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

• Type of Material: Article
• Authors: Brandon E. Haines, Emory University; Takahiro Kawakami, Nagoya University; Keiko Kuwata, Nagoya University; Kei Murakami, Nagoya University; Kenichiro Itami, Nagoya University; Djamaladdin Musaev, Emory University
• Language: English
• Date: 2016-10-19
• Publisher: Royal Society of Chemistry: Open Access
• Publication Version: Final Published Version
• Copyright Statement: © The Royal Society of Chemistry 2016 This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1039/C6SC04145K
• Title of Journal or Parent Work: Chemical Science
• ISSN: 2041-6520
• Volume: 8
• Issue: 2
• Start Page: 988
• End Page: 1001
• Grant/Funding Information: 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.
• Research Categories: Biology, Molecular; Chemistry, Biochemistry

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.