Pd(II)-Catalyzed Asymmetric [4 + 1] Annulation via Ligand Relay-Enabled Carbenylative Insertion/E1cB-Type Heck Cascade

作者：Zhou Luo, Yihao Zhang, Chao Zhang, Kewei Dong, Pranab K. Pramanick, Shen Zhao, Yuanyuan Liu, Guoqiang Yang · 发表于：Journal of the American Chemical Society · 年份：2026 · DOI：10.1021/jacs.5c20265 · 被引用次数：4 · 研究领域：Cyclopropane Reaction Mechanisms、Catalytic C–H Functionalization Methods、Catalytic Cross-Coupling Reactions

Pd-catalyzed asymmetric annulation via metal carbene is highly desired for efficient access to chiral cyclic compounds; however, such a strategy remains a considerable challenge. In this study, we report an unprecedented Pd-catalyzed asymmetric [4 + 1] annulation through a tandem carbene migratory insertion/Heck reaction, facilitated by an asymmetric ligand relay strategy. This approach provides an efficient protocol to access enantio-enriched α-alkylidene 3-substituted indanones. A wide range of substrates could be tolerated in the catalytic system, furnishing products with good to excellent enantioselectivity. A mechanistic study has also been conducted, which offers insights into the ligand relay catalytic system. Control experiments and DFT calculations elucidated a plausible novel E1cB mechanism for the elimination step of the Heck process, well explaining the generation of the olefin product of the Heck reaction bearing an unusual configuration. The enantio-determining step is revealed by DFT calculations to be a concerted process involving carbene formation and migratory insertion.