Acylphosphonates synthesis

Sekine, M. and Hata, T., Convenient synthesis of unesterified acylphosphonic acids, Chem. Commun., 285, 1978. 

Reaction of Azolium Ylides with Dialkyl Acylphosphonate New Synthesis of Heterocyclic Compounds A. Takamizawa et al., Heterocycles, 1974, 2, 521-554. 

Stevens, C. V., Vanderhoydonck, B. Use of acylphosphonates forthe synthesis of a-chlorinated carboxylic and a,a -dichloro dicarboxylic acids and their derivatives. Tetrahedron 2001, 57, 4793-4800. 

Facile acylphosphonate enolization was exploited in a synthesis of a-chlori-nated fatty acids [40]. The a-chloro acylphosphonates obtained via chlorination of acylphosphonates with sulfuryl chloride were cleaved to form the target products using hydrogen peroxide-sodium bicarbonate. 

Hanis. R.L.N., and McFadden, H.G., Acylphosphonates as substrates for Wittig and Homer-Wittig reactions. Unusual stereoselectivity in the synthesis of P-phosphinoylacrylates, Aust. J. Chem., 37, 417. 1984. 

The course of the reaction between acylphosphonates and 1-nitroalkane carbanions depends on the nature of the acyl group. Thus, nucleophilic addition of nitromethane to acetylphosphonates in the presence of di- or triethylamine results in the formation of dialkyl 1-hydroxy-l-methyl-2-nitro-ethylphosphonates (R = Me, = H, Scheme 7.75)." " However, the procedure is not applicable to the synthesis of dialkyl 1 -hydroxy-l-pheny 1-2-nitrocthyIphosphonate because the electron-with-drawing ability of the benzene ring destabilizes the molecule toward alkali and results in C-P or C-C bond cleavage. The fact that diisopropyl 1-hydroxy-l-phenyl-2-nitroethylphosphonate was... 

Brittelli, D.R., A study of the reaction of 2-haloacyl halides with trialkyl phosphites. Synthesis of 2-siibsliliilcd acylphosphonates, J. Org. Chem.. 50. 1845, 1985. 

Takaki, K., Itono, Y., Nagafuji, A., Naito. Y.. Shishido, T., Takehira, K., Makioka, Y, Taniguchi, Y, and Fujiwara, Y. Three-component coupling of acylphosphonates and two carbonyl compounds promoted by low-valent samariums. One-pot synthesis of P-hydroxyphosphonates, J. Org. Chem., 65, 475, 2000. 

Iyer, R.P., Phillips, L.R., Biddle, J.A., Thakker, D.R., Egan, W., Aoki, S., and Mitsuya, H., Synthesis of acyloxyalkyl acylphosphonates as potential prodrugs of the antiviral, trisodium phosphonoformate (foscarnet sodium). Tetrahedron Lett., 30, 7141, 1989. 

Two fairly recently announced procedures allow the synthesis of fluorinated phospho-nic esters from acylphosphonic diesters. In the first of these, aroylphosphonic diesters are treated with dast reagent at room temperature and in the absence of a solvent, when the products are dialkyl (a,a-difluorobenzyl)phosphonates. ... 

The (oxoalkyl)-phosphonic and -phosphinic acids form a remarkable group of compounds whose ease or formation, stability and versatility in use depend to a high degree on the relative positions of the oxo and phosphoryl groups. From the points of view of both synthesis and reactivity, the (1-oxoalkyl) compounds, also termed acylphosphonates, stand apart from the remaining compound types, and they have been considered separately in this volume and elsewhere the discussion here is designed to offer a comparison between syntheses of acylphosphonic acids with those of other important oxoalkyl phos-phonic and phosphinic acids. 

Rare examples of normal Michaelis-Becker reactions which involve co-chloroalkanal diethyl acetals are to be found, and although the formation of dialkyl acylphosphonates from sodium dialkyl phosphites and, for example, benzoyl chloride, is to be observed at -85 °C, the system is further complicated, even at -10 °C, by further addition steps followed by rearrangements which would seem to render the process of little value for the synthesis of oxoalkyl phosphonic esters On the other hand, in a more detailed and systematic study of reactions between sodium dialkyl phosphites, (RO)2PONa(R = Et or Bu), and the ketones R CO(CH2) Cl, Sturtz and others have observed the formation of epoxides when n = 1 and (1-hydroxy alk-2-enyl)phosphonic diesters when n = 2(R = Me or Pr ), according to the displacement in 532, and of derivatives of tetrahydrofuran or tetrahy-dropyran, according to 533 n = 3 or 4) when R = Et, the formation of the cyclic ethers was accompanied by low yields of the expected (oxoalkyl)phosphonic diester, but otherwise the latter were isolated as a single product only for R = Me, n = 5, and R = Et or Pr when n = 2. 

