Stream-Lined Synthesis of 3-Hydroxy-β-Lactams: Norrish-Yang Type Ii Photocyclizations of β-Ketoformamides

A photochemical approach to 3-phenyl-3-hydroxy-β-lactams (3-HβLs) is reported. Irradiation of aryl-β-ketoformamides with a UV light band centered at 300 nm provides the corresponding 3-aryl-3-HβLs with good conversion. The scope of the  photocyclization  is explored with an electronically diverse panel of substrates that provides mechanistic insight supporting a Norrish-Yang type II  cyclization . A flexible synthetic route to phenyl-β-ketoformamides, followed by photoirradiation, allows for efficient incorporation of the  β-lactam   pharmacophore  into aromatic organic scaffolds. Taken collectively, the improved and optimized synthetic route to provide both β-ketoformamides and 3-HβLs—in combination with the expanded analysis of substrate scope and limitations—reported herein will serve as a necessary reference for the direct, atom-economical, radical-mediated installation of 3-HβL scaffolds en route to the generation of other biologically active small molecules.