Pd/Cu-catalyzed direct alkenylation of azole heterocycles with alkenyl halides

Direct alkenylation of azole heterocycles through Pd-Cu-catalyzed C-H bond activation has been reported using alkenyl bromides as the coupling partners. The reaction enables the introduction of various mono-, di-, or trisubstituted alkenyl bromides as well as a benzyl chloride to the caffeine core. The use of alkenyl bromides as partners in the direct Pd-Cu-catalyzed C-H alkenylation of xanthine allows the preparation of biologically interesting 3 in good yields.Extension of this process to various heterocycles is reported. In addition, the first example of the Pd-catalyzed direct benzylation of caffeine is described.