Dialkyl phosphites phosphonates

A different method was worked out for radic al substitution by cyclohexane.169 Irradiation of this hydrocarbon together with a dialkyl phosphite, phosphonous... 

Diesters of phosphorous acid are in general neutral because the phosphorous acid exists mostly in the phosphonate form with one hydrogen directly attached to the phosphorus. But with alkali metals the H can be changed against the alkali and reactive intermediates formed. Such alkali metal derivatives of dialkyl phosphites react with alkyl halides to give dialkyl alkanephosphonates, according to Eqs. (45) and (46). 

Reaction of Unsaturated Compounds with Dialkyl Phosphites The diesters of phosphorous acid are somewhat resistant to oxidation and used as intermediates for the reaction with olefins forming phosphonic acids. The reaction takes place in the presence of free radical initiators, such as di-/-bu-tyl peroxide [104,105]. 

Another method for the preparation of hydroxyalkanephosphonic acids is the conversion of aldehydes with dialkyl phosphites in the presence of triethylamine or sodium methylate leading directly to the corresponding a-hydroxyalkane-phosphonates. This reaction is reversible, leading to the starting materials aldehyde and diethyl phosphite again [143,146]. 

Et or Bu) and the phosphonation of iodoaromatics with dialkyl phosphonates, although in this case with poorer yields (better results of the dialkyl arylphosphonates are obtained by photostimulation). Chemical oxidation (using AgNO -peroxodi-sulphate) and anodic oxidation of aromatics in the presence of trialkyl phosphites produces dialkyl arylphosphonates in good yields. The Cul-catalysed arylation of dialkyl (cyanomethyl)-phosphonates affords dialkyl (a-cyanobenzyl)phosphonates. ... 

The base-catalyzed reaction of dialkyl phosphite with nitroalkenes results in the formation of alkenyl phosphonates (Eq. 4.33).39... 

Preparation of diethyl pyridine-2-phosphonate — Reaction of an N-methoxy pyridinium salt with a dialkyl phosphite salt... 

Preparation of diethyl 3,3-diethoxypropynyl-l-phosphonate — Reaction of a sodium salt of a dialkyl phosphite with an acetylenic halide492... 

Corresponding replacement of halide from an unconjugated vinylic site has also been reported. The use of the sodium salts of dialkyl phosphites in tetrahydrofuran at low temperature has been found to provide the vinylic phosphonate in good yield,72 (Figure 6.22) and triisopropyl phosphite serves similarly to replace a fluoride of trifluoroiodoethene (Figure 6.23).91 The reaction proceeds ste-reospecifically to replace the fluoride cis to the iodide, and in continuing reaction the iodide is replaced. 

Nitrone reactions with lithiated dialkyl phosphite results in the formation of a-(hydroxyamino)phosphonate, which, depending on the character of the R substituent at a-C lead to a-phosphorylated nitrones (429) or fS-phosphorylated nitroxyl radicals (430) after successive oxidations (Scheme 2.200) (686—689). 

Pudovik AN (1952) Addition of dialkyl phosphites to imines. New method of synthesis of esters of amino phosphonic acids. Dokl Akad Nauk SSSR 83 865-868... 

The ornithine related phosphonate (n = 3) can be guanidylated at the 4-amino group by treatment with formamidinesulfonic acid to provide Argp(OPh)2. This method can be used for the synthesis of substrate-related thrombin inhibitors such as Ac-Phe-Pro-Argp(OPh)2. 41 Proline analogues required a special approach and a few synthetic methods are reported since dipeptides of Prop(OPh)2 are excellent inhibitors of dipeptidyl peptidase IV (DPP IV or CD 26), the serine protease involved in immune response. 4 Diphenyl phosphite and dialkyl phosphites react smoothly with 1-pyrrolidine (3,4-dihydro-2//-pyrrole) trimer 20 to give the corresponding pyrrolidine-2-phosphonate 21 (Scheme 14). 42 ... 

Palladium-catalyzed cross-coupling reactions of diaryliodonium tetrafluo-roborates have recently been employed for conversions of mercaptans to aryl-and diaryl sulfides, sodium arenesulfinates to diaryl sulfones, and dialkyl phosphites to aryl phosphonates (Scheme 43) [120-122]. 

The dialkyl phosphites can be readily converted into their corresponding free a-hydroxy phosphonic acids, as has been shown by Wynberg and co-workers... 

The 9-carbonyl group of diazafluorenones behaves in an analogous manner to that in fluorenone reduction to the 9-ol and to the fluorene <70AJC1023>, reaction with dialkyl phosphites to yield 9-hydroxy-9-phosphonic esters <84JPR349>, and with acetone to give the 9-hydroxy-9-(2-oxopropyl) analogue <62CB2137>. 

Dialkyl phosphites and their metal salts seldom undergo the Perkow reaction with a-halo-aldehydes or -ketones but usually yield a-hydroxy- and/or epoxy-phosphonate esters (i.e. Pudovik reaction products, cf. Section 6).78... 

Acyclic sugars behave similarly, thus, 2,3 4,5-di-0-isopropylidene-D-arabinose reacts with dialkyl phosphites affording (15)-2,3 4,5-di-0-isopropylidene-D-arabitol-l-phosphonates 11. The formation of the new stereogenic center is a fully stereoselective process. The phosphonates obtained can be hydrolyzed to give enantiomerically pure (lS)-D-arabitol-l-phosphonic acid32. 

