An Intermolecular Hydroarylation of Highly Deactivated Styrenes Catalyzed by Re2O7/HReO4 in Hexafluoroisopropanol

Here, we describe an activation mode for unactivated alkenes on the basis of a synergy between Re2O7/HReO4 and hexafluoroisopropanol (HFIP). Highly electron-deficient styrenes have been activated to effect a challenging intermolecular hydroarylation with different arenes to give a variety of diarylalkanes in high efficiency. This method is characterized by mild reaction condition, broad substrate scope, high chemical yields, and minimal waste generation. The potential synthetic application of this methodology was exemplified by the efficient synthesis of a retinoic acid receptor (RAR) agonist. DFT calculations and deuterium-labeling experiments were conducted to elucidate the reaction mechanism, and both confirmed the critical role of HFIP, which significantly reduced the energetical barriers for several key steps of this transformation via a network of hydrogen bonding to perrhenate anion with two equivalents of HFIP.

Automated summary

An activation mode for unactivated alkenes using Re2O7/HReO4 and hexafluoroisopropanol (HFIP) was described. This method enables the intermolecular hydroarylation of highly electron-deficient styrenes with various arenes, leading to the synthesis of a variety of diarylalkanes in high efficiency. The reaction conditions are mild, the substrate scope is broad, and the yields are high, with minimal waste generation. The importance of HFIP in reducing the energy barriers for key steps of the transformation was confirmed through DFT calculations and deuterium-labeling experiments.