Abstract
Although the ruthenium-catalyzed C–H arylation of arenes bearing directing groups with haloarenes is well-known, this process has never been achieved in the absence of directing groups. We report the first example of such a process and show that unexpectedly the reaction only takes place in the presence of catalytic amounts of a benzoic acid. Furthermore, contrary to other transition metals, the arylation site selectivity is governed by both electronic and steric factors. Stoichiometric and NMR mechanistic studies support a catalytic cycle that involves a well-defined η6-arene-ligand-free Ru(II) catalyst. Indeed, upon initial pivalate-assisted C–H activation, the aryl-Ru(II) intermediate generated is able to react with an aryl bromide coupling partner only in the presence of a benzoate additive. In contrast, directing-group-containing substrates (such as 2-phenylpyridine) do not require a benzoate additive. Deuterium labeling and kinetic isotope effect experiments indicate that C–H activation is both reversible and kinetically significant. Computational studies support a concerted metalation–deprotonation (CMD)-type ruthenation mode and shed light on the unusual arylation regioselectivity.
Highlights
The development of new synthesis tools for the production of biologically and industrially relevant compounds fuels the efforts of the chemistry community
Given the reversible nature of the C−H metalation step often observed in ruthenium catalysis,[20,21,24] we decided to attempt the ruthenium-catalyzed D/H scrambling on the nonvolatile perfluorinated arene 1a
We have described the first ruthenium-catalyzed system capable of C−H arylation of arenes without the need for a directing group
Summary
The development of new synthesis tools for the production of biologically and industrially relevant compounds fuels the efforts of the chemistry community In this context, the biaryl motif is ubiquitous among a wide range of compounds, many of them of industrial importance.[1] Transition-metal-catalyzed cross-coupling reactions are the most powerful methods for the construction of the biaryl skeleton.[2] highly effective, this approach requires prefunctionalization of both coupling partners. Transition-metal-catalyzed C−H activation has emerged as a promising route toward the direct functionalization of organic compounds.[3,4] In particular, direct C−H arylation, the coupling of an arene (CAr−H) with an aryl halide (CAr−X), is developing as an atom- and step-economical and environmentally friendly approach to biaryls.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
