Tris phosphite phosphonic acids

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

This protocol was used by Iyer and co-workers in their synthesis of potential antiviral prodrugs,46 and is derived from the method of Sekine and Hata.50 It is important not to use excess tris(trimethylsilyl) phosphite (18) in such reactions to avoid formation of carbonyl adducts (20 Scheme 11). Removal of the trimethylsilyl groups is facile (e.g. methanolysis yields the free phosphonic acids) and may be undertaken on the crude product. 

The reaction of trimethyl phosphite with sodium iodide in acetonitrile, when tried on 2,6-diphenylthiopyrylium cation (18), failed to give the desired phosphonate 323 (80JOC2453). It has been reported, however, that 2,6-diphenyl-pyrylium (17) and -thiopyrylium (18) bromides react with triethyl phosphite to give the diethyl phosphonates 322 and 323, respectively (7IDOK600). These can be hydrolyzed with HCl to give the pyranyl-and thiopyranyl-phosphonic acids 326 and 327, which treated with triphe-nylmethyl perchlorate give the pyrylium- and thiopyrylium-4-ylphospho-nic acids 328 and 329. 

With tris(trimethylsilyl)phosphite, regiospecific and irreversible adduct formation with 2( H)-pyrimidinones gives 3,4-dihydro-4-phosphonic acid silyl esters (317) which furnish the phosphonic acid (318) on treatment with methanol (Scheme 53). The regiochemistry is attributed to the bulkiness of the phosphite reagent. The carbon-phosphorus bond resisted cleavage by TFA <87ACS(B)448>. 

The diethyl ester of 2,3-epoxypropyl phosphonic acid reacts with equimolar quantities of dialkyl H-phosphonate and the corresponding sodium dialkyl phosphite, forming 1,2,3-tris-dialkylphosphono-propane. This reaction is suggested to take place according to the following scheme [386] ... 

Reducing agents Aluminum hydride. Bis-3-methyl-2-butylborane. n-Butyllithium-Pyridine. Calcium borohydride. Chloroiridic acid. Chromous acetate. Chromous chloride. Chromous sulfate. Copper chromite. Diborane. Diborane-Boron trifluoride. Diborane-Sodium borohydride. Diethyl phosphonate. Diimide. Diisobutylaluminum hydride. Dimethyl sulfide. Hexamethylphosphorous triamide. Iridium tetrachloride. Lead. Lithium alkyla-mines. Lithium aluminum hydride. Lithium aluminum hydride-Aluminum chloride. Lithium-Ammonia. Lithium diisobutylmethylaluminum hydride. Lithium-Diphenyl. Lithium ethylenediamine. Lithium-Hexamethylphosphoric triamide. Lithium hydride. Lithium triethoxyaluminum hydride. Lithium tri-/-butoxyaluminum hydride. Nickel-aluminum alloy. Pyridine-n-Butyllithium. Sodium amalgam. Sodium-Ammonia. Sodium borohydride. Sodium borohydride-BFs, see DDQ. Sodium dihydrobis-(2-methoxyethoxy) aluminate. Sodium hydrosulflte. Sodium telluride. Stannous chloride. Tin-HBr. Tri-n-butyltin hydride. Trimethyl phosphite, see Dinitrogen tetroxide. 

A variant of the Mannich reaction using an equilibration between phosphorus acid and a trialkyl phosphite was developed [36]. The trialkyl phosphite was synthesised in situ by the reaction of phosphorus trichloride with PO, with the formation of tris (2-chloropropyl) phosphite (reaction 18.14). By equilibration of phosphorus acid with tris (2-chloropropyl) phosphite, bis (2-chloropropyl) phosphite (reaction 18.15) is formed which, by reaction with oxazolidine, gives an interesting phosphonate polyol containing phosphorus, chlorine and nitrogen (reaction 18.16) ... 

Optically active phosphorus(iii) acid esters PhR P (OR ) have recently been prepared for the first time by the reaction of a chiral phosphorus chloride and an alcohol or thiol in the presence of an optically active amine, in this case (-)-NN-dimethyl-(l-phenylethyl)amine. (See also Refs. 449 and 450). A kinetic investigation shows that phosphorous acid and chloral react to give 2,2,2-trichloro-l-hydroxyethyl phosphonate at a much lower rate than the corresponding reaction with dimethyl hydrogen phosphite. Phosphorus trichloride and dialkyl phosphites (R0)2P(0)H have been shown to react at low temperature in the presence of pyridine, producing tris(dialkoxyphosphoryl)phosphines [(RO)2P(0)]3P. ... 

