The Catalyzed Nucleophilic Addition of Aldehydes to Electrophilic Double Bonds

Stetter, Hermann; Kuhlmann, Heinrich


The cyanide-ion-catalyzed dimerization of aromatic and heterocyclic aldehydes to α-hydroxy ketones, also known as the benzoin condensation, is one of the oldest reactions in organic chemistry. A key intermediate in this reversible reaction is a nitrile-stabilized carbanion. In 1973 it was shown that these carbanions add irreversibly to α,β-unsaturated ketones, esters, and nitriles to give 1,4-diketones, 4-ketocarboxylic esters, and 4-ketocarbonitriles, respectively. The reaction succeeds only in aprotic solvents, preferably dimethylformamide. Benzoins and aldehydes can be used interchangeably as starting materials since they are in rapid equilibrium. Cyanide ion catalysis fails with aliphatic aldehydes because they resinify under the strongly basic conditions. Vitamin B1 (thiamine) has long been known to convert aliphatic aldehydes into acyloins in buffered aqueous solution. The catalytic effect of vitamin B1 is due to the presence of a thiazolium cation. Thiazolium salts in general as well as other azolium salts also catalyze the formation of acyloins. The optimum conditions for thiazolium salt catalysis have been worked out. It was shown subsequently that thiazolium salts, in combination with bases, also catalyze the addition of aliphatic, aromatic, and heterocyclic aldehydes to α,β-unsaturated carbonyl compounds. The 1,4-diketones, 4-ketocarboxylic esters, and 4-ketocarbonitriles are usually formed in good to excellent yields. Cyanide ion and thiazolium salt catalysis thus complement each other.

This chapter covers the literature of the catalyzed nucleophilic addition of aldehydes to electrophilic double bonds up to 1988. The reaction has been reviewed previously.