Herein we report a synthetic method for photochemical or electrochemical carbonylative ring expansion of cyclic carboxylic acids. The reaction involves single electron reduction of a carbonyl group derived cyclic a-heterocarboxylic acids to form a ketyl radical, which undergoes spin-center shift (SCS) to generate an a-carbonyl radical and a heteroatom anion along with ring opening. Then, the radical undergoes hydrogen atom transfer (HAT) with a reductant or radical coupling, while the anion undergoes intramolecular acyl substitution with the recovered carbonyl group. This protocol allows to convert readily available cyclic a-heterocarboxylic acids to lactams, lactones and thiolactone through taking the exocyclic carbonyl group of carboxylic acid into the cyclic framework. This reaction is also applicable to 2-aryl-substituted cyclopropane and cyclobutane carboxylic acids. In such cases, mechanistic studies indicated that the reaction would proceed via ring opening through C–C bond homolysis on the ketyl radical followed by a reductive radical-polar crossover of the resultant benzyl radical to the benzyl anion, which then participates in the recyclization. When coupled with a-amino C–H carboxylation of cyclic aliphatic amines, this process functions as a molecular editing platform that enables the carbonylative ring expansion of ticlopidine and nicotine, as well as the streamlined synthesis of an ivabradine fragment.
DOI: 10.1021/jacs.5c08640