Catalytic, Vicinal Difluorination of Olefins: Creating a Hybrid, Chiral Bioisostere of the Trifluoromethyl and Ethyl Groups

Abstract

Contemporaneous reports describing the vicinal difluorination of olefins relying on I(I)/I(III) catalysis have augmented the arsenal of dihalogenation methods and provided a solution to this longstanding challenge in olefin functionalization. In both studies, success was contingent on the in situ generation of ArIF 2 from a simple aryl iodide, HF source, and suitable terminal oxidant. The first report by Jacobsen and co-workers employed a resorcinol-derived aryl iodide/ m -CPBA oxidant combination, while this laboratory relied on p -iodotoluene and Selectfluor. The complementarity of these approaches ensures that a wide variety of electronically distinct olefins are viable substrates for this transformation. This perspective describes our development of a catalytic difluorination of terminal olefins as a means to efficiently construct a hybrid, chiral bioisostere of the trifluoromethyl and ethyl groups in the broader context of molecular design and highlights key reports from other laboratories that accelerated the study.