Ring expansion of indene by photoredox-enabled functionalized carbon-atom insertion

Nat Catal. 2024 Mar;7(3):242-251. doi: 10.1038/s41929-023-01089-x. Epub 2024 Jan 9.

Abstract

Skeletal editing has received unprecedented attention as an emerging technology for the late-stage manipulation of molecular scaffolds. The direct achievement of functionalized carbon-atom insertion in aromatic rings is challenging. Despite ring-expanding carbon-atom insertion reactions, such as the Ciamician-Dennstedt re-arrangement, being performed for more than 140 years, only a few relevant examples of such transformations have been reported, with these limited to the installation of halogen, ester and phenyl groups. Here we describe a photoredox-enabled functionalized carbon-atom insertion reaction into indene. We disclose the utilization of a radical carbyne precursor that facilitates the insertion of carbon atoms bearing a variety of functional groups, including trifluoromethyl, ester, phosphate ester, sulfonate ester, sulfone, nitrile, amide, aryl ketone and aliphatic ketone fragments to access a library of 2-substituted naphthalenes. The application of this methodology to the skeletal editing of molecules of pharmaceutical relevance highlights its utility.