Cu-Catalyzed aromatic C–H imidation with N-fluorobenzenesulfonimide: mechanistic details and predictive modelsReport as inadecuate

Cu-Catalyzed aromatic C–H imidation with N-fluorobenzenesulfonimide: mechanistic details and predictive models - Download this document for free, or read online. Document in PDF available to download.

Journal Title:

Chemical Science


Volume 8, Number 2


Royal Society of Chemistry: Open Access | 2016-10-19, Pages 988-1001

Type of Work:

Article | Final Publisher PDF

Abstract: The LCuBr-catalyzed C–H imidation of arenes by N-fluorobenzenesulfonimide NFSI, previously reported by us, utilizes an inexpensive catalyst and is applicable to a broad scope of complex arenes. The computational and experimental study reported here shows that the mechanism of the reaction is comprised of two parts: 1 generation of the active dinuclear CuII–CuII catalyst; and 2 the catalytic cycle for the C–H bond imidation of arenes. Computations show that the LCuIBr complex used in experiments is not an active catalyst. Instead, upon reacting with NFSI it converts to an active dinuclear CuII–CuII catalyst that is detected using HRMS techniques. The catalytic cycle starting from the CuII–CuII dinuclear complex proceeds via a one-electron oxidation of the active catalyst by NFSI to generate an imidyl radical and dinuclear CuII–CuIII intermediate, b turnover-limiting single-electron-transfer SET1 from the arene to the imidyl radical, c fast C–N bond formation with an imidyl anion and an aryl radical cation, d reduction of the CuII–CuIII dinuclear intermediate by the aryl radical to regenerate the active catalyst and produce an aryl-cation intermediate, and e deprotonation and rearomatization of the arene ring to form the imidated product. The calculated KIE for the turnover-limiting SET1 step reproduces its experimentally observed value. A simple predictive tool was developed and experimentally validated to determine the regiochemical outcome for a given substrate. We demonstrated that the pre-reaction LCuX complexes, where X = Cl, Br and I, show a similar reactivity pattern as these complexes convert to the same catalytically active dinuclear CuII–CuII species.

Subjects: Biology, Molecular - Chemistry, Biochemistry - Research Funding: This work was supported by the National Science Foundation under the CCI Center for Selective C–H Functionalization CHE-1205646 for D. G. M., the ERATO program from JST K. I., a Grant-in-Aid from JSPS 15K17821 to K. M., and the Takeda Pharmaceutical Company Award in Synthetic Organic Chemistry, Japan K. M

The authors gratefully acknowledge NSF MRI-R2 grant CHE-0958205 for D. G. M. and the use of the resources of the Cherry Emerson Center for Scientific Computation.

Author: Brandon E. Haines, Takahiro Kawakami, Keiko Kuwata, Kei Murakami, Kenichiro Itami, Djamaladdin Musaev,



Related documents