The diversification of complex molecules through late stage functionalization is an important challenge in contemporary chemical synthesis. For example, the alkylation of pharmacophores can modulate the biological properties of a molecule, altering the metabolism or selectivity. Minisci-type reactions have been developed as an attractive method for the decarboxylative alkylation of aromatic systems, but often suffer from the requirement of harsh conditions and strong oxidants. Herein, we report a method for the redox-neutral decarboxylative alkylation of heterocyclic N-oxides via photoredox catalysis. The developed system applies a single electron reduction to induce decarboxylation, producing alkyl radicals in mild conditions, a method that will likely improve the functional group tolerance of the proposed transformation. Importantly, the catalytic system also allows for the use of simple, commercially available carboxylic acids as low cost alkylating agents. Overall, this method allows for the mild alkylation of biologically important heterocyclic scaffolds.

Alkylation of heterocycles through a photoredox catalytic reductive decarboxylation

253rd National Meeting (2017)

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