Enolization phosphate

The coupling reaction between lithium dimethylcuprate and acyclic enol phosphates must be carried out between -47 and -98 C for stereoselective formation of g-methyl-a,g-unsaturated esters. 

This procedure illustrates a new method for the preparation of 6-alkyl-a,g-unsaturated esters by coupling lithium dialkylcuprates with enol phosphates of g-keto esters. The procedure for the preparation of methyl 2-oxocyclohexanecarboxylate described in Part A Is based on one reported by Ruest, Blouin, and Deslongcharaps. Methyl 2-methyl-l-cyc1ohexene-l-carboxylate has been prepared by esterification of the corresponding acid with dlazomethane - and by reaction of methyl 2-chloro-l-cyclohexene-l-carboxyl ate with lithium dimethylcuprate. -... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Dimethyl 2,3-pentadienedioate has also been prepared from the enol phosphate of diethyl acetone-1,3-dicarboxylate. ... 

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... 

Table 6. Aldol Reaction of Fluorinated Enol Phosphates with Aldehydes [14 ...

Sometimes the structure is such that the reaction is forced into a single path regardless of catalyst. Hydrogenation of the (Z)-enol phosphate 30 over PtOj, 5% Pd-on-C, or 5% Rh-on-C in EtOAc at 3 atm gave a 95% yield of 31, obtained by hydrogenolysis followed by hydrogenation (46a). 

A method for conversion of one of two keto functions to the methylene involves hydrogenolysis of an enol phosphate. 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

When cyanoacetylene (5), which is produced when an electric discharge is passed through a mixture of methane and nitrogen, is dissolved in a phosphate buffer a stable enol-phosphate (6) is formed. Pyrophosphate is produced when neutral aqueous solutions of (6) and orthophosphate are heated, and the phosphorylation of UMP has been achieved. However, from a study of the rate of phosphorylation and a consideration of environmental factors, especially the likely phosphate concentration in oceans, it is suggested that (6) is not an important intermediate in prebiotic phosphorylation. The conversion of the 3 -phosphate of 0 2 -cyclocytidine (7) into 2, 3 -cyclic CMP under mild conditions in aqueous solution has... 

The monomeric phosphate ion 102 was first postulated in 1955 as an intermediate of the hydrolysis of monoesters of phosphoric acid in an aqueous medium 57,58). Another 24 years were to elapse before compound 102 was observed directly, and then not in solution but in the mass spectra of some pesticides. The negative ion Cl spectra of enol phosphates 94 and of the thiophosphorie ester 95 display an intense peak at m/e == 78.9590, which is unequivocally assigned to the POf ion 59). 

It was demonstrated that the IR spectrum of the ethyl metaphosphate 147 accessible from the enol phosphate 146 is identical with that of the cyclic triethyl metaphosphate 149,05) synthesized by an independent route. 

If monomeric 151 is generated from the phosphonic monoester 171 (OH in place of Oe) in the presence of 2,2,6,6-tetramethylpyridine as base, then it also adds to carbonyl compounds U9,120). Thus acetophenone is smoothly phosphorylated to the corresponding enol phosphate in 90% yield. 

When monomeric metaphosphate anion POf (102) is generated form the phos-phonate dianion 170 in the presence of the hindered base 2,2,6,6-tetramethylpiper-idine, it undergoes reaction with added carbonyl compounds147), Thus, it phosphoryl-ates acetophenone to yield the enol phosphate, whereas in the presence of acetophenone and aniline the Schiff base is formed from both compounds, probably by way of the intermediate C6H5—C(CH3) (OPO e) ( NH2C6HS). This reactivity pattern closely resembles that of monomeric methyl metaphosphate 151 (see Sect. 4.4.2). 

Erker and Trinkl synthesized the tricycles 177 as novel GABA-A/benzodiazepine receptor ligands via synthesis of enol phosphates such as 175 and reaction with isocyanides 176 (Scheme 13) <2001H1963>. 

These authors also noted that the electron-donor ability of various derivatives of 2,2-dimesityl-1-phenylethenol decreases in the order enolate > enol > enol silyl ether > enol phosphate > enol acetate. As such, a simple derivatization allows the ready modulation of the electron-donor properties of ends. 

Enantioselective hydrogenation of a series of enol phosphates with a Bu-Mini-Phos-Rh or a Bu-BisP -Rh catalyst provides moderate to excellent ee-values (Scheme 26.7) [99]. 

Attack on Oxygen. Nitrones have been deoxygenated to the parent imine with trimethyl phosphite under vigorous conditions.45 Virtually quantitative yields of the enol-phosphates (54) and (55) were obtained from the reaction of tris(trimethylsilyl) phosphite with a-diketones and /j-benzoquinone. 4 6... 

---