Copper-mediated C–C Coupling of Alkenyl Boronates and Bromodifluoroacetates

Abstract

The reaction of alkenyl boronates and bromodifluoroacetates in the presence of copper powder and TMEDA as the catalytic system was developed. The corresponding C–C coupling products were obtained in 35–93% yield. The method tolerated a variety of functional groups, namely, phenol, (thio)ether, protected amino-, hydroxy-, ketone, and carboxylic acid moieties, as well as various saturated carbo- and heterocycles, and was compatible with multigram scale-up (to 76 g). The diastereoselectivity of the process was typically low so that ca. 1:1 <i>E</i>/<i>Z</i> isomeric mixtures were formed from pure <i>E</i> or <i>Z</i> alkenyl boronates. Further functional group transformations demonstrated the utility of the prepared compounds as valuable building blocks for synthetic and medicinal chemistry. Based on the obtained results and the literature data, a plausible reaction mechanism was proposed involving the formation of radical and organocopper intermediates.