HFIP-mediated, regio- and stereoselective hydrosulfenylation of ynamides: a versatile strategy for accessing ketene N,S-acetals

Abstract

Herein, we report an HFIP-mediated, versatile, sustainable, atom-economical, and regio- and stereoselective hydro-functionalization of ynamides with various S-nucleophiles (1 equiv.) such as thiols, thiocarboxylic acids, carbamates, xanthates, and O,O-diethyl S-hydrogen phosphorothioate to access a wide variety of stereodefined trisubstituted ketene N,S-acetals under mild conditions. This protocol requires only HFIP, which plays multiple roles, such as acting as a Brønsted acid to protonate the ynamide regioselectively at the beta carbon to generate the reactive keteniminium intermediate, stabilizing the intermediate as solvent through H-bonding. After the nucleophilic attack of the S-nucleophile on the keteniminium intermediate and deprotonation, HFIP is regenerated in most of the cases and can be easily recovered and recycled, revealing the high sustainability of the protocol. Remarkably, all the reactions are highly efficient and furnish ketene N,S-acetals in excellent yields and in many cases pure products were obtained just by washing the crude reaction mixture with pentane. Significantly, the green chemistry metrics of the protocol are found to be excellent.