Synthesis ofα-Aryl Nitriles through Palladium-Catalyzed Decarboxylative Coupling of Cyanoacetate Salts with Aryl Halides and Inflates

摘要

α-Aryl nitriles are versatile intermediates for the synthesis of carboxylic acids, amides, primary amines, aldehydes, and heterocycles. They can also have biological activity as exemplified by medicinal compounds such as anastrozole. Traditional methods for the synthesis of α-aryl nitriles include cyanation of benzylic halides or alcohols, Friedel-Crafts reactions, and dehydration of α-aryl amides. Recently, the groups of Hartwig and Verkade developed new methods that involve palladium-catalyzed α-arylation of nitriles (and also 2-cyanoacetate esters) with aryl chlorides and bromides. The requirement of a strong base (e.g., NaN(SiMe3)2) in these palladium-catalyzed α-arylation reactions limits the functional group tolerance, and monoarylation is difficult to achieve for acetonitrile and primary nitriles. To solve these two problems, Hartwig et al. described improved methods that use relatively expensive α-silyl nitriles and zinc cya-noalkyl reagents to couple with aryl bromides (but not chlorides).1 Herein we report a new synthetic strategy for α-monoarylated nitriles through palladium-catalyzed decarboxylative coupling of aryl bromides, chlorides, and even triflates with readily accessible cyanoacetate salts. This new reaction expands the scope and synthetic utility of the catalytic decarboxylative coupling reactions previously developed by the groups of Myers, Forgione, Goossen, and others. This work also shows that for some synthetic purposes the decarboxylative coupling not only provides a conceptually alternative method, but also can be practically favored in terms of both reagent accessibility and reaction scope.