Dialkyl phosphites esters

Dialkyl phosphites react with acyl halides such as lauroyl chloride to yield surface-active acid esters of acylphosphonic acid [84-87] see Eq. (40). 

Dialkyl phosphites are added to unsaturated compounds in the presence of sodium ethylate or triethylamine forming, for instance, 2-(dialkylphosphono) propionic ester [152]. The same compounds are obtained by catalytic conversion of phosphites with propiolactones [153,154] see Eq. (85) ... 

The 9,10-phosphonostearic acid in form of its sodium salt shows a good thermal stability and was efficient as an inhibitor in rust protection. The diethyl-phosphonoacetoxystearic acid methyl ester is used as additive in high-pressure lubricants. Rust protection properties are also shown by 9,10-phosphonostearyl alcohol [157]. Trisodium 9,10-phosphonostearate possesses the best surface activity in an 0.2% aqueous solution showing 33 mN/m at 30°C and a pH value of 10.5 [156]. By the addition of dialkyl phosphite to a,p-unsaturated ketones the y-oxophosphonic acids are available [159]. Addition of dialkyl phosphite to y-ketoacids leads to a-hydroxy-y-carboxyphosphonates see Eq. (86) ... 

Reduction by hydrogen atom donors involves free radical intermediates and usually proceeds by chain mechanisms. Tri-n-butylstannane is the most prominent example of this type of reducing agent. Other synthetically useful hydrogen atom donors include hypophosphorous acid, dialkyl phosphites, and tris-(trimethylsilyl)silane. The processes that have found most synthetic application are reductive replacement of halogen and various types of thiono esters. 

A Michaelis-Becker approach using the sodium salt of dialkyl phosphites has been successful for the formation of C-P bonds to aromatic rings.184 Reaction of the dialkyl phosphite in DMF with the appropriate diaryliodonium halide provides the corresponding dialkyl arylphosphonate in good yield (81 to 93%). This approach to the arylphosphonate esters proceeds in superior yield under relatively mild conditions and therefore is one to be accorded serious consideration for the preparation of such materials. 

Steinberg, G.M., Reactions of dialkyl phosphites — synthesis of dialkyl chlo-rophosphates, tetraalkyl pyrophosphates, and mixed orthophosphate esters, /. Org. Chem., 15, 673, 1950. 

Pudovik, A.N. and Arbuzov, B.A., Addition of dialkyl phosphites to unsaturated ketones, nitriles, and esters, Dold. Akad. Nauk S.S.S.R., 73, 327, 1950. 

Two reports are available on the rearrangement of mixed vinyl phosphite esters to produce phosphonate diesters in moderate yield.94 95 In both instances, the vinyl phosphite esters were prepared by reaction of the dialkyl phosphorous chloride with highly enolized carbonyl compounds. The mixed ester products undergo thermal rearrangement to the phosphonate diesters (Figure 6.25). 

On pp. 45 and 57 we referred to the action of chlorine1 and of N-chlorosuccinimide2 on dialkyl phosphites producing dialkyl phosphorochloridates. We have made use of the latter in producing a variety of esters of orthophosphoric acid and of phos-phoramidates, and reference has already been made to many such reactions (p. 82). These processes are, in a sense, phosphorylations of the alcohols or of the amines respectively. 

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 chemical basis for the phosphite triester approach is the observation, that dialkyl phos-phorochloridites such as (CjHjOJjPCI react very rapidly at the 3 -OH of nucleosides in pyridine even at low temperatures. In contrast, the reactions of analogous chloridates, e.g. (C2HjO)2POCIi require several hours at room temperature. It was later found that phosphite esters can be oxidized quantitatively to the phosphates by using iodine in water and that clean condensation of phosphorochloridites with nucleosides can be achieved in THF at -78 °C. To develop this chemistry into a useful synthetic procedure it was necessary to establish which... 

Formylindole 47a and 1-acetyl-3-formylindole 47b react with dialkyl phosphites [85, 86] with the formation of 3-(hydroxyphosphonyl)methylindoles (91), from which ethers (isopropyl, butyl) and esters (benzoate) were obtained by reaction at the hydroxyl group via the alcoholate formation. 

