Silyl phosphates

Wada et al. found that 2-phenylsulfonyl-3-(3-nitrophenyl)oxaziridine 198 is an effective reagent for the oxidation of silyl phosphates to the corresponding silyl phosphonates under neutral and anhydrous conditions <1997JA12710>. For example, diethyl trimethylsilyl phosphonate 199 was obtained in quantitative yield within 5 min on oxidation of 197. Oxidations using r-BuOOH and its derivatives resulted in much lower yields and longer reaction times. 

D. The calculations confirm that the negative end of the dipole is towards phosphorus. - The calculated dipole moments of phosphole (1.9 D) and pyrrole (2.0 D) are similar, and, unlike furan, the positive ends of the dipoles are towards the heteroatoms. Dipole moments have been used, in combination with results from other methods of study, to estimate the preferred conformations of the dichloride (179), of the phosphites (180), and of triarylphosphine oxides. The use of dipole moments to aid stereochemical studies of compounds has been reviewed. Additive polarizability parameters should not be used in the calculations, and it has been recommended that data should be obtained from model compounds containing identical environments for the phosphorus atoms. The sensitivity of bond moments to structural changes has been studied perfluoroalkyl groups lower the phosphoryl bond moment, and the P—N bond moment is very sensitive to the valence state of the phosphorus atom. The conformational analyses of phospho-nates, phosphonamides, silyl phosphates, and a number of dioxaphosphori-nans (181) - have been reported. The P—Se bond moment has been estimated to be 1.24 D. The zwitterionic structure (182) was identified by its high dipole... 

Mass spectra have been used to identify the position of 0 labels in phosphinic acid derivatives and to estimate the content of inorganic phosphate after silylation. The molecular distance between silylated phosphate groups and/or silylated hydroxy-groups has been estimated from the abundance of the rearrangement ions (195) and (196). ... 

Stereochemistry — The conformational analysis of various deuteriated ethyl-phosphine-borane adducts and dimethyl methylphosphonates were based on vibrational spectral data. The stereochemistry of diethylphosphonyl acetamide,the unusual vinyl compounds (60 X = L.E.P., O, and a number of l,3,2-dioxaphosphorinanes have been studied. It was found that the Raman-active ring vibration is related to the orientation of the phosphoryl group. Conformational data for dioxaphosphepane was compared with calculated parameters. A low-temperature study of several cyclopropyl-phosphonates (61) revealed rotational isomerization about the P-O bonds but not about the P-C bond. The variable temperature i.r. and Raman spectra of the silyl phosphates (62) also revealed rotational isomerism. ... 

Several books and other publications on the stabilization of polymers have been mentioned in this chapter. In addition, two patents are noteworthy. The one by Hamilton discusses protection of polymer blends against transesteri-fication. For example,blends of PC with semi-crystalline PEST (e.g., PET) finds application in the automotive industry. Since the resistance to solvents depends on the PET crystallinity, which decreases with advancing transreactions, its control is essential. The patent specifies addition of a sUyl phosphate compound for inhibiting the ester-carbonate interchange. The stabilization is achieved by deactivation of the residual metaUic catalyst in the reaction with silyl phosphate stabilizers or their mixture. 

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

These groups, along with a number of other trialkylsilylethyl derivatives, were examined for protection of phosphorothioates. Only the phenyl-substituted silyl derivative was useful, because simple trialkylsilyl derivatives were prone to acid-catalyzed thiono-thiolo rearrangement. Other trialkylsilylethyl derivatives also suffer from inherent instability upon storage,but the trimethylsilylethyl group has been used successfully in the synthesis of the very sensitive agrocin 84 and for intemucleotide phosphate protection with the phosphoramidite approach. 

In contrast, another group35 found that extracts of E. coli contained a mixture of pentulose phosphates at a concentration near 0.3 nmol per mg of the dry weight of cells. The sugars were estimated by gas chromatography-mass spectrometry after treatment of the extract with phosphatase followed by silylation, or borohydride reduction and acetylation. Furthermore, a partially purified preparation from these extracts catalyzed the synthesis of 1-deoxypentulose... 

