Bifunctional Iminophosphorane Catalyzed Amide Enolization for Enantioselective Cyclohexadienone Desymmetrization

• Published in: Angewandte Chemie International Edition Vol. 63; no. 5; pp. e202315401 - n/a
• Main Authors: Poh, Charmaine Y. X., Rozsar, Daniel, Yang, Jinchao, Christensen, Kirsten E., Dixon, Darren J.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.01.2024; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: asymmetric catalysis; Chemistry; Chemistry, Multidisciplinary; conjugate Addition; C−C bond formation; Enantiomers; enantioselectivity; organocatalysis; Physical Sciences; Science & Technology; conjugate Addition; enantioselectivity; organocatalysis; ALKYL THIOLS; C-C bond formation; ACIDITIES; SULFA-MICHAEL ADDITION; ESTERS; CRYSTAL-STRUCTURES; ALPHA; asymmetric catalysis; ASYMMETRIC TRANSFORMATIONS; C−C bond formation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202315401

The organocatalytic enolization of 2‐arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5‐cyclohexadienones, yielding 3D fused N‐heterocycles, is described. The transformation represents the first strong activating group‐free activation of carboxamides via α‐C−H deprotonation in a metal‐free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase. The enolization of 2‐arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5‐cyclohexadienones, yielding saturated fused N‐heterocycles, is described. The transformation is achieved by employing a bifunctional iminophosphorane (BIMP) superbase catalyst and represents the first unactivated carboxamide deprotonation in a metal‐free, catalytic, and enantioselective transformation.