Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐b]azepine Skeletons

• Published in: Angewandte Chemie International Edition Vol. 59; no. 3; pp. 1238 - 1242
• Main Authors: Liu, Yang‐Zi, Wang, Zhongao, Huang, Zesheng, Zheng, Xing, Yang, Wu‐Lin, Deng, Wei‐Ping
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 13.01.2020
• Subjects: [4+3] cyclization; asymmetric catalysis; Chemistry; Chemistry, Multidisciplinary; chiral azepines; cycloaddition; palladium; Physical Sciences; Science & Technology; chiral azepines; [4+3] cyclization; ALPHA,BETA-UNSATURATED IMINES; ANNULATION; AZADIENES; asymmetric catalysis; AZIRIDINES; 3+2 CYCLOADDITION; cycloaddition; HETEROCYCLES; PYRROLIDINES; palladium; 3-DIAZOINDOLIN-2-IMINES; DERIVATIVES; ACCESS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201909158

The palladium‐catalyzed asymmetric [4+3] cyclization of trimethylenemethane donors with benzofuran‐derived azadienes furnishes chiral benzofuro[3,2‐b]azepine frameworks in high yields (up to 98 %) with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee). This catalytic asymmetric [4+3] cyclization of Pd‐trimethylenemethane can enrich the arsenal of Pd‐TMM reactions in organic synthesis. In addition, this strategy provides an alternative approach to chiral azepines by a transition‐metal‐catalyzed asymmetric [4+3] cyclization. A wide range of chiral benzofuro[3,2‐b]azepine skeletons can be synthesized in excellent yields, high diastereoselectivities, and excellent enantioselectivities through the title reaction. The diastereoselectivity of the reaction can be controlled through ligand R1, with a cyano group affording trans products and a diphenyl ketimine group affording cis products.