Intermolecular Regio‐ and Stereoselective Hetero‐[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines

• Published in: Angewandte Chemie International Edition Vol. 58; no. 3; pp. 887 - 891
• Main Authors: Zhao, Changgui, Glazier, Daniel A., Yang, Daoshan, Yin, Dan, Guzei, IIia A., Aristov, Michael M., Liu, Peng, Tang, Weiping
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.01.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: [5+2] cycloaddition; azepanes; Chemistry; Chemistry, Multidisciplinary; Cycloaddition; heterocycles; Imines; Natural products; Nitrogen; oxidoprylium ylide; Physical Sciences; Science & Technology; Stereochemistry; Stereoselectivity; Substitution reactions; VINYL AZIRIDINES; azepanes; oxidoprylium ylide; imines; ALKYNES; [5+2] cycloaddition; heterocycles; RING; 3-ACYLOXY-1,4-ENYNES; CHIRALITY; ACCESS; INTRAMOLECULAR 5+2 CYCLOADDITION; ALKALOIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201811896

We have developed the first intermolecular hetero‐[5+2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio‐ and stereoselectivity. Surprisingly, divergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide. This new reaction provides quick access to highly substituted nitrogen‐containing seven‐membered rings—azepanes. Notably, a broad range of oxidopyrylium ylides and cyclic imines participate in this novel hetero‐[5+2] cycloaddition reaction and the cycloadducts can be readily transformed into the core skeletons of bioactive natural products. DFT calculations revealed that the cycloaddition proceeds through a stepwise pathway and the imine nitrogen atom serves as the nucleophile to initiate the cycloaddition. Step by step: A hetero‐[5+2] cycloaddition of oxidopyrylium ylides and cyclic imines has been realized. This method provides efficient access to highly substituted azepane scaffolds. DFT calculations indicate that a stepwise mechanism is favored over a concerted one.