Phosphonoacetates

Triethyl phosphonoacetate, reaction of sodium derivative with cyclohexanone to yield ethyl cvclo hexy lideneacetate, 46, 45 1 nfluoroacetic anhydride, 46, 98 p,0 0 Trifluorostyrene, 47, 52 Trusopropvl phosphite as reagent in dechlorination of decachlorobi 2,4 cyclopentadienyl, 46, 93 1,3,5-Tnketones, from aroylationof 1,3-diketones, 46, 59 from 4-pyrones, 46, 59 Tnmethylamine oxide, reaction with x-octyl iodide to yield octanal, 47, 96... 

Phosphonoacetic acid antiviral activity, 6, 771 Phosphoprotein phosphatases activation... 

An improved route to fluorinated 4-hydroxycoumarins has been reported, based on a facile decarboxylation-deacetylation of their 3-(3-oxopropanoic acid) derivatives <96TL15S1>. The reaction of methyl salicylates with triphenylphosphoranylidene ketene, Ph3P=C=C=0, affords 4-methoxycoumarins <96JCS(P1)2799> and the formation of coumarin 3-phosphonates from salicylaldehydes and phosphonoacetates, Et02CCH2P(0)(0R)2, has been investigated <96T12597>. 

The phosphonatase (hydrolase) pathway is less widely used, typically for the degradation of 2-aminoethylphosphonate via phosphonoacetaldehyde to acetaldehyde, and the degradation of phosphonoacetate that involves a specific hydrolase (Kulakova et al. 2001). 

Kulakova AN, LA Kulakov, NY Akulenko, VN Ksenzenko, JTG Hamilton, JP Quinn (2001) Structural and functional analysis of the phosphonoacetate hydrolase (phnA) gene region in Pseudomonas fluorescens 23F. J Bacteriol 183 3268-3275. 

Reactions with phosphonoacetate esters are used frequently to prepare ,[ -unsaturated esters. This reaction is known as the Wadsworth-Emmons reaction and usually leads to the E-isomer. 

Several modified phosphonoacetate esters show selectivity for the Z-enoate product. Trifluoroethyl,256 phenyl,257 2-methylphenyl,258 and 2,6-difluorophenyl259 esters give good Z-stereoselectivity with aldehydes. The trifluoroethyl esters also give Z-selectivity with ketones.260... 

An alternative procedure for effecting the condensation of phosphonoacetates is to carry out the reaction in the presence of lithium chloride and an amine such as diiso-propylethylamine. The lithium chelate of the substituted phosphonate is sufficiently acidic to be deprotonated by the amine.262... 

Fig. 2.6. Free-energy profile (B3LYP/6-31 + G with ZPE correction) for intermediates and transition structures for Wadsworth-Emmons reactions between the lithium enolate of trimethyl phosphonoacetate anion and formaldehyde in the gas phase and in tetrahydrofuran or ethanol. Adapted from J. Org. Chem., 63, 1280 (1998), by permission of the American Chemical Society.

There do not appear to be any simple phosphines that bear a CH2F group. However, fluorine NMR spectra of phosphonates, phosphane oxides, and phosphonium compounds with CH2F and —CHF- bound to phosphorous have been reported. Examples are given in Scheme 3.26, including spectral data for the useful Horner-Wadsworth-Emmons reagent, triethyl 2-fluoro-2-phosphonoacetate. 

Another multicomponent synthesis giving N-3-substituted compounds 28 consisted of the sequential reaction of metallated phosphonoacetates, in one pot, with a nitrile then an aldehyde and finally an isocyanate. This was an extensive study of the scope and limitations of the different substituents on all the components. The most important feature was that, for good yields, the isocyanate should bear an electron-withdrawing group - tosyl was the most successful. However, an exchange reaction could be carried out by reaction of the tosyl products with aryl isocyanates under microwave irradiation, giving the N-3-aryl derivatives 29 <06CEJ7178>. 

C2]-Squalene, 80, has been produced71 in the reaction sequence shown in equation 31 which involves alkylation of 3-13C-ethyl acetoacetate with geranyl bromide, followed by hydrolysis, decarboxylation and treatment with triethyl phosphonoacetate and then reduction of the ester 82 with LiAlHr, bromination with CBr4/PPh3 and coupling the farnesyl bromide with Cul/Li-pyrrolidine. Epoxidation of 80 has been effected by... 

Herrin, T.R. and Fairgrieve, J.S., Triglyceride Ester of Phosphonoacetic Acid Having Antiviral Activity, U.S. Patent 4,150,125, 1979. 

Triethyl phosphonoacetate is available from Aldrich Chemical Co. 

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

Vigreux column) (74-7/0.03) to get 96% yield of triethyl-phosphonoacetate (I). In a 3 liter flask fitted with a stirrer,... 

The catalytic asymmetric Horner-Wadsworth-Emmons reaction was realized by use of the quaternary ammonium salts 7 derived from cinchonine as a phase transfer catalyst.1631 Thus, tert-butylcyclo-hexanone 85 reacted with triethyl phosphonoacet-ate 86 together with RbOH-H20 in the presence of the ammonium salts 7, and then the product 87 was isolated after reesterification by treatment with acidic ethanol, as shown in Scheme 27 Among the... 

General.—The relatively unreactive diethyl arylmethylphosphonates have been used quite successfully in alkene synthesis with phase-transfer catalysis.100 In a comparative study it was shown that anions derived from /S-ketophosphonamides (109) have very low reactivity whereas those from 0-ketophosphonates (110) react quite well with aldehydes to give frwjj-alkenes.101 Benzyl dimethyl phosphonoacetate (111) can be used to form alkenes, e.g. (112), from which the benzyl group can be removed by hydrogenolysis without disturbing the C=C bond.102 The carbanions (113) can be... 

Having established a very effective method for the synthesis of tricar-bonyl(T74-vinylketene)iron(0) complexes, Thomas has subsequently undertaken the most comprehensive study on the reactivity of these complexes to date. The reactions of 221 with phosphoramidate anions,90134 coordinating ligands such as phosphines3 and isonitriles,69,87,89,135,142,143 a variety of nucleophiles,86,89135142 phosphonoacetate anions,88,89 alkynes,108,109,144,145 and al-kenes146,147 have ah been investigated. Crucially, Thomas has also developed a method138 for the kinetic resolution of the vinylketene complexes (221) that ultimately yields enantiomerically pure samples of the complex. This... 

In 1991, Thomas reported88a that the reaction between vinylketene complexes (221) and several phosphonoacetate anions generated vinylallene complexes (246), in some cases with extremely high stereoselectivity.88,89 This Wadsworth-Emmons type reaction occurs via attack by the phosphonoacetate carbanion at the ketene carbonyl carbon, and product ratios clearly depend on the steric bulk of the R and R substituents. The relative stereochemistry of the major isomers of 246 were determined by X-ray analysis. Upon oxidation of the vinylallene complexes with iron(III) chloride, a range of substituted furanones were isolated.8813,89... 

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