Dialkyl phosphites dimethyl phosphite

Pudovik, A.N. and Arbuzov, B.A., Addition of dialkyl phosphites to unsaturated compounds. I. Addition of dialkyl phosphites to 2,2-dimethyl vinyl ketone, Zh. Obshch. Khim. S.S.S.R., 21, 382, 1951. 

Other sugars and related compounds undergo the Abramov reaction with dialkyl phosphites with much lower stereoselectivity. For example, 2,3 4,5-di-0-isopropylidene-D-xylose and dimethyl phosphite give a mixture of epimers 12 (86 14), from which the epimer formed in excess crystallizes. The absolute configuration of the newly formed stereogenic center at C-l in this epimer was found to be R33. 

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. 

The Pd-catalyzed hydrophosphonylation of terminal alkynes with dialkyl phospliites seems destined to become the method of choice for tlie synthesis of a-substituted vinylphosphonates. The reaction proceeds by regioselective attack of dialkyl phosphite at the internal carbon of the triple bond (Scheme 6.37). Thus, 5-cyano-l-pentyne reacts efficiently with dimethyl phosphite in the presence of cZv-PdMe2(PPh2Me)2 affording dimethyl l-(3-cyanopropyl)vinylphosphonate in 94% yield. In the absence of catalyst, the hydrophosphonylation product is not detected. ... 

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. 

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. ... 

Barton and coworkers have introduced the use of dialkyl phosphites as reducing agents [86, 87]. Dimethyl phosphite was found to reduce bromides, iodides, thio-noesters and isocyanides (in good yield) in refluxing dioxane as the solvent and in the presence of large amounts of benzoyl peroxide as the radical initiator. Interestingly, the reaction cannot be initiated by AIBN in refluxing benzene (or toluene),... 

This reaction is. a welcome expansion of the base-catalysed addition of dialkyl phosphites which fails with sterically hindered olefins and with unsaturated aldehydes occurs at the carbonyl group. An example of the efficiency of the method with sterically hindered alkenes is afforded by the reaction of mesityl oxide which leads to diethyl (1, l-dimethyl-3-oxobutyl)phosphonate 7 0... 

The addition of dialkyl phosphites to isocyanates has been studied more often.118-122 The uncatalysed reaction gives poor yields119 (addition of dimethyl thiophosphite to phenyl isocyanate does not require a catalyst120), and weak bases such as sodium carbonate, sodium cyanide, and tributylamine are poor catalysts, and the reaction proceeds best on addition of sodium, sodium dialkyl phosphites, or triethylamine.122 A typical example is the preparation of diisopropyl [A-(p-clilorophenyl)carbamoyl]phosphonate 122... 

Gaseous ammonia was bubbled through a stirred mixture of hept-5-en-2-one (0.10 mol) and dialkyl phosphite (0.11 mol) at 60" C. The reaction was monitored by TLC and generally finished within 4 h. The reaction mixture was then treated with 1 M aqueous HCl and extracted with ether. Aqueous NaOH was then added to adjust the pH to 10, and the mixture was then extracted with ether. The organic phase was washed with brine and dried over Na2S04. Evaporation of the solvent under reduced pressure afforded 70% dialkyl (1-amino-l,5-dimethyl-4-enyl)phosphonate as a yellow oil. 

The first Pd -catalyzed P-arylation of dialkyl phosphites with arylboro-nic acids or aryl trifluoroborates has been carried out by using palladium acetate, the rigid bidentate ligand dmphen (dmphen = 2,9-dimethyl-1,10-phenanthroline), and without addition of a base or acid. The arylated phosphonates (512) were isolated in 44-90% yields (Scheme 132). 

Although there is no direct experimental evidence for the existence of the three-coordinated phosphite form, the tautomerization of dialkyl H-phosphonates to dialkyl phosphites has often been invoked to explain the mechanism of other reactions of dialkyl H-phosphonates, which result in a P-H bond cleavage. Dimethyl phosphite, although never experimentally observed, has been studied recently by ab-initio computations. Conformational analysis for this compound [6] results in four stable conformers (Figure 2.2). Conformer... 

These products result from three types of reactions that take place in this system—elimination, O-alkylation, and P-alkylation. Quantitative O-alkylation takes place in dimethyl-formamide, while in dioxane and toluene, the yield of the O-alkylated products varies from 56 to 70%. The formation of the two products corresponding to O-alkylation and P-alkylation is explained by the authors in terms of Pearson s theory of hard and soft adds and bases, with phosphorus being the soft and oxygen the hard base. The elimination is suggested to take place as an attack of the oxygen atom of the dialkyl phosphite anion, considered as a hard base toward the H atom in the P position with respect to the mesityl group ... 

The sodium salts of dialkyl phosphite, except for the dimethyl homologue, react with dialkyl H-phosphonates to form dialkyl alkylphosphonate and the corresponding sodium salt of monoaUcyl H-phosphonic acid [372]. 

These compounds can be prepared by the action of bromine on a trialkyl phosphite,2 but a more satisfactory method recently worked out by Goldwhite and Saunders3 consists in treating the dialkyl hydrogen phosphite with iV-bromosuccinimide. In this way dimethyl, diethyl w-propyl and isopropyl phosphoro-bromidates have been obtained as pure liquids by distillation at very low temperature. When kept at ordinary temperatures, they gradually decompose with the evolution of the corresponding alkyl bromide. 

