding the effect of additives on asymmetric catalytic reactions. The addition of suitable achiral additives and cocatalysts to support the asymmetric catalyst system, enhance the yield and surprisingly, in many cases also enhance the enantioselectivity efficiently. Currently, asymmetric cyanosilylation of ketones is intensively studied due to the importance of cyanohydrins as the versatile synthons. Significant contribution was made by Belokon, Shibasaki, Deng, Hoveyda and Snapper, the latter also developed this reaction by employing MeOH and 3 A molecular sieves as additives. Furthermore, chiral N-oxides were extensively used in asymmetric synthesis such as allylation of aldehydes, addition of Et2Zn to aldehydes, 8 Strecker reaction, aldol reaction, and reduction of ketones. However, there are only a few achiral N-oxides used as additives in asymmetric reactions. Recently, our group has reported the asymmetric cyanosilylation of ketones in which N-oxides play a key role for activation of TMSCN in the catalytic system. We improved this reaction with a catalytic double-activation method (CDAM), in which salen-Ti(IV) complex acted as the Lewis acid and achiral N-oxide acted as the * Corresponding author. Fax: +86-28-85418249; e-mail: xmfeng@