Addition and Substitution Reactions of Nitrile-Stabilized Carbanions

Arseniyadis, Siméon; Kyler, Keith S.; Watt, David S.


The utilization of carbanions stabilized by various electron-withdrawing groups to effect carboncarbon bond formation occupies a central position in organic synthesis. This chapter focuses on the reactions of nitrile-stabilized carbanions with an array of carbon electrophiles and updates another chapter along these lines in this series. Subsequent review articles have dealt with various aspects of the chemistry of nitrile-stabilized carbanions. In this review, the reactions of nitrile-stabilized anions are grouped according to the nature of the substituents attached to the carbanion center bearing the nitrile group. These substituents include alkyl, alkenyl, alkynyl, and aryl groups as well as various α-oriented halogen-, oxygen-, nitrogen-, sulfur-, and selenium-containing groups. Notably absent from this survey are the carbanions derived from active methylene compounds bearing two electron-withdrawing groups such as cyanoacetate esters, malononitriles, α-sulfonylnitriles, and α-phosphorylnitriles. Also absent are those carbanions such as Reissert compounds, which are the subject of comprehensive reviews.

The chapter is arbitrarily subdivided into six sections: (1) reactions of alkyl-, aryl-, and heteroaryl-substituted nitriles; (2) reactions of α,β- and β,γ-unsaturated nitriles as well as tolunitriles; (3) reactions of cyanohydrins and their hydroxyl-protected derivatives; (4) reactions of nitriles bearing α-sulfur and α-selenium substituents; (5) reactions of α-(dialkylamino)nitriles; and (6) reactions of α-halonitriles. Within each of these sections, the reactions are further subdivided according to the nature of the electrophile: (1) alkylation reactions employing alkyl halides, alkyl sulfonates, dialkyl sulfates, and epoxides; (2) arylation reactions involving the substitution of hydrogen, halogen, nitro, or alkoxy groups on aryl or heteroaryl substrates; (3) acylation reactions employing carboxylic esters, anhydrides, acid chlorides, dialkyl carbonates, and nitriles; (4) addition reactions involving aldehydes, ketones, imines, alkenes, and alkynes; and (5) Michael-type addition reactions to unsaturated aldehydes, ketones, imines, sulfoxides, sulfones, and nitro compounds. Finally, a section involving cyclization reactions is included for each of the six groups of nitrile-stabilized anions.