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Zhou and Roelfes MA_EP.pdf (4.36 MB)

Synergistic Catalysis of Tandem Michael Addition/Enantioselective Protonation Reactions by an Artificial Enzyme

preprint
submitted on 09.04.2021, 10:12 and posted on 09.04.2021, 13:18 by Zhi Zhou, Gerard Roelfes
Enantioselective protonation is conceptually one of the most attractive methods to generate an α-chiral center. However, enantioselective protonation presents major challenges, especially in water as a solvent. Herein, we report an artificial enzyme catalyzed tandem Michael addition and enantioselective protonation reaction of α-substituted acroleins with 2-acyl imidazole derivatives in water. The artificial enzyme uses a synergistic combination of two abiological catalytic sites: a genetically encoded non-canonical p-aminophenylalanine residue and a Lewis acid Cu(II) complex. The exquisite stereochemical control achieved in the protonation of the transient enamine intermediate generated by conjugate addition of the Michael donor is illustrated by the >20:1 dr and up to >99% ee obtained for the products. These results illustrate the potential of exploiting synergistic catalysis in artificial enzymes for challenging reactions.

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek, no.724.013.003

Ministerie van Onderwijs, Cultuur en Wetenschap, no. 024.001.035

European Research Council, Advanced Grant 885396

History

Email Address of Submitting Author

z.zhou@rug.nl

Institution

University of Groningen

Country

the Netherlands

ORCID For Submitting Author

0000-0001-7926-118X

Declaration of Conflict of Interest

no conflict of interest

Version Notes

1st version

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