Phosphonic acid silyl esters

With tris(trimethylsilyl)phosphite, regiospecific and irreversible adduct formation with 2( H)-pyrimidinones gives 3,4-dihydro-4-phosphonic acid silyl esters (317) which furnish the phosphonic acid (318) on treatment with methanol (Scheme 53). The regiochemistry is attributed to the bulkiness of the phosphite reagent. The carbon-phosphorus bond resisted cleavage by TFA <87ACS(B)448>. 

Phosphonic acid silyl esters from phosphonic acid esters s. 19,13... 

Phosphonic acids from their esters via phosphonic acid silyl esters with trimethylchlorosilane s. 19, 13 preferably with trimethylbromosilane s. C. E. McKenna et al., Tetrah. Let. 1977, 155... 

Phosphonic acids from phosphonic acid esters via phosphonic acid silyl esters under mild conditions... 

Phosphonic acid amide esters. A soln. of ethyl [l-[[(phenylmethoxy)carbonyl]amino]-2-methylpropyl]phosphinate in acetonitrile under argon treated with bis(trimethyl-silyl)acetamide, followed after 1 min by L-alanine hydrochloride methyl ester, CCI4, and Et3N, the soln. stirred at room temp, for 30 min, cooled to 0°, and quenched with methanol N-[ethoxy[ 1 -[[(phenylmethoxy)carbonyl]am no]-2-methylpropyl]-... 

Trimethylsilyl esters of tris(thio)phosphonic acids 2070 are readily oxidized by DMSO in toluene at -30 °C to give the dimeric tetra(thia)diaphosphorinanes 2071 and HMDSO 7 [208] (cf. also the oxidation of silylated thiophenol via 2055 to diphenyl disulfide). The polymeric Se02 is depolymerized and activated by reaction with trimethylsilyl polyphosphate 195 to give the corresponding modified polymer... 

Silyl esters of phosphorous, phosphonous, and phosphinous acids... 

In the instances of phosphorous and phosphonous acid systems, the generation of a new C-P bond via the classical Michaelis-Arbuzov reactions as noted above leads to products that are esters themselves. Isolation of the free acid product requires cleavage of the ester linkage in a separate reaction step, generally after isolation and purification of the initial product. The advent of silyl phosphorus reagents for the Michaelis-Arbuzov reaction allowed free acid products to be isolated simply by water workup of the reaction system. Further, since the byproduct was a silyl-halide, the general concern that the by-product halide would participate in an extraneous Michaelis-Arbuzov reaction was obviated. 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

A successful route to the dialkyl (l-raethyl-3-oxo-l-buCenyl)phosphonates (150) involves the conversion of compounds (148) via their enol silyl ethers into the phosphonic acid esters (149) which are then desilylaCed to give the desired esters (150) (Scheme 13). ... 

The use of mass spectrometry as a detector in g.l.c. has the advantage that isomeric materials with the same retention times may still be distinguished, e.g. a phosphate and phosphonate. Mono-, di-, and tri-butyl phosphates may be separated by g.l.c. after conversion of the acidic components into their silyl esters. A dual flame photometric detector has been described for the simultaneous determination of phosphorus-, sulphur-, and chlorine-containing compounds. The method is based on the measurement of the... 

Amino-l-hydroxyethyl)phosphonic acid occurs in the plasma membrane of Acanthamoeba castellani and the 2R isomer is formed, in that organism, by the hydroxy-lation of (2-aminoethvl)phosphonic acid This biosynthesis step in vitro has been studied by Hammerschmidt" who synthesized various chiral deuterium-labelled derivatives of both compounds using the isotopically labelled 2-benzyloxyethanal in Abramov reactions to obtain, initially, the dimethyl (2-benzyloxy-l-hydroxyethyl)phosphonate (362). This ester was resolved through the diastereoisomeric carbamates 363 the separated carbamates were sequentially de-l-O-protected, silylated at the a-HO group, debenzylat-ed and, by means of the Mitsunobu reaction, converted into dimethyl [2-eizido- -(tert-butyldimethylsilyloxy)ethyl]phosphonates. Subsequently, standard reactions were used to transform the latter into the diastereoisomeric, isotopically labelled (2-amino-1-hydroxy-ethyl)phosphonic acid. 

The role of silylated reagents in the formation of oligopeptides has been explored . Here, the bis(trimethylsilyl) ester of the [l-(trimethylsilylamino)alkyl]phosphonic acid is coupled with an activated A -cbz-amino acid and the silyl groups are subsequently removed under aqueous conditions the process can then be repeated. Oligopeptides have also been obtained as the result of enzyme catalysis when the condensations between amino carboxylic esters and (a) A -protected (aminoalkyl)phosphonic esters or (b) A -protected [(aminoalkyl)methyl]phosphinic esters is brought about in the presence of (a) alkaline phosphatase (Ej) and phosphodiesterase (E2) and (b) alkaline phosphatase and total bee venom (E3) (the latter aiding in the removal of both carboxylate ester and A -acetyl groups) ... 

Preparation of Phosphonic Acid Chlorides. Disilyl esters of phosphonic acids react with oxalyl chloride-DMF to give the phosphonyl chlorides and silyl chlorides under mild conditions (eq (>) Prior treatment of an acid-sensitive phosphonate monoester with Trimethylsilyldiethylamine was used to minimize exposure to HCl (eq 7). ... 

A general process suitable for large scale synthesis of phosphonic acid dichlorides, which avoids the need for preforming silyl esters, has been reported (eq 8). ... 

The Pummerer rearrangement can also be invoked by the use of polyphosphoric acid trimethylsilyl ester (PPSE). Using this method, Kakimoto and Imai reported the synthesis of the unusual product phenyl phenylthioglyoxylate 33. The reaction was thought to proceed via phosphorylation of the sulfoxide oxygen rather than silylation as rearrangement did not take place when tris(trimethylsilyl)phosphonate was... 

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