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Arylacetonitriles are versatile building blocks for the construction of heterocyclic scaffolds in medicinal chemistry. These intermediates are able to engage in a variety of synthetic transformations, giving rise to diverse biologically active structures. This digest focuses on recent applications of this synthetic methodology by drug discovery teams across several disease areas, with an emphasis on different reaction types. [ABSTRACT FROM AUTHOR]

A two-stepprotocol has been developed for the introduction ofcyanomethylene groups to metalated aromatics through the intermediacyof substituted isoxazoles. Apalladium-mediated cross-coupling reaction was used to introduce theisoxazole unit, followed by release of the cyanomethylene functionunder thermal or microwave-assisted conditions. The intermediate isoxazoleswere shown to be amenable to further functionalization prior to deprotectionof the sensitive cyanomethylene motif, allowing access to a wide rangeof aryl- and heteroaryl-substituted acetonitrile building blocks. [ABSTRACT FROM AUTHOR]