Dialkyl vinylphosphonates

Dialkyl vinylphosphonates.13 Pd(0) catalyzes the reaction of vinyl bromides and dialkyl phosphites in the presence of trielhylamine (1 equivalent) to form dialkyl vinylphosphonates. The configuration of the starting material is retained. An example is the synthesis of phosphonomycin (1, equation I). 

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

Dialkyl vinylphosphonates react with bromoform, in the presence of 50% aqueous sodium hydroxide and a phase-transfer catalyst (10% mol), resulting in the formation of 1,1-di-bromocyclopropane derivatives, exclusively.The best yields were obtained with tetramethyl-ammonium chloride, e.g. formation of 2. 

The most attractive and potentially most general route for the synthesis of dialkyl 1,2-epoxyalkylphosphonates appears to be the direct epoxidation of the corresponding dialkyl vinylphosphonates (Scheme 4.13). The syntheses of dialkyl vinylphosphonates with essentially any desired combination of a and 3 substituents can be achieved readily by a number of procedures. The use of vinylphosphonates offers appreciable advantages. The cis- and /ran.v-vinylphosphonates (R- or R ... 

Preparation of dialkyl 1-formylethylphosphonates can be achieved in low to good yields (27-71%) by reacting dialkyl vinylphosphonates with carbon monoxide and hydrogen (1/1 CO/H2 ratio) in the presence of a conventional rhodium-containing hydroformylation catalyst [Rh(COD)Cl]2 at temperatures ranging from 60°C to 130 C under a pressure of 20-1500 bars (Scheme 5.15). Hydroformylation can be carried out with or without solvent. Loading of rhodium catalyst from 0.5 to 500 ppm have proved suitable. 

Another attractive, though limited, route to fully protected (o-amino-(n-(hydroxycarbonyl)alkylphos-phonic acids involves the addition of sodium acetamidomalonate or potassium A-(diphenylmeth-ylene)glycine esters to dialkyl vinylphosphonates (Scheme 8.80). ° - ... 

Such methods are scarce. The addition of aldehydes to dialkyl vinylphosphonate occurs in the presence of l,4-diazabicyclo[2.2.2]octane to give good yields of (2-hydroxy-1-... 

Dialkyl vinylphosphonates, where the alkyl groups are methyl, ethyl, n-propyl, isopropyl, -butyl, and K-pentyl have been studied. The polymerization kinetics of these monomers indicate that chain termination may be by chain transfer through the alkyl groups of the monomer and that this chain transfer takes place in the later stages of polymerization [89]. 

Oxidation of 1,2-unsaturated phosphonates with a peroxide. The direct oxidation of dialkyl vinylphosphonates appears to be the most attractive synthetic route for the preparation of dialkyl 1,2-epoxyalky Iphosphonates [264],... 

The palladium-catalyzed phosphonylation was successfully applied to stereoselective synthesis of dialkyl vinylphosphonates from vinyl bromides and dialkyl H-phosphonates [368]. 

With the exception of vinylphosphonic acid showing unusual behavior in radical polymerization (polymerization was shown to proceed through a cyclopolymerization mechanism, resulting in either five- or six-membered rings), relatively few investigations into homopolymerization of dialkyl vinylphosphonate monomers have been reported. The few reports show the failure of vinylphosphonate monomers to homopolymerize, which usually results in polymers of low molecular weight. This behavior was ascribed to chain transfer onto either the polymers or monomers. Indeed, recently. 

Arbuzov and Michaelis-Becker reactions provide facile and versatile procedures for the formation of carbon-phosphorus bonds. These methods, however, are not applicable to the formation of sp hybridized carbon-phosphorus bonds. Only few methods have been reported for the syntheses of arylphosphonates and vinylphospho-nates. Direct reaction of aryl or vinyl halides with trialkyl phosphite in the presence of nickel halide requires severe reaction conditions [21,22], and the stereochemistry of vinylphosphonates has not been clarified. Synthesis of dialkyl arylphosphonates 22 [23, 24] is achieved by the palladium-catalyzed reaction (Scheme 2.12), which is called by Hirao reaction . The stereoselective synthesis of dialkyl vinylphosphonates 23 [24-26] is similarly accomplished by this method (Scheme 2.13). A variety of modified procedures have been developed recently [27-37]. 

