Mechanistic Studies on the Synthesis of Pyrrolidines and Piperidines via Copper-Catalyzed Intramolecular C.H Amination

Abstract

We have recently developed a method for the synthesis of pyrrolidines and piperidines via intramolecular C-H amination of N-fluoride amides using [TpxCuL] complexes as precatalysts [Tpx = tris(pyrazolyl)borate ligand and L = THF or CH3CN]. Herein, we report mechanistic studies on this transformation, which includes the isolation and structural characterization of a fluorinated copper(II) complex, [(TpiPr2OH)CuF] [TpiPr = hydrotris(3,5-diisopropylpyrazolyl)borate], pertinent to the mechanistic pathway. The effects of the nature of the Tpx ligand in the copper catalyst as well as of the halide in the N-X amides employed as reactants have been investigated both from experimental and computational perspectives.