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Chemists untangle metal-free C–C coupling reactions

Radical versus cationic pathway depends on electron-hogging nature of functional groups

by Leigh Krietsch Boerner
March 20, 2021 | A version of this story appeared in Volume 99, Issue 10

A frustrated Lewis pair catalyze the coupling reaction between an alkyne and an ester.

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 shown). The team found that when there are electron-withdrawing groups on the alkyne, the mechanisms are most likely radical based. “But if you have electron-donating groups, which can stabilize the positively charged intermediate, these are probably going by the cationic pathway,” Melen says. She adds that chemists may be able to use the findings to design a greater variety of C–C coupling reactions that don’t depend on metal-based catalysts.


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