A comparison of Me₂(CH₂Cl)SiCN and Me₃SiCN in catalytic enantioselective cyanation of aldehydes

We report the comparative studies of Me₂(CH₂Cl)SiCN and Me₃SiCN in the catalytic enantioselective cyanation reactions of aldehydes, which were catalyzed by the merger of 5 mol% Jacobsen's catalyst (salen)AlCl (R,R)-1 and 6 mol% ylide 2a, and are conducted at -50 ℃ using i-Pr₂O as the solvent. This was based on our recent finding that (R,R)-1 could be effectively activated by ylide to form an enhanced chiral Lewis acid. Generally, the use of Me₂(CH₂Cl)SiCN as the cyanating reagent afforded obviously higher activity in the reaction of all the aldehydes we examined, along with by-and-large similar enantioselectivity. This further suggested that Me₂(CH₂Cl)SiCN might be useful cyanating reagent to develop reaction involving the use of less active substrates. Under the indicated condition, aromatic aldehydes worked well to give the desired adducts in up to 99% yield and 94% ee, but the reactions of vinyl aldehydes and aliphatic aldehydes were not successful. All the reactions were performed by the following general procedure. To a 4 mL vial were successively added complex (R,R)-1 (30.3 mg, 0.05 mmol), ylide 2a (22.6 mg, 0.06 mmol) and i-Pr₂O (1.0 mL). The resulting solution was stirred at -50℃ for 0.5 h before the addition of aldehydes (1.0 mmol) and the cyanating reagent, Me₂(CH₂Cl)SiCN or Me₃SiCN (250 μL, 2.0 mmol). After TLC analysis indicated the full consumption of the aldehydes, the reaction mixture was filtrated with a pad of silica gel and eluted with Et₂O. The filtrate is concentrated under reduced pressure to give a crude residue for column chromatography purification. In contrast, when Me₂(CH₂Cl)SiCN is used, both cyanohydrins and its silyl ethers were obtained, so a further deprotection by p-TsOH is adopted to obtain free cyanohydrins as the only product.