Stetter Reaction is a synthesis of 1,4-diketones and γ-oxo nitriles from aliphatic or aromatic aldehydes and a variety of activated α,β-unsaturated carbonyl compounds, β-unsaturated nitriles in the presence of a nucleophilic catalyst (catalytic amounts of sodium cyanide).
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What does Stetter Reaction explain?
The addition of aliphatic or aromatic aldehydes across activated double bonds in the presence of a nucleophilic catalyst for the synthesis of 1,4-diketones and γ-oxo nitriles is known as the Stetter reaction.
Many activated alkene substrates can be used, and the yields are incredibly high with α,β-unsaturated ketones. Straight-chain aldehydes tend to give higher yields than α-branched aldehydes
The limitation of the Stetter Reaction is that the reaction fails with aromatic aldehydes that have nitro substituents and 2,6-disubstituted aromatic aldehydes because of steric hindrance.
Stetter Reaction Mechanism
Mechanism of Stetter Reaction involve 3 steps as shown bellow :
- Reversible benzoin condensation
- Irreversible addition to the Michael acceptor
- Formation of catalytically active species from thiazolium salts
Asymmetric intramolecular or intermolecular Stetter reaction mechanism is an example of umpolung chemistry because aldehyde is converted from an electrophile to a nucleophile under standard reaction conditions.
Asymmetric Stetter Reaction mechanism involves the rapid, reversible formation of benzoins from aromatic aldehyde substrates; benzoins can be used instead of the aldehydes.
Applications of Stetter Reaction:
- The short synthesis of (±)-trans-sabinene hydrate, an important flavor chemical found in a variety of essential oils
from mint and herbs, was developed by C.C. Galopin
- Synthesis of rac-hirsutic acid C has done by Trost and coworkers by employing a Stetter reaction.
Stetter Reaction Related Reaction :
- Benzoin condensation
- Baylis–Hillman reaction
- Paal-Knorr synthesis
My name is Pradip Sanjay W. I’m an organic chemist originally from Maharashtra, India. I have qualified UGC NET-JRF, GATE in chemical sciences and MH-SET exam for assistant professor. I’m currently pursuing my Ph.D. in organic chemistry at the Indian Institute of Technology Hyderabad, India.