Metal-free C–C couplings untangled

Abstract

Most reactions that make new carbon-carbon bonds need some kind of transition-metal catalyst. Because these metals can be toxic, scientists want to ditch them, especially when synthesizing pharmaceutical compounds. Recent research shows that metal-free C–C coupling reactions can be activated through frustrated Lewis pairs: compounds or pairs of compounds that have Lewis acid (electron acceptor) and Lewis base (electron donor) groups. However, how these types of reactions work is not clear. Now, Rebecca Melen of Cardiff University and coworkers there and at the University of Tasmania have found that this reaction usually goes through a carbocation, but depending on the solvent and the reactants’ functional groups, it can react via a radical mechanism as well ( J. Am. Chem. Soc. 2021, DOI: 10.1021/jacs.1c01622 ). Using alkynes and esters, the team coupled groups with single C–C bonds to ones with triple bonds using frustrated Lewis pairs, making over 50 compounds (example