Enantioselective cyanosilylation of ketones by a catalytic double-activation method with an aluminium complex and an N-oxide

Double-activation catalysis promises high catalytic efficiency in the enantioselective cyanosilylation of ketones through the combined use of a Lewis acid and a Lewis base. Catalyst systems composed of a chiral salen-Al complex and an N-oxide have high catalytic turnovers (200 for aromatic ketones, 1000 for aliphatic ones). With these catalysts, a wide range of aliphatic and aromatic ketones were converted under mild conditions into tertiary cyanohydrin O-TMS ethers in excellent yields and with high enantioselectivities (94% ee for aromatic ketones, 90% ee for aliphatic ones). Preliminary mechanistic studies revealed that the salen-Al complex played the role of a Lewis acid to activate the ketone and the N-oxide that of a Lewis base to activate TMSCN; that is, double activation.