Novel Copper Catalysts for C-H Bond Amination and Olefin Aziridination

Categories: “Chemistry“

Reference #:
2008-051
2006-038

OTC Contact: Sharon E. Pula, M.S., J.D. (Directory Information | Send a Message)

Description

Amines and amides represent important chemical functional groups for a variety of applications. These groups are especially important in biologically active compounds used in pharmaceuticals and as biological probes. The ability to synthesize an amine or amide by converting a simple C-H bond represents a powerful synthetic tool. Unfortunately, most aminations of C-H bonds require expensive catalysts and are limited in scope. At Georgetown, researchers have made strides to overcome this challenge with novel copper-coordination complexes that mediate catalytic C-H bond amination, amidation and aziridination. This catalyst system demonstrates unusual substrate flexibility; for example, allylic, benzylic, aldehyde and alkyl C-H bonds may undergo activation and amination. Viable amine sources include primary and secondary amines, amides and azides. Furthermore, the amine source does not need a protecting group. Reactions mediated by these copper catalyst systems regularly exceed 90% yield with catalyst loadings as low as 0.05 mol %. This technology provides environmentally friendly syntheses and use of readily available starting materials at significantly lower cost than other systems, such as rhodium-based catalyst systems.

Applications

  • Amination and amidation of allylic, benzylic aldehyde and alkyl C-H bonds with amines, organoazides and amides
  • Aziridination of alkenes with organoazides

Advantages

  • Environmentally friendly syntheses, which are atom economical and
  • Lower cost compared to existing ruthenium and rhodium-based catalysts
  • Use of copper in catalyst is favorable for its ready availability, and acceptable reactivity with a wide range of olefins and diazo compounds.
  • Can be conducted in aerobic environment.
  • Can be extended to use stereoselective C-H bond aminations and olefin aziridinations.

Stage of Development

Proof of concept studies completed.

Relevant Publications

Badiei, Y.M.; Dinescu, A.; Dai, X.; Palomino, R.M.; Heinemann, F.W.; Cundari, T.R.; Warren, T.H. “Copper-Nitrene Complexes in Catalytic C-H Amination.” Angewandte Chemie Intl. Ed. 2008, 47 (51), Pages: 9961-9964. *Selected as a Hot Paper by reviewers.

INVENTOR

Timothy H. Warren

Patent Status

U.S. Patent No. 8,895,781