Catalytic 4-exo-dig carbocyclization for the construction of furan-fused cyclobutanones and synthetic applications
Kemiao Hong, Yi Zhou, Haoxuan Yuan, Zhijing Zhang, Jingjing Huang, Shanliang Dong, Wenhao Hu, Zhi‐Xiang Yu, Xinfang Xu
Abstract
Abstract Cyclobutanone is a strained motif with broad applications, while direct assembly of the aromatic ring fused cyclobutanones beyond benzocyclobutenone (BCB) skeletons remains challenging. Herein, we report a Rh-catalyzed formal [3+2] annulation of diazo group tethered alkynes involving a 4-exo-dig carbocyclization process, providing a straightforward access to furan-fused cyclobutanones. DFT calculations disclose that, by comparison to the competitive 5- endo - dig process, 4- exo - dig carbocyclization is mainly due to lower angle strain of the key sp -hybridized vinyl cationic transition state in the cyclization step. Using less reactive catalysts Rh 2 (carboxylate) 4 is critical for high selectivity, which is explained as catalyst-substrate hydrogen bonding interaction. This method is proved successful to direct access previously inaccessible and unknown furan-fused cyclobutanone scaffolds, which can participate in a variety of post-functionalization reactions as versatile synthetic blocks. In addition, preliminary antitumor activity study of these products indicates that some molecules exhibite significant anticancer potency against different human cancer cell lines.