Interrupting Associative π–σ–π Isomerization Enables <i>Z</i>-Retentive Asymmetric Tsuji–Trost Reaction
Jiandong Liu, Zhongkang Dong, Wenbin Cao, Chao Zheng, Shu‐Li You
Abstract
The asymmetric Tsuji–Trost reaction has been extensively studied due to its importance in establishing stereogenic centers, often adjacent to an E -olefin moiety in organic molecules. The generally preferential formation of chiral E -olefin products is believed to result from the thermodynamically more stable syn -π-allylpalladium intermediate. The rapid associative π–σ–π isomerization makes it challenging to synthesize chiral Z -olefin products via the transient anti -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 Z -retentive asymmetric Tsuji–Trost reaction toward an array of α-amino acid derivatives bearing a Z -olefin motif in high yields (up to 95%) and excellent stereoselectivity (up to 99% ee and >19:1 Z / E ) 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 Z -retentive asymmetric Tsuji–Trost-type reactions.