State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, 300071, China.
Nat Commun. 2022 May 5;13(1):2470. doi: 10.1038/s41467-022-30152-7.
Due to high bond dissociation energies of Csp-F bonds, using fluorinated compounds in Csp-Csp cross-coupling is difficult. Here the authors report a protocol for enantioselective Csp-Csp coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. This reaction represents the first example of asymmetric Csp-Csp cross-coupling involving an inert Csp-F bond and provides expeditious access to chiral α-alkenyl α-amino acids with high enantioselectivity. Control experiments suggest that the Csp-F bond activation occurs through a pathway involving PdH migratory insertion and subsequent allylic defluorination, rather than by direct oxidative addition of the Csp-F bond to Pd(0). The detailed mechanism is further investigated by DFT calculation and the enantioselectivity is rationalized.
由于 Csp-F 键的键离解能很高，因此在 Csp-Csp 交叉偶联中使用氟化化合物是困难的。在这里，作者报道了一种通过协同铜和钯催化实现二烯基氟化物与亚胺酯的对映选择性 Csp-Csp 偶联的方案。该反应代表了首例涉及惰性 Csp-F 键的不对称 Csp-Csp 交叉偶联的实例，为具有高对映选择性的手性 α-烯基 α-氨基酸提供了快速途径。控制实验表明，Csp-F 键的活化是通过涉及 PdH 迁移插入和随后的烯丙基脱氟的途径发生的，而不是通过 Csp-F 键直接氧化加成到 Pd(0)。通过 DFT 计算进一步研究了详细的机理，并对立体选择性进行了合理化。
