Aqueous Cross-Coupling For Proteins

Proteins can now easily participate in the popular Suzuki-Miyaura cross-coupling reaction, thanks to a new catalyst developed by researchers in England (J. Am. Chem. Soc., DOI: 10.1021/ja907150m). The Suzuki-Miyaura reaction, which uses a palladium catalyst to wed aryl halides and aryl boronic acids, offers chemists a potentially powerful method to modify proteins. But until now, attempts to use the cross-coupling strategy with proteins have suffered from low conversion or have required conditions that denatured the proteins. By using 2-amino-4,6-dihydroxypyrimidine as a ligand for palladium, Oxford University’s Benjamin G. Davis, Justin M. Chalker, and Charlotte S. C. Wood found that they can cross-couple proteins containing an aryl iodide with boronic acids. The reaction proceeds in less than an hour with gentle heating. “The cross-couplings reported on protein substrates are the first to proceed to completion and vindicate extensive effort to genetically incorporate cross-coupling partners into proteins,” the researchers note. The catalyst also works without the protein, coupling aryl iodides and aryl bromides under aqueous conditions. The researchers point out that the phosphine-free catalyst is far cheaper than those typically used in aqueous cross-couplings, and they are currently using it to explore other palladium-mediated transformations in water.