Li Zhenhua, Rong Dayou, Yuan Longfeng, Zhao Zhihong, Dai Fenghao, Chen Lijun, Xie Yuanyuan
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China.
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, China.
Org Biomol Chem. 2024 Jun 5;22(22):4559-4567. doi: 10.1039/d4ob00623b.
Electron-rich and hindered aryl chlorides are the most challenging substrates in Suzuki-Miyaura cross-coupling (SMC) reactions. Herein, we report a highly efficient catalytic system for the SMC reaction using trace amounts of commercially available catalysts [Pd(PPh)/(-Bu)PCy; Pd loading as low as 9.5 × 10 mol%]. This catalytic system can efficiently couple deactivated and sterically hindered aryl chlorides with various substituted phenylboronic acids, even in one-pot multiple coupling reactions (yield of products up to 92%). The impact of solvents on SMC reactions and the mechanisms of by-product formation in aryl boronic acid couplings are analyzed using density functional theory (DFT). Utilizing trace amounts of commercially available catalysts avoids complex synthesis, reduces costs, and minimizes metal residues.
富电子且位阻较大的芳基氯化物是铃木-宫浦交叉偶联（SMC）反应中最具挑战性的底物。在此，我们报道了一种用于SMC反应的高效催化体系，该体系使用痕量的市售催化剂[Pd(PPh)/(-Bu)PCy；钯负载量低至9.5×10 mol%]。即使在一锅多步偶联反应中，这种催化体系也能有效地使钝化和位阻较大的芳基氯化物与各种取代苯基硼酸偶联（产物收率高达92%）。利用密度泛函理论（DFT）分析了溶剂对SMC反应的影响以及芳基硼酸偶联反应中副产物形成的机理。使用痕量的市售催化剂避免了复杂的合成过程，降低了成本，并使金属残留量降至最低。
