Wolff–Kishner reduction
| Wolff-Kishner reduction | |
|---|---|
| Named after |
Ludwig Wolff Nikolai Kischner |
| Reaction type | Organic redox reaction |
| Identifiers | |
| Organic Chemistry Portal | wolff-kishner-reduction |
| RSC ontology ID | RXNO:0000226 |
The Wolff–Kishner reduction is a reaction used in organic chemistry to convert carbonyl functionalities into methylene groups. In the context of complex molecule synthesis, it is most frequently employed to remove a carbonyl group after it has served its synthetic purpose of activating an intermediate in a preceding step. As such, there is no obvious retron for this reaction. Originally reported by Nikolai Kischner in 1911 and Ludwig Wolff in 1912, it has been applied to the total synthesis of scopadulcic acid B, aspidospermidine and dysidiolide.
In general, the reaction mechanism first involves the in situ generation of a hydrazone by condensation of hydrazine with the ketone or aldehyde substrate. Sometimes it is however advantageous to use a pre-formed hydrazone as substrate (see modifications). The hydrazone is deprotonated by alkoxide base followed by a concerted, rate-determining step in which a diimide anion is formed. Collapse of this alkyldiimide with loss of N2 leads to formation of an alkylanion which can be protonated by solvent to give the desired product.
Because the Wolff–Kishner reduction requires highly basic conditions, it is unsuitable for base-sensitive substrates. However, this method can be superior over the related Clemmensen reduction for acid-sensitive compounds such as pyrroles and for high-molecular weight compounds.
The Wolff–Kishner reduction was discovered independently by N. Kishner in 1911 and L. Wolff in 1912. Kishner found that addition of pre-formed hydrazone to hot potassium hydroxide containing crushed platinized porous plate led to formation of the corresponding hydrocarbon. A review titled “Disability, Despotism, Deoxygenation—From Exile to Academy Member: Nikolai Matveevich Kizhner” describing the life and work of Kishner was published in 2013.
Wolff later accomplished the same result by heating an ethanol solution of semicarbazones or hydrazones in a sealed tube to 180 °C in the presence of sodium ethoxide.
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