Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

• Published in: Angewandte Chemie International Edition Vol. 62; no. 10; pp. e202216396 - n/a
• Main Authors: Xie, Jia‐Hao, Hou, Yi‐Ming, Feng, Zuolijun, You, Shu‐Li
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.03.2023; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Allylic Substitution; Asymmetric Catalysis; Asymmetry; Catalysts; Chemistry; Chemistry, Multidisciplinary; Conjugate Addition; Conjugates; Cyclohexanone; Enantiomers; Iridium; Physical Sciences; Reagents; Science & Technology; Stereodivergent; Stereoselectivity; Substitution reactions; Transition Metal Catalyzed; Stereodivergent; Conjugate Addition; ENANTIOSELECTIVE SYNTHESIS; IRIDIUM; ALLYLATION; ALPHA-AMINO-ACIDS; Allylic Substitution; DIASTEREODIVERGENT ACCESS; IR/ZN DUAL CATALYSIS; Transition Metal Catalyzed; Asymmetric Catalysis; NONADJACENT STEREOCENTERS; ORGANOMETALLIC REAGENTS; SYNERGISTIC CATALYSIS; METAL CATALYSIS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202216396

Herein, we report a synthesis of cyclohexanones bearing multi‐continuous stereocenters by combining copper‐catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium‐catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction of adjacent stereocenters (1,2‐position) reported in the literature, the current reaction can achieve the stereodivergent construction of nonadjacent stereocenters (1,3‐position) by a proper combination of two chiral catalysts with different enantiomers. Herein, we report a synthesis of cyclohexanones bearing multi‐continuous stereocenters by combining copper‐catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium‐catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. The current reaction can achieve the stereodivergent construction of nonadjacent stereocenters.