Hefei National Laboratory for Physical Sciences at the Microscale, iChEM, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, Department of Chemistry, University of Science and Technology of China , Hefei 230026, People's Republic of China.
Department of Chemistry and Centre for Atomic Engineering of Advanced Materials, Anhui University , Hefei 230601, China.
J Org Chem. 2016 Aug 5;81(15):6235-43. doi: 10.1021/acs.joc.6b00778. Epub 2016 Jul 28.
Mechanistic study has been carried out on the B(C6F5)3-catalyzed amine alkylation with carboxylic acid. The reaction includes acid-amine condensation and amide reduction steps. In condensation step, the catalyst-free mechanism is found to be more favorable than the B(C6F5)3-catalyzed mechanism, because the automatic formation of the stable B(C6F5)3-amine complex deactivates the catalyst in the latter case. Meanwhile, the catalyst-free condensation is constituted by nucleophilic attack and the indirect H2O-elimination (with acid acting as proton shuttle) steps. After that, the amide reduction undergoes a Lewis acid (B(C6F5)3)-catalyzed mechanism rather than a Brønsted acid (B(C6F5)3-coordinated HCOOH)-catalyzed one. The B(C6F5)3)-catalyzed reduction includes twice silyl-hydride transfer steps, while the first silyl transfer is the rate-determining step of the overall alkylation catalytic cycle. The above condensation-reduction mechanism is supported by control experiments (on both temperature and substrates). Meanwhile, the predicted chemoselectivity is consistent with the predominant formation of the alkylation product (over disilyl acetal product).
已对 B(C6F5)3 催化的酸与胺的烷基化反应进行了机理研究。该反应包括酸-胺缩合和酰胺还原步骤。在缩合步骤中，发现无催化剂机制比 B(C6F5)3 催化机制更有利，因为稳定的 B(C6F5)3-胺配合物的自动形成使后者的催化剂失活。同时，无催化剂缩合由亲核进攻和间接的 H2O 消除（酸作为质子穿梭剂）步骤构成。酰胺还原经历路易斯酸（B(C6F5)3）催化机制，而不是布朗斯台德酸（B(C6F5)3 配位的 HCOOH）催化机制。B(C6F5)3 催化的还原包括两次硅基-氢化物转移步骤，而第一次硅基转移是整个烷基化催化循环的速率决定步骤。上述缩合-还原机理得到了控制实验（温度和底物）的支持。同时，预测的化学选择性与烷基化产物的主要形成（而不是二硅基缩醛产物）一致。
