Stetter Reaction

The Stetter Reaction is a 1,4-addition (conjugate addition) of an aldehyde to an a,β-unsaturated compound, catalyzed by cyanide or a thiazolium salt. This reaction competes with the corresponding 1,2-addition, which is the Benzoin Condensation. However, the Benzoin-Condensation is reversible, and since the Stetter Reaction leads to more stable products, the main product will be derived from 1,4-addition.

Some of the possible products are: 1,4-diketones, 4-ketocarboxylic acids and the corresponding nitriles.

Mechanism

The cyanide ion effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation:

This in situ generated nucleophile reacts with the unsaturated compound:

The thiazolium salts may be converted into ylides by deprotonation. These ylides are comparable to the cyanide adducts in their ability to catalyze the Stetter Reaction effectively.

Recent Literature

The First Asymmetric Intramolecular Stetter Reaction
D. Enders, K. Breuer, J. Runsink, Helv. Chim. Acta, 1996, 79, 1899-1902.

A Highly Enantio- and Diastereoselective Catalytic Intramolecular Stetter Reaction
J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc., 2005, 127, 6284-6289.