Other sugar aldonitrones also give phosphonates on treatment with dialkyl phosphites. For example, a-deoxysugar derivatives give the (5A)-epimer of the phosphonate as the major product (the epimers could be separated by column chromatography). Flowever, in the case of nitrones with an unsubstituted 3-hydroxy group (R1 = H), the (5R)-epimcric phosphonates 12 and 13 (R1 = H) are the sole products44. 

Two methods have been presented for the phosphonation of poly(bro-moaryloxyphosphazenes), viz. via sodium dialkyl phosphite as reagent or via a treatment with Bu Li in combination with dialkyl chlorophosphate. The reactions are visualized by the product formation of (206) and (208) from (205) and (207), respectively. Polyphosphazenes with diphenyl phosphonate groups (209) have been synthesized by the reaction of the bromophenoxy substituted polymer (207) with Bu Li followed by a rapid addition of diphenyl chlorophosphate in thf. Only 50% of the available bromophenoxy groups are converted to diphenyl phosphonate esters groups. ... 

Both a-amino- (21) and a-hydrazino-phosphonic acids (22) have been prepared from aliphatic aldazines by the addition of dialkyl phosphites, followed by reduction and hydrolysis, respectively (see Scheme 4). ... 

Sturtz, G., Chartier, C., and Normant, H., Effect of 1-bromoacetylene derivatives on sodium dialkyl phosphites. Preparation of long-chain P-oxo phosphonates. Bull. Soc. Chim. Fr., 1707, 1966. 

Conant, J.B.. and Coyne, B.B., Addition reactions of the phosphorus halides. Part 5. The foimation of an unsaturated phosphonic acid, J. Am. Chem. Soc., 44, 2530, 1922 Chem. Abstr., 17, 273a. 1923. Gajda. T.. A convenient synthesis of diethyl 1-chloroalkylphosphonates, Synthesis, 111, 1990. Pudovik, A.N.. Zimin, M.G., and Sobanov, A.A., Reactions of dialkyl phosphites withketones activated by electronegative groups, Zh. Obshch. Khim., 42, 2174. 1972 Chem. Abstr., 78, 58543, 1973. Johnson. R.A.. Aryhnethylphosphonates and phosphonic acids useful as anti-inflammatory agents, their preparation, and their activity, Upjohn, U.S. Patent Appl. US 5500417, 1996 Chem. Abstr. 124. 307587. 1996. 

The reaction between a-halo ketones and sodium dialkyl phosphites has been extended to phosphonate carbanions. For example, diisopropyl 1 -lithio-1-fluoromethylphosphonate, generated from diisopropyl fluoromethylphosphonate and LDA, reacts with 3-chloro-2-butanone at low temperature in THF to give diisopropyl l-fluoro-2-nicthyl-2,3-cpoxybutylphosphonate in 46% yield. 33.134... 

Dialkyl phosphites react slowly with epoxy ketones at room temperature in the presence of a catalytic amount of sodium metal to form dialkyl l-hydroxy-2,3-epoxypropylphosphonates in 41-99% yields.Similarly, dialkyl phosphites react with f7.v-]-fonnyl-l-trimethylsilyl-l,2-cpoxy-alkanes in the presence of DBU in THF to give dialkyl ] -hydroxy-2-trirnethylsilyl-2,3-epoxy ilkyl-phosphonate in high yields (84%, Scheme 4.16).By contrast, DBU or EtjN in C,H, at reflux was found inefficient for the addition of dimethyl phosphite to the epoxide derived from chalcone. The reaction is best carried out in the presence of KF2H2O to produce a diastereomeric mixture of hydroxyphosphonates free from other organophosphorus compounds. 

Hammerschmidt, E, Addition of dialkyl phosphites and dialkyl trimethylsilyl phosphites to 2-(ben-zyloxy)propanal. Preparation of all four stereoisomeric (l,2-dihydroxy-[l-2H,]propyl)phosphonic acids from chiral lactates. Liebigs Ann. Chem., 469, 1991. 

Koh, Y.J., and Oh, D.Y, A new synthesis of vinyl phosphonates from a-phenyl-P-oxo phosphonates and dialkyl phosphite, Synth. Commun., 25, 2587, 1995. 

Other applications of the hydrophosphonylation reaction include the addition of dialkyl phosphite to 2-(alkoxycarbonyl)- or 2-cyanoacrylonitriles. The reaction is carried out in the absence of catalysT - or in the presence of NaNH2, RONa,- - or TFAA. The Michael addition can be combined with an elimination reaction. For example, because of the presence of a methylthio leaving group, dialkyl 2,2-dicyano- or 2-cyan()-2-clhoxyc irbonyl-l-methyl thio-(/ )-vinyl phosphonates are the products of the conjugate addition of dialkyl phosphite to the corresponding ketene dithioacetals in the presence of NaH (2 eq) in THF (Scheme 6.24).--°... 

Pudovik, A.N., and Khlyupina, N.L, New method of synthesis of esters of phosphonic and thiophos-phonic acids. Part 25. Addition of mixed dialkyl phosphites, dialkyl thiophosphites, and diallyl phosphite to unsaturated compounds, Zh. Obshch. Khim., 26, 1672, 1956 Chem. Abstr., 51, 3439f, 1957. 

Ohler, E., and Zbiral, Ii., Reaction of dialkyl phosphites with a-enones. Part 1. Synthesis and allylic reanangement of dimethyl (l-hydroxy-2-alkenyl)- and (l-hydroxy-2-cycloalkenyl)phosphonates, Chem. Ber.. 124, 175, 1991. 

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