School of Chemistry and Chemical Engineering, Guangdong Cosmetics Engineering and Technology Research Center, Guangdong Pharmaceutical University , Zhongshan, Guangdong 528458, China.
School of Materials Science and Engineering, MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-sen University , Guangzhou 510275, China.
J Org Chem. 2017 Mar 17;82(6):2914-2925. doi: 10.1021/acs.joc.6b02867. Epub 2017 Mar 6.
To achieve efficient palladium-catalyzed cross-coupling reaction under mild reaction conditions with the flexible steric bulk strategy, a series of Pd-PEPPSI (PEPPSI: pyridine-enhanced precatalyst preparation, stabilization, and initiation) complexes C1-C6 were synthesized and characterized, in which unsymmetric flexible steric bulk was introduced on the N-aryl of ancenaphthyl skeleton. These well-defined palladium complexes were found to be excellent precatalysts for Buchwald-Hartwig amination of aryl chlorides with amines in air. The electronic effect of the Pd-PEPPSI complexes and the effect of ancillary pyridine ligands were evaluated, among which complex C3 exhibited the most efficiency. It was demonstrated that the cross-coupling products were obtained in excellent yields in the presence of 0.5-0.1 mol % palladium loading. A wide range of aryl- and heteroaryl chlorides as well as various amines were compatible. The oxidative addition of aryl chlorides is revealed to be the rate-determining step in the catalytic cycle. The catalytic activity can be enhanced by introducing electron-donating groups to the Pd-PEPPSI complexes. This type of Pd-PEPPSI precatalyst showed the most efficiency reported to date for the challenging C-N cross-coupling reactions requiring no anhydrous and inert atmosphere protections, suggesting flexible steric bulk as a promising catalyst design strategy.
为了实现具有灵活空间位阻策略的温和反应条件下的高效钯催化交叉偶联反应，合成并表征了一系列 Pd-PEPPSI（PEPPSI：吡啶增强的前催化剂制备、稳定和引发）配合物 C1-C6，其中在薁基的 N-芳基上引入了不对称的灵活空间位阻。这些结构明确的钯配合物被发现是空气中芳基氯化物与胺的 Buchwald-Hartwig 胺化的优异前催化剂。评估了 Pd-PEPPSI 配合物的电子效应和辅助吡啶配体的效应，其中配合物 C3 表现出最高的效率。结果表明，在 0.5-0.1 mol%钯负载量的存在下，可获得优异收率的交叉偶联产物。广泛的芳基和杂芳基氯化物以及各种胺都具有兼容性。揭示了芳基氯化物的氧化加成是催化循环中的速率决定步骤。通过向 Pd-PEPPSI 配合物中引入供电子基团可以增强催化活性。这种类型的 Pd-PEPPSI 前催化剂对于需要无水和惰性气氛保护的具有挑战性的 C-N 交叉偶联反应，显示出迄今为止最高的效率，表明灵活的空间位阻是一种有前途的催化剂设计策略。
