Dual-activation-driven iodofunctionalization of electron-deficient alkenes: sulfonamidation, esterification, phosphorylation, and etherification

Abstract

Iodofunctionalization of alkenes is a key strategy in synthetic chemistry but has traditionally been limited to electron-rich alkenes. Here, we present a versatile method for iodofunctionalizing electron-deficient alkenes, with an unprecedented substrate scope and the ability to incorporate a variety of nucleophiles, including sulfonamides, carboxylic acids, phosphoric acids, and alcohols. This versatile iodofunctionalization methodology relies on a dual-activation strategy that combines trifluoromethanesulfonic acid (TfOH) and hexafluoroisopropanol (HFIP). We demonstrate the scalability of this method through gram-scale synthesis and late-stage modification of complex products, underscoring its practical applicability. Mechanistic experiments and density functional theory (DFT) calculations provide compelling evidence that the dual-activation mode is critical for the efficient transformation.