To protonate or alkylate? Stereoselective Brønsted acid catalysis of C-C bond formation using diazoalkanes

Abstract

A new means to activate diazoalkanes has been discovered and applied broadly over the past few years. Brønsted acids, both achiral and chiral, have been used to promote the formation of carbon-carbon and carbon-heteroatom bonds with a growing number of diazoalkane derivatives. Aside from their straightforward ability to build structural and stereochemical complexity in innovative new ways, these transformations are remarkable owing to their ability to skirt competitive diazo protonation--a reaction that has long been used to prepare esters efficiently and cleanly from carboxylic acids. In cases where achiral Brønsted acids are used, high diastereoselection can be achieved. Meanwhile, chiral Brønsted acids can deliver products with both high diastereo- and enantioselectivity. More recently, systems have emerged that combine Brønsted acids and either Lewis acids or transition metals to promote carbon-carbon bond formation from diazoalkanes.