Enol phosphate esters

The chemical properties of an enol phosphate ester are quite different from simple phosphate esters. The only important example is the glycolytic intermediate, phosphoenolpyruvic acid (Fig. III-32). 

Cyclization. Treatment of the unsaturated enol phosphate ester 1 with 1 equiv. of mercury(II) trifluoroacetate in nitromethane at 0° followed by aqueous sodium chloride produced the mercurated bicyclic keto ester 2 in 60% yield along with 20% of the monocarbocyclic product 3. Keto ester 2 is an intermediate in a total synthesis of aphidicolin (4). This reaction is the first example of the use of a mercury(II) salt tor simultaneous construction of two carbocyclic rings. ... 

What is the difference between an enol-phosphate ester and a normal phosphate ester that gives PEP such a high phosphate group transfer potential ... 

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). 

The simplest mechanism consistent with the experimental facts is depicted for 2-cyclopentenone in equation 12. While initial attack by the phosphorus reagent at the carbonyl (eqs. 13 and 14) is conceivable, subsequent rearrangement of phosphorus from oxygen to carbon via a phosphorane intermediate is not possible, due to the restricted geometry of the intermediate in equation 13. Since only the 7-ketocyclopentyl-phosphonate ester (72%) and none of the enol phosphate ester (eq. 13) or hydroxyphosphonate ester (eq. 14) were detected in the product, attack by phosphorus is exclusively at the terminal carbon atom of the conjugated system. It is reasonable to assume that a similar mechanism holds for the majority of dienophiles. 

It should be noted that, unlike the reactions between phosphorus(III) esters and mono-haloalkanoic acid derivatives which, almost without exception, lead to the expected Michaelis-Arbuzov products, similar reactions which involve derivatives of poly-halogenoalkanoic acids tend strongly to yield enol phosphate esters as the major, if not the sole, product ... 

Both 2-chloro- and 2-bromo-cyclohexanone react with phosphorus(III) esters to yield the enol (1-cyclohexenyl) esters. 2,6-Dibromocyclohexanone yields initially the enol phosphate ester 508, which reacts with more phosphite ester to give 509. The thermal decomposition of 508 liberates HBr, which dealkylates some triethyl phosphite, and the resultant diethyl hydrogenphosphonate then reacts with 509 to give 2-(diethoxyphosphi-noyl)cyclohexanone (510) 2,6-dichlorocyclohexanone does not behave in this complex fashion and furnishes only an enol phosphate " The 2-halocyclohexanones represent examples of secondary haloketones, from which only enol esters are obtained directly on reaction with triethyl phosphite. Other secondary halides, e.g. PhCOCHBrR (R = Me or Ph) or bromocamphor yield mixtures of oxoalkyl phosphonates and enol phosphates. Tertiary halides, as exemplified by 2-halo-2-methylcyclohexanones MeCOCMe2Br and PhCOCMe2Br yield only enol phosphate esters. 

Although it has been stated that di- and tri-haloketones and a-haloaldehydes (irrespective of the degree of halogen substitution) tend to yield only enol phosphate esters, further qualification of this statement is appropriate. The formation of silyl ethers from aldehydes or ketones and silyl phosphites has already been noted (see section III.A). Reactions between silyl phosphites and trifluoroacetaldehyde or perfluoroacetone and other similar compounds initially lead to silyl ethers of (a-hydroxyalkyl)phosphonic diesters in which all the fluorine is retained, although subsequent change leads to fluorinated enol phosphate esters. Sekine et also observed the formation of (a-silyloxyalkyl)phospho-... 

CTP is formed by amination of UTP The carbonyl oxygen at C-4 of UTP is replaced with an amino group via the formation of an enol phosphate ester intermediate. In E. coli, NH4 serves as the source of the nitrogen atom that displaces the phosphate group, whereas the amide group of glutamine serves this purpose in mammals. 

The products from a treatment of the enol phosphate esters (53)(R, R, and R = H or Me), prepared in situ, with the nucleophiles (MeOH, PrOH, Bu OH, EtSH, MeNHOMe) in the presence of Et3N and with cooling, are of type (55) these result from the acylation of the nucleophile by the mixed anhydrides (54), evidently formed as the result of Claisen rearrangements. ... 

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

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