Treatment of trialkyl phosphites with dimethyl acetylenedicarboxylate in toluene at 80 °C in the presence of the fullerene, Ceo, results in the formation of the stabilised phosphite-ylides (81), involving a cyclopropane ring on the fullerene unit. These ylides readily undergo hydrolysis with hydrobromic acid to give the phosphonates (82) in good yield. Protonation of the initial adducts of trimethyl phosphite and dialkyl acetylenedicarboxylates by indane-1,3-dione leads to the formation of vinyltrimethoxyphosphonium cations. 

When performed in ether at —70 °C containing HCl, the reaction between triethyl phosphite and either chloral or bromoacetone affords higher yields of the a-hydroxyphosphonates (34), relative to vinyl phosphate, than are normally obtained. The rate-determining step in the formation of the phosphonate (35) from chloroacetone and dimethyl hydrogen phosphonate appears to be the tautomerism of dialkyl phosphonate to phosphite. ... 

An alternative procedure for the preparation of dialkyl 1,2-epoxyalky Iphosphonates from a-haloketones is the action of MeONa (1 eq) on a mixture of a-chloroketones and dimethyl or diethyl phosphite (1 eq) in MeOH at room temperature. The yields of 53-87% obtained by this technique are reproducible and represent a signilicant improvement over the yields of 27% and 65% reported for the one-step reaction of oc-chloroketones with sodium diethyl phosphite. This procedure appears to be limited to aliphatic oc-chloroketones (Scheme 4.6). The reaction of a-chloroacetophe-none with dimethyl phosphite resulted in the formation of dimethyl l-phenylvinyl phosphate. However, in spite of the difficulties frequently encountered in the choice of a-chloroketones, this facile and convenient procedure is a useful variant of the classical approach as illustrated by the results presented in Table 4.3. 

Dawson and Burger first demonstrated that the Michaelis-Arbuzov reaction of chloroacetonitrile and triethyl phosphite furnishes diethyl cyanomethylphosphonate. In its most general form, it involves the addition of triethyl phosphite to chloroacetonitrile at 150-170°C to give diethyl cyanomethylphosphonate in up to 80% yields (Scheme 6.2). ° This procedure has been developed on an industrial scale The use of bromo- or iodoacetonitrile (X = Br, I, Scheme 6.2) was also reported. The reaction may be used to prepare any dialkyl cyanomethylphosphonate, and a variety of trialkyl phosphites have produced the corresponding phosphonates in reasonable to good yields (29-90%, Scheme 6.2). " Cyclic phosphites, 4,5-dimethyl-2-methoxy-l,3,2-dioxaphos-pholane (meso and racemic) and 5,5-dimethyl-2-methoxy-l,3,2-dioxaphosphorinane, react with chloroacetonitrile to produce 5- and 6-membered cyclic phosphonates in 50% and 72% yields, respectively. ... 

Griffiths, D.V., Harris, J.E., and Whitehead, B.J., Reactions of carbene intermediates from the reaction of trialkyi phosphites with dialkyl benzoylphosphonates. Preparation and reactions of dimethyl 2-(N-rerf-butyl-iV-methylamino)benzoyIphosphonate and dimethyl 2-(methylamino)benzoyIphosphonate, J. Chem. Soc., Perkin Trans. 1, 2545, 1997. 

The reactions of trialkyl phosphites with dialkyl acetylenedicarboxylates have been studied in some detail, and the products explained as proceeding via 1 1 intennediates. Thus, the addition of a solution of dimethyl acetylenedicarboxylate to either (MeO 13 or (EtOjjP (2 eq) at 0°C leads to the formation of the corresponding 1,2-diphosphoranes. Treahnent of the diphosphorane with anhydrous HBr leads to protonation and subsequent dealkylation to give tetramethyl l,2-/ (meth-oxycarbonyl)-l,2-ethylenediphosphonate in 94% yield (Scheme 8.49). Trialkyl phosphites add vigorously to acetylenedicarboxylic acid in EtjO to give tetraalkyl 1,2-Z z5 (alkoxycarbonyl)-1,2-ethylenediphosphonates in modest yields. ... 

The reactive 1 1 intermediate formed in the initial reaction between trialkyl phosphite and dialkyl acetylenedicarboxylates can be trapped. Thns, reaction of dialkyl acetylenedicarboxylates with trimethyl phosphite in the presence of indane-1,3-dione leads to dimethyl 2-(3-methoxy-l-oxoindenyl)-l,2-fczXalkoxycarbonyl)ethylphosphonate in high yields. Treatment of trialkyl phosphites with Cgo and dimethyl acetylenedicarboxylate at 80°C give fullerenecyclopropyl phosphite ylides, which, on hydrolysis at ambient temperature, give the corresponding phosphonates. ... 

General procedure for the preparation of dialkyl aroylphosphonates 279 The aroyl chloride (0.03 mole) is treated under nitrogen dropwise with the trialkyl phosphite (0.04 mole) at such a rate that the internal temperature does not exceed 35°. The resulting mixture is fractionated in a vacuum. As example, dimethyl benzoylphosphonate, b.p. 146°/2.5 mm, is obtained in 81 % yield from benzoyl chloride and trimethyl phosphite. 

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