Diaryl H-phosphonates

The disproportionation of diphenyl H-phosphonate to the corresponding triester and the H-phosphonate monoester was found to be practically an irreversible process. Both compounds were completely stable and did not undergo any reactions. Kers et al. [289] proposed a plausible mechanism for the disproportionation of diphenyl H-phosphonate to take into account the characteristic chemical features of diaryl H-phosphonates. The presence of electron-withdrawing substituents (two phenyl groups) makes the phosphorus more electrophilic in diphenyl H-phosphonate and enables abstraction of the proton from the P-H group even by a weak base (e.g. pyridine). 

It is known that the addition of dialkyl or diaryl H-phosphonates to bis-imines should generate two diastereomeilc products (meso and racemic forms) owing to the chirality of the groups preset in the bis(anunophosphonate) molecule [58], The NMR studies revealed that the reaction product is a nuxture of the two possible (hastereomeric forms R, S (meso) and the enantiomeric pair R, R and S, S. 

High molecular weight polycarbamides and polythiocarbamides are formed by the condensation of carbon dioxide or carbon disulfide with aromatic diamines in the presence of diaryl H-phosphonates and tertiary amines [130]. 

Peptides containing a P-terminal aminophosphonic acid have been prepared by coupling protected amino acids with dialkyl or diaryl esters of aminoalkanephosphonic acids or free acids. Protection of the amino phosphonic acid groups is an important step in the phospho-nopeptide synthesis. Aminophosphonates based on the H-phosphonate diesters are used directly for the preparation of phosphonopeptides. Diphenyl aminoalkanephosphonates are attractive starting materials for phosphonopeptide synthesis because they are readily available, and efficient coupling is easily achieved by most methods used in peptide chemistry. 

Pyridines with phosphonate substituents are valuable for medicinal chemistry or iV,P-bisdentate ligands (Scheme 46) (13JA9322).Thus, a C-H phosphorylation process was developed where the heterocycle directs ortho-palladation. This intermediate can be intercepted by H-phosphonates and diaryl phosphine oxides to provide phosphonate-substituted pyridines. 

There were a couple of reports of cross-coupling reactions of pyrazoles published. Palladium-catalyzed cross-coupling between 3,4-, and 5-halopyr-azoles 32 and H-phosphonates, H-phosphinates, and secondary phosphine oxides to give pyrazoles 33 was accomplished in moderate-to-good yields (13OL5550). 1,3,5-Triarylaminopyrazoles 35 were prepared by Ullmann coupling firom l,3-diaryl-5-aminopyrazoles 34 and aryl halides in the presence ofcopper(I) iodide (13T570). 

Alkenes are much less reactive in the H-P bond addition reactions than alkynes. However, 1,3,2-dioxaphospholane 2-oxide (4a), a five-membered hydrogen phosphonate of pinacol, is exceptionally reactive with alkenes although dialkyl and diaryl phosphonates such as 4b-d are totally unreactive (Scheme 25) [26]. Very interestingly, six-membered hydrogen phosphonates 4e,f are also unreactive under identical conditions. 

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... 

Table 3. Steric Effects of Dialkyl or Diaryl Phosphites on Addition to ( — )-(S)-l-Phe-nyl-A-benzylideneethylamine (X = H) in the Formation of Amino Phosphonate 942...

Conjugated yne-2-ynylidene 1,3-dithioles 228 were synthesized via Wittig reactions of phosphonium salts 225 with 3-phenyl-substituted propargyl aldehydes 227 (R = H, = Ph). Diaryl-substituted derivatives 228 were prepared in Horner-Wittig reactions of phosphonates 226 with ketones 225 (R =R = Ph or -02NC6H4) (Equation 13) <2004CL1190>. 

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. 

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