Enol phosphates Perkow reaction

Ethyl 2-bromoacetoacetate reacts with triethyl phosphite to give a mixture of diethyl l-(ethox-ycarbonyl)-2-oxopropylphosphonate (29%, Michaelis-Arbuzov product) aud diethyl l-methyl-2-(ethoxycarbonyl)vinyl phosphate (31%, Perkow product). By contrast, the reaction of diethyl bromomalonate with trialkyl phosphites takes only one course, and the products formed at either temperature are the enol phosphates (Perkow product) ... 

Protocol 2 produces the protected fi-formylphosphonate 12 f)-ketophospho-nates may also be synthesized by other methods,23 however, they may not be prepared in unprotected form by the Michaelis-Arbuzov reaction because the Perkow reaction, in which an a-haloaldehyde or ketone and a trialkyl phosphite yield an enol phosphate (e.g. 13, Scheme 5,24 i.e. [P—O] bond formation), competes and frequently dominates (see Section 4). Conversely halocarboxylic acid derivatives (e.g. see Table 7.1, entry 3) and acyl halides (see Protocol 3) react well in the Michaelis-Arbuzov reaction to yield useful functionalized phosphonates. fi-Ketophosphonates are useful reagents for the synthesis of a,fi-unsaturated carbonyl compounds by the Horner-Wadsworth-Emmons reaction,3,4 25 and have other applications.23... 

In the Perkow reaction, a trialkyl phosphite reacts with an a-halo-aldehyde or -ketone to yield an enol phosphate (i.e. [P—O] bond formation, e.g. Scheme 5).76 a-Haloaldehydes react cleanly but with a-haloketones the Michaelis-Arbuzov reaction usually competes with the product distribution depending on the reaction... 

Enol phosphates may be reduced to alkenes,79 eliminated to alkynes,80,81 employed as synthetic intermediates in organophosphorus chemistry and are useful in their own right, for example, as insecticides. For reviews covering enol phosphates and the Perkow reaction, see Refs 17, 82, and 83. 

Perkow reaction. Formation of enol phosphates on treatment of a-halocarbonyl compounds with trialkyl phosphites. 

As might be expected, keto-sugar acetates undergo the Perkow reaction with trimethyl phosphite to give a mixture of enol phosphates (27) and (28). In other cases the products appear to be dependent on the leaving group, and the Perkow products... 

Lichtenthaler, F.W., The chemistry and properties of enol phosphates, Chem. Rev., 61, 607, 1961. 1964 Arbuzov, B.A., Michaelis-Arbuzov and Perkow reactions. Pure Appl. Chem., 9, 307, 1964. 

Enol phosphates (332) have also been obtained reductive debromination of the 2a-bromo-3-ketone with triethyl phosphite (Perkow reaction) gave the... 

The Perkow reaction has been used to generate a wide range of vinyl phosphates. Reaction of trialkyl phosphites with a-halogeno-ketones provide vinyl phosphates.1-5 Alkenes are produced via reduction of the dialkyl enol phosphate using either sodium or lithium in liquid ammonia. 

Tris(trimethylsilyl)phosphites, analogous to trialkylphosphites, undergo Perkow reaction with a-halo carbonyl compounds to give vinyl phosphates.223 Reaction of a-chloroketone 19 with trimethylphosphite produces dimethyl enol phosphate 20, which is further converted to b is [trimethyls ilyl] esters 21 using MeaSiBr. 21 is also produced directly from a-chloroketone 19 on reacting with P(SiMe3)3. 

Enol adenosine 5 -phosphate derivatives (28, 29, 30) are formed by the Perkow reaction of a-chloromethyl ketone with an in situ-generated adenosine-5 -yl bis(trimethylsilyl)phosphite (27). Among these reactions, the use of a-chloro-2, 4 -difluoroacetophenone gave predominantly the enol phosphate derivative over the Arbuzov reaction product and the carbonyl adduct, which were formed as by-products.25... 

Diethyl enol phosphate 47 rearranges to p-ketophosphonates 49 upon treatment with LDA.34 This reaction probably proceeds via cleavage with LDA to give an enolate phosphonium ion pair 48 which then interacts to give the anion under equilibrium conditions.34 The reaction mixture is quenched with acetic acid. The enol phosphate 47 is prepared by Perkow reactions from the corresponding a-halocyclohexanone.34... 

While a wide variety of alkyl halides have been employed successfully in the Michaelis-Arbuzov reaction, in certain instances the reaction may follow an abnormal course. The major example is the Perkow reaction (cf. Section III), which occurs with certain a-halo carbonyl compounds, and which has achieved commercial importance as a route to the biologically active enol phosphate esters [e.g., the insecticide Phosdrin (MeO)2-P(0)C(CH3)=CHC02Mel. 

Confirmation of Perkow s discovery came rapidly from other laboratories and the scope of the reaction was extended to a-halo ketones and in some cases a-halo esters. As a route to the important and otherwise difficultly accessible enol phosphate esters, this reaction has been investigated extensively and is the subject of a comprehensive review (210). 

J 2-Steroids. A soln. of crude startg. enol phosphate, obtained by Perkow reaction (s. Synth. Meth. 12, 167), in dry ter -butanol-tetrahydrofuran added dropwise to a soln. of Li in liq. NHg j2.androsten-17/ -ol. Y 85%. F. e. and limitation s. M. Fetizon, M. Jurion, and N. TrongAnh, Chem. Commun. 1969, 112. 

In the Perkow reaction, [8] a trialkyl phosphite combines with a halo carbonyl compound to give an enol phosphate ester and an alkyl halide. 

Without additional reagents Perkow reaction Enol phosphates from [Pg.343]

The preparation of carbohydrate enol phosphates, using the Perkow reaction, and of uridine 2, 3 -(adamant-l-yI)phosphonates are dealt with in Chapters 18 and 21, respectively. 

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