Enantioselective addition of trimethylsilyl cyanide to aldehydes catalysed by bifunctional BINOLAM-AlCl versus monofunctional BINOL-AlCl complexes

A highly enantioselective cyanation of aldehydes takes place by using a bifunctional catalyst derived from 3,3′-bis(diethylaminomethyl) substituted binaphthol (BINOLAM) and dimethylaluminium chloride. The addition is of wide scope and runs best in toluene at temperatures ranging from −20 to −40 °C, in the presence of 4 Å MS and triphenylphosphine oxide as additives. The (R)- or (S)-cyanohydrins result when using (S)- or (R)-BINOLAM-AlCl complexes, respectively. The valuable ligand can be recovered by simple extractive work-up and recycled without loss of efficiency (both in terms of chemical and stereochemical yields). This methodology is applied to the Shibasaki synthesis of epothilone A. All the evidence available for the BINOLAM-AlCl enantioselective addition of TMSCN to aldehydes call for the intervention of a hydrocyanation reaction, addition of a catalytic amount of hydrogen cyanide, generated in situ, to an aldehyde, followed by O-silylation. In order to determine the role of the basic amino groups of BINOLAM, comparative studies are carried out with the monofunctional 1,1′-binaphthol-derived complex BINOL-AlCl.