It is possible to obtain derivatives of acylphosphonic diesters when less basic nucleophiles are employed " or from preparations carried out in anhydrous media. Thus, the phenylhydrazones and 2,4-dinitrophenylhydrazones of many esters are known and hydrazones and methylhydrazones of diethyl (l-oxoalkyl)phosphonates have been satisfactorily obtained through reactions in acetic acid. Hydrazones of (l-oxoalkyl)phos-phonic diesters have been employed in the synthesis of (17/-indole-2-yl)phosphonic esters, and the derivatives from dialkyl (2-oxoalkyl)phosphonates have been used to make indole-3-yl)- and [2-(l/f-indolemethyl)]-phosphonic esters by cyclization in polyphos-phoric acid. ... 

Oximes, which are valuable intermediates for the conversion of oxoalkyl phosphonic diesters into those of aminoalkylphosphonic acids (Chapter 4, Section IV.C. 1. d), are also readily available, although it is necessary to prepare them with some care. Nevertheless, the feature of interest here is their ready degradability, particularly under aqueous conditions, and which has been intensively investigated by Breuer and coworkers. The necessity for care in the preparation of oximes of acylphosphonic diesters, is illustrated by the synthesis of dimethyl [a-(hydroxyimino)benzyl]phosphonate this compound exists in the thermodynamically more stable ( ) form which, under the influence of acid is converted into the less stable (Z) form, and both forms have been separately characterized by X-ray crystallography. The geometric isomers of the oxime differ in their behaviour under basic conditions with NaOH-MeOH, the ( ) form undergoes monodealkylation, whereas the (Z) isomer decomposes to dimethyl phosphate and benzonitrile. In aqueous solution, ( )-[a-(hydroxyimino)benzyl]phosphonic acid also decomposes into benzonitrile together with phosphoric acid, in a manner which is pH dependent, and consistent with a dissociative mechanism that involves the early formation of monomeric metaphosphate. ... 

The treatment of diethyl aroylphosphonates with 3-chloroperoxybenzoic acid yields diethyl aroyl phosphates (oxygen insertion) in 70-85% yields together with smaller amounts of mixed carboxylic anhydrides, ethyl benzoate and diethyl hydrogenphosphate (Scheme 31). The main reaction is a typical Baeyer-Villiger oxidation, applied here to an acylphosphonate The reaction generally has little value in the synthesis of acyclic mixed anhydrides, which are easily obtained by other procedures, but it is of value in some slightly modified but specific cases as, for example, in the synthesis of compounds in the 2,3-oxaphosphabicyclo[2.2.2]octane series (Section III.A.2). The 1 1 adducts of H-phospholes and A-phenylmaleimide (177) or dimers of the same phospholes (178 R =... 

Indeed, one of the main uses of j -phosphorylated ketones is the synthesis of C-phos-phorylated heterocyclic systems, and in this respect the reactions very often complement those of isomeric acylphosphonates. In the first of the examples chosen, the ketone 304 cannot be converted into 305 in a direct reaction with the appropriate amine instead, the carbonyl group must be protected as in 307, when a reaction with the amine then gives 308 hydrolysis of 308 with 3 M HCl yields 305. When treated with ZnCl2 under toluene, 305 yields the indolylphosphonic diester 310" In the same way, a direct reaction between 304 and ArONa fails to give 306, which must therefore be prepared via 307 and 309 with acid hydrolysis to 306 when the latter is treated with hot polyphosphoric acid, cyclization occurs to give the benzofuranylphosphonic diester In order to obtain the isomeric... 

Synthesis of mixed dialkyl acylphosphonates by the Arbuzov reaction is of practical value only with mixed phosphites in which there is clear preference of the different alkyl groups to be cleaved. For example reaction of diethyl phenyl phosphite with benzoyl chloride give phenyl ethyl benzoylphosphonate (equation 6) . 

Alkyl hydrogen acylphosphonates have been converted into alkyl acylphosphonochlo-ridates by thionyl chloride (equation 36). The latter are versatile intermediates that have been used for the synthesis of mixed dialkyl acylphosphonates or alkyl acylphospho-namidates (equation 36) . ... 

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