Potassium dialkyl phosphite ions react rapidly with aryl iodides in liquid ammonia under irradiation to form diethyl esters of arylphosphonic acid in almost quantitative yields238. The photostimulated reaction of (EtO)2PO ions with 5-chloro-7-iodo-8-isopropoxyquinoline gave 70% of the substitution product with retention of the 5-chloro substituent239. The same nucleophile was formed in THF, and in a mixture of solvents (1 4 THF MeCN) reacts under irradiation with ArX (o-, ra-,/ -iodoanilines, 2-iodo, 3-iodo, 2-bromo and 3-bromopyridines and 3-bromoquinoline) rendering the substitution product in high yields (70-98%) (equation 130)240. 

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... 

Carbohydrate moieties have also been used as chiral auxiliaries in the addition of dialkyl phosphites to the C = N bond. Thus, 0-pivaloylated iV-benzylidene-/ -D-galactosylamine reacts with diethyl phosphite to give four diastereomeric esters (the a and (i forms not shown), in which those with the S configuration at the newly created stereogenic center prevail69. 

As this chapter covers two years of the literature relating to the above area, it has been necessary to be somewhat selective in the choice of publications cited. Nevertheless, it is hoped that most significant developments have been noted. As in previous reports, attempts have been made to minimise the extent of overlap with other chapters, in particular those concerned with the synthesis of nucleic acids and nucleotides to which the chemistry of tervalent phosphorus esters and amides contributes significantly, the use of known halogen-ophosphines as reagents for the synthesis of phosphines (see Chapter 1), and the reactions of dialkyl- and diaryl-phosphite esters in which the contribution of the phosphonate tautomer, (R0)2P(0)H), is the dominant aspect, which are usually covered elsewhere in these volumes. 

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. ... 

Arylphosphonate esters are conveniently prepared from aryl iodides and potassium dialkyl phosphites on photolysis in ammonia, Eq. (29). Isolated yields of products containing methyl, methoxy, trifluoromethyl or halogen substituents range from 87 to... 

Sodium dialkyl phosphites readily react with 1,1-difluoroalkenes at low temperature to provide the corresponding dialkyl a-fluorovinylphosphonates in excellent yields (88-93%, Scheme 3.8). Some of them (R = OBn) can be converted into P-fluoro-a-keto esters, which are useful precursors of P-fluoro-cx-amino acids. ... 

Although the reaction of dialkyl phosphites with orthoformic esters has been extended to triethyl trithioorthoformate," the preferred synthesis of formylphosphonate dithioacetals is usually the high-yield Michaelis-Arbuzov reaction of trivalent phosphorus compounds with the appropriate chlo-rodithioacetals.""" For the corresponding hemithioacetals, a Pummerer-type reaction of a-phos-phoryl sulfoxides with alcohols in the presence of iodine is usually the method of choice (Scheme 5.3). " ° However, hemithioacetal formation is solvent dependent and generally gives a moderate yield of product in a mixture with several other byproducts arising from transesterification reactions. 

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. 

When the reaction is allowed to proceed with protected carbonyl groups, the expected protected P-ketophosphonates resulting from a nucleophilic substitution at the carbon atom of a-chloroke-tones are isolated in reasonable yields (Scheme 7.16). 152-154 However, unprotected y-bromo-P-oxobutanoic ester or amides - undergo phosphonylation in satisfactory yields with sodium or potassium dialkyl phosphites in THF at 0°C. 

Pudovik, A.N., New synthesis of esters of phosphonic and thiophosphonic acids. Part 12. Addition of dialkyl phosphites to unsaturated dibasic acids and esters, /zv. Akad. Nauk SSSR, Ser Khim., 926, 1952 Chem. Abstr, 47, 10467e, 1953. 

Wenzel and Jacobsen reported the thiourea 15b-catalyzed Mannich-type reaction of a ketene silyl acetal with an N-Boc-aldimine, furnishing (3-amino esters with excellent enantioselectivities (Equation 10.30) [59]. Subsequently, Jacobsen and co-workers reported the hydrophosphonylation of dialkyl phosphites with aldimines to yield a-amino phosphonates [60]. 

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. ... 

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