Copper Catalyzed C-H Functionalization: Method Development via Enabling Intermediates

Catalytic C-H functionalization offers the promise of atom economical introduction of molecular diversity into organic molecules by direct transformation of C-H bonds to C-C, C-N, or C-O bonds. Compared to more traditional approaches that involve functional group manipulations, the direct utilization of C-H bonds in synthesis can minimize chemical steps, economic cost, and environmental impact.

Employing a copper-based catalyst system, we have employed both organoazides as well as alkyl- and arylamines in sp3 C-H amination. Experimental and theoretical insights into the mechanism of C-H amination by our -diketiminato copper(I) catalyst system have revealed three different classes of H-atom abstracting species that break sp3 C-H bonds in substrates R-H to afford radicals R•. Combining these mechanistic findings with efficient radical capture by copper(II) intermediates has resulted in a range of new catalytic C-H functionalization reactions that result in C-N, C-O, and C-C bond formation. For instance, synthetic investigation of these copper(II) intermediates results in novel examples of copper(II) aryl and alkynyl complexes that participate in C-C bond forming reactions.

Speaker: Timothy Warren, Georgetown University