Silver‐Catalyzed Dearomative [2π 2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes.

Tang, Lei; Xiao, Yuanjiu; Wu, Feng; Zhou, Jin‐Lan; Xu, Tong‐Tong; Feng, Jian‐Jun

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver‐catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N‐unprotected indoles and bicyclobutane precursors is described. The strain‐release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale‐up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.

INDOLE compounds; HEXANE; INDOLINE; DRUG design; DRUG development; BICYCLIC compounds

Angewandte Chemie, 2023, Vol 135, Issue 48, p1

0044-8249

Academic Journal

10.1002/ange.202310066