Synthesis of Polysubstituted Benzenes via the Tandem Addition-Rearrangement Aryne Reaction of Substituted 2-Bromoanisoles

Article abstract of DOI:10.1021/jo00256a004

Lithioarenenitriles add regiospecifically to substituted 3-methoxybenzynes generated in situ from the corresponding haloarenes by using lithium diisopropylamide as a base.The addition to methoxybenzynes substituted with an electron-releasing group is followed by rearrangement to substituted 2-cyano-3-(arylmethyl)anisoles.The rearrangement pathway involves cyclization of the initially formed nitrile-aryne adducts to benzocyclobutanone imines which are converted to rearranged products after ring opening and neutralization.In contrast, 3-methoxybenzynes substituted withan electron-attracting group proceed via the usual aryne pathway, yielding products of simple anion addition.Disubstituted 3-methoxybenzynes possessing an electron-releasing group and an electron-attracting substituent yield mixtures of rearranget and typical nitrile products.An explanation in terms of the ability of the substituents to influence the nucleophilicity of the 2-lithio cyclization site of the initially formed nitrile-aryne adducts is presented.