School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China.
Org Biomol Chem. 2011 Aug 21;9(16):5845-55. doi: 10.1039/c1ob05501a. Epub 2011 Jul 8.
Density functional theory calculations (B3LYP) have been carried out to understand the mechanism and stereochemistry of an asymmetric reductive aldol reaction of benzaldehyde and tert-butyl acrylate with hydrosilanes catalyzed by Rh(Phebox-ip)(OAc)(2)(OH(2)). According to the calculations, the reaction proceeds via five steps: (1) oxidative addition of hydrosilane, (2) hydride migration to carbon-carbon double bond of tert-butyl acrylate, which determines the chirality at C2, (3) tautomerization from rhodium bound C-enolate to rhodium bound O-enolate, (4) intramolecular aldol reaction, which determines the chirality at C3 and consequently the anti/syn-selectivity, and (5) reductive elimination to release aldol product. The hydride migration is the rate-determining step with a calculated activation energy of 23.3 kcal mol(-1). In good agreement with experimental results, the formation of anti-aldolates is found to be the most favorable pathway. The observed Si-facial selectivity in both hydride migration and aldol reaction are well-rationalized by analyzing crucial transition structures. The Re-facial attack transition state is disfavored because of steric hindrance between the isopropyl group of the catalyst and the tert-butyl acrylate.
密度泛函理论计算（B3LYP）已经被用于理解苯甲醛和叔丁基丙烯酸酯与硅烷在 Rh(Phebox-ip)(OAc)(2)(OH(2))催化下的不对称还原羟醛反应的机理和立体化学。根据计算，反应经过五个步骤进行：（1）硅烷的氧化加成，（2）氢化物向叔丁基丙烯酸酯的碳-碳双键迁移，这决定了 C2 的手性，（3）从铑结合的 C-烯醇化物到铑结合的 O-烯醇化物的互变异构，（4）分子内羟醛反应，这决定了 C3 的手性，进而决定了反式/顺式选择性，（5）还原消除以释放羟醛产物。氢化物迁移是速率决定步骤，计算得到的活化能为 23.3 kcal mol(-1)。与实验结果非常吻合，发现反式羟醛产物的形成是最有利的途径。通过分析关键过渡态，很好地解释了在氢化物迁移和羟醛反应中观察到的 Si-面选择性。由于催化剂的异丙基和叔丁基丙烯酸酯之间的空间位阻，Re-面进攻过渡态是不利的。
