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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 Introduction2 Nucleophilic Additions2.1 Cyanohydrin Formation2.2 Corey–Gilman–Ganem and Related Oxidation Reactions2.3 Conjugate Addition2.4 Intramolecular Carbocyanation3 Transacylation Reactions3.1 Ester Hydrolysis and Transesterification3.2 Formation of Amides3.3 Ketones from Esters3.4 Esters from Ketones4 Transformations Involving an Umpolung4.1 Benzoin Condensation4.2 Aldimine Coupling4.3 Michael–Stetter Reaction4.4 Imino-Stetter Reaction5 Formation of Heterocycles5.1 Oxazolines from Isocyanoacetates5.2 Imidazoles from TosMIC via Oxazolines5.3 Bargellini Reaction6 Conclusion

4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted thiophenes, furans, pyrrols, and piperazines. Key steps are an addition–elimination reaction to ETFBO followed by the thiazolium-catalyzed Stetter reaction. The scope of this chemistry was demonstrated in a new synthetic approach towards the COX-2 selective, nonsteroidal anti-inflammatory drug Celebrex® (celecoxib).

Highly concise total syntheses of paullone and kenpaullone were developed. Cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines derived from methyl 2-aminocinnamate derivatives and 2-nitrobenzaldehyde provided 2-(2′-nitrophenyl)indole-3-acetic acid derivatives. Subsequent reduction of the nitro group with zinc under acidic conditions to an amino group followed by spontaneous lactam formation allowed for the total syntheses of paullone and kenpaullone to be completed in two steps starting from commercially available materials. The direct use of a nitro group as the precursor of an amino group present in the phenyl ring at the 2-position in the indole ring significantly streamlined the total syntheses of these target molecules.

N-Heterocyclic carbene catalysis allows the rapid formation of functionalized carbon–carbon bonds. Our group has spent the previous decade focusing on broadening practical applications of this type of catalysis. The design and discovery of novel reactivities and catalysts in our group can best be divided into work focusing on the Stetter, ring-expansion, and cross-benzoin reactions. Along with our expansion of the reaction scope, our introduction of novel bis(amino)cyclopropenylidene catalysts for the Stetter reaction successfully suppresses formation of side products, increasing synthetic utility. Concurrent work on ring-expansion reactions allows access to functionalized lactones and lactams. In addition to expanding the scope of the cross-benzoin reaction through use of α-ketoesters and α-amino aldehydes, the introduction of a new triazolylidene catalyst has allowed access to general chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. 1 Introduction 2 Stetter Reactions 2.1 Domino Stetter Reactions 3 Ring-Expansion Reactions 4 Cross-Benzoin Reactions 5 Summary and Outlook

The use of multiple catalytic systems for cascade reactions has found widespread application in recent years. The combination of two important organocatalysts, chiral amines and N-heterocyclic carbenes (NHCs), is of extraordinary interest since they can both potentially mediate a variety of reactions with aldehyde derivatives. In this short review, we discuss the successful combination of asymmetric aminocatalysis and carbene catalysis in the efficient construction of complex chiral architectures, either in a relay or sequential manner. 1 Introduction 2 NHC-Catalyzed Redox Reaction Combined with Aminocatalysis 3 NHC-Catalyzed Benzoin Condensation Combined with Aminocatalysis 4 NHC-Catalyzed Stetter reaction Combined with Aminocatalysis 5 Miscellaneous NHC Catalysis Combined with Aminocatalysis 6 Summary

Recent developments in the N-heterocyclic carbene (NHC)-catalyzed umpolung of aldehydes followed by their interception with activated carbon–carbon double bonds, namely the Stetter reaction, are presented. Advances in the inter- and intramolecular versions of this reaction, enantioselective transformations as well as the use of unactivated olefins in this type of reaction are discussed. 1 Introduction 2 Proposed Mechanism of the Stetter Reaction 3 Intramolecular Stetter Reactions 4 Intermolecular Stetter Reactions 5 Hydroacylation Reactions 6 Applications in Total Synthesis 7 Conclusion

