Fused N‐Heterocycles with Contiguous Stereogenic Centers Accessed by an Asymmetric Catalytic Cascade Reaction of Tertiary Enamides

• Published in: Chemistry : a European journal 2020-01, Vol.26 (2), p.401-405
• Main Authors: Zhen, Li, Tong, Shuo, Zhu, Jieping, Wang, Mei‐Xiang
• Format: Article
• Language: English
• Subjects: alkaloids; Aromatic compounds; asymmetric synthesis; Carbonyl compounds; Carbonyls; Cascade chemical reactions; cascade reactions; Catalysis; Chemical synthesis; Chemistry; cyclization; Enantiomers; Heterocyclic compounds; Stereoselectivity; tertiary enamides
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201904596

We report in this article a cascade reaction strategy for the synthesis of complex N‐heterocyclic compounds with contiguous and tetrasubstituted stereogenic carbons. Under the sequential catalysis of a chiral binol–Ti complex and BF3, cyclopentanone‐derived tertiary enamides undergo an enantioselective enamine addition to ketone carbonyls followed by diastereoselective trapping of the resulting acyliminiums by electron‐rich aryl moieties to furnish four‐ and five‐membered ring‐fused N‐heterocyclic products as the sole diastereomers in high yields with up to 99 % ee. A domino game: Under treatment of a chiral binol–Ti complex and BF3, cyclopentanone‐derived tertiary enamides undergo the enantioselective enamine addition to ketone carbonyls followed by diastereoselective trapping of the resulting acyliminiums by electron‐rich aryl moieties to furnish ring‐fused N‐heterocyclic products in high yields and excellent enantioselectivities.