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

Seminar | November 8 | 4-5 p.m. | 120 Latimer Hall

 Timothy Warren, Department of Chemistry, Georgetown University

 College of Chemistry

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.

Selected References

“Copper-Catalyzed C(sp3)-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity” Bakhoda, A.; Jiang, Q.; Bertke, J. A.; Cundari, T. R.; Warren, T. H. Angew. Chem. Int. Ed. 2019, 58, 3421-3425.

“Three-Coordinate Copper(II) Aryls: Key Intermediates in C–O Bond Formation” Kundu, S.; Greene, C.; Williams, K. D.; Salvador, T. K.; Bertke, J. A.; Cundari, T. R.; Warren, T. H. J. Am. Chem. Soc. 2017, 139, 9112-9115.

“Copper Catalyzed sp3 C-H Etherification with Acyl Protected Phenols” Salvador, T. K.; Arnett, C. H.; Kundu, S.; Sapiezynski, N. G.; Bertke, J. A.; Boroujeni, M. R.; Warren, T. H.
J. Am. Chem. Soc., 2016, 138, 16580-16583.