2001 Volume 59 Issue 8 Pages 766-778
The design, synthesis, and application of a new bifunctional enantioselective catalyst, containing both Lewis acidity and Lewis basicity, are described. The catalysts are composed of a Lewis acid metal (aluminum or titanium) and a Lewis base (the oxygen atom of a phosphine oxide), of which positions are defined by BINOL or carbohydrate scaffold. Utilizing these catalysts, we have developed a variety of enantioselective cyanation reactions, such as cyanosilylation of aldehydes and ketones, Strecker-type reaction, and Reissert-type reaction. These reactions showed a broad sub-strate generality. Investigations toward elucidation of the reaction mechanism, involving kinetic studies, comparison with results by control catalysts, and absolute configurations of the products, revealed that these reactions are catalyzed by a dual activation of a substrate and TMSCN by the Lewis acid and the Lewis base of these catalysts. Catalytic enantioselective total synthesis of anticancer epothilones and a potent NMDA receptor antagonist was achieved, using these reactions as key steps.
