Catalytic Aerobic Cross-Dehydrogenative Coupling of Phenols and Catechols

We describe a selective, catalytic aerobic cross-dehydrogenative coupling (CDC) reaction of phenols and catechols that creates aryl ethers. To avoid challenges of selectivity, we employ copper (Cu) coordination to confine substrate redox to the inner coordination sphere of the metal. This minimizes nonselective radical processes to provide high levels of selectivity for cross over homo coupling, by C-O instead of C-C bond formation. The method remains efficient on synthetically useful substrates and scales and enables a convergent synthesis of the tetrahydroisoquinoline alkaloid (S, S)-thalicarpine featuring diaryl ether formation in the late stages of the synthesis. Related molecules are difficult to prepare by traditional Ullman-type coupling and provide a benchmark for evaluating the potential utility of our methodology.