A- alkylphosphonates

Hanessian, S., and Bennani, Y.L., A versatile asymmetric synthesis of a-amino a-alkylphosphonic acids of high enantiomeric purity, Tetrahedron Lett., 31, 6465, 1990. 

Triethyl phosphite is a colourless mobile liquid, insoluble in water. Trialkyl phosphites are valuable intermediates in the preparation of many organophosphorus compounds they readily form dialkyl esters of alkylphosphonic acids by the Arbusov reaction (p. 311). 

If R = R, the reaction appears to be catalytic as a small quantity of R Cl will suffice to convert a considerable quantity of the trialkyl phosphite into the dialkyl alkylphosphonate (I). As little as o-i mol. of the alkyl iodide will suffice to isomerise the trialkyl phosphite. 

Trialkyl esters of phosphonic acid exist ia two structurally isomeric forms. The trialkylphosphites, P(OR)2, are isomers of the more stable phosphonates, 0=PR(0R)2, and the former may be rearranged to resemble the latter with catalytic quantities of alkylating agent. The dialkyl alkylphosphonates are used as flame retardants, plasticizers, and iatermediates. The MichaeUs-Arbusov reaction may be used for a variety of compound types, including mono- and diphosphites having aryl as weU as alkyl substituents (22). Triaryl phosphites do not readily undergo the MichaeUs-Arbusov reaction, although there are a few special cases. 

Compounds with a P-C bond can be observed to a large extent in the field of bi- and poly functional phosphorus-containing surfactants. Alkylphosphonic... 

The strained hydrocarbon [1,1,1] propellane is of special interest because of the thermodynamic and kinetic ease of addition of free radicals (R ) to it. The resulting R-substituted [ 1.1.1]pent-1-yl radicals (Eq. 3, Scheme 26) have attracted attention because of their highly pyramidal structure and consequent potentially increased reactivity. R-substituted [1.1.1]pent-1-yl radicals have a propensity to bond to three-coordinate phosphorus that is greater than that of a primary alkyl radical and similar to that of phenyl radicals. They can add irreversibly to phosphines or alkylphosphinites to afford new alkylphosphonites or alkylphosphonates via radical chain processes (Scheme 26) [63]. The high propensity of a R-substituted [1.1.1] pent-1-yl radical to react with three-coordinate phosphorus molecules reflects its highly pyramidal structure, which is accompanied by the increased s-character of its SOMO orbital and the strength of the P-C bond in the intermediate phosphoranyl radical. 

During the last decade, Bentrude et al. [65] has shown that the triplet-sensitized photorearrangement of allylphosphites and analogs (Scheme 28) is a powerful method for preparation of alkylphosphonates from phosphites. Moderate to high yields were observed when triphenylene was used as photosensitizer [66,67]. 

G.l.c. studies of tributylphosphine, dialkyl phosphites, and dialkyl alkylphosphonates are reported. Tributyl phosphate in nitric acid can be estimated by g.l.c. if a glass column is used. Tetraethyl pyrophosphate has been directly determined on a nanogram scale by g.l.c., whereas it was found most convenient to first convert the tetra-aryl pyrophosphates by methanolysis to diarylmethyl phosphates. Phosphorochloridates were converted by t-butyl alcohol into t-butyl chloride before analysis. G.l.c. studies of pesticides have been reported and the isomeric thiophosphates (138a) and (138b) have quite different retention times. ... 

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

Reactions and Properties of Phosphonic and Phosphinic Acids and their Derivatives.-A free radical mechanism has been proposed to account for the cleavage of the phosphorus-carbon bond in the alkylphosphonic acids (155) by E coli to give a mixture of alkane (methane only, from methylphosphonic acid) and terminal alkene. 

Shpaisman FI, Salomon E, Nesher G, Vilan A, Cohen H, Kahn A, Cahen D (2009) Electrical transport and photoemission experiments of alkylphosphonate monolayers on GaAs. J Phys ChemC 113 3313-3321... 

The reactions used for synthesis of II-VI (CdSe, CdTe), III-V (InP, InAs), and IV-VI (PbS, PbSe, PbTe) semiconductor nanocrystals are outlined by Schemes 3-5.4,17,30-32 The syntheses are carried out at high temperatures, and in the presence of long-chain alkylphosphines (trioctylphosphine,TOP), alkyl-phosphine oxides (trioctylphosphine oxide, TOPO), alkylamines (hexadecyl-amine, HD A), and alkylphosphonic acids as the stabilizing agents. 

A similar approach, using toluene instead of dioxane and molten white phosphorus rather than a suspension of red phosphorus, has been described in two patents for the preparation of alkylphosphonic... 

Sekine, M., Nakajima, M., Kume, A., Hashizume, A., and Hata, T., Versatile utility of a-(trimethylsiloxy)alkylphosphonates as key intermediates for transformation of aldehydes into several carbonyl derivatives, Bull. Chem. Soc. Jpn., 55, 224, 1982. 

In the example shown in Fig. 7.6, using an alkylphosphoric acid, about 60 stages are required to give a Co/Ni ratio of about 100. So many stages would be too many for mixer-settler operation, and other types of contactors would have to be considered. In this particular example, a sieve plate pulsed column has been shown to be very effective [3]. Flowever, with the development of the alkylphosphonic and alkylphosphinic acids, the separation of cobalt and nickel can be achieved in very few stages, owing to the high rejection of nickel (see Chapter 11). 

In the asymmetric addition to alkenylphosphonate 33 (Eq. 2) [25], the yield is dependent on the amount of water present. The combination of boroxine and water (1 equiv. relative to boron) gave a high yield of the desired product 34, with 96% enantiomeric excess. The alkylphosphonate 34 can be used as a chiral building block for the synthesis of optically active alkenes, using a Horner-Emmons type of reaction. 

Hydrolysis of the phosphonodiamides 2 (R1 = CH3) under mild conditions gave a-substi-tuted alkylphosphonic acids 3 (R1 = CH3) with excellent yields, with concomitant recovery of the chiral auxiliary. For further examples see Table 1. 

Peptide synthesis. The anhydride effects peptide synthesis as shown in equation (I). Free acid groups arc buffered with a tertiary amine such as N-elhylmorpholine. The reaction is complete after 24 hours at room temperature. No raccmization is detected in the Anderson-Young test. The resulting alkylphosphonic acid derivative is soluble in water and easily removed. 

To a soln of the methyl alkylphosphonate 50 (0.5 mmol), the alcohol 59 (0.75 mmol), and Ph3P (0.75 mmol) dissolved in anhyd THF (5mL) were added DIAD (0.75 mmol) and TEA (5 mmol), followed by the a-hydroxy acid (lmmol). Upon completion of the condensation reaction, TMSBr (1.5 mmol) was added and stirring continued for an additional 1 h. The mixture was diluted with E O (10 mL) and extracted with 5% NaHC03 (2xl0mL). The aqueous phase was washed with E O (3 x 10mL), acidified to pH 2 with coned HC1, and extracted with EtOAc (3 x lOmL). The EtOAc phase was dried (MgS04), filtered, and concentrated under reduced pressure. This material was suitable for additional synthetic steps or could be isolated in pure form as the 1-adamantanamine salt from E O or hexane. Characterization of (R,5)-Z-Valp-(0)-D-Val-OMe (60 R1 = R2=iPr), isolated in 69% yield after 4h reaction 31P NMR (5) 24.23, 23.94. 

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