The meta-carboxylation of arenes containing pyridine and other azine-directing groups is reported. Using carbon tetrabromide as the C1 source, ruthenium(III) trichloride catalysis enables functionalization of the arene meta-C-H position, affording carboxy methyl ester products after in situ reaction with methanol.

A range or electron-poor and heterocyclic sulfonamides react with phenylacetyl chlorides to produce benzhydryl derivatives in a single step. The reaction proceeds via tandem amide bond formation -Dohmori-Smiles rearrangement under simple conditions of aqueous base. In the case of o-nosylamides further reaction takes place at the nitro group to yield indazoles. Aryl and heteroaryl structures are fundamental to natural products and man-made molecules, and are frequently synthesized using stoichiometric organometallics and precious transition metal catalysts. These methods, while effective and hugely influential, are costly and environmentally unsustainable, making metal-free arylation methods 1 a key objective for future strategies in synthetic chemistry. We are interested in harnessing simple aryl sulfonamides as metal-free arylating agents in this regard, through the process set out in Scheme 1. The nitrogen atom acts as a nucleophilic trap for an electrophilic coupling partner, a benzyne in this example, generating an incipient carbanion (3) that triggers a 1,5-desulfonylative Smiles rearrangement. 2,3,4 Overall, the process repositions a cheap and readily available building block as both an arylating and aminating agent, critical transformations in the pharmaceutical industry, whilst proceeding without recourse to metal reagents.

Stilbenes are important and useful structural moieties, but methods for their preparation typically possess numerous inefficiencies. Presented here is a methodology for the two‐step, one pot preparation of unsymmetrical stilbenes via sequential Heck reactions. The first Heck reaction with ethylene gas was analysed as a function of temperature and pressure for electronically differentiated naphthyl bromides and model‐aided reaction optimization was utilized to define the system. In addition, reactNMR was utilized to determine ethylene solubility in common organic solvents useful for Heck reactions. Finally, an optimized sequential Heck reaction process was developed and applied to a range of substrates allowing for efficient preparation of unsymmetrical stilbenes, including the natural antioxidant, pterostilbene.magnified image

A practical method for the regiocontrolled synthesis of substituted quinoline-4-carboxylic acids is described. Solubility differences between the product quinoline regioisomers enable their facile separation, thus avoiding any challenging chromatographic purifications and allowing access to highly substituted quinoline compounds in three steps from commercially available anilines.

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