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In contrast to both its parent “troika” acid ( E - 1 , a phosphorylating agent at pH 7 and 25 °C) and its C-methyl isomer ( E - 2 , which is stable at both acidic and neutral pH), ( E )-(hydroxyimino)(hydroxymethoxyphosphinyl)acetic acid E - 3 was unreactive at pH 7 and 25 °C but at pH 1.5 fragmented to methyl phosphate 10 (15%) and methyl phosphorocyanidate 11 (85%). The minor product is consistent with solvent phosphorylalion, the reaction exclusively observed with E - 1 . The non-phosphorylating fragmentation pathway is proposed to involve a preliminary E → Z isomerizalion of 3 prior to C α -C β cleavage. Dual fragmentation pathways were also detected ( 31 P NMR) when the DCHA + salt of E - 3 ( E - 9 ) was heated in acetonitrile or EtOH; in addition to phosphorylation products (16–19%), 11 was formed (81–84%). Reaction of E - 9 in refluxing EtOH: t -BuOH (1:1) showed low stereoselectivity in product formation (~3:1 ethyl methyl phosphate: t -butyl methyl phosphate), supporting a dissociative phosphorylation process.

Carbonylphosphonates are defined for the purposes of this Review as phosphonates containing a proximal C=O function. In this review we focus on α-keto and β-ketophosphonates, including two classes of trifunctional carbonyl phosphonates, α-ketophosphonoglyoxylates and carbonylbisphosphonates. These compounds (and analogous derivatives) exhibit distinctive, multiple chemical properties reflecting in part the mutual intereaction of their neighboring carbonyl and phosphonate groups. In some cases, they present special problems in synthesis, and they have useful applications ranging from metal chelation to medicinal chemistry. Here they are considered from the points of view of synthesis, reactivity, value as synthons, and actual or potential bioactivity. Recent (>1995) advances are emphasized.

The paper describes a simple, direct synthesis of enantiopure cyclic α-aminophosphonic acids on the basis of silyldealkylation and followed by hydrolysis of the parent diastereoisomeric cyclic 1,4,2-oxazaphosphorines, which have been obtained by intramolecular stereospecific nucleophilic addition of phosphites to imines. In this approach, the high diastereoselectivity of the stereocontrolling penultimate step is preserved by conversion of the intermediate ester to the final phosphonic acid under very mild, nonracemizing conditions. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:575–582, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20480

Triethyl fluorophosphonoacetate and triethyl difluorophosphonoacetate are directly synthesized from triethyl phosphonoacetate by treatment with NaH and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor®). Contrary to a recent report [C.J. Hamilton, S.M. Roberts, J. Chem. Soc., Perkin Trans. 1 (1999) 1051–1056], the reaction proceeded in THF without the need for DMF as a co-solvent. This method is more selective and provides greater convenience and safety than fluorination of the same substrate by treatment with t-BuOK and perchloryl fluoride (FClO3) in toluene while offering advantages over a number of previously described methods employing alternative electrophilic fluorinating reagents or other approaches. Either the monofluoro or the difluoro product can be obtained predominantly by adjusting the molar ratio of base and Selectfluor®. Triethyl 2-fluoro-2-phosphonopropionate (ethyl 2-(diethoxyphosphinyl)-2-fluoropropanoate) is also more conveniently made from triethyl 2-phosphonopropanoate using NaH/Selectfluor® in THF than with FClO3/t-BuOK in toluene. Detailed procedures are given for obtaining the corresponding triacids in quantitative yield from the fluorinated triesters by P,P-silyldealkylation with bromotrimethylsilane followed by one-pot double hydrolysis with H2O, and isolation as stable dicyclohexylammonium (DCHA) or pyridinium (Py) salts. Substitution of EtOH for H2O in the latter procedure provides the CO-ester phosphonic diacids, isolated as DCHA salts, in one step. 1H, 13C, 31P and 19F NMR data are given for the compounds prepared.