He Ze-Liang, Li Li, Chen Zhi-Chao, Du Wei, Chen Ying-Chun
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University Chengdu 610041 China
College of Pharmacy, Third Military Medical University Shapingba Chongqing 400038 China.
Chem Sci. 2024 Dec 27;16(7):3124-3129. doi: 10.1039/d4sc07823c. eCollection 2025 Feb 12.
As a class of readily available and multifunctional building blocks, the chemistry of 4-alken-2-ynyl carbonates remains to be explored. Presented herein is a palladium-catalysed cascade transformative reaction between 4-alken-2-ynyl carbonates and -functionalised activated alkenes. Achiral 1,1-bisalkyl-4-alken-2-ynyl carbonates undergo highly regioselective propargylic substitution with -hydroxyphenyl-tethered activated alkenes, and an auto-tandem vinylogous addition, unusual central-carbon Tsuji-Trost alkylation, protonation and β-H elimination process is followed to furnish fused and spirocyclic frameworks with high structural complexity. Even kinetic transformations with racemic 1-monoalkylated 4-alken-2-ynyl carbonates can be accomplished in the assemblies with -aminophenyl-tethered activated alkenes to afford the analogous alkaloid architectures. This palladium-catalysed auto-tandem protocol exhibits excellent chemo-, regio-, stereoselectivity and reaction efficacy, and substantial functionality compatibility is also observed.
作为一类易于获得的多功能结构单元，4-烯基-2-炔基碳酸酯的化学性质仍有待探索。本文介绍了一种钯催化的4-烯基-2-炔基碳酸酯与官能化活性烯烃之间的级联转化反应。非手性的1,1-双烷基-4-烯基-2-炔基碳酸酯与对羟基苯基连接的活性烯烃发生高度区域选择性的炔丙基取代反应，随后进行自动串联的烯丙基化加成、不寻常的中心碳Tsuji-Trost烷基化、质子化和β-H消除过程，以提供具有高结构复杂性的稠合和螺环骨架。甚至外消旋的1-单烷基化4-烯基-2-炔基碳酸酯与对氨基苯基连接的活性烯烃在组装中也能实现动力学转化，得到类似的生物碱结构。这种钯催化的自动串联反应方案表现出优异的化学、区域、立体选择性和反应效率，并且还观察到了显著的官能团兼容性。
