Carbonylative Ring Expansion of Cyclic Carboxylic Acids through Spin-Center Shift

Herein we focus on spin-center shift (SCS) as a radical-mediated ring opening process and exploit it to a photochemi-cal or electrochemical carbonylative ring expansion of cyclic carboxylic acids. The reaction involves single electron reduc-tion of a carbonyl group derived cyclic carboxylic acids to form a ketyl radical, which undergoes SCS to generate an α-carbonyl radical and a heteroatom anion or a carbanion 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 carboxylic acids to lactams, lactones and ketones through taking the exocyclic carbonyl group of carboxylic acid into the cyclic framework. The process com-bined with α-amino C–H carboxylation of cyclic aliphatic amines becomes a molecular editing technology for carbonyla-tive ring expansion of ticlopidine and streamlined synthesis of ivabradine fragment.