Table 2.1 HPLC capacity factors for secbuto-barbitone and vinbarbitone with an octadecyl silyl stationary phase and mobile phases of methanoiyO.l M sodium dihydrogen phosphate (40 60) at (a) pH 3.5, and (b) pH 8.5. From Moffat, A.C. (Ed.), Clarke s Isolation and Identification of Drugs, 2nd Edn, The Pharmaceutical Press, London, 1986. Reproduced by permission of The Royal Pharmaceutical Society...

A recent paper [44] shows that the treatment of silyl thioketones 68 with lithium diethylphosphite proceeds via a thiophiUc attack followed by a thio-phosphate mercaptophosphonate (69 70) carbanionic rearrangement and the migration of the silyl group from the carbon to the sulfur atom leading to the S-silylated sulfanylphosphonate carbanion 71. The last step represents the first example of the thia-Brook rearrangement (Scheme 18). 

On silylation-amination of the disodium salts of inosine-5 -phosphate 238a or of guanosine-5 -phosphate 238 b with benzylamine, the phosphate moieties are also transiently protected during amination by silylation (cf also the silylation of uridine-5 -phosphate 224) to give, after transsilylation with methanol and addition of NaOH, the desired sodium salt of N -benzyladenosine-5 -phosphate 239a in 80% yield and the sodium salt of the 2-amino derivative 239 b in 78% yield [64] (Scheme 4.23). 

In this context, it is interesting to note that the first synthesis of 2, 3 -0,0-cyclic phosphorothioate 22a was reported by Eckstein in 1968 [25], He also isolated pure Rp diastereomer by fractional crystallization of the triethylammonium salts [26] and used it as reference to determine the absolute configurations of the other phosphorothioate analogues [27], 2, 3 -0,0-Cyclic H-phosphonate 20a was used as a key substrate for the synthesis of uridine 2, 3 -0,0-cyclic boranophosphate 27. Silylation of H-phosphate 20a gave the phosphite triester 25 (two diastereomers). Its boronation, with simultaneous removal of the trimethylsilyl group, was achieved by its reaction with borane-A.A-diisopropylethylamine complex (DIPEA-BH3). 

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. 

Hata, T. and Sekine, M., Silyl- and stannyl-esters of phosphorus oxyacids — intermediates for the synthesis of phosphate derivatives of biological interest, in Phosphorus Chemistry Directed Toward Biology, Stec, W.J., Ed., Pergamon, New York, 1980, p. 197. 

The deprotection procedure is based on transesterification of benzyl phosphate into the corresponding silyl ester followed by hydrolysis or alcoholysis. 

The phosphitylation procedure activated by tetrazole led to the phosphite structure (step a) which was effectively oxidized by TBHP to yield the corresponding phosphate (step b). Finally all 2-cyanoethyl protecting group were removed by the action of DBU in the presence of the silylating reagent bis(trimethylsilyl)acetamide BSA (step c). The latter is indispensable to secure total deprotection. 

The intermediate formed by action of DBU in the process of yS-elimina-tion (step a) is silylated by BSA to produce a neutral phosphate (step b) which undergoes a second -elimination (step c). The bis-trimethylsi-lylphosphate formed (step d) can be fully deprotected on exposure to water (step e). 

The etiolate intermediate, generated by the addition of higher-order cyanocuprates to enones, has been trapped with several electrophiles. Thus the addition of trimethylsilyl chloride, diethyl or diphenyl phosphorochloridate and iV-phenyltrifluoro methane-sulphonamide affords the corresponding vinyl silyl ethers, vinyl phosphates and vinyltri-flates. " ... 

Seong (2002) compared silylated (aldehyde) and silanated (amine and epoxy) compounds from several commercial sources to the performance of an antigen (IgG) microarray. In addition, the efficiency of phosphate-buffered saline (PBS) (pH 7.4) and carbonate (pH 9.6) printing buffers were compared. While the various slides and surface chemistries showed differences in their binding isotherms, they ultimately reached similar levels of saturation. Silylated (aldehyde) slides showed comparable loading in both buffer systems. Apparently, tethering of antibody to the surface by Schiff s base formation of the surface aldehyde and lysine residues on the protein was applicable over a broad pH. However, carbonate buffer increased binding of proteins on silanated surfaces. 

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