Solvent-Dependent Asymmetric Synthesis of Alkynyl and Monofluoroalkenyl Isoindolinones by CpRhIII-Catalyzed C-H Activation
Solvent-Dependent Asymmetric Synthesis of Alkynyl and Monofluoroalkenyl Isoindolinones by CpRhIII-Catalyzed C-H Activation
复制标题
通过 CpRh(Ⅲ) 催化的 C-H 活化，溶剂依赖性不对称合成炔基和单氟烯基异吲哚啉酮
DOI：
10.1002/anie.201712691
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发表时间：
2018-04-03
影响因子：
16.6
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Li, Teng;Zhou, Chao;Wang, Jun
通过手性 CpRhIII 催化剂的 C-H 活化，可以从 N-甲氧基苯甲酰胺和 ,-二氟亚甲基炔烃不对称合成炔基和单氟烯基异吲哚啉酮。值得注意的是，产物的形成取决于溶剂。炔基异吲哚啉酮在 MeOH 中产生（高达 86% 产率，99.6% ee），而单氟烯基异吲哚啉酮在 (PrCN)-Pr-i 中生成（高达 98:2 Z/E，93% 产率，86% ee）。机理研究揭示了手性丙二烯和E-构型烯基铑物质作为反应中间体。后者在 (PrCN)-Pr-i 系统中质子化后转化为相应的 Z-构型单氟烯烃，并在 MeOH 系统中通过不寻常的反 F 消除转化为炔烃。值得注意的是，该反应中发生了动力学拆分过程。尽管对手性丙二烯的形成进行了适度的对映体控制，但通过一两个连续的动力学拆分过程获得了良好对映体纯度的Z-单氟烯基异吲哚啉酮和炔基异吲哚啉酮。
The asymmetric synthesis of alkynyl and monofluoroalkenyl isoindolinones from N-methoxy benzamides and ,-difluoromethylene alkynes is enabled by C-H activation with a chiral CpRhIII catalyst. Remarkably, product formation is solvent-dependent; alkynyl isoindolinones are afforded in MeOH (up to 86% yield, 99.6% ee) whereas monofluoroalkenyl isoindolinones are generated in (PrCN)-Pr-i (up to 98:2 Z/E, 93% yield, 86% ee). Mechanistic studies revealed chiral allene and E-configured alkenyl rhodium species as reaction intermediates. The latter is transformed into the corresponding Z-configured monofluoroalkene upon protonation in the (PrCN)-Pr-i system and into an alkyne by an unusual anti -F elimination in the MeOH system. Notably, kinetic resolution processes occur in this reaction. Despite the moderate enantiocontrol for the formation of the chiral allene, the Z-monofluoroalkenyl isoindolinones and alkynyl isoindolinones were obtained in good enantiopurities by one or two sequential kinetic resolution processes.