Direct transfer of a trifluoromethylsulfinyl group by a general reagent N-trifluoromethylsulfinylphthalimide under a catalytic or stoichiometric Lewis acid or Lewis base?

Organic Chemistry Frontiers Pub Date: 2023-07-18 DOI: 10.1039/D3QO00908D

Abstract

Herein, we report a strategy for direct transfer of the trifluoromethylsulfinyl group by a general and broadly applicable reagent, N-trifluoromethylsulfinylphthalimide, under a catalytic or stoichiometric Lewis acid or Lewis base. This process allows efficient trifluoromethylsulfinylation of C/N/O nucleophiles, including electron-rich heteroarenes, amines, alcohols, and especially challenging weakly nucleophilic phenols, in satisfactory to excellent yields with superb functional group compatibility and no excessive oxidation or reduction products, compared with traditional reagents. Further applications in late-stage trifluoromethylsulfinylation of complexed biologically active molecules highlight the synthetic utility of this protocol. Mechanistic investigations indicate that a quaternary ammonium ion pair or trifluoromethanesulfinyl chloride, generated in situ from N-trifluoromethylsulfinylphthalimide and a Lewis acid or Lewis base, may be responsible for the electrophilic trifluoromethylsulfinylation of C/N/O nucleophiles.

Graphical abstract: Direct transfer of a trifluoromethylsulfinyl group by a general reagent N-trifluoromethylsulfinylphthalimide under a catalytic or stoichiometric Lewis acid or Lewis base
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