Methylphosphonates, synthesis

Waschbusch, R., Carran, J., Marinetti, A., Savignac, P. The synthesis of dialkyl a-halogenated methylphosphonates. Synthesis 1997, 727-743. 

Mikolajczyk, M., and Balczewski, P, Qrganosulfur compounds. Part 48. Synthesis and reactivity of diethyl (methylthio)(trimethylsilyl)methylphosphonate. Synthesis, 101, 1989. 

The phosphonamidite reagents needed to synthesize methylphosphonate oligonucleotides are commercially available. The standard procedures used for the synthesis of phosphodiester oligonucleotides work poorly for methylphosphonate synthesis, particularly at >l- jmol scale. There are two primary factors that account for the poor efficiency of methylphosphonate synthesis. First, NMR studies have shown that the methylphosphonite P(III) diester intermediate is more susceptible to hydrolysis by tetrazole, the capping reagent, and water compared to the phosphite diester intermediate see Fig. 1 for a schematic of the synthesis cycle and degradative side reactions). For this reason, it is necessary to ... 

In order to compare standard and improved methylphosphonate synthesis conditions, an all-methylphosphonate oligonucleotide (5 -ACTAGTGCATCGACTGA) was synthesized on a 15- 0mol scale. 

Soroka, M., A simple preparation of methylphosphonous dichloride, Synthesis, 450, 1977. 

Elkaim, J.C., Casabianca, F., and Riess, J.G., The direct synthesis of dibromo-methylphosphonic dibromide and some of its derivatives, Synth. React. Inorg. Met.-Org. Chem., 9, 479, 1979. 

Example 55 iV,iSr-diisopropyl-4-nitrophenylmethylphosphonoamidite has been applied in the synthesis of oligonucleoside methylphosphonates [89]. This stable crystalline compound prepared from methyldichlorophosphine, was employed in two ways in a procedure similar to that presented in the Examples 42 and 43. 

Jayaraman, K., McParland, K., Miller, P., and Tso, P.O.P. 1981. Non-ionic oligonucleoside methylphosphonates. 4. Selective inhibition of Escherichia coli protein synthesis and growth by non-ionic oligonucleotides complementary to the 3 end of 16S ribosomal-RNA. Proc. Natl. Acad. Sci. U.S.A. 78 1537-1541. 

Synthesis of l,4,2-benzodiazaphosphepin-5-one 2-oxides 277 was conducted in good overall yield from 5-chloro-2-nitrobenzoyl chloride 273 and substituted (amino)methylphosphonates 274. The key step in this method is the base-induced cyclization of (2-aminobenzamido)methylphosphonates 276 to the l,4,2-benzodiazaphosphepin-5-one 2-oxides 277 <1999JOC8156>. 

Hydrazines reacted with 4-, 5-, and 6-chloro-l-alkynylphosphonates to provide the corresponding 4,5-dihydropyr-azolo-3-methylphosphonates <2007TL3213>. A novel one-pot synthesis of substituted pyrazoles from chalcones and hydrazines in a tandem cyclization-dehydrogenation approach on Pd/C/K-10 catalyst has been described <2007SL1600>. 

Alkyl, Cycloalkyl, Arylalkyl and Related Acids. An improved synthesis of alkyl methylphosphonic acids (159) has been reported. It involves partial trans-esterification of trimethyl phosphite, followed by an Arbuzov reaction of the... 

A scale-up synthesis of isosteric phosphonate analogue (178) of mannose-6-phosphate (M6P) has been perfonned via regioselective nucleophilic displacement of the protected 4,6-cyclic sulfate precursor (179) by lithiated dialkyl methylphosphonates in the key step. ... 

The synthesis of novel HBV-specific antiviral agents, the 2-amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl]purine bis (2,2,2-trifluoroethyl) esters (87a-r) has been reported. These phosphonate diesters were prepared by the reaction of substituted purines with bis-(trifluoroethyl) (2-iodoethoxy)methylphosphonate in the presence of DBU. ... 

Horner-Wadsworth-Emmons Reactions of Phosphonate Anions. - As with the Horner modification of the Wittig reaction, the principal focus of papers that mention the Horner-Wadsworth-Emmons reaction relate to synthetic applications. The use of pressure to induce the synthesis of P-amino esters, p-thioesters and P-thionitriles via tandem Horner-Wadsworth-Emmons and Michael reactions has been reported. The reagent (l-tritylimidazol-4-yl)methylphosphonate (99) has been prepared and, when treated with aldehydes and ketones, affords (E)-vinylimidazoles in high yields. ... 

Remarkable diastereoselectivity has been achieved in the synthesis of dinucleoside methylphosphonates from the reactions of dichloro-(methyl)phosphine with suitably protected nucleosides at low temperatures.Various phosphapolyboranes have been obtained from the reactions of dichloro(methyl)phosphine with polyborane... 

G.A. Kraus and co-workers utilized the quasi-Favorskii rearrangement of a bicyclic bridgehead bromide as the key step in their formal total synthesis of ep/-modhephene. The required bicyclo[3.3.1]nonenone bridgehead bromide precursor was prepared by a Robinson annulation reaction between 3-bromo-2-oxocyclohexanecarboxylate and MVK. Upon treatment with lithiated dimethyl methylphosphonate, the bicyclic bromo ketone underwent a facile quasi-Favorskii rearrangement to afford the key intermediate bicyclo[3.3.0]octane derivative. 

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