Nickel-Catalyzed Suzuki Coupling of Phenols Enabled by SuFEx of Tosyl Fluoride

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy3)(2)/2PCy(3) as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with C-Ar-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3-10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone.

Automated summary

Researchers have developed a practical and efficient Suzuki coupling reaction of phenols using trans-NiCl(o-Tol)(PCy3)(2)/2PCy(3) as a catalyst and tosyl fluoride as an activator. The compatibility of the nickel catalyst with tosyl fluoride and its fluorosulfate exchange reaction with C-Ar-OH are crucial for the direct use of phenols. Water improves the one-pot reaction significantly, and a variety of electronically and sterically diverse biaryls can be obtained in good yields using 3-10 mol% of the nickel catalyst.