2,2-Difluoroethylation of Heteroatom Nucleophiles via a Hypervalent Iodine Strategy.

Angew Chem Int Ed Engl

School of Chemistry, University of Nottingham, University Park, NG7 2RD, Nottingham, UK.

Published: October 2024

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.

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Source
http://dx.doi.org/10.1002/anie.202410954DOI Listing

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