Enantioselective Construction of Eight‐Membered N‐Heterocycles from Simple 1,3‐Dienes via Pd(0) Lewis Base Catalysis

• Published in: Angewandte Chemie Vol. 136; no. 6
• Main Authors: Pan, Jiaoting, Ho, Takumi Ogawa, Chen, Ying‐Chun, Yang, Bin‐Miao, Zhao, Yu
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 05-02-2024
• Subjects: 1,3-Diene; Catalysis; Catalysts; Cycloaddition; Dienes; Eight-Membered Ring; Enantiomers; Enantioselective Cycloaddition; Fused Polycycles; Lewis base; Palladium; Pd Lewis Base Catalysis; Stereoselectivity
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202317703

We report herein an unprecedented enantioselective (4+4) cycloaddition of simple 1,3‐dienes with azadienes for the construction of fused eight‐membered N‐heterocycles. In this transformation, the π‐Lewis basic Pd(0) catalyst achieves activation of 1,3‐dienes to induce nucleophilic addition to azadienes followed by ring cyclization via a selective terminal allylic substitution. Furthermore, highly efficient and diastereoselective derivatizations of the eight‐membered rings provide a facile access to diverse enantiopure fused tetra‐ to hexacyclic compounds with potential application in medicinal chemistry.
An unprecedented (4+4) cycloaddition of simple 1,3‐dienes with azadienes is achieved by π‐Lewis basic palladium (0) catalysis, delivering benzofuran‐fused eight‐membered heterocycles in high efficiency, regio‐ and enantioselectivities. Highly diastereoselective derivatizations of the resultant eight‐membered cyclic alkenes provide a facile access to diverse fused polycyclic compounds in excellent efficiency.