Halogen bonding-induced 1,3-carbohydroxylation of allyl carboxylates <i>via</i> 1,2-cationic acyloxy migration (1,2-CAM)
Halogen bonding has emerged as a powerful yet underexplored tool for modulating radical reactivity. Here we demonstrate that halogen-bonding interactions between alkyl iodides and water can lower the C-I bond dissociation energy, enabling visible-light-induced photolysis to generate alkyl radicals under mild conditions. Harnessing this activation mode, we achieved a previously unknown 1,3-carbohydroxylation of allyl carboxylates, wherein radical addition is coupled with 1,2-cationic acyloxy migration (CAM) to furnish β-acyloxy alcohols. The transformation exhibits broad structural tolerance, accommodating diverse esters, thioesters, amides, and perfluoroalkyl iodides, and is effective in the late-stage diversification of natural products and drug-derived scaffolds. Mechanistic studies, including isotopic labeling, radical trapping, UV-vis spectroscopy, and DFT calculations, reveal a pathway in which halogen bonding initiates radical alkene addition, followed by rearrangement and carbocation capture. These findings showcase halogen-bonding-assisted photochemistry as a viable platform for radical-cationic cascades, opening new opportunities for reaction development.
Authors
- Djamaladdin G. Musaev (ORCID: https://orcid.org/0000-0003-1160-6131)
- Ming‐Yu Ngai (ORCID: https://orcid.org/0000-0002-3055-6662)
- Arman Khosravi (ORCID: https://orcid.org/0009-0000-6768-7132)
- Sahil Sharma
- Loay Bedda
- Gaoyuan Zhao
Institutions
- Emory University (US)
- Purdue University West Lafayette (US)
Publication Details
- Journal
- Chemical Science
- Published
- 2025-12-24
- DOI
- https://doi.org/10.1039/d5sc08514d
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Purdue University
- Emory University
- University of Pittsburgh
- National Institutes of Health
- Center for Research Computing, University of Pittsburgh
- Office of Advanced Cyberinfrastructure
- Division of Chemistry