Diastereoselective Synthesis of Enantioenriched Trifluoromethylated Ethylenediamines and Isoindolines Containing Two Stereogenic Carbon Centers by Nucleophilic Trifluoromethylation Using HFC-23

Abstract

Fluoroform, HFC-23, is an industrial byproduct from the synthesis of polytetrafluoroethylene and is a vastly underused resource; however, its physicochemical properties have hindered progress toward synthetic uses. Herein, we describe the use of HFC-23 as a cheap trifluoromethylating agent in two reactions for the highly diastereoselective synthesis of medicinally attractive chiral amines with two stereogenic carbon centers: a base-dependent, stereodivergent nucleophilic addition to synthesize enantioenriched vicinal diamines and a tandem nucleophilic addition/aza-Michael sequence toward enantioenriched isoindolines.