Mechanism of Boron-Catalyzed N-Alkylation of Primary and Secondary Arylamines with Ketones Using Silanes under "Wet" Conditions
Chen, HC (Chen, Hongcai)[ 1 ] ; Yan, LN (Yan, Lina)[ 1 ] ; Wei, HY (Wei, Haiyan)[ 1 ]*（卫海燕）
[ 1 ] Nanjing Normal Univ, Jiangsu Prov Key Lab NSLSCS, Sch Chem & Mat Sci, Jiangsu Key Lab Biofunct Mat, Nanjing 210097, Jiangsu, Peoples R China
Density functional theory (DFT) calculations have been carried out to study the mechanism of N-alkylation of primary and secondary arylamines with aldehydes and ketones under the catalysis of the Lewis acid B(C6F5)(3) using silanes. The B(C6F5)(3)-mediated reduction of organic substrates is usually reported under anhydrous conditions. It is noteworthy that Ingleson and co-workers have established that B(C6F5)(3) could act as a water tolerant catalyst in N-alkylation of arylamines with aldehydes/ketones. Our DFT calculation results revealed that both Lewis acid B(C6F5)(3) and water play important roles in the condensation of amine and aldehyde to generate an imine intermediate and in the subsequent reduction of imine to yield an amine product. In the condensation reaction, Brensted acid B(C6F5)(3)-H2O acts as the effective catalyst to promote the proton transfer process. The activation free energy barrier is calculated to be 21.1 kcal/mol, which is 23.0 kcal/mol lower than that of the water-assisted condensation pathway. In the second stage of imine reduction, our DFT studies specifically show that a "one-pot" ionic outer-sphere S(N)2@Si transition state is the favorable pathway, featuring the imine hydrate nucleophilically attacking the eta(1)-silane boron adduct to activate silane, with an activation free energy barrier of 17.3 kcal/mol. With direct removal of silanol, a subsequent facile hydride transfer from the boronhydride anion [HB(C6F5)(3)](-) to the protonated iminium ion generates the alkylated amine product.