Acylphosphonates, acylation

Dialkyl phosphites react with acyl halides such as lauroyl chloride to yield surface-active acid esters of acylphosphonic acid [84-87] see Eq. (40). 

Sekine, M., Kume, A., Nakajima, M., and Hata, T., A new method for acylation of enolates by means of dialkyl acylphosphonates as acylating agents, Chem. Lett., 1087, 1981. 

Acylphosphonates generate acyl anion equivalents with cyanide via phosphonate-phosphate rearrangement. These anions react with aldehydes to provide cross-benzoin... 

The reaction is also facile (no external heating) and proceeds in high yield when the snbstrate is an acyl halide or related material. Snch reactions, producing acylphosphonate derivatives (eqnation 28), are of nse for the preparation of componnds for a variety of practical applications. ... 

A number of acylphosphonic acids are of interest for their biological activity, or as intermediates in syntheses of potentially bioactive phosphonic acids [7, 34, 48 - 50]. In many cases, they are most conveniently prepared by hydrolysis of the corresponding esters. Due to the presence of the keto function, acid hydrolysis (heating in aqueous HCl) is generally not a practical method to achieve this. Silyldealkylation of methyl-, ethyl- or isopropyl phosphonates with BTMS, followed by very mild hydrolysis is normally compatible with acyl and other sensitive functionalities [7,34,48]. 

LTBA can also cleave selectively the P—C bond of acyl phosphonates 2.58, while preserving other functional groups [DSl] (Figure 2.28). Nevertheless, the reduction of similar compounds such as 2.59 by NaBH4 in EtOH buffered by boric acid does preserve the P—C bond and leads to diastereomeric a-phosphorylated alcohols [BS5, DSl] (Figure 2.28). After enolization by NaH, the P—C bond cleavage of acylphosphonates (Et0)2P(0)CH2C0R can be realized with LAH [HS7]. 

Dialkyl acylphosphonates were obtained for the first time by Kabachnik and Rossiiskaya in 1945 by the reaction of acyl chlorides with trialkyl phosphites. The reaction proceeds readily at room temperature and even on cooling by slowly adding trialkyl phosphite to acyl chlorides. Improvements have been made, especially by controlling the temperature of the reaction. The different versions of this reaction, which are distinguished by the nature of the acylating agent and the structure of the phosphite, have been covered by the reviews of Zhdanov et al. in 1980, Breuer in 1996," and McKenna and Kashemirov in 2002. ... 

The Michaelis-Arbuzov reaction has been applied to t/7.v(trialkylsilyl) phosphites, which, on reaction with aliphatic or aromatic acyl halides in Et2O or CgHg at room temperature, undergo the rearrangement in mild conditions to produce the valuable fczXtrialkylsilyl) 1-oxoalkyl- or 1-oxoarylphosphonates in good yields (50-77%, Scheme 7.6). - Free acylphosphonic acids are obtained by treatment of the trimethylsilyl) esters with EtOH or by exposure to air for several hours. 

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... 

Acylphosphonates are suilable carbonyl substrates for Wittig and Homer-Wadsworth-Emmons reactions, but with certain limitations. 5° These limitations are the result of competing side reactions involving proton iransfer or acylation. Homer-Wadsworth-Emmons reactions fail with... 

Sekine. M.. Satoh, M., Yamagata, H., and Hata. T. Acylphosphonates. Phosphorus-carbon bond cleavage of dialkyl acylphosphonates by means of amines. Substituent and solvent effects for acylation of amines../. Org. Chem., 45, 4162, 1980. 

Maeda. H., Takahashi. K.. and Ohmori. H., Reactions of acyl tribulylphosphonium chlorides and dialkyl acylphosphonates with Grignard and organohthium reagents. Tetrahedron, 54, 12233, 1998. 

Acylphosphonates, expected to be the primary products from reaction of dialkyl phosphites with acid anhydrides, add a further equivalent of the phosphite, thus yielding oc-acyloxy diphosphonates which can be isolated in good yield after acylation 334... 

The reaction between tris(trimethylsilyl) phosphite and a perfluoroacyl chloride proceeds without any apparent difficulty to give the predicted phosphonate diester 489 [R = Me3Si, R = CF3 or (CF3)2CH] but the use of longer chain polyfluorinated acyl halides or other heavily halogenated acyl chlorides leads to complications with such substrates, the initially formed acylphosphonate reacts with more phosphorus(III) ester to give the (Z)-enol phosphate 490 (Scheme 47). The halides, XCH2COX (X = Cl or Br) afford only the esters 491 (X = H). ... 

The course of the condensation between an acylphosphonate and a 1-nitroalkane car-banion depends on the nature of the acyl group. Base catalysts are commonly employed, but an acylphosphonate derived from an aromatic acid requires an acidic catalyst otherwise the intermediate anion fragments to hydrogenphosphonate and nitroketone (Scheme 20)207 jYiQ reaction between a nitroalkane carbanion and a dialkyl (trichloroacetyl)phos-phonate results in a rearrangement to phosphate with additional dehydrochlorination (Scheme 21) . ... 

The facility with which the phosphorus-carbon bond in acylphosphonic derivatives is cleaved by the action of the more basic nucleophiles has already been commented upon. Those nucleophiles include alkoxides and amines, but it may be noted that thiols undergo normal addition to the carbonyl group. With regard to the latter, diethyl acetylphosphonate yields the monothioacetals 256 the derivatives may not be stable thermally but their decomposition occurs with cleavage of the phosphorus-carbon bond Reactions between the same substrate and simple carboxamides in the presence of an acid catalyst under dry conditions furnish the acylated enamides 257 ". ... 

In addition to (aminoalkyl)phosphonic diesters, several other, well characterized products have been obtained from the oximes, or derivatives of oximes, of acylphosphonic diesters. Methylation of the oximes 283 [Z = CONHR, COOR (R = Et or Pr ), R = H of undefined geometry] with MeI-K2C03, or with Me2S04, yields the O-methyl oximes 283 (Z = CONHR R = Me) methylation with diazomethane also yields the latter but together with the phosphorylated nitrones 284 (Z = CONHR or COOR), which have been characterized in E and Z forms. The interaction of283 (R = Me) and diazomethane yields the corresponding 285 . Methylene insertion also occurs in reactions between diazomethane and 0-acylated oximes ... 

In contrast, dialkyl chlorophosphites behave differently. They react with acyclic acid anhydrides with the formation of dialkyl acylphosphonates and acyl halides (equation 8)". ... 

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