Arylphosphonates

The Bart reaction has now been extended to the synthesis of arylphosphonic acids by the interaction of the diazonium fluoroborate and phosphorus trichloride (Doak and Freedman, 1951). 

Dialkyl arylphosphonates and alkenylphosphonates are prepared by the coupling of halides or triflates with the dialkyl phosphonate 783[64l-643]. 

The photo-Arbuzov rearrangement of allyl-, benzyl- and naphtylmethyl-phosphites (Scheme 13), first developed by Bentrude et al. [20], found applications in the preparation of phosphonates (70-90%) [38]. Arylphosphonates have been shown to act as protein tyrosine kinase inhibitors [39] or non-hy-drolyzable analogs of phosphorylated tyrosine residues [40]. 

The free radical Arbuzov reaction has been developed for the preparation of vinyl- and arylphosphonates in good to excellent yields. Oligonucleotides, suitably modified in the vicinity of the phosphorus backbone to impart nuclease... 

A useful new method of preparing arylphosphonates (123) involves the reaction of trialkyl phosphites with aryl halides in the presence of a nickel catalyst.The suggested mechanism is via the nickel complex (124), and is non-radical. 

The chemical shifts, Sp, of substituted arylphosphonic acids (9) have been found to be linearly related to the Hammett a and Taft ojt and cti parameters. The shielding of the phosphorus nucleus increases with the electron-withdrawing properties of the substituents, which is analogous... 

Scheme 11.12 provides some examples of the preparative use of the SRN 1 reaction. Entries 1 and 2 involve arylations of ketone enolates, whereas Entry 3 involves a dianion. Entry 4 is an example of a convenient preparation of arylphosphonates. Entry 5 is an example of application of the SRW1 reaction to a chloropyridine. 

Trimethylsilyl esters of arylphosphonic acids have been... 

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. ... 

Diethyl arylphosphonates were synthesized by reactions of diethyl phosphonate with aryl iodides or bromides containing electron-donor or electron-acceptor substituents in the aromatic ring in aqueous MeCN or neat H2O in the presence of Pd complexes with water-soluble ligands.34 For example, MeCN/H20 (1 mL), PhBr (8.2 mmol), and Ph2P(C6H4S03Na-m) (approximately 0.4 mmol) were successively... 

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. 

Liu, Z. and Chen, Z., Studies on the application of hypervalent iodine in synthesis. 11. Synthesis of arylphosphonates by arylation of phosphite anions using diaryliodonium salts, Synthesis, 373, 1993. 

The earliest developments in transition metal-assisted formation of aromatic C-P linkages were the result of the efforts of Tavs28 that were concerned with the use of Ni(II) halide salts for the reaction of aryl halides with trialkyl phosphites. These reactions involved conditions reminiscent of the Michaelis-Arbuzov reaction (heating at an elevated temperature) and produced arylphosphonate products in reasonable yield (Figure 6.8). 

Similarly, copper salts (cupric and cuprous) facilitate the reaction of aryl halides with trialkyl phosphites in the formation of dialkyl arylphosphonates under conditions like those found in nickel systems.37-39 Again, the copper salts appear to undergo an initial reaction with the phosphites to form a complex that subsequently undergoes reaction with the aryl halide. The requirement for copper is also similar to that for nickel saltstonly a catalytic amount is needed. Further, a preference among halides on the aromatic ring is noted iodide is replaced preferentially to other halides (Figure 6.10).40... 

Obrycki, R. and Griffith, C.E., Phosphonic acids and esters. XIX. Syntheses of substituted phenyl- and arylphosphonates by the photoinitated arylation of trialkyl phosphites,. Org. Chem., 33, 632, 1968. 

Ohmori, FI., Nakai, S., and Masui, M., Formation of dialkyl arylphosphonates via arylation of trialkyl phosphites, ]. Chem. Soc., Perkin I, 2023, 1979. 

Issleib, K., Balszuweit, K., Richter, S., and Koetz, J., Arylphosphonic or Arylphosphinic Acid Trimetyhylsilyl Esters, East German Patent 219,776, 1985. 

Miles, J.A., Beeny, M.T., and Ratts, K.W., A general route to methoxy-substi-tuted arylphosphonous dichlorides via mild Lewis acid catalysis, /. Org. Chem., 40, 343, 1975. 

A new entry for the synthesis of vinyl- and arylphosphonates has been achieved by reaction of vinyl or aryl halides with trialkyl phosphites in the presence of (TMS)3SiH under standard radical conditions [72]. An example of this intermolecular C—P bond formation is given in Reaction (7.62). Interestingly, the reaction works well either under UV irradiation at room temperature or in refluxing toluene. 

The esters of arylphosphonic acids are cleaved to the acids by HC1, HBr, or HI.9b Arylphosphonic dichlorides (ArPOCl2) are easily converted to esters by reaction with the alcohol in pyridine solution.10... 

Other methods for synthesis of arylphosphonic acids or their derivatives fall into four main categories. First, many aromatic compounds react with PC13 under catalysis by A1C13 to form aryldichlorophosphines (ArPCl2).9a n These add chlorine to form... 

Second, arylphosphonic acids may be prepared by the copper-catalyzed reactions of arenediazonium fluoborates with PC13 or PBr3. This method has found wide use.12... 

Third, arylphosphonic acid derivatives have been made by or-ganometallic reactions, such as the reaction of C6H5MgBr with (C2H50)2P0C1 or of phcnyllithium with phosphorodipiperididic chloride.9"11... 

Fourth, the present procedure bears a resemblance to the photochemical reaction of aryl iodides with trialkyl phosphites, by means of which several dialkyl arylphosphonates have been prepared.13 However, prolonged irradiation (>24 hours) in quartz vessels was employed. 

Arylphosphonic acid derivatives, 58, 137 Arylphosphonic dichlorides, 58, 136 Aryltetrachlorophosphoranes, 58, 137 L-Asparagine, carbobenzoxy-, 56, 89 L-Asparagine, NJ-(tnfluoroacetyl)- 56, 125 L ASPARAGINYL-L-LEUCINE, CARBOBENZOXY-,METHYL ESTER, 56, 88 Z-Asp Gly-OEt, 56, 93 (l-Azido-3,3-dimethoxy-l-propenyl)ben-zene, 57, 84... 

Table 4 Yields of Dialkyl Arylphosphonates Formed in the Photostimulated Reaction of Dialkyl Phosphite Ions with Aryl Halides ArX + (ROhPO" - (RO>2P( —Q)Ar ...

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