Photocatalytic α-arylation of cyclic ketones

Abstract

The direct α-arylation of carbonyl compounds using aryl halides represents a powerful method to synthesize critical building blocks for diverse useful compounds. Numerous synthetic methods exist to forge C(sp2)–C(sp3) bonds although mild and metal-free direct α-arylation of ketones remains a challenging transformation. Here we report a green-light-mediated α-arylation of ketones from readily available aryl halides via activation of a C(sp2)–X bond (X = I, Br, Cl) and an α-carbonyl C(sp3)–H bond in a single photocatalytic cycle. This approach is characterized by its mild reaction conditions, operational simplicity and wide functional group tolerance. Importantly, the impressive outcome of the multigram photocatalytic reaction underpins the strength of this method as a potentially practical and attractive approach for scale-up industrial purposes. The utility and scope of this reaction were further demonstrated by formal syntheses of several feedstock chemicals that are commercially expensive but critical for synthesizing numerous pharmaceutical agents. Mild and metal-free direct α-arylation of ketones has long been a challenging transformation. Now, a metal-free photoredox approach has been developed using electron-rich acridinium ions to photoactivate C(sp2)–X bonds under low-energy green light and to catalyse the α-arylation of cyclic ketones. This approach is a multigram and sustainable methodology for the synthesis of pharmaceutical synthons.