An Efficient Titanium Catalyst for Enantioselective Cyanation of Aldehydes: Cooperative Catalysis

摘要

Cvanohydrins contain a nitrile and an alcohol, and can be readily manipulated to produce a large range of biologically important compounds including α-hydroxy acids and esters, n-hydroxy aldehydes and ketones, α-amino acids, and |3-arnino alcohols, which have been widely used as the components of industrially valuable products such as pharmaceuticals, agrochemicals, flavorings, and fragrances. The addition of cyanide to a carbonyl compound to form a cyanohy-drin is one of the most fundamental carbon-carbon bond-forming reactions in organic chemistry. Since the first report of the enantioselective addition of hydrogen cyanide to benzaldehyde catalyzed by an extract of almonds, numerous enzymatic methods for the synthesis of enantioenriched cyanohydrins have been developed. However, it is still a great challenge in terms of the efficiency, cost, and adaptability of the catalysis. Alternatively, catalytic enantioselective synthesis of optically active cyanohydrin derivatives using either an artificial chiral Lewis acid, base, or a hybrid bifunctional Lewis acid/base catalyst has been reported to give very high enantioselectivity. Most of the reported methods have seen limited applications on preparative scales since the practical catalysts must enable reactions to be rapid, capable of being scaled up, and selective in the product formation. The remaining challenges include low activity and high cost of the catalysts, or the requisite use of expensive cyanide sources. Herein we report an efficient method for asymmetric syntheses of highly enantioenriched natural or nonnatural cyanohydrin derivatives using an elegantly designed catalyst to control the key cyanation step.