Me_2(CH_2Cl)SiCN和Me_3SiCN在醛的不对称氰化反应中的比较研究

A Comparison of Me_2(CH_2Cl)SiCN and Me_3SiCN in Catalytic Enantioselective Cyanation of Aldehydes

研究考察了在手性(salen)AlCl-叶立德络合物(R,R)-1/2a作为催化剂和异丙醚作为溶剂的条件下,两种不同硅氰化试剂[Me_2(CH_2Cl)SiCN和Me_3SiCN(TMSCN)]在对醛的不对称氰化中的应用情况.一系列不同取代的芳香醛均可分别与这两种试剂发生反应,以高到优秀的产率和对映选择性得到目标产物.脂肪醛的反应产物的对映选择性最高只能达到中等.对比研究发现,Me_2(CH_2Cl)SiCN在醛的硅氰化反应中显示出了明显高于TMSCN的反应活性,但是产物的对映选择性大体相当.

We report the comparative studies of Me_2（CH_2Cl）SiCN and Me_3SiCN 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-Pr2 O 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 Me_2（CH_2Cl）Si CN 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 Me_2（CH_2Cl）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 m L vial were successively added complex（R,R）-1（30.3 mg, 0.05 mmol）, ylide 2a（22.6 mg, 0.06 mmol） and i-Pr_2O（1.0 m L）. The resulting solution was stirred at-50 ℃ for 0.5 h before the addition of aldehydes（1.0 mmol） and the cyanating reagent, Me_2（CH_2Cl）SiCN or Me_3Si CN（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 Et_2O. The filtrate is concentrated under reduced pressure to give a crude residue for column chromatography purification. In contrast, when Me_2（CH_2Cl）Si CN is used, both cyanohydrins and its silyl ethers were obtained, so a further deprotection by p-Ts OH is adopted to obtain free cyanohydrins as the only product.