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.
Recommended Citation
Y. Gao et al., "Electrocatalytic Asymmetric Nozaki-Hiyama-Kishi Decarboxylative Coupling: Scope, Applications, And Mechanism," Journal of the American Chemical Society, vol. 146, no. 7, pp. 4872 - 4882, American Chemical Society, Feb 2024.
The definitive version is available at https://doi.org/10.1021/jacs.3c13442
Department(s)
Chemistry
International Standard Serial Number (ISSN)
1520-5126
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2024 American Chemical Society, All rights reserved.
Publication Date
21 Feb 2024
PubMed ID
38324710
