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Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

preprint
submitted on 01.04.2021, 11:44 and posted on 02.04.2021, 12:56 by Daniel Rozsar, Michele Formica, Ken Yamazaki, Trevor Hamlin, Darren J. Dixon
The first metal-free catalytic intermolecular enantioselective sulfa-Michael addition to unactivated α,β- unsaturated amides is described. Consistently high enantiomeric excesses, and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane (BIMP) catalyst. Low catalyst loadings (2 mol%) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity, corresponding transition states, and provided substantial evidence for specific non-covalent activation of the carbonyl group of the α,β-unsaturated amide by the catalyst.

Funding

EP/L015838/1

NWO

Honjo International Scholarship Foundation

History

Email Address of Submitting Author

daniel.rozsar@chem.ox.ac.uk

Institution

University of Oxford

Country

United Kingdom

ORCID For Submitting Author

0000-0002-0516-1722

Declaration of Conflict of Interest

The authors declare no competing financial interests.

Version Notes

version 1.0