Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Am Chem Soc. 2010 Apr 21;132(15):5522-31. doi: 10.1021/ja101687p.
We report that a hard Lewis base substantially affects the reaction efficiency of direct catalytic asymmetric gamma-addition of allyl cyanide (1a) to ketones promoted by a soft Lewis acid/hard Brønsted base catalyst. Mechanistic studies have revealed that Cu/(R,R)-Ph-BPE and Li(OC(6)H(4)-p-OMe) serve as a soft Lewis acid and a hard Brønsted base, respectively, allowing for deprotonative activation of 1a as the rate-determining step. A ternary catalytic system comprising a soft Lewis acid/hard Brønsted base and an additional hard Lewis base, in which the basicity of the hard Brønsted base Li(OC(6)H(4)-p-OMe) was enhanced by phosphine oxide (the hard Lewis base) through a hard-hard interaction, outperformed the previously developed binary soft Lewis acid/hard Brønsted base catalytic system, leading to higher yields and enantioselectivities while using one-tenth the catalyst loading and one-fifth the amount of 1a. This second-generation catalyst allows efficient access to highly enantioenriched tertiary alcohols under nearly ideal atom-economical conditions (0.5-1 mol % catalyst loading and a substrate molar ratio of 1:2).
我们报告称，强碱在由软路易斯酸/硬布朗斯台德碱催化剂促进的烯丙基氰化物（1a）与酮的直接催化不对称γ-加成反应中显著影响反应效率。机理研究表明，Cu/(R,R)-Ph-BPE 和 Li(OC(6)H(4)-p-OMe) 分别作为软路易斯酸和硬布朗斯台德碱，允许 1a 的去质子化活化作为速控步骤。三元催化体系由软路易斯酸/硬布朗斯台德碱和外加硬路易斯碱组成，其中硬布朗斯台德碱 Li(OC(6)H(4)-p-OMe) 的碱性通过磷氧化物（硬路易斯碱）通过硬-硬相互作用得到增强，优于先前开发的二元软路易斯酸/硬布朗斯台德碱催化体系，在使用十分之一催化剂负载量和五分之一 1a 用量的情况下，产率和对映选择性更高。这种第二代催化剂允许在几乎理想的原子经济性条件下（催化剂负载量为 0.5-1 mol%，底物摩尔比为 1:2）高效获得高对映体过量的叔醇。