This article describes a number of catalytic methods for enantioselectively desymmetrizing prochiral dienone systems. The core structures obtained using these methodologies appear in several bioactive natural products, and the processes appear to be effective tools for producing key intermediates in the synthesis of complex structures. 1 Introduction 2 Covalent Organocatalyzed Desymmetrizations 2.1 Formation of Chiral Enamines 2.2 The Stetter Reaction 2.3 Other Covalent Desymmetrizations 3 Noncovalent Organocatalyzed Desymmetrizations 4 Transition Metals 5 Cycloadditions 6 Conclusion

N-Heterocyclic carbene catalyzed desymmetrization of cyclohexadienones to construct tricyclic carbocycles via an intramolecular enantioselective Stetter reaction was realized. With 10 mol% of D-camphor-derived triazolium salt E and 10 mol% of KOAc, variou

Two exocyclic and endocyclic olefin tautomers of chromone phosphonates were obtained in good to excellent yields at different temperatures by utilizing an N-heterocyclic carbene catalyst in the intramolecular reactions between the formyl group and alkynylphosphonates. The exocyclic olefins can isomerize to the endocyclic derivatives completely when treated with a thiazolium salt precatalyst and potassium carbonate at 30 °C for three to five hours. In addition, the chromone phosphonate derivatives were also applied in the one-pot synthesis of benzopyranopyridine phosphonates in moderated yields.

The synthesis of spiro bis-indanes by means of N-heterocyclic carbene (NHC) catalysis is reported. The dimerization of various o-formylchalcone substrates or their combination with phthaldialdehyde derivatives under the catalysis of thiazolium-derived carbenes afforded Stetter-aldol-Michael products and Stetter-aldol-aldol products, respectively. The use of poor Michael acceptors in conjunction with an N-alkyltriazolium-derived catalyst furnished a variety of dibenzo[8]annulene products. This work highlights the interplay of a variety of factors affecting competing pathways in NHC-catalyzed domino reactions.

An efficient method for the synthesis of 4,5-disubstituted 2-aminofuran-3-carbonitriles via a cascade Stetter―γ-ketonitrile cyclization reaction of aromatic aldehydes with acylidenemalononitriles, catalyzed by N-heterocyclic carbenes, has been developed. This procedure provides the corresponding products in moderate to high yields under mild conditions.

The diastereoselective synthesis of 2,2-disubstituted-3-hydroxy-indanones was realized by the N-heterocyclic carbene catalyzed [4+1] annulation of phthalaldehyde and 1,2-diactivated Michael acceptors, which involves a tandem process of Stetter reaction, proton shift, and aldol reaction.

The first synthesis of alkylthiazolium-based ionic liquids under 'green chemistry' conditions is described. Thiazolium salts and triethylamine have been found to catalyze efficiently the intramolecular Stetter reaction, giving excellent yields within very short reaction times using solvent-free microwave activation conditions.

The use of a commercially available thiazolium salt facilitatedan intramolecular Stetter reaction between an aliphatic aldehydeand an acrylate unit, which delivered a TRANS, SYN-fused bicyclic pyranone in high yieldas a single diastereomer. The pyranone was used to synthesize a TRANS, SYN, TRANS-fused polycyclic ether array andwas ring expanded to give the corresponding oxepanone.

The asymmetric Michael addition of aromatic heterocyclic aldehydes to arylidenemalonates catalyzed by N-heterocyclic carbenes is described. The ketomalonates are obtained in 84-98% yields and moderate to good enantioselectivities (30-78% ee). The enantiomeric excesses could be improved to excellent levels of up to 99% ee after a single recrystallization.

The effect of different Michael acceptors was evaluated in the catalytic asymmetric intramolecular Stetter reaction. Utilizing a readily prepared chiral triazolium salt as a nucleophilic carbene precursor, the reactivity and selectivity of substrates containing different electron-deficient double bonds was shown to vary significantly under identical reaction conditions.