Direct δ-Lactone Synthesis from Free Alcohols via Photoinduced δ-C(sp³)-H Carbonylation in Flow
Year: 2026
Type: preprint
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 PCET or LMCT pathways. Continuous-flow conditions facilitate efficient gas-liquid mass transfer and safe handling of CO, enabling rapid 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: ChemRxiv
Authors: Prakash Tiwari, Runkang Liu, Timothy Noël
Institution: University of Amsterdam
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7133293558
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