Asymmetric counteranion-directed Lewis acid organocatalysis for the scalable cyanosilylation of aldehydes

Abstract

Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest. However, efficient protocols that function at a preparative scale with low catalyst loading are still rare. Here, asymmetric counteranion-directed Lewis acid organocatalysis proves to be remarkably successful in addressing this problem and enabled a molar-scale cyanosilylation in quantitative yield and with excellent enantioselectivity. Also, the catalyst loading could be lowered to a part-per-million level (50 ppm: 0.005 mol%). A readily accessible chiral disulfonimide was used, which in combination with trimethylsilyl cyanide, turned into the active silylium Lewis acid organocatalyst. The nature of a peculiar phenomenon referred to as a “dormant period”, which is mainly induced by water, was systematically investigated by means of in situ Fourier transform infrared analysis.

Abstract

Asymmetric cyanosilyation is a powerful method to convert carbonyls to chiral, configurationally stable cyanohydrins. Here, the authors report a catalyst capable of carrying out this reaction on large scales with extremely low catalyst loading, and also identify and explain a dormant period in the cycle.