Ketones Perkow reaction

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... 

The range of suitable participants in the Michaelis-Becker reaction is essentially the same as for the Michaelis-Arbuzov reaction. Halo-aldehyde and -ketone substrates suffer the competing reaction of direct attack at the carbonyl group leading to Perkow reaction products (with a-halocarbonyl compounds) or Pudovik reaction products, which often cyclize (cf. Sections 4 and 6). 

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... 

Dialkyl phosphites and their metal salts seldom undergo the Perkow reaction with a-halo-aldehydes or -ketones but usually yield a-hydroxy- and/or epoxy-phosphonate esters (i.e. Pudovik reaction products, cf. Section 6).78... 

With the presence of more than one halogen atom in the a-position of the halo ketone, the formation of 2-oxoalkylphosphonates becomes more difficult, and the reactions proceed exclusively according to the Perkow reaction. Thus, dichloromethyl, dibromomethyl, and tribromomethyl methyl ketones, in reaction with trialkyl phosphites, lead to the corresponding vinyl phosphates... 

Perkow reaction.1 Perkow2 noted that a-halo aldehydes and ketones react with trialkyl phosphites to give dialkyl vinyl phosphates ... 

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

Not only the a-polyhalogen aldehydes, but also the oc-polyhalogen ketones give the Perkow reaction with trialkyl phosphites, whereby vinyl phosphates are formed containing one chlorine atom less. In the reaction of triethyl phosphite with dichloromethyl-2,4-dichlorophenylketone, 0,0-diethyl-0-[l-(2,4-dichlorophenyl)-... 

Polish research workers prepared several analogues of chlorfenvinphos in order to develop a derivative with similar action but less toxic. The result of this work was 0,0-diethyl-0-[2-bromo-1 -(2,4-dichlorophenyl)vinyl] phosphate (bromfenvin-phos, 72). It is prepared by the Perkow reaction with triethyl phosphite and dibromoethyl-2,4-dichlorophenyl ketone (Fulde et al., 1974 Zwierzak, 1974). 

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. 

Perkow reaction of ketone (16) with P(OEt>3 and P(OEt)Ph2 afforded the vinyl phosphate 17 and vinyl phosphinate 18, respectively.21... 

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... 

Because the Arbuzov reaction can be carried out with an a-bromo ketone or an a-bromo ester (in which case it is called a Perkow reaction), it provides a way to S3uithesize a,/S-unsaturated ketones and esters. 

A number of reports of the 1,4-cycloaddition of phosphites to conjugated dienes and ajS-unsaturated ketones have appeared (see also Chapter 2). a-Allenyl ketones undergo the expected cycloaddition of phosphite or phosphinite to give the phosphoranes (45), and for the chloroketone (46) cycloaddition is preferred to the alternative Perkow reaction. The adduct (47) undergoes exothermic acidic hydrolysis to give a mixture of vinylphosphonates. 

The reaction of a silyl phosphite with an a-haloaldehyde or ketone generally leads to a 1 1 adduct (i.e. addition at the carbonyl carbon atom to yield a silyloxyphosphonate by the Abramov reaction, cf. Section 5). However, both the Perkow and the Michaelis-Arbuzov pathways are significant and frequently dominate, the outcome depending on the nature of the reactants and the reaction conditions.47... 

The reaction of trimethyl phosphite with an allenic chloromethyl ketone proceeds with the formation of an oxaphospholene and not through the Michaelis-Arbuzov or Perkow rearrangements. ... 

Toke, L, Petnehazy, I., Keglevich, G., and Szakal, G., Reaction of trialkyl phosphites and a-halo-ketones in aprotic media (Perkow-Arbuzov reaction) and in protic solvents. Period. Polytech., Chem. Eng., 32, 101, 1988. 

Borowitz and his co-workers have carried out a detailed comparative study of the reactions of phosphinites, phosphonites, and phosphites with -halogenoketones. The balance between keto-phosphorylation and enol-phosphorylation favours the former with increasing oxygen content of the phosphorus compound, higher temperature, more polar solvents, and bromo-rather than chloro-ketones. a -Dibromobiacetyl reacts with two moles of phosphite to give the double Perkow product (43) and no trace of the alternative Arbusov product or of the phosphorane (45). The rate of the first Perkow... 

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). 

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