Organophosphorus compounds (OPs) are utilized on a large scale as flame retarding agents and plasticizers in a variety of products, such as plastic materials, rubbers, varnishes, lubricants, hydraulic fluids, and other industrial applications. This family of chemicals consists of alkylated and arylated phosphate or phosphonate esters and related compounds such as phosphites, phosphines, and related dimeric forms as well as ionic forms (Figure 31.2). " The low volatility of phosphoric acid and derivatives makes it the preferred choice of the phosphorus based FRs. These FRs are most effective in polymers that char readily. Also halogenated phosphate esters, such as tris(l-chloroisopropyl) phosphate (TCPP), and tris(2-chloroethyl) phosphate (TCEP), are widely used. These combine the properties of both the halogen and the phosphorus compounds. 

A parallel series of reactions has been observed for tris(2-chloroethyl)phosphite . The formation of diethyl (2-oxoalkyl)phosphonates by the oxidation (by m-chloroperoxyben-zoic acid) of the products from the interaction of triethyl phosphite and nitroalkenes in the presence of TiCl4, is consistent with the intermediate formation of C-phosphorylated aci-nitro complexes When the phosphite triester species is a dialkyl trimethylsilyl phosphite. 

In addition to the classical form of the Michaelis-Arbuzov reaction, several non-classical variations have proved to be of great use with regard to general applicability and for the preparation of specific compounds. For instance, the ring opening of A-acylaziridines, by either trialkyl phosphites or phosphonous diesters, or by tris(trimethylsilyl)phos-phite, leads to dialkyl [2-(A-alkylamino)ethyl]phosphonates, or their bis(trimethylsilyl) diesters in A-protected forms from which A-protection may be removed under aqueous acid conditions (Scheme 13). 

Enol phosphates phosphonates were also obtained by the reaction of perfluoroalkanoyl chlorides with triethyl phosphite. In this case, it was not possible to isolate the putative intermediate perfluoroacylphosphonates. This result is in contrast with the facile formation of bis (trialkylsilyl) trifluoroacetylphosphonates (see previous section), and it indicates that acylphosphonates derived from carboxylic acids with strongly electron-withdrawing groups can be prepared using tris(trialkylsilyl) phosphites. Such silyl phosphites seem to be uniquely suitable for this purpose, by virtue of their high reactivity in the first step and their steric hindrance, which presumably retards the second step. 

Attack on Saturated Carbon. - Ethylene dicarboxylic diphosphonic acid (EDCP, 2) has been prepared in 70% yield from 2,3-dichlorosuccinic anhydride (3) and trimethyl phosphite, followed by hydrolysis of the Arbuzov product. Tris(trimethylsilyl) phosphite, in contrast to trialkyl phosphites, attacks an oxirane carbon of epibalohydrins (4) to give the phosphonates (5). Bis(trimethylsilyl) phosphonite (6) has previously been prepared in situ and used to obtain y-ketophosphinic acids similar reactions with simple alkyl halides to give alkylphosphinic and dialkylphosphinic acids acids in high yields have now been described. ... 

Titanium tetrachloride is an efficient reagent for the conversion of trialkyl phosphites and dialkyl hydrogen phosphonates into dialkyl phosphorochloridates. Imidazolides and dialkyl or diaryl phosphoric acids react with acyl fluorides - benzoyl fluoride and oxalyl difluoride being the reagents of choice - to give quantitative yields of the phosphoryl fluorides. The procedure is adaptable to the preparation of fluorides of carbohydrate phosphates in this field, the reaction between the ceu bohydrate and tris-l//-imidazolylphosphine oxide or sulphide with the replacement of one imidazole... 

Shibasaki developed the first catalytic enantioselective hydropho-sphonylation of aldimines with the use of chiral heterobimetallic lantha-num(iii) potassium(i) tris(binaphtholate) 89, which provides optically active a-amino phosphonates with high enantioselectivities (Scheme 2.50). Similar to lithium catalyst 26 and sodium catalyst 67, potassium catalyst 89 acts as an acid-base bifunctional catalyst to activate both nucleophiles and electrophiles. In particular, in this reaction, deprotonation of dimethyl phosphite by more basic potassium catalyst 89 was essential for increasing the reactivity and enantioselectivity, while less basic lithium catalyst 26 and sodium catalyst 67 were not effective. 

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