High-yielding Suzuki coupling reactions of basic, amine containing substrates: The role of CO2, solvent, and pH.

摘要

Suzuki coupling is a transition-metal catalyzed reaction of an aryl halide and a boronic acid that forms carbon-carbon bonds. In large part due to its versatility, the Suzuki reaction has emerged as an important reaction in industrial synthesis. While the choice of catalyst, ligand, base and solvent system all play key parts in the success of the reaction, the role played by the substrate is just as important. Suzuki reactions involving substrates with basic nitrogen centers often obtain poor yields, a result attributed to the deactivation of the metal catalyst by the coordination of these nitrogen moieties. These poor yields are problematic, for nitrogen containing compounds are important building blocks in many biological and pharmaceutical compounds. Common strategies to achieve high-yielding reactions include adding additional amine protection and deprotection steps or the use of expensive, “designer” ligands. By running reactions under CO2 pressure and manipulating the amount of water present in the reaction system, we have developed a successful protocol for high-yielding Suzuki coupling reactions of 4-NH2-2-halopyridines and 2-halopyridines using Pd(TPP)2Cl2/K3PO4 in acetonitrile/water solvent systems. The results of this investigation will be discussed.