Enol phosphates ketones

Fluoroalkenolphosphates are not only stable but also sufficiently reactive to undergo olefinaaon reactions with yiides themselves. These enol phosphates are not only precursors to enolates or ketones but also can be used directly as electrophilic reagents [79] (equation 66) (Table 26). 

Partial control of enolate geometry occurs also when the enol phosphate, prepared by treatment of fluoroalkyl ketones with sodium diethyl phosphite, is... 

One of the key steps in building the fused ring involves the reaction of the activated acetoacetate methylene group in that compound with toluenesulfonyl azide to give the diazo intemediate (12-1). Treatment of that product with rhodium acetate leads to a loss of nitrogen with the consequent formation of carbene (12-2) this inserts into the adjacent amide N—H bond to form a five-membered ring and thus the carbapenem (12-3) [15]. The first step in the incorporation of the thioenol function consists in the conversion of the ketone to the enol phosphate derivative... 

CONVERSION OF METHYL KETONES INTO TERMINAL ACETYLENES VIA ENOL PHOSPHATES... 

I-Alkynes from methyl ketones This reaction can be effected by conversion to Ihe enol phosphate followed by -elimination with LDA (equation I). In the case of a simple ketone such as 2-octanone the yield is low because of formation also of an allene. In such cases lithium tetramethylpiperidide is recommended as base. 

The same SN2 addition is also observed in reactions of the cuprate with the silyl enol ether or the enol phosphate of the epoxy ketone. This regiosclectivity is applicable to five- and six-membered ring systems and, to a lesser extent, to acyclic systems, which are generally less reactive. 

Trapping the kinetic enolate of a methyl ketone with diethyl phosphochloridate provides an enol phosphate, that can, in turn, be converted to an alkyne ... 

Step c of Eq. 24-34 may occur by ring opening to an enol phosphate which ketonizes to the observed product, but step e is a more complex multistep oxidative process.314a,b The last step is transamination to methionine with a glutamine-specific aminotransferase. Another enzyme from Klebsiella converts the same intermediate anion to methylthiopropionate, formate, and CO (Eq. 24-34, step/).315... 

The aryl and enol triflates 306 and 307 couple with Me3Al, Et3Al and BU3AI [136], The enol phosphate 309, derived from ketone 308, is displaced with methyl group of Me3Al using Pd catalyst in dichloroethane. Based on this reaction, 4-tert-butylcyclohexanone (308) is converted to 2-methyl-5-tert-butylcyclohexanone (311) via 310 [137],... 

When the fragmentations yielding monomeric methyl metaphosphate (8,9.) or metaphosphate ion (10) are carried out in the presence of 2,2,6,6-tetramethylpiperidine in acetophenone as solvent, the major products are the enol phosphates. Presumably the processes take place by initial attack of the monomeric metaphosphates on the carbonyl group of the ketone. 

Fig. 13.25. O-Phosphoryla-tion of a ketone enolate to afford an enol phosphate (see Figure 13.4 regarding the stereochemistry of the enolate formation).

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... 

Partial control of the enolate geometry also occurs when the enol phosphate 19, prepared by treatment of fluoroalkyl ketones with sodium diethyl phosphite, is treated with a lithium aluminum hydride/copper(II) bromide reagent. " These enolates 20 react with modest diastc-reoselectivity with aldehydes to give products 21. 

Coupling with the enoi phosphate of fi-keto esters. The coupling of lithium dialkylcuprates with enol phosphates of ketones (7,93) is also possible with enolates... 

Highly reactive metallic titanium, prepared from TiCb and potassium, reduces enol phosphates to alkenes, permitting regioselective synthesis of dienes from a,p-unsaturated ketones. ... 

A new cyclising reagent is proposed for the synthesis of 5-unsubstituted 1,3,4-thiadiazoles (133). The latter are formed in good yield by the reaction of thiohydrazides (134) with diethyl chlorophosphate (Scheme 39). A useful, one-pot protocol has been developed for the conversion of enolizable ketones (135) to alkylated or arylated olefins (136) by Pd-catalysed cross coupling of in-situ generated enol phosphates (137) with Grignard reagents (Scheme 40). ... 

Phosphorylation of the cyclic ketones (156), pretreated with LDA, leads to the cyclic enol phosphates (157) for which the isomeric structures a and b are possible, and which, under the influence of more base, rearrange to S-phosphorylated cyclic ketones (158). 

Treatment of enolates with (R0)2P(0)C1 also results in 0-trapping to yield the corresponding enol phosphates. Dissolving metal reduction of enol phosphates is a useful procedure for the deoxygenation of ketones with concomitant, regiospecific formation of the alkene. ... 

A mild and efficient synthesis of terminal alkynes starts with readily accessible methyl ketones and converts them to the corresponding enolates with LDA. The eno-lates produced are trapped with diethyl chlorophosphate to give enol phosphates, which possess a good leaving group for elimination. Subsequent treatment of the enol phosphates with LDA furnishes the corresponding lithium alkynylides and on protonation of these, the corresponding terminal acetylenes. 

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