Stereoselective Synthesis of Polycycles Containing an Aziridine Group: Intramolecular aza-Diels-Alder Reactions of Unactivated 2H-Azirines with Unactivated Dienes

• Published in: Angewandte Chemie International Edition 2016-02, Vol.55 (7), p.2540-2544
• Main Authors: Xu, Hua-Dong, Zhou, Hao, Pan, Ying-Peng, Ren, Xin-Tao, Wu, Hao, Han, Mei, Han, Run-Ze, Shen, Mei-Hua
• Format: Article
• Language: English
• Subjects: Alkenes; aziridines; Chemical synthesis; cycloadditions; Diels-Alder reactions; Dienes; heterocycles; small-ring systems; Stereoselectivity; synthetic methods; Thermal decomposition
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201510096

Vinyl azide with a pendent diene can undergo thermal decomposition to a related azirine intermediate, which was used immediately in an intramolecular aza‐Diels–Alder reaction to furnish an aziridine‐containing trans‐fused tricyclic core structure with excellent stereoselectivity. The method provides a facile entry to complex polycyclic alkaliods which can be further elaborated by ring‐opening reactions and ring expansion of the aziridine moiety, as well as by dihydroxylation of the alkene group. Cycling through: 5‐6‐3 and 6‐6‐3 tricycles, as well as more complex polycycles having a fused aziridine ring were constructed through an unprecedented intramolecular aza‐Diels–Alder reaction of 2H‐azirine with high stereoselectivity. The use of vinyl azide as the in situ azirine precursor precludes difficulties encountered in the direct handling of the corresponding azirine.