Integrated Electro-Biocatalysis for Amine Alkylation with Alcohols

The integration of electro and bio-catalysis offers new ways of making molecules under very mild, environmentally benign conditions. We show that TEMPO mediated electro-catalytic oxidation of alcohols can be adapted to work in aqueous buffers, with minimal organic co-solvent, enabling integration with biocatalytic reductive amination using the AdRedAm enzyme. The combined process offers a new approach to amine alkylation with native alcohols, a key bond formation in the chemical economy that is currently achieved via precious metal-catalyzed hydrogen-borrowing technologies. The electrobio transformation is effective for primary and secondary alcohols undergoing coupling with allyl, propargyl, benzyl, and cyclopropyl amines, and has been adapted for use with solid-supported AdRedAm for ease of operation.

Automated summary

The integration of electro and bio-catalysis offers new ways of making molecules under very mild, environmentally benign conditions. The combined process offers a new approach to amine alkylation with native alcohols, a key bond formation in the chemical economy that is currently achieved via precious metal-catalyzed hydrogen-borrowing technologies.