Liu Jiandong, Dong Zhongkang, Cao Wen-Bin, Zheng Chao, You Shu-Li
New Cornerstone Science Laboratory, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
Shanghai-Hong Kong Joint Laboratory of Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
J Am Chem Soc. 2025 Jan 22;147(3):2776-2785. doi: 10.1021/jacs.4c15635. Epub 2025 Jan 8.
The asymmetric Tsuji-Trost reaction has been extensively studied due to its importance in establishing stereogenic centers, often adjacent to an -olefin moiety in organic molecules. The generally preferential formation of chiral -olefin products is believed to result from the thermodynamically more stable -π-allylpalladium intermediate. The rapid associative π-σ-π isomerization makes it challenging to synthesize chiral -olefin products via the transient -π-allylpalladium intermediate. Herein, we report a strategy for regulating associative π-σ-π isomerization by tuning the steric bulkiness of the ligands, allylic leaving groups, and counteranions. The utilization of a Pd catalyst derived from chiral phosphoramidite ligands interrupts the associative π-σ-π isomerization, enabling a highly efficient -retentive asymmetric Tsuji-Trost reaction toward an array of α-amino acid derivatives bearing a -olefin motif in high yields (up to 95%) and excellent stereoselectivity (up to 99% ee and >19:1 /) with low catalyst loading (0.1 mol %). The mechanistic insights and the design strategy reported in this work pave the way for rational developments of -retentive asymmetric Tsuji-Trost-type reactions.
由于不对称的辻-特罗斯特反应在构建立体中心方面具有重要意义，而这些立体中心通常与有机分子中的α-烯烃部分相邻，因此该反应已得到广泛研究。人们认为，手性α-烯烃产物的普遍优先形成是由热力学上更稳定的η³-烯丙基钯中间体导致的。快速的缔合π-σ-π异构化使得通过瞬态η³-烯丙基钯中间体合成手性α-烯烃产物具有挑战性。在此，我们报告了一种通过调节配体、烯丙基离去基团和抗衡阴离子的空间位阻来调控缔合π-σ-π异构化的策略。使用源自手性亚磷酰胺配体的钯催化剂可中断缔合π-σ-π异构化，从而实现高效的α-保留型不对称辻-特罗斯特反应，该反应可用于一系列带有α-烯烃基序的α-氨基酸衍生物，产率高（高达95%），立体选择性优异（高达99% ee和>19:1 dr），且催化剂负载量低（0.1 mol%）。这项工作中报道的机理见解和设计策略为合理开发α-保留型不对称辻-特罗斯特型反应铺平了道路。
