Direct δ-Lactone Synthesis From Free Alcohols via Photoinduced δ-C(sp³)-H Carbonylation in Flow

The direct carbonylation of unactivated C(sp³)─H bonds remains a fundamental challenge in synthesis. Herein, we report a photo-flow strategy for the δ-C(sp³)─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.