Enantioselective Synthesis of Medium‐Sized Lactams via Chiral α, β‐Unsaturated Acylammonium Salts. Issue 22 (2nd May 2018)

• Record Type: Journal Article
• Authors: Kang, Guowei; Yamagami, Masaki; Vellalath, Sreekumar; Romo, Daniel
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 22(2018)
• Page Start: 6527
• Page End: 6531
• Publication Date: 2018-05-02
• Subjects: enantioselectivity -- medicinal chemistry -- medium-ring compounds -- Michael addition -- organocatalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201802483
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Medium‐sized lactams are important structural motifs found in a variety of bioactive compounds and natural products but are challenging to prepare, especially in optically active form. A Michael addition/proton transfer/lactamization organocascade process is described that delivers medium‐sized lactams, including azepanones, benzazepinones, azocanones, and benzazocinones, in high enantiopurity through the intermediacy of chiral α, β‐unsaturated acylammonium salts. An unexpected indoline synthesis was also uncovered, and the benzazocinone skeleton was transformed into other complex heterocyclic derivatives, including spiroglutarimides, isoquinolinones, and δ‐lactones. Abstract : Mid‐sized, no problem : A Michael addition/proton transfer/lactamization organocascade delivers medium‐sized lactams, including azepanones, benzazepinones, azocanones, and benzazocinones, via α, β‐unsaturated acylammonium salt intermediates with high enantioselectivity. The benzazocinones were converted into spiroglutarimides and isoquinolines. An unexpected indoline was also prepared by the capture of a tetrahedral intermediate in this organocascade.