Direct δ‐Lactone Synthesis From Free Alcohols via Photoinduced δ‐C(sp ³ )–H Carbonylation in Flow

Abstract

ABSTRACT The direct carbonylation of unactivated C(sp 3 )─H bonds remains a fundamental challenge in synthesis. Herein, we report a photo‐flow strategy for the δ‐C(sp 3 )─H carbonylative lactonization of free alcohols using carbon monoxide. The transformation proceeds via photochemical generation of alkoxyl radicals, selective 1,5‐hydrogen atom transfer, CO trapping to form δ‐acyl radicals, and a crucial radical–polar crossover event that enables intramolecular cyclization to δ‐lactones. The use of a strongly oxidizing acridinium photocatalyst is essential to promote acyl radical oxidation, distinguishing this manifold from conventional proton‐coupled electron transfer (PCET) or ligand‐to‐metal charge transfer (LMCT) pathways. Continuous‐flow conditions facilitate efficient gas–liquid mass transfer and safe handling of CO, enabling short reaction times and scalability. The method tolerates diverse functional groups and provides direct access to structurally complex and bioactive δ‐lactone motifs from simple alcohol feedstocks.