Hydrogen-phosphonate

Phosphonic acid and hydrogen phosphonates are used as strong but slow-acting reducing agents. They cause precipitation of heavy metals from solutions of their salts and reduce sulfur dioxide to sulfur, and iodine to iodide in neutral or alkaline solution. 

Methyl p-D-ribofuranoside 5-(hydrogen phosphonate) or methyl 5-deoxy-p-D-ribofuranosid-5-yl hydrogen phosphonate... 

Scheme 21 summarizes further reactions leading to phosphonic acid analogues of amino acids. Treatment of the nitrone (138 R =Me or Pr ) with a dialkyl hydrogen phosphonate (best as the Li derivative which shows greater diastereoselectivity than the Na or K salts), and subsequent steps involving acidolysis of the oximino compound (139) lead to the free (ot-aminoalkyl)-phosphonic acids (140)(phosphonoalanine, phosphonova1ine). 

Addition of the P—H bond of hydrogen phosphonates (R0)2P(0)H across alkynes (hydrophosphorylation) may be catalyzed using both Pd° and Pd11 complexes.196 Reaction of oct-l-yne with either (MeO)2P(0)H or (EtO)2P(0)H affords the Markovnikoff adduct (Equation (18)) as the... 

Diethanol Sulfide Diethanolamine Diethanolethylamine Diethanolmethylamine Diethoxyethylphosphine Oxide Diethoxymethylphosphine Oxide Diethoxyphosphine Oxide Diethyene Disulfide Diethyl Acid Phosphate Diethyl Ethanephosphonate Diethyl Ethylphosphonate Diethyl Hydrogen Phosphate Diethyl Hydrogen Phosphite Diethyl Hydrogen Phosphonate Diethyl Isopropylphosphonate Diethyl Methanephosphonate Diethyl Methylphosphonate Diethyl Phosphate Diethyl Phosphite Diethyl Phosphonate Diethyl Phosphoric Acid Diethyl(2-hydroxyethyl)amine Diethyl(/S-hydroxyethyl)amine Diethylaminoethanol Diethylethanolamine Diethylfosfit... 

Although transition metal-mediated P-H addition across ordinary alkenes proceeds well only with five-membered cyclic hydrogen phosphonates, addition across the olefinic linkage of a,P-unsaturated compounds occurs readily with a range of phosphorus species and catalytic agents. Of particular note are the reaction systems involving platinum,96-107 palladium,108-115 and the lanthanides.116-122... 

Han, L.-B., Mirzaei, F., Zhao, C.-Q., and Tanaka, M., High reactivity of a five-membered cyclic hydrogen phosphonate leading to development of facile palladium-catalyzed hydrophosphorylation of alkenes, /. Am. Chem. Soc., 122, 5407, 2000. 

Improved yields of epoxyphosphonates of type (48) are reported for a development of existing synthetic methods, involving mixing of stoicheiometric amounts of hydrogen phosphonate, a-halogeno-ketone, and alkoxide.42... 

A novel demonstration of the latent reactivity of the phosphoryl bond and the apparent ease with which the number of ligands around the phosphorus atom can change under very mild conditions is provided by the hydrogen phosphonate (100), prepared from catechol and phosphorous acid or PC13. When treated with DCC,... 

Diastereoisomeric cyclic isothiocyanates (111) are formed when the bromidates (108 X = Br) react with KCNS, and when the hydrogen phosphonates (108 X = H) are treated with (SCN)a these reactions proceed with predominant retention and with inversion of configuration, respectively.81 This initial study of the formation of the thiocyanatidates (109) was rendered difficult by the rapid epimeriza-... 

Further studies on 1,3-dipolar addition reactions of diazophosphonates have been recorded,122 and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155 R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbonyl)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155 R = Me) does not react in the manner described above. 

When a solution of the ester (155 R = H) in dioxan is warmed at 80 °C, the phosphonate (156) is produced together with about 5% yields of each of dimethyl hydrogen phosphonate and diazoacetoacetic ester (Scheme 8) the enol phosphate (157) could not be detected. The explanation for this sequence of reactions also relies on proton mobility, and the reaction is known to be acid-catalysed.124... 

Transition Metal-Catalyzed Addition of Hydrogen Phosphonate. 36... 

Hydrogen phosphonates [(R0)2P(0)H] and secondary phosphine oxides R2P(0)H exist in equilibrium with their P(III) tautomers, (RO)2P(OH) and R2P(0H), respectively, the P(V) tautomers being more favored under ambient conditions. As ligands, they coordinate, like tertiary phosphines, to transition metals to form complexes, which have been used as catalysts for organic reactions. However, catalytic addition reactions of P(V)-H bonds have not been scrutinized until recently. 

The H-P bond in hydrogen phosphonates readily adds across a C=C bond [22]. Upon treatment of 1-octyne with dimethyl phosphonate in the presence of a palladium complex in refluxing tetrahydrofuran, the addition reaction proceeds smoothly to afford dimethyl l-octen-2-ylphosphonate (2) regio-and stereo-selectively (Scheme 18). 

When the reaction is run using excess hydrogen phosphonate (3 equivalents), sequential addition of two molecules of the phosphonate takes place to form 1,2-bisphosphonate as shown in Scheme 21 [23]. As described above, the first addition affords the branched isomer with a trace of the linear byproduct. Only the former is reactive to undergo the second addition forming the bisphosphonate as illustrated in Scheme 22. 

Rhodium complexes are not active in the addition reaction of acyclic hydrogen phosphonates such as dimethyl phosphonate. However, RhCl(PPh3)3 has proved to catalyze the reaction efficiently when the five-membered one 4a was used [24]. 

The favorable performance of polar solvents is associated with the concentration of the active species. At least five species (5-9) are generated in the mixture upon treatment of RhCl(PPh3)3 with the five-membered hydrogen phosphonate 4a (Scheme 23). Species 8 and 9, which are not ligated by triphenylphosphine, have proved to be inactive, while 5-7 are all able to catalyze the reaction. 

Alkenes are much less reactive in the H-P bond addition reactions than alkynes. However, 1,3,2-dioxaphospholane 2-oxide (4a), a five-membered hydrogen phosphonate of pinacol, is exceptionally reactive with alkenes although dialkyl and diaryl phosphonates such as 4b-d are totally unreactive (Scheme 25) [26]. Very interestingly, six-membered hydrogen phosphonates 4e,f are also unreactive under identical conditions. 

As for the oxidative addition (step i), both cyclic and acyclic hydrogen phosphonates, 4a and 4b, react with Pd(0) to generate the corresponding adducts 12a and 12b (Scheme 29). Although five-membered 4a is somewhat more reactive, this small difference in reactivity does not account for the lack of catalytic addition of 4b. 

As expected, hydrogen phosphinate, which is a hybrid structure of hydrogen phosphonate and secondary phosphine oxide, adds to alkynes in the presence of the Pd-diphenylphosphinic acid catalyst system (Scheme 44) [36]. Normally, branched isomers are the major products, while trimethylsily-lacetylene exceptionally affords the corresponding terminally phosphinylat-ed product. Diphenylacetylene also reacts to afford the corresponding adduct in 99% yield. 

By using Josiphos ligands, palladium-catalysed hydrophosphorylation of norbomen-es with hydrogen phosphonates proceeds efficiently to give the corresponding phos-phonates in high enantioselectivities.90... 

Phosphonylation. This reagent is useful for preparation of protected deoxy-ribonucleoside-3-hydrogen phosphonates (2), which can be used for synthesis of deoxyribonucleotides. 

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