The Aminomethylation of Electron-Rich Aromatics with an N-Silyl-N,O-Acetal Catalyzed by a Metal Triflate-TMSCl System: Facile Synthesis of Aromatic Primary Amines, 1-Aryl-trichloroethylamines

The copper(II) triflate- and hafnium(IV) triflate-catalyzed aminomethylation of indole (2) with an N-silyl-N,O-acetal 1 containing a trichloromethyl group provides the primary amine derivative (3a) in modest yield. When 1 equiv of trimethylchlorosilane (TMSCl) was added to the reaction mixture, the reaction proceeded smoothly, and the yield of 3a was dramatically improved (>90%). The use of this catalytic system permitted the introduction of an aminomethyl group onto indoles 2a-h bearing a variety of functional groups, which appears to deactivate the Lewis acid, in 52-92% yields. Hf(OTf)4-doped TMSCl catalyzed the successful aminomethylation of various electron-rich aromatic compounds 4a-j to produce 1-aryl-trichloroethylamine derivatives 5a-j.