Because heteroatom-substituted vinylphosphonates such as enol phosphates and vinyl halides are masked acetylenic compounds, a variety of methods have been developed for their elaboration and subsequent use in the synthesis of dialkyl 1-alkynylphosphonates. These eliminations usually have the leaving group P to the phosphoryl group, although cases in which the leaving group is a to the phosphorus center are also known (Scheme 1.12). 

The (2-bromovinyl)trimethylsilane reacts with dialkyl phosphites in toluene at 50°C in the presence of catalytic amounts of PdtPPh iyht N to give Z/az .v-dialkyl 2-(trimethylsilyl)vinylphosphonates in 76-80% yields. This coupling reaction is very sensitive to the steric hindrance of the substrate. The dialkyl 2-(trimethylsilyl)vinylphosphonatcs so obtained have been used in a Diels-Alder reaction with cyclopentadiene. ... 

Aboujaoude, E.E., Lietje, S., Collignon, N., Teulade, M.P., and Savignac, P, A one step generation of a-lithio(trimethylsilyl)alkanephosphonates. A new preparative route to dialkyl l-(trimethylsi-lyl)alkanephosphonates and vinylphosphonates. Synthesis, 934, 1986. 

The halohydroxylation method has been developed for exploiting the reactivity of the double bond present in dialkyl vinyl- and propenylphosphonates. Preparation of the halohydrins of diethyl vinylphosphonate failed using NBS or NBA. Treatment of diethyl vinylphosphonate on large scale with NaOCl or NaOBr in aqueous medium at pH < 3 gives the halohydrins with the hydroxyl group in the P-position (anti-Markovnikoff addition) with 95% or 65-85% purity, respectively (Scheme 4.9). As a consequence of the acid conditions, the preparation of halohydrins is generally accompanied by the formation of undesired diethyl 1,2-dihalogenophosphonates. ... 

A report of the synthesis of thermodynamically stable ( )-vinylphosphonates from diethyl 1-formyl-l-phenylalkylphosphonates by a Homer-Wadswoilh-Ermnons-type reaction has appeared. Sodium P-hydroxyphosphonates, generated by the reaction of sodium dialkyl phosphites with... 

Because the exploitation of the chemistry of unprotected phosphonylated acetaldehydes is handicapped by the sensitivity of the P-C bond in acidic media, a reliable alternative procedure for the preparation of dialkyl 1-chloro-1-formylmethylphosphonates from dialkyl 2-ethoxy-vinylphosphonates has been developed. Room-temperatme chlorination of 2-ethoxyvinylphosphonates with dry chlorine in CCI4 followed by hydrolysis of the phosphonylated a,p-dichloro ethers with water at 50-60°C gives the expected monochlorinated aldehydes in 73-82% yields (Scheme 5.70). A similar treatment with bromine in water at 0°C converts diisopropyl 2-ethoxyvinylphosphonate smoothly into diisopropyl 1-bromo-1-formylmethylphosphonate in 92% yield. ... 

Most of the information available on this topic is derived from works on the reactions of alkali metal salts (sodium or potassium) of dialkyl cyanomethylphosphonates with sp or sp electrophihc center. Thus, in the presence of a further equivalent of sodium hydride, sodium dialkyl cyanomethylphosphonates add to carbon disulfide in I I2O at room temperature to give alkenedithiolates, which are further characterized by alkylation or oxidation. For example, reaction with methyl iodide provides dialkyl 1-cyano-2,2-/ /.v(methylthio)vinylphosphonates in 21—40% yields (Scheme 6.16),-° whereas treatment with acetyl chloride in refluxing THF leads to l,3-dithietane-2,4-diylidene/ /.v(cyanorncthylphos-phonate) in low to fair yields (10-54%, Scheme 6.16). -... 

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. ... 

Another procedure for the preparation of dialkyl 2-oxoalkylphosphonates features the trapping of acyl chlorides by phosphonate carbanions produced by the conjugate addition of organolithiums or organocuprates to vinylphosphonates, as illustrated by the conversion of diethyl l-(trimethylsi-lyljvinylphosphonate into diethyl l-ethyl-2-oxobutylphosphonate in 80% yield (Scheme 7.25) ... 

