Acid-Catalyzed Hydrothiolation of gem-Difluorostyrenes to Access α,α-Difluoroalkylthioethers
Jacob P. Sorrentino, Douglas L. Orsi and Ryan A. Altman*
*Department of Medicinal Chemistry and Molecular Pharmacology and Department of Chemistry, Purdue University, West Lafayette, Indiana 47906, United States, Email: raaltmanpurdue.edu
J. P. Sorrentino, D. L. Orsi, R. A. Altman, J. Org. Chem., 2021, 86, 2297-2311.
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Under basic conditions, nucleophilic addition to gem-difluorostyrenes generates an anionic intermediate that can undergo facile elimination of fluoride to generate α-fluorovinylthioethers. An acid-based catalyst system facilitates simultaneous nucleophilic addition and protonation of the unstable intermediate to afford the desired α,α-difluoroalkylthioethers in high selectivity and good yields.
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proposed mechanism - direct use of octanesulfonic acid eliminates the need to run the reaction in an atmosphere of air