Cyanide Anions as Nucleophilic Catalysts in Organic Synthesis

Abstract The nucleophilic addition of a cyanide anion to a carbonyl group is the basis for several cyanide-catalyzed organic reactions, which are summarized in this review. Since cyanide is also a good leaving group, it is an excellent catalyst for transacylation reactions. As an electron-withdrawing group, it also stabilizes a negative charge in its α-position, thus allowing the umpolung of aldehydes to formyl anion equivalents. The two leading examples are the benzoin condensation and the Michael–Stetter reaction furnishing α-hydroxy ketones and 1,4-dicarbonyl compounds, which are both catalyzed by cyanides. The review also covers variants like the silyl-benzoin coupling, the aldimine coupling and the imino-Stetter reaction. Moreover, some cyanide-catalyzed heterocyclic syntheses are reviewed. 1 Introduction 2 Nucleophilic Additions 2.1 Cyanohydrin Formation 2.2 Corey–Gilman–Ganem and Related Oxidation Reactions 2.3 Conjugate Addition 2.4 Intramolecular Carbocyanation 3 Transacylation Reactions 3.1 Ester Hydrolysis and Transesterification 3.2 Formation of Amides 3.3 Ketones from Esters 3.4 Esters from Ketones 4 Transformations Involving an Umpolung 4.1 Benzoin Condensation 4.2 Aldimine Coupling 4.3 Michael–Stetter Reaction 4.4 Imino-Stetter Reaction 5 Formation of Heterocycles 5.1 Oxazolines from Isocyanoacetates 5.2 Imidazoles from TosMIC via Oxazolines 5.3 Bargellini Reaction 6 Conclusion