New way to make chiral fluorinated arenes

Abstract

A trifluoromethyl-substituted cyclopropane group can play a key role in a drug candidate. The group’s rigid cyclopropyl ring can increase the compound’s lipophilicity and metabolic stability while its fluorines can boost the candidate’s stability and ability to permeate membranes. But installing trifluoromethylcyclopropyl groups in a highly enantioselective manner is hard. A team led by Rudi Fasan at the University of Rochester now reports a combined chemical and biocatalytic approach that could make it easier to add trifluoromethylcyclopropyl groups to compounds enantioselectively for drug design (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b00768). Erick M. Carreira of the Swiss Federal Institute of Technology (ETH), Zurich, and coworkers developed the only previous method for adding the fluorinated groups in a fairly stereoselective manner. In that technique, cobalt catalysts generate trans-trifluoromethylcyclopropyl derivatives of arene substrates with enantiomeric excesses between 84 and 94% (Angew. Chem. Int. Ed. 2011, DOI: 10.1002/anie.201004269). Fasan notes that medicinal chemists