Difunctionalization Processes Enabled by Hexafluoroisopropanol

Abstract

In the past 5 years, hexafluoroisopropanol (HFIP) has been used as a unique solvent or additive to enable challenging transformations through substrate activation and stabilization of reactive intermediates. In this Review, we aim at describing difunctionalization processes which were unlocked when HFIP was involved. Specifically, we focus on cyclizations and additions to alkenes, alkynes, epoxides, and carbonyls that introduce a wide range of functional groups of interest.

Controlling the regioselectivity of the bromolactonization reaction in HFIP

“… 6 HFIP has also demonstrated its ability to facilitate a wide range of difunctionalization reactions. 7 In relevant context to this work, there have been seminal contributions from the Gulder group 8 on HFIP-mediated halocyclization of terpenes, and the Lebœuf and Gandon groups 9 on HFIP-mediated haloamidation and halolactonization of alkenes with excellent reaction outcomes ( Scheme 1b ). Building upon these research studies and our prior investigations on halide-promoted addition reaction to alkenes, 10 acid-promoted cyclization reactions 11 and HFIP-assisted Brønsted acid-catalyzed chemistry, 12 we envisaged that HFIP can be used to activate bromonium sources such as NBS and promote endo -bromolactonization of readily available conjugated unsaturated carboxylic acids 13 ( Scheme 1c , upper route).…”