Electrochemical Enantioselective Nucleophilic α-C(sp3)–H Alkenylation of 2-Acyl Imidazoles

• DOI: 10.1021/jacs.2c01686
• Publication Date: 2022-04-06T21:35:27Z
• Authors: Peng Xiong; Marcel Hemming; Sergei I. Ivlev; Eric Meggers
• Keywords: Imidazoles; Rhodium; Stereoisomerism; Ketones; 01 natural sciences; Lewis Acids; 0104 chemical sciences

Merging electrochemistry with asymmetric catalysis promises to provide an environmentally friendly and efficient strategy for the construction of nonracemic chiral molecules. However, in practice, significant challenges arise from instability or incompatibility catalysts under electrochemical conditions at interface electrode solution. Herein, we report a catalytic indirect electrolysis employing combination redox mediator chiral-at-rhodium Lewis acid, which achieves previously elusive enantioselective nucleophilic α-C(sp3)−H alkenylation ketones. Specifically, 2-acyl imidazoles react potassium alkenyl trifluoroborates high yields (up 94%) exceptional enantioselectivities (27 examples ≥99% ee) without need any additional stoichiometric oxidants (overall 40 examples). The new electrosynthesis can be scaled gram quantities was applied straightforward synthesis intermediates natural product cryptophycin A cathepsin K inhibitor.