2,2-Difluoroethylation of heteroatom nucleophiles via a hypervalent iodine strategy

Das, Suman; McIvor, Charlotte; Greener, Andrew; Suwita, Charlotte; Argent, Stephen; O'Duill, Miriam

Abstract

The 2,2-difluoroethyl group is an important lipophilic hydrogen bond donor in medicinal chemistry, but its incorporation into small molecules is often challenging. Herein, we demonstrate electrophilic 2,2 difluoroethylation of thiol, amine and alcohol nucleophiles with a hypervalent iodine reagent, (2,2-difluoro-ethyl)(aryl)iodonium triflate, via a proposed ligand coupling mechanism. This transformation offers a complementary strategy to existing 2,2-difluoroethylation methods and allows access to a wide range of 2,2-difluoroethylated nucleophiles, including the drugs Captopril, Normorphine and Mefloquine.

Citation

Das, S., McIvor, C., Greener, A., Suwita, C., Argent, S., & O'Duill, M. (in press). 2,2-Difluoroethylation of heteroatom nucleophiles via a hypervalent iodine strategy

• Working Paper Type: Working Paper
• Acceptance Date: Jun 20, 2024
• Online Publication Date: Jun 20, 2024
• Deposit Date: Jun 20, 2024
• Publicly Available Date: Jun 20, 2024
• DOI: https://doi.org/10.1002/anie.202410954
• Keywords: Hypervalent compounds, Fluorine, Medicinal Chemistry, Alkylation, Synthetic methods
• Public URL: https://nottingham-repository.worktribe.com/output/36016330
• Publisher URL: https://chemrxiv.org/engage/chemrxiv/article-details/6667f4a4e7ccf7753a7ce502