Asymmetric Synthesis of Spirocyclic β‐Lactams through Copper‐Catalyzed Kinugasa/Michael Domino Reactions

• DOI: 10.1002/anie.201806931
• Publication Date: 2018-07-03T11:26:32Z
• Authors: Tao Shu; Long Zhao; Sun Li; Xiang‐Yu Chen; Carolina von Essen; Kari Rissanen; Dieter Enders
• Keywords: Molecular Structure; Alkynes; beta-Lactams; ta116; 01 natural sciences; Catalysis; Copper; 0104 chemical sciences

AbstractThe first copper‐catalyzed highly chemo‐, regio‐, diastereo‐, and enantioselective Kinugasa/Michael domino reaction for the desymmetrization of prochiral cyclohexadienones is described. In the presence of a chiral copper catalyst, alkyne‐tethered cyclohexadienones couple with nitrones to generate the chiral spirocyclic lactams with excellent stereoselectivity (up to 97 % ee, >20:1 dr). The new method provides direct access to versatile highly functionalized spirocyclic β‐lactams possessing four contiguous stereocenters, including one quaternary and one tetra‐substituted stereocenter.