The sodium salts of dialkyl l-(alkoxycarbonyl)methylphosphonates. in the presence of a further equivalent of NaH, undergo addition of carbon disulfide in EtjO at room temperature to give alkenedithiolates, which are characterized by protonation, alkylation (Mel, EtI, BnCl), oxidation, and phosgenation. For example, reaction with metliyl iodide provides the dialkyl 1-alkoxycarbonyl-2,2-/7i.v(mcthylthio)vinylphosphonates in good yields (68-75%), whereas room-temperature treatment with acetyl or benzoyl clilonde produces l,3-dithietane-2,4-diylidene-foZ5 [(alkoxycarbo-nyl)methylphosphonates] in moderate yields (18-39%, Scheme 8.23). The same oxidation product is obtained by reaction with iodine. 

The readily accessible dialkyl 1 -alkoxycarbonyl-2,2-h/i(methylthio)vinylphosphonates react smoothly with lithium dimethylcuprate to give the diethyl l-(alkoxycarbonyl)-2,2-dimethylpropyl-phosphonates in good yields (75-80%) ... 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

Thus, trialkyl phosphites react with acrylates and methacrylates to afford trialkyl phosphono-propionates and phosphonoisobutyrates in low yields (20-30%). These reactions require high temperatures (140-150°C) and long reaction times in the presence of hydroquinone, so the method has only limited utility. By contrast, trialkyl phosphites react smoothly with alkyl 2-bromoacrylates on heating to produce dialkyl 2-(alkoxycarbonyl)vinylphosphonates. ... 

Two Pd(0)-catalyzed coupling reactions are reported for the synthesis of dialkyl 2-(ethoxycar-bonyl)vinylphosphonates. Thus, alkenyl triflates in DMF at room temperature and p-bromo acrylates in toluene at 80°C undergo very facile and efficient Pd(PPh3)4-catalyzed coupling with dialkyl phosphites to provide alkenyl phosphonates in high isolated yields (87-90%, Scheme 8.52). ... 

Phosphonate carbanions (97), generated by the addition of various carbanions to vinylphosphonates, provide routes to functionalized alkenes. Thermolysis of the dienes (98) prepared in this way offers a route to 1,4-disubstituted benzenes via electrocyclization of the intermediate trienes (99) (Scheme 17). The reaction of phosphonate carbanion (100) with alkyl or aryl benzenethiosulphonates provides a general synthesis of the useful dialkyl alkyl- and aryl-thiomethyl-phosphonates (101). ... 

Vinylphosphonates are not easily produced by the Arbuzov-Michaelis reaction, and are often obtained without control of the geometry. A new route to these compounds makes use of a palladium-catalysed coupling between vinyl bromides and dialkyl phosphites in a stereoselective manner and in correspondingly high yields. ... 

Dialkyl aryl- and vinylphosphonates (RPO(OR )2) are readily prepared in excellent yields by the reaction of aryl or vinyl bromides, respectively, with dialkyl phosphite (HPO(OR )2) in the presence of catalytic Pd(Ph3P)4 and EtsN. In a related process, unsymmetrical alkyl diarylphosphinates (ArPhPO(OR)) are obtained in good yields, regardless of aromatic substitution, by the Pd(Ph3P)4-catalyzed coupling reaction between aryl bromides and alkyl benzenephosphonites (HPhPO(OR)). ... 

At this stage, two enantiomers of several optically active [-(substituted phenoxy-acetoxy)alkylphosphonates lA and IC were synthesized by the asymmetric hydrogenation of the corresponding prochiral 0,0-dialkyl [-(substituted phenoxy acetoxy)vinylphosphonate M25 (Scheme 6.11) [49]. 

Scheme 6.12 Synthesis of 0,0-dialkyl 1-(substituted phenoxy acetoxy)vinylphosphonates M25...

Optically active substituted ethylphosphonates lA and IC were prepared from 0,0-dialkyl 1-(substituted phenoxyacetoxy)vinylphosphonate M25 asymmetrically hydrogenated using chiral Rh(l)-complexes as catalysts (Scheme 9.35). 

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