Stereoselective Synthesis of Complex Polyenes through Sequential α‐/β‐C−H Functionalization of trans ‐Styrenes

作者：Yuhang Zhu, Yini Wang, Wenzhou Shen, Xiaoyu Chen, Qiuhua Liu, Limin Yang, Guofu Zhong, Jian Zhang · 发表于：Angewandte Chemie International Edition · 年份：2024 · DOI：10.1002/anie.202315273 · 被引用次数：11 · 研究领域：Catalytic C–H Functionalization Methods、Synthesis and Catalytic Reactions、Radical Photochemical Reactions

Sequential C-H functionalization of molecules containing multiple C-H bonds can efficiently lead to structural diversity. Herein we present the first chelation-assisted sequential α-/β-C-H functionalization of E-styrenes with simple alkenes and alkynes in excellent regio- and stereo-selectivity. The process involves α C-H functionalization by six-membered exo-cyclopalladation to result in tri- and tetrasubstituted 1,3-dienes and β C-H functionalization through seven-membered endo-cyclopalladation to produce tetra- and pentasubstituted 1,3,5-trienes in up to 97 % yield with up to >99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram-scale synthesis as well as one-pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity.