Hypervalent Iodide(III)-Mediated Thiofluorination of Alkenes and Alkynes from Thioureas/Thiocarbamoyl Fluorides with Water and Nucleophilic Fluoride Source

Abstract

Hypervalent iodines(III) mediated oxo/aza/carbon/difluorination of alkenes have made significant progress although the corresponding fluorination of alkynes cannot been 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 tolune 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 broad substrate scope, excellent functional group tolerance and excellent regioselectivity. Configurations of some products were found to be opposite to those expected from traditional mechanism of activation olefin by hypervalent iodines(III). Based on mechanistic study and product configurations, another mechanism involving 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 unprecedented thiofluorination of alkenes/alkynes in one operation directly from nucleophilic sulfur reagents and nucleophilic fluorine reagent.