Friedel-Crafts Benzylations Mediated by FeCl3-based Deep Eutectic Solvents. Access to Substituted 1,1-diarylalkanes using Activated and Deactivated Electrophiles

Abstract

The development of new, more efficient Friedel-Crafts arylation methodologies that provide access to 1,1- diarylalkanes is an important objective of interest for the production of pharmaceuticals and fine chemical products. In this regard, this study introduces a novel synthetic route to 1,1-diarylalkanes conducted in the Deep Eutectic Solvent (DES) 3FeCl3 · 6H2O/Gly, which serves as both a reaction medium and promoter. Under these conditions, Friedel-Crafts benzylations of various arenes bearing activating and deactivating ortho-/para-directing groups, can be performed using diverse benzylating reagents such as styrenes, alcohols, acetates, ethers, and chlorides. Importantly, highly electronically deactivated electrophiles, including those with CF3 and NO2 groups, are suitable substrates. This methodology provides a wide range of asymmetric 1,1-diarylalkanes (up to 124 examples) with generally good yields and high regioselectivities. The efficacy of this approach was demonstrated with the multigram-scale synthesis (10 mmol) of 1-phenyl-1-xylyl ethane (PXE), a liquid with great industrial applicability. Moreover, the Fe(III)-based DES could be reused for a minimum of 20 consecutive cycles with no appreciable erosion of the yields.