Direct δ‐Lactone Synthesis From Free Alcohols via Photoinduced δ‐C(sp 3 )–H Carbonylation in Flow
Year: 2026
Type: article
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.
Source: Angewandte Chemie
DOI: 10.1002/ange.5570038
Institution: University of Amsterdam
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W7162771529