Hypervalent iodide(iii)-mediated thiofluorination of alkenes and alkynes from thioureas/thiocarbamoyl fluorides with water and a nucleophilic fluoride source

Abstract

The hypervalent iodine(III) mediated oxo/aza/carbon/difluorination of alkenes has made significant progress, although the corresponding fluorination of alkynes cannot be accomplished. However, hypervalent iodine(III) mediated thiofluorination of both alkenes and alkynes has never been achieved before. Herein, three-component alkenyl thiocarbamoyl fluorides, water, and Et₃N·3HF or two-component alkenyl thioureas and Et₃N·3HF proceeded through cascade hydrolysis/thiofluorination or thiofluorination of terminal/internal unactivated/activated alkenes upon phenyliodine(III)bis(pivalate) in toluene at room temperature, providing access to diversified monofluorinated 1,3-thiazolidin-2-ones, 1,3-thiazinan-2-ones, 2-imino-thiazolidines and 1,3-thiazinan-2-imines with a broad substrate scope, excellent functional group tolerance and excellent regioselectivity. Configurations of some products were found to be opposite to those expected from the traditional mechanism of olefin activation by hypervalent iodines(III). Based on mechanistic studies and product configurations, another mechanism involving a cyclic sulfonium ion intermediate was proposed. This inspired us to further discover that phenyliodine(III)bis(pivalate) with dioxane as solvent enabled thiofuorination of alkynes from alkynyl thioureas and Et₃N·3HF, furnishing 2-imino-thiazolidines bearing an exocyclicfluoromethylene as tetrasubstituted fluorinated alkenes with remarkable regio-, chemo- and stereoselectivity (absolute E-isomer). These transformations represent the unprecedented thiofluorination of alkenes/alkynes in one operation directly from nucleophilic sulfur reagents and nucleophilic fluorine reagents.