Carbon quaternization of redox active esters and olefins by decarboxylative coupling

Abstract

The synthesis of quaternary carbons often requires numerous steps and complex conditions or harsh reagents that act on heavily engineered substrates. This is largely a consequence of conventional polar-bond retrosynthetic disconnections that in turn require multiple functional group interconversions, redox manipulations, and protecting group chemistry. Here, we report a simple catalyst and reductant combination that converts two types of feedstock chemicals, carboxylic acids and olefins, into tetrasubstituted carbons through quaternization of radical intermediates. An iron porphyrin catalyst activates each substrate by electron transfer or hydrogen atom transfer, and then combines the fragments using a bimolecular homolytic substitution (S_H2) reaction. This cross-coupling reduces the synthetic burden to procure numerous quaternary carbon---containing products from simple chemical feedstocks.

Fig. 1.. Carbon quaternization overview and application.

(A). Nitrogen quaternization compared to methods for carbon quaternization. (B) Overview of method reported here. (C) Simplification imparted by this cross-coupling strategy compared to traditional multi-step synthesis.

Fig. 2.. Examples of simplified syntheses.

Lengthy routes to quaternary carbon-containing materials are compressed into short sequences using radical quaternization.