Perkow reaction

The Perkow reaction is an organic reaction in which a trialkyl phosphite ester reacts with a haloketone to form a dialkyl vinyl phosphate and an alkyl halide.Ref|Perkow

In the related Michaelis-Arbuzov reaction the same reactants are known to form a beta-keto phosphonate which is an important reagent in the Horner-Wadsworth-Emmons reaction on the road to alkenes. The Perkow reaction, in this respect is considered a side-reaction.

Reaction mechanism

The reaction mechanism of the Perkow reaction consists of a nucleophilic displacement of the α-halogen atom by the phosphorus nucleophile. The phosphite ester salt is subject to keto-enol tautomerism and if the enol isomer is predominant the Perkow adduct is formed otherwise the keto form results in the Michaelis-Arbuzov adduct. The second step of the reaction is a second nucleophilic displacement of the halide anion on one of the phosphite alkoxide substituents forming an enol phosphonium oxide.

Scope

The Perkow reaction has been applied in the synthesis of a novel insect repellentRef|Baldur based on hexachloroacetone and triethylphosphite which is able to engage in a secondary [4+3] cycloaddition with furane through the action of the very strong base sodium 2,2,2-trifluoroethoxide. The authors report mediocre yields but are undeterred.

The Perkow reaction is also used in the synthesis of novel quinolines.Ref|Paleta When the substituent is n-butyl the reaction product is the classical Perkow adduct. In this reaction the leaving group is an electron deficient acyl group (owing to the presence of three fluorine groups). When the substituent on the other hand is phenyl (not shown) the phospite has a preference for reaction with the acyl group leading to an ethyl enol ether. Key in explaining the difference in reactivity is the electron density on the α-keto carbon atom.

Aryl enol phosphates formed in good yields (ca. 90%) in the Perkow reaction can be used as phosphorylating reagents, e.g. able to transform AMP into ATP.Ref|Sekine

References

# Perkow, W. Chemische Berichte 1954, 87, 755–758
# "Hexachloroacetone as a Precursor for a Tetrachloro-substituted Oxyallyl Intermediate: [4+3] Cycloaddition to Cyclic 1,3-Dienes" Baldur Föhlisch and Stefan Reiner Molecules 2004, 9, 1-10 [http://www.mdpi.org/molecules/papers/90100001.pdf Online Article]
# "New Modification of the Perkow Reaction: Halocarboxylate Anions as Leaving Groups in 3-Acyloxyquinoline-2,4(1H,3H)-dione Compounds" Oldrich Paleta, Karel Pomeisl, Stanislav Kafka, Antonin Klasek, Vladislav Kubelka Beilstein Journal of Organic Chemistry 2005 [http://bjoc.beilstein-journals.org/content/pdf/1860-5397-1-17.pdf Online Article]
# T. Moriguchi, K. Okada, K. Seio, and M. Sekine. "Synthesis and Stability of 1-Phenylethenyl Phosphate Derivatives and their Phosphoryl Transfer Activity", "Letters in Organic Chemistry", 1 (2):140-144, 2004