Isocyanide-Based Multicomponent Reactions: Rapid Synthesis of a 5,5-Fused Bicyclic Skeleton from α,β-Unsaturated Ketones and Allenoates

• Published in: Synthesis (Stuttgart) 2015-08, Vol.47 (16), p.2414-2430
• Main Authors: Xu, Shibo, Su, Shikuan, Zhang, Huiting, Tian, Lumin, Liang, Pengcheng, Chen, Jiawen, Zhang, Yuan, Li, Chunju, Jia, Xueshun, Li, Jian
• Format: Article
• Language: English
• Subjects: special topic
• ISSN: 0039-7881; 1437-210X
• DOI: 10.1055/s-0034-1378736

Abstract An efficient multicomponent reaction of isocyanides, allenoates, and α,β-unsaturated ketones is disclosed, thus providing rapid access for the synthesis of bicyclic skeletons. From a mechanistic standpoint, the present cycloaddition proceeds through cascade cycloaddition followed by hydration and intramolecular cyclization. Several controlled experiments are also conducted to gain further insight into the reaction mechanism; some valuable and interesting findings were observed during this process. To enrich the structural diversity, 3-(2-oxo­ethylene)indolinones (i.e. with an α,β-unsaturated ketone at position 3) were also found to be compatible in this reaction. In addition, this method is also characterized by its broad substrate scope, mild conditions, and high efficiency, which makes it valuable for further application.