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Updated: Jul 4, 2025

Light-driven Enzymatic Decarboxylation
Published on: May 22, 2016
Electrocatalytic Asymmetric Nozaki-Hiyama-Kishi Decarboxylative Coupling: Scope, Applications, and Mechanism
Yang Gao1, Baiyang Jiang1, Nathan C Friede2
1Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Abstract:
The first general enantioselective alkyl-Nozaki-Hiyama-Kishi (NHK) coupling reactions are disclosed herein by employing a Cr-electrocatalytic decarboxylative approach. Using easily accessible aliphatic carboxylic acids (via redox-active esters) as alkyl nucleophile synthons, in combination with aldehydes and enabling additives, chiral secondary alcohols are produced in a good yield with high enantioselectivity under mild reductive electrolysis. This reaction, which cannot be mimicked using stoichiometric metal or organic reductants, tolerates a broad range of functional groups and is successfully applied to dramatically simplify the synthesis of multiple medicinally relevant structures and natural products. Mechanistic studies revealed that this asymmetric alkyl e-NHK reaction was enabled by using catalytic tetrakis(dimethylamino)ethylene, which acts as a key reductive mediator to mediate the electroreduction of the CrIII/chiral ligand complex.
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