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

We have recently developed a method for the synthesis of pyrrolidines and piperidines via intramolecular C-H amination of -fluoride amides using [Tp CuL] complexes as precatalysts [Tp = tris(pyrazolyl)borate ligand and L = THF or CHCN]. Herein, we report mechanistic studies on this transformation, which includes the isolation and structural characterization of a fluorinated copper(II) complex, [(TpOH)CuF] [Tp = hydrotris(3,5-diisopropylpyrazolyl)borate], pertinent to the mechanistic pathway. The effects of the nature of the Tp 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.

Iodine Catalysis for C(sp )-H Fluorination with a Nucleophilic Fluorine Source.

Iodine catalysis was developed for aliphatic fluorination through light-promoted homolytic C-H bond cleavage. The intermediary formation of amidyl radicals enables selective C-H functionalization via carbon-centered radicals. For the subsequent C-F bond formation, previous methods have typically been limited by a requirement for electrophilic fluorine reagents.

Copper-Catalyzed N-F Bond Activation for Uniform Intramolecular C-H Amination Yielding Pyrrolidines and Piperidines.

The dual function of the N-F bond as an effective oxidant and subsequent nitrogen source in intramolecular aliphatic C-H functionalization reactions is explored. Copper catalysis is demonstrated to exercise full regio- and chemoselectivity control, which opens new synthetic avenues to nitrogenated heterocycles with predictable ring sizes. For the first time, a uniform catalysis manifold has been identified for the construction of both pyrrolidine and piperidine cores.