N‐Heterocyclic Carbene Catalyzed [4+2] Annulation of Enals via a Double Vinylogous Michael Addition: Asymmetric Synthesis of 3,5‐Diaryl Cyclohexenones

• Published in: Angewandte Chemie International Edition Vol. 56; no. 22; pp. 6241 - 6245
• Main Authors: Chen, Xiang‐Yu, Liu, Qiang, Chauhan, Pankaj, Li, Sun, Peuronen, Anssi, Rissanen, Kari, Jafari, Ehsan, Enders, Dieter
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.05.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: annulations; Asymmetric synthesis; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; cyclohexenones; Michael addition; Modularity; N-heterocyclic carbenes; Organic chemistry; Physical Sciences; Science & Technology; Michael addition; DOMINO REACTIONS; DIELS-ALDER REACTIONS; ENANTIOSELECTIVE SYNTHESIS; BENZOIN REACTIONS; cyclohexenones; ALPHA,BETA-UNSATURATED ALDEHYDES; GAMMA-BUTYROLACTONES; SPIROCARBOCYCLIC OXINDOLES; asymmetric synthesis; COOPERATIVE CATALYSIS; annulations; KINETIC RESOLUTION; STEREOSELECTIVE-SYNTHESIS; N-heterocyclic carbenes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201702881

A strategy for the N‐heterocyclic carbene (NHC) catalyzed asymmetric synthesis of 3,5‐diaryl substituted cyclohexenones has been developed via oxidative [4+2] annulation of enals and alkenylisoxazoles. It is the first example of using NHC organocatalysis in a double vinylogous Michael type reaction, a challenging but highly desirable topic. This unprecedented protocol affords good yields as well as high to excellent diastereo‐ and enantioselectivities. N‐heterocyclic carbene organocatalysis allows the [4+2] annulation of enals with electron‐deficient 2,4‐dienes via a double vinylogous Michael addition sequence. The corresponding 3,5‐diaryl cyclohexenones are obtained in good to excellent yields with high to excellent diastereo‐ and enantioselectivities.