Hexafluoroisopropanol: the magical solvent for Pd-catalyzed C-H activation

Chem Sci. 2021 Feb 10;12(11):3857-3870. doi: 10.1039/d0sc06937j.

Abstract

Among numerous solvents available for chemical transformations, 1,1,1,3,3,3-hexafluoro-2-propanol (popularly known as HFIP) has attracted enough attention of the scientific community in recent years. Several unique features of HFIP compared to its non-fluoro analogue isopropanol have helped this solvent to make a difference in various subdomains of organic chemistry. One such area is transition metal-catalyzed C-H bond functionalization reactions. While, on one side, HFIP is emerging as a green and sustainable deep eutectic solvent (DES), on the other side, a major proportion of Pd-catalyzed C-H functionalization is heavily relying on this solvent. In particular, for distal aromatic C-H functionalizations, the exceptional impact of HFIP to elevate the yield and selectivity has made this solvent irreplaceable. Recent research studies have also highlighted the H-bond-donating ability of HFIP to enhance the chiral induction in Pd-catalyzed atroposelective C-H activation. This perspective aims to portray different shades of HFIP as a magical solvent in Pd-catalyzed C-H functionalization reactions.

Publication types

  • Review