Corey-Kwiatkowski reaction

What is Corey-Kwiatkowski reaction?

The Corey-Kwiatkowski reaction, which involves the preparation of olefins by reacting aldehydes or ketones with lithium alkylphosphonamides, followed by the decomposition of β-hydroxyphosphonamide intermediates in refluxing benzene or toluene, was first reported by Corey and Kwiatkowski in 1966.

Corey-Kwiatkowski reaction - general reaction scheme
Corey-Kwiatkowski reaction (general reaction scheme)

The direct addition product, i.e., the lithio derivative, is quite stable even at 0 ºC in THF under nitrogen. Hydroxyphosphonamides from ketones tend to decompose faster than those from aldehydes, and those with α-substituents decompose even faster. This method is useful for a wide range of olefins, including mono-, di-, tri-, and tetra-substituted olefins.

Compared to the Wittig Reaction, the Corey-Kwiatkowski reaction offers several advantages, including the absence of triphenylphosphine oxide, which can complicate the isolation of the olefin; the possibility of purifying at the β-hydroxyphosphonamide stage; relatively easy control of the olefin stereochemistry to form either cis- or trans-olefins; and the availability and potential low cost of the phosphonamides, which can be prepared from phosphonyl dichlorides and dimethylamine or cyclic diamines. Phosphonyl dichloride can be synthesized by alkylation of phosphorus trichloride with alkyl chloride and AlCl3.

Furthermore, the alkyl phosphonamides can be substituted with alkyl phosphonothiates, where the formed β-hydroxyphosphonothiate can decompose at low temperature, such as room temperature, and silver salt can be used as a catalyst. The lithio derivatives of both phosphonamides and phosphonothiates can be derivatized via alkylation with alkyl halides. The reaction between lithium phosphonamide or phosphonate and an ester to give β-keto phosphonamide or phosphonate is called the Corey-Kwiatkowski condensation.

References

The Synthesis of Olefins from Carbonyl Compounds and Phosphonic Acid Bisamides
E. J. Corey and George T. Kwiatkowski
Journal of the American Chemical Society 1966 88 (23), 5652-5653
DOI: 10.1021/ja00975a055

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