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 of the Stetter Reaction
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.
NHC-Catalyzed Dual Stetter Reaction: A Mild Cascade Annulation for the Syntheses of Naphthoquinones, Isoflavanones, and Sugar-Based Chiral Analogues
R. N. Mitra, K. Show, D. Barman, S. Sarkar, D. K. Maiti, J. Org. Chem., 2019, 84, 42-52.
Synthesis of 2-Aryl Naphthoquinones by the Cross-Dehydrogenative Coupling Involving an NHC-Catalyzed endo-Stetter Reaction
A. Ghosh, A. Patra, S. Mukherjee, A. T. Biju, J. Org. Chem., 2019, 84, 1103-1110.