Minor enantiomer recycling: metal catalyst, organocatalyst and biocatalyst working in concert.

A minor enantiomer recycling one-pot procedure employing two reinforcing chiral catalysts has been developed. Continuous regeneration of the achiral starting material is effected via selective enzyme-catalyzed hydrolysis of the minor product enantiomer from Lewis acid-Lewis base catalyzed addition of acyl cyanides to prochiral aldehydes in a two-phase solvent system. The process provides O-acylated cyanohydrins in close to perfect enantioselectivities, higher than those obtained in the direct process, and in high yields.

High-throughput synthesis and analysis of acylated cyanohydrins.

The yields and optical purities of products obtained from chiral Lewis acid/Lewis base-catalysed additions of alpha-ketonitriles to prochiral aldehydes could be accurately determined by an enzymatic method. The amount of remaining aldehyde was determined after its reduction to an alcohol, whilst the two product enantiomers were analysed after subsequent hydrolysis first by the (S)-selective Candida antarctica lipase B and then by the unselective pig liver esterase. The method could be used for analysis of products obtained from a number of aromatic aldehydes and aliphatic ketonitriles.

Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes using acetyl cyanide and cyanoformate as cyanide sources.

Dual activation by a chiral Lewis acid and an achiral or chiral Lewis base enabled cyanation of both aromatic and aliphatic aldehydes with acetyl cyanide and ethyl cyanoformate to provide direct access to O-acetylated and O-alkoxycarbonylated cyanohydrins, respectively, under mild conditions. With a combination of a Ti-salen catalyst and Et3N, benzaldehyde was converted to the O-acetylated cyanohydrin with 94% ee within 10 h at -40 degrees C in 89% isolated yield.