Oxoalkyl -phosphonic Acids

Reduction methods-Thtix. have included the reduction of oximes of the esters of (I-oxoalkyl)phosphonic acids, and of (l-azidoalkyl)phosphonic acids. in both cases to (1 -aminoalkyl)phosphonic diesters. and the reduction of nitro groups at C(2) with hydrogen/Pt02 or Raney nickel.  

Use of the Arbuzov reocfio/i-This was applied to the introduction of the pho.sphono moiety into appropriate intermediates, e.g. in the conversion of (333 R = H 

Addition methods -The addition of dialkyl hydrogen phosphonates to compounds 

The interaction of dialkyl hydrogen phosphonates with ketones and /V-substituted 

Amirumethylation methods-Tha.t of phosphonite esters has provided polyaza 

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Hydroxyalkyl)phosphonic acids, and also the related phosphinic acids, are normally obtained from hydrogen phosphonates and aldehydes or ketones. The reactions between perfluoroacetone and mixed dialkyl hydrogen phosphonates are noteworthy in that the expected products (129) may be accompanied by the phosphoric triesters (130). Trimethylsilyl alkylene P(III) triesters (131) are also useful starting materials when acted upon by aromatic aldehydes or by (1-oxoalkyl)phosphonic acid esters, the initial... 

The use of phenylphosphonous dichloride in the preceding reactions leads to derivatives of the [(1-aminoalkyl)phenyl]phosphinic acids. Oximes of (1-oxoalkyl)phosphonic acids react with Ph2PCl/Et2N to give l-(diphenylphosphinoyliminoalkyl)phosphonates (166) by spontaneous... 

In the presence of [PdMe2(PMePh2)3] diethyl benzoylphosphonate is degraded during minutes and with quantitative yield, into diethyl phenylphosphonate (l-oxoalkyl)phosphonic esters suffer a similar fate but the process may take several hours under the same conditions. When mixtures of aroylphosphonic diesters and esters of (l-oxoalkyl)phosphonic acids are brought into contact with the... 

Chakravarty, P.K., Greenlee, W.J., Parsons, W.H., Patchett, A.A., Combs, P, Roth, A., Busch, R.D., and Mellin, T.N., (3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine. c-Alanine ligase, J. Med. Chem., 32, 1886, 1989. 

Arylhydrazones of 1- and (2-oxoalkyl)phosphonic acid diesters cyclize in polyphosphoric acid to give indolephosphonic acid diesters e.g., (277) from (276), and (279) from (278),... 

Equation 28 represents the formation of oxoalkyl phosphonic acid esters (488 R = OR) or phosphinic esters (488 R = alkyl or aryl) from phosphite or phosphonite esters and appropriate halogen-containing ketones ( > 1) or acyl halides (n = 0), and supplements the formation of the phosphonoylated or phosphinoylated alkanoic acids through reactions 21 and 22 in the previous section. 

In complete contrast to the (l-oxoalkyl)phosphonic acids, for which essentially only one synthesis is available, based on the Michaelis-Arbuzov or Michaelis-Becker reactions, there are several procedures available for the synthesis of those acids with the 0x0 group at C(2) or at a carbon atom site even further from the phosphoryl centre. Historically, esters of (2-oxoalkyl)phosphonic acids were also obtained through application of the Michaelis-Arbuzov and Michaelis-Becker reactions, but it soon became apparent that complications occur, the major one being the concomitant formation, in many instances, of enol phosphates and, in some cases, this reaction became the main one, indeed, sometimes the only one. Several other procedures are now available for the preparation of oxoalkyl acids which place the 0x0 group accurately and with no side reactions of any importance, and these are therefore considered first in the following survey. 

Of these reactions, the simplest direct procedure seems to be that of reductive amina-tion of (l-oxoalkyl)phosphonic acids which occurs when these are treated with... 

The range of phosphonic acids which can be utilized enzymically (at least by those enzymes present in Pseudomonas fluorescens) has recently been extended to include aminoalkyl-, hydroxyalkyl- and oxoalkyl-phosphonic acids, as well as phosphonodipep-tides only slight growth was seen with the herbicide glyphosate (A-phosphonomethyl-glycine (83), which is metabolized to (aminomethyl)phosphonic acid, and neither phos-phinothricin (84) nor its dialanyl tripeptide bialaphos supports growth in contrast to the behaviour of other bacterial extracts isolated from soil ". ... 

Oxoalkyl)phosphonic acids and their acid derivatives are also tautomeric with equilibration between oxo and (carbon) enol forms, and with a potential third contributor in the phosphoryl group (Scheme 40) ... 

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