Ruthenium‐Catalyzed meta‐Selective CH Bromination

Abstract

The first example of a transition-metal-catalyzed, meta-selective C–H bromination procedure is reported. In the presence of catalytic [{Ru(p-cymene)Cl2}2], tetrabutylammonium tribromide can be used to functionalize the meta C–H bond of 2-phenylpyridine derivatives, thus affording difficult to access products which are highly predisposed to further derivatization. We demonstrate this utility with one-pot bromination/arylation and bromination/alkenylation procedures to deliver meta-arylated and meta-alkenylated products, respectively, in a single step.

Ligand-Promoted Meta-C–H Arylation of Anilines, Phenols, and Heterocycles

“…Meta -functionalization of this class of compounds 4b,5c,6d,e is highly valuable as electrophilic aromatic substitution reactions predominantly afford ortho - and/or para -substituted products due to the electronic effects of the nitrogen atom. Our initial evaluation of aniline substrates focused on finding a reactive and readily removable directing group that would be compatible with the desired catalytic cycle.…”

“…A third and thought provoking strategy using Ru(II) catalysts has recently gained attention and holds significant promise if the substrate scope can be expanded to a wide range of directing groups. 5 This approach hinges on the use of an initial ortho -cycloruthenation which activates the meta -position ( para to the newly formed C-Ru bond) of an aromatic ring to react with electrophiles. 5 The mechanism of this transformation is somewhat unclear, though a radical pathway has recently been proposed.…”

“…5 This approach hinges on the use of an initial ortho -cycloruthenation which activates the meta -position ( para to the newly formed C-Ru bond) of an aromatic ring to react with electrophiles. 5 The mechanism of this transformation is somewhat unclear, though a radical pathway has recently been proposed. 5c Several other approaches towards the meta -C–H functionalization of aromatics have also been demonstrated, though the scope and generality of these approaches remains to be fully explored.…”

“…5 The mechanism of this transformation is somewhat unclear, though a radical pathway has recently been proposed. 5c Several other approaches towards the meta -C–H functionalization of aromatics have also been demonstrated, though the scope and generality of these approaches remains to be fully explored. 6 …”

Ligand Promoted meta-C–H Chlorination of Anilines and Phenols

“…2 The Ru(II) catalyzed meta -C–H functionalization via ortho -cyclometallation and subsequent functionalization at the meta -position is also a promising and elegant approach, though it has only been demonstrated with a small set of substrates thus far. 3 Several other approaches towards the meta -C–H functionalization of aromatics have also been reported, though the generality of these approaches remains to be established. 4 Recently, directed meta -C–H arylation 5 and alkylation 5a,5c has been achieved by using norbornene as a transient mediator.…”