title: Two-step cyanomethylation protocol: convenient access to functionalized aryl- and heteroarylacetonitriles.
abstract: 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.
authors.affiliation: Eli Lilly and Company Limited , Erl Wood Manor, Windlesham, Surrey GU20 6PH, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lindsay-Scott
authors.forename: Aimee
authors.initials: A
authors.lastname: Clarke
authors.forename: Jeffery
authors.initials: J
authors.lastname: Richardson
mesh_terms: D000097:Acetonitriles / Q000138:chemical synthesis* / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D007555:Isoxazoles / Q000737:chemistry*; D008872:Microwaves; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
chemical_list: D000097:Acetonitriles; D001897:Boronic Acids; D007555:Isoxazoles; D010165:Palladium; C032159:acetonitrile