Metal-Free Intramolecular Carbocyanation of Activated Alkenes: Functionalized Nitriles Bearing β-Quaternary Carbon Centers

摘要

Nitriles constitute one of the most important classes of organic compounds in both academic and industrial laboratories, and are found in a number of pharmaceuticals, agrochemicals, and materials. Furthermore, they can serve as synthetic scaffolds to a diverse array of building blocks such as aldehydes, ketones, amides, carboxylic acids, and amines. Because of their great importance in chemistry and biology, the development of novel and efficient synthetic methods for nitriles has been a major topic in synthetic organic chemistry. As a straightforward and atom-economical strategy to access functionalized nitriles, the cyanofunctionalization reactions of alkenes and alkynes have thus gained much interest. Among them, the metal-catalyzed intramolecular carbocyanation reactions of alkenes have received considerable attention, because they address challenging issues such as generating all-carbon quaternary centers and the efficiency of C—C bond formation in synthetic organic chemistry. Although significant achievements have been made over the years, this type of transformation has been confined to a fixed mode involving an initial metal-catalyzed cleavage of FG—CN bonds (FG = functional group having a C(sp~2) center) under harsh reaction conditions and subsequent addition of both FG and CN groups to an electron-rich C=C bond, having limited functional-group compatibility, thus providing cyclic compounds (Schemela). An alternative approach involving a different activation mode, and delivers complex and densely functionalized nitriles by adding cyano as well as other functional groups across a C=C bond simultaneously is rare, despite the fact that nonmetal-catalyzed cyanofunctionalization reactions of carbonyl compounds and imines have been studied extensively in recent years. In addition, although a range of metal-catalyzed intramolecular carbocyanation reactions have been developed, intramolecular alkenylcya-nation of alkenes has never been achieved. In this context, the exploration of a conceptually novel intramolecular carbocyanation, having an alternative synthetic pathway, to access a number of structurally diverse functionalized cyano-con- taining building blocks with improved functional group compatibility is needed.