Mechanistic insight into ruthenium catalysed meta-sulfonation of 2-phenylpyridine

Abstract

The catalytic meta-functionalization of arenes has emerged as important synthetic methodology in the last decade. We report herein structural and mechanistic studies of the meta-sulfonation of phenylpyridine using ruthenium complexes.Furthermore, we disclose that the catalytically active species does not require the presence of a   -arene ligand.Furthermore, the novel cycloruthenated phenylpyridine complex tosylated at the para position to the metal has been isolated and fully characterised. Protodemetallation studies suggest that a concerted C-H activation-demetallation process may be involved. Overall, this study provides fundamental insight into the meta-sulfonation phenylpyridine reaction pathway and uncovers new reaction intermediates that will guide the design of new catalytic systems for remote metafunctionalization.

Access to the meta position of arenes through transition metal catalysed C–H bond functionalisation: a focus on metals other than palladium

“…Following these reports which strongly implicated a radicaltype mechanism, the Frost group published a detailed mechanistic study of their pioneering meta-selective sulfonation in which they had originally hypothesised an SEAr-type mechanism. 86 Importantly, for the first time, they were able to isolate and fully characterise the meta-tosylated ruthenium complex VI (Scheme 8a) and show that it is catalytically active (Scheme 8b), proving the long hypothesised pathway of the reaction via activation para to the ruthenium. Their study also provided strong evidence, in line with other studies, that the C-S bond formation occurs via a radical mechanism as well as further insight into the protodemetalation step of the mechanism.…”

A computational study on the identity of the active catalyst structure for Ru(ii) carboxylate assisted C–H activation in acetonitrile

“…Explicit modelling of solvent molecules in computational studies is rarely considered, as it can exponentially complicate an already complex reaction surface. Knowing that experimentally arene loss is a likely process, 8,9 alternative coordination options at the metal centre should be explored. Hence, for the remainder of this study direct acetonitrile coordination at Ru is modelled.…”

“…Therefore, not only has evidence of free arene been observed by researchers in NMR spectra, but further confirmation has been provided by the isolation of crystal structures with no coordinated arene, but acetonitrile solvent molecules instead. From Frost in 2016, 9 the six coordinate Ru crystal structure of [Ru(a-m-SO 2 C 6 H 4 -p-Me)(NCMe) 4 ] was published, and in 2018, 12 Larrosa isolated [Ru(a-4,5,10,11-Me-9,12-F) 2 (NCMe) 2 ], also a six-coordinate structure.…”

Ruthenium‐Mediated Distal C−H Activation

“…His revision to the radical pathway gave much deeper insight into each catalytic step, and isolation of the catalytically active meta ‐tosylated ruthenium compound provided evidence for preferential selectivity to the para position of the Ru Ar −C bond. Also, experiments involving the use of TEMPO as a radical scavenger resulted in diminished efficacy of the reaction, which led the authors to opine that the reaction proceeds through the formation of a tosyl radical …”

“…Also, experiments involving the use of TEMPO as ar adicals cavenger resulted in diminished efficacy of the reaction, which led the authors to opine that the reactionp roceeds through the formationo fat osyl radical. [20] Scheme6.Ruthenium-catalyzed meta-bromination. DMA = dimethylacetamide.…”