Two-Step Cyanomethylation Protocol: Convenient Access to Functionalized Aryl- and Heteroarylacetonitriles

Figure

Two-Step Cyanomethylation Protocol: Convenient Access to Functionalized Aryl- and Heteroarylacetonitriles

Publication Date (Web): January 15, 2015 (Letter)
DOI: 10.1021/ol503479g

http://pubs.acs.org/doi/abs/10.1021/ol503479g

 

A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.

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