Modular Synthesis of Planar-Chiral Cyclononenes via <i>trans</i>-Retentive Trapping of π-Allyl-Pd Dipoles
Zheng‐Xin Zhou, Yue-Liu-Ting Fu, Chen Zhang, Yuan-Heng Li, B. Zhang, Yuqing Xiao, Yujie Li, Liyan Chen, Li Rao, Ying Tan, Wenjing Xiao, Liang‐Qiu Lu
Abstract
Trans -cycloalkenes are abundant in bioactive natural products and have been used as powerful tools in chemical biology and drug discovery. However, strategies for the modular synthesis of trans -cycloalkenes, especially planar-chiral medium-sized ones, with high efficiency and selectivity, still remain elusive. Herein, we report a Pd-catalyzed asymmetric [7 + 2] cyclization strategy to address this challenge. As a result, two types of planar-chiral trans -cyclononenes bearing all-carbon chiral quaternary stereocenters are produced in up to 85% yield, >99% ee, and >19:1 dr (42 examples). The key to this success is the maintenance of the trans -2H configuration of the π-allyl-Pd species along with unusual linear selectivity during the H-bond-assisted cyclization process. In addition, the conversion of planar chirality to central chirality and its application in selective bioimaging of cancer cells via a bioorthogonal reaction were performed to demonstrate the synthetic value of this methodology.