C(sp3)–H fluorosulfonylvinylation/aza-Michael addition approach to FSO2-functionalized tetrahydropyridines

Abstract

A novel cascade approach is presented for the synthesis of FSO₂-functionalized tetrahydropyridines from propargyl alcohols, FSO₂Cl, and anilines. This strategy successively involves radical fluorosulfonylation of the alkyne, C(sp³)–H fluorosulfonylvinylation, enamine formation, and intramolecular aza-Michael addition. Notably, the fluorosulfonyl radical can be generated efficiently via simple blue light irradiation of an electron donor–acceptor (EDA) complex between propargyl alcohols and FSO₂Cl, which requires no base, catalyst, and additive. The versatile follow-up derivatizations allow rapid ligation of tetrahydropyridines with other bioactive molecules that will be of value for drug discovery.