Wolff–Kishner reduction

The Wolff–Kishner reduction is a reaction used in <a href="/facts/Organic_chemistry/djxhxaNg">organic chemistry</a> to convert <a href="/facts/Carbonyl/KJ71bo3X">carbonyl</a> functionalities into <a href="/facts/Methylene_group/sdGv7zMu">methylene groups</a>. 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 <a href="/facts/Retrosynthetic_analysis/PwP65DjN">retron</a> for this reaction. The reaction was reported by <a href="/facts/Nikolai_Kischner/D9gPlzva">Nikolai Kischner</a> in 1911 and <a href="/facts/Ludwig_Wolff/xNY84lLR">Ludwig Wolff</a> in 1912.

In general, the reaction mechanism first involves the in situ generation of a <a href="/facts/Hydrazone/XsIDpYpW">hydrazone</a> by condensation of <a href="/facts/Hydrazine/G7P5ITzU">hydrazine</a> with the ketone or aldehyde substrate. Sometimes it is however advantageous to use a pre-formed hydrazone as substrate (see modifications). The rate determining step of the reaction is de-protonation of the hydrazone by an alkoxide base to form a diimide anion by a concerted, solvent mediated protonation/de-protonation step. 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. In some cases, formation of the required hydrazone will not occur at sterically hindered carbonyl groups, preventing the reaction. However, this method can be superior to the related <a href="/facts/Clemmensen_reduction/h1AT6KU4">Clemmensen reduction</a> for compounds containing acid-sensitive functional groups such as pyrroles and for high-molecular weight compounds.

Wolff–Kishner reduction open-in-new

Wolff–Kishner reduction