氢化吡咯烷基甲醇催化二乙基锌对苯甲醛的不对称加成反应机理的理论研究

Theoretical study on the potential energy surface of the asymmetric addition reaction of diethylzincs to benzaldehydes using hydrogenated Pyrrolidinyl methanols

用密度泛函理论在B3LYP-SCRF/6-31G(d)水平上研究了氢化吡咯烷基甲醇催化二乙基锌对苯甲醛不对称加成反应的反应机理和反应势能面。结果表明,催化剂的结构对反应机理和产物的对映选择性有重要影响。对于结构复杂的催化剂,二聚体难以生成,二聚体理论模型不适用。反应的决速步骤与吡咯环N取代基密切相关,吡咯环N取代基越大,由催化剂cata生成M1是反应的决速步骤;吡咯环N取代基越小,由M4发生分子内乙基迁移生成M5是反应的决速步骤。反应的立体化学控制步骤总是M4发生分子内乙基迁移生成M5的反应步骤。产物构型的保持和翻转与手性催化剂吡咯环N取代基、羟基α碳的取代基性质密切相关,与羟基α碳的构型没有必然的联系。催化剂氢化吡咯烷基甲醇为伯醇、R构型的仲醇和无手性的叔醇时都可以得到光学产率较好的产物,而氢化吡咯烷基甲醇为S构型的仲醇时得到光学产率较低的产物,并有可能发生产物构型的翻转。此外,还研究了温度对反应机理及反应能垒的影响,低温降低了反应的能垒,有利于反应的进行。

Density functional theory has been employed to explore the mechanism of asymmetric addition reaction of diethylzincs to benzaldehydes using chiral hydrogenated pyrrolidinyl methanols as catalysts. All the intermediates and transition states were optimized completely at the B3 LYP-SCRF/6-31 G(d) level. The obtained results indicate that the total reaction is an exothermic reaction and the structure of the chiral catalyst has an important influence on the reaction mechanism and enantioselectivity. For complex catalysts, the theoretical model of dimers is not applicable.The rate-controlling step of the reaction is closely related to the substituent on the pyrrole ring N, the larger the substituent on the pyrrole ring N, the formation of the active ligand M1 from the catalyst cata is the rate-controlling step of the reaction. The smaller the substituent on the pyrrole ring N,the rate-controlling step of the reaction changes to the formation of complex M5. The intramolecular ethyl migration reaction in which M5 is generated from the complex M4 is a stereochemical control step of the reaction.There is two possibility to attack the achiral carbonyl carbon in the complex M4 when the ethyl group migrates, that is, from the Re or Si surface of the carbonyl carbon to form the complex M5. Studies have shown that the maintenance and turnover of the product configuration are closely related to the structure of the chiral catalyst and are not necessarily related to the configuration of the hydroxyl alpha carbon. When the catalyst hydrogenated pyrrolidinyl methanol is a primary alcohol, a secondary alcohol in the R configuration, and a achiral tertiary alcohol, a chiral secondary alcohol having a better optical yield can be obtained. When the hydrogenated pyrrolidinyl methanol is a secondary alcohol in the S configuration, a product having a lower optical yield is obtained, and the product configuration may be reversed. In addition, the effect of temperature on the reaction mechanism and reaction energy barrier has also been considered. The low temperature reduces the energy barrier of the reaction and is beneficial to the reaction.