Cost-Effective Carbon Quaternization with Redox-Active Esters and Olefins

Quaternary carbons are embedded in various natural products, pharmaceuticals, and organic materials. However, constructing this valuable motif is far from trivial. Conventional approaches mainly rely on classical polar disconnections and encounter bottlenecks concerning harsh conditions, functional group tolerance, regioselectivity, and step economy. In this context, Kawamata, Baran, Shenvi, and co-workers recently demonstrated that two feedstock chemicals, alkyl carboxylic acids and olefins, could be utilized to construct tetrasubstituted carbons in the presence of an inexpensive iron porphyrin catalyst and a suitable reductant combination through quaternization of the radical intermediates. The method enables access to various sterically encumbered quaternary carbons under mild and robust conditions. Taking a complete detour from conventional approaches, the present heteroselective radical-radical coupling simplifies the synthesis of quaternary carbon-containing molecules through an innovative and distinctive disconnection approach. Kawamata, Baran, and Shenvi disclose a solitary iron-catalyzed conceptually distinct platform for constructing quaternary carbons using readily available and structurally diverse redox-active esters (RAEs) and olefins as modular coupling fragments. The heteroselective radical quaternization exhibits appreciable functional group tolerance and enables the synthesis of a palette of quaternary carbon-containing molecules under practical conditions. image