Alkyl diphenyl phosphonates

ALKENES Alkyl diphenyl phosphonates. o-Chloroallyllithium. Chlorotrynethyl-silane-Sodium iodide. Grignard reagents. Otganocuprates. Triphenylphosphine-lodoform-Imidazole. Trityl tetrafluoro-borate. 

W1TT1G-HORNER REACTION Alkyl diphenyl phosphonates. 1,3-Bis(di-methyl-phosphonoE2-propanone. Crown ethers. Dimethyl diazomethylphos-phonate. Tetra-n-hcxylammonium bromide. 

Tests in pure water, river water, and activated sludge showed that commercial ttiaryl phosphates and alkyl diphenyl phosphates undergo reasonably facile degradation by hydrolysis and biodegradation (163—165). The phosphonates can undergo biodegradation of the carbon-to-phosphoms bond by certain microorganisms (166,167). 

An optimised solid-phase method for the generation of diverse a-amino-alkyl or -aryl phosphonates derived from peptides and polymer-assisted solution-phase parallel synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates have been reported. A modular method for the construction of polypeptides containing the Phe-Arg phosphinic acid isostere has been described. A novel methodology for the solid-phase synthesis of phosphinic peptides has been developed in which the phosphorus-carbon bond was formed... 

Table 1 Synthesis of Diphenyl [l-(Benzyloxycarbonylamino)alkyl]phosphonates...

A soln of the diphenyl [l-(benzyloxycarbonylamino)alkyl]phosphonate 4 in 45% HBr/AcOH (150 mL per 0.1 mol) was kept at rt for 1 h. Removal of the solvent and volatile products in vacuo yielded the oily hydrobromide, which crystallized upon addition of anhyd Et20. The free amine was obtained by suspending the hydrobromide in CHC13 and shaking in a separatory funnel with an equal volume of 2M NaOH until all the solid dissolved. The CHC13 layer was separated, washed with brine, dried (MgS04), and concentrated to yield 19 in >90% yield mp (R1 = Me) 36-39°C mp (R = iPr) 60-63°C mp (R1 = iBu) 57-58 °C mp (R = Ph) 63-65 °C mp (R = Bzl) 65-67 °C. 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

The reaction of diphenyl methylphosphonate with lithium alkoxides gives phenyl alkyl methylphosphonates even with hindered alcohols and, in the case of chiral alcohols, with high diastereoselectivity at phosphorus. [Hydroxy(pho-sphoryloxy)X, iodo]benzenes 289, prepared from reactions of iodosobenzene with phosphonic or phosphinic acids react with ketones, esters or phenyl acetylene to give esters 290. Racemic l-hydroxy-4-(3-phenoxyphenyl)butylphosphonate diethyl ester undergoes stereoselective acetylation in the presence of a lipase to... 

General method for preparation of diphenyl esters of Gong-chain alkyl)phosphonic acids Equivalent amounts of the alcohol and triphenyl phosphite, together with 10 moles-% of sodium iodide, are placed in a flaskfitted with a thermometer, gas-inlet tube, stirrer, and distillation head water at about 50° is circulated through the attached condenser to prevent crystallization of the phenol. Nitrogen is led into the flask while the mixture is heated at the required temperature by a radiant heater until no more phenol distils (about 20 h). The remaining material is distilled at < 0.05 mm and the distillate is taken up in ether. The ethereal solution is washed with 2N-sodium hydroxide solution, dried and evaporated, and the residue is redistilled. 

Amino Acids and Peptides. - Wasserman s method of one-carbon homologation of carboxylic acids to give a-ketocarboxylates involves reaction with cyanomethylenetriphenyl-phosphorane followed by ozone (Scheme 24) and has been used as a key step in a chemo-enzymatic synthesis of isotopically labelled L-valine, L-isoleucine, and o/fo-isoleucine. Alkylation of the carbanion derived from the imino-substituted methylphosphonate diphenyl ester (186) with indol-3-ylmethyl bromide followed by appropriate deprotection has been used to prepare the phosphonate analogue (187) of tryptophan (Scheme 25). The deprotected analogue (188) and derived peptides show activity as inhibitors of chymotrypsin. Two approaches to solid phase Wadsworth-Enunons reactions which have applications in combinatorial chemistry have been reported. In one diethylphosphonoacetamide is bound to PEG-PAL resin via a peptide link, while... 

Morgan and Herr noted previously that di-(p-tolyl) methylphosphine oxide formed in 60% of the theoretical amount from diphenyl methyl-phosphonate with a one mole excess of p-tolyl Grignard reactant (148). No effort was made to imcover optimum conditions. Similarly, diallyh phenylphosphine oxide and other monomers were made by this general route (12,13). An excellent method for the synthesis of diphenyl alkyl-phosphonates was developed recently (126). No report has revealed an attempt to effect single displacement on phosphonates to give phos-phinates, and the effort to do so would probably be unprofitable. Phos-phinates have not been investigated in this type of reaction, but rapid conversion to phosphine oxides would be expected in spite of the mild... 

Although it might be expected that reactions which employed triarylmethyl halides would occur very readily, such reactions are rendered potentially more complex by the known nature of the halides and their propensity for involvement in free radical reactions. Whereas normal alkylation proceeds between sodium diethyl phosphite and diphenyl-methyl halides, success, or otherwise, in the use of the triphenylmethyl halides depends to some extent on the individual halide and on the metal in the phosphite salt. Thus, in an early study (in 1939), Arbuzov found that in reactions between silver dialkyl phosphites and triphenylmethyl bromide, dialkyl triphenylmethylphosphonates were indeed formed, but the use of the corresponding alkyl chloride provided the phosphite triester instead (metal dialkyl phosphites possess ambident anions ). A later study confirmed the behaviour of the silver salts towards the chloride, but also showed that, whereas dialkyl phophites with primary alkyl groups yielded phosphonic diesters (as had already been found), those with secondary alkyl groups afforded phosphite triesters moreover, the presence and nature of aromatic substituents were also able to control the course of the reaction. Reactions which involve triarylmethyl halides and sodium dialkyl phosphites may well be of a free radical nature since repeated studies have demonstrated the forma-... 

The mode of addition of hydrogenphosphonates to fluorinated ketones can also be complex. The addition of dialkyl, diphenyl or bis(trimethylsilyl) hydrogenphosphonates to methyl trifluoromethyl ketones occurs in the expected manner, but this contrasts with the behaviour of aryl perfluoralkyl ketones in the presence of triethylamine at room temperature, when the products, obtained even under such mild conditions, are phosphate esters (reaction 6), a situation which represents lack of stability of the hydroxyphospho-nate rather than novelty of the reaction under identical conditions, the corresponding alkyl aryl ketones fail to react. The same reaction with mixed-halogen ketones is still more involved, and the nature of the products depends on the reaction conditions if these are of a mild nature, and with catalysis by triethylamine or pyridine (depending on the particular ketone), the product is the expected (hydroxyalkyl)phosphonate 177, whereas with... 

---