A-Aminophosphonous acids

Racemic and optically active a-aminophosphonic acids, derivatives of various heterocycles 97ZOR1605. 

A. Aminophosphonic Acids.— The Michael addition of a dialkyl phosphite to acrylonitrile leads to C—P bond formation and the production in high yield of derivatives of 2-aminoethylphosphonic acid (45). This synthetic method appears to be preferable to those already described. ... 

Tyka, R. and Oleksyszyn, J., a-Aminophosphonic Acids, Polish Patent 105,825, 1980. 

Tyka, R., Novel synthesis of a-aminophosphonic acids, Tetrahedron Lett., 677, 1970. 

Wieczorek, J.S. and Gancarz, R., a-Aminophosphonic Acid Esters, Polish Patent 105,252, 1980. 

Hamilton, R., Walker, B., and Walker, B.J., A highly convenient route to optically pure a-aminophosphonic acids, Tetrahedron Lett., 36, 4451, 1995. 

A useful review of the chemistry of a-aminophosphonic acids has been published.47 Treatment of a-aminomethylphosphonic mono-esters with bromoacetyl halides... 

The beneficial effect of surfactants on enantioselective hydrogenations in water was exploited in the synthesis of a-aminophosphinic and a-aminophosphonic acids. These compounds are stmctural analogues of a-aminocarboxylic acids and their peptides find use as herbicides, bactericides and antibiotics [150,151]. With [Rh(BPPM)(COD)]Bp4 and similar catalysts fast ractions and e.e.-s up to 98% could be obtained in water in the presence of SDS (Scheme 3.12). 

Novel syntheses of a-aminophosphonic acid derivatives (453 and 454) were disclosed, using the Beckmann rearrangement as a key synthetic step. The ring size was crucial and only seven-membered cycles could be formed in fair yield (51-62%) (equations 193 and 194). 

Only one a-aminophosphonous acid, the glycine analogue, was reported in the literature at the outset of this work. 

The first three steps show that the reaction sequence in Figure 14.45 actually provides a widely applicable approach to such a-aminophosphonic acids. The step leading to the acyl azide F, i.e., the nitrite oxidation of an acyl hydrazide (Formula C in Figure 14.45), is as commonly used for the preparation of an acyl azide synthesis as that shown in Figure 14.44. 

Fig. 14.45. Transformation of an a-phosphonylcarboxylic acid ester (B) via the related carboxylic acid azide F and its Curtius degradation in ethanol to furnish an ethoxycarbonyl-protected a-aminophosphonic acid ester E. The N- and 0-bound protective groups of the latter compounds are cleaved off under acidic conditions. In this manner a-aminophosphonic acids are synthesized. They are interesting analogs of the biologically important a-amino carboxylic acids.

Electrophilic Azidation of (Chiral) Phosphorus-Stabilized Carbanions. Formation of Optically Active a-Aminophosphonic Acids... 

Once the methods for electrophilic azidation of phosphorus-stabilized carbanions were established a variety of chiral auxiliaries were surveyed to obtain nonraccmic a-aminophosphonic acids. All the compounds tested with the exception of 9 were used in optically active form. (The precursor of 9 was more readily available in racemic form.) The results of electrophilic azidation of these substrates are summarized in Tablet, together with those of ( )-l. Where possible, both methods A and B were tested. 

Asymmetric addition of phosphorus compounds to C-N double bonds has been widely studied and mainly concerns the synthesis of chiral a-aminophosphonic acids (for reviews on the synthesis of aminophosphonic acids, see refs 36, 37 and 67). For this purpose, the following types of organic nitrogen compounds have been used aldimines and cyclic imines, nitrones, ureidoimino derivatives and imidothioloesters. A separate example is the addition of dialkyl phosphites to hydrazones, which was used for the synthesis of phosphonosugars. 

R Catalyst (Equiv) Solvent Temp ( Q a-Aminophosphonic Acid 16 ... 

Chiral P-Hydroxy-a-Aminophosphonic Acids. An enan-tioselective synthesis of substituted dihydrooxazolin-4-yl phos-phonates was reported by the reaction of an aldehyde with a-isocyanomethylphosphonate ester catalyzed by (i )-(5)-(l) (eq 12). The enantiomeric purity of the product was determined by P H NMR spectroscopy using the chiral solvating reagent (.S)-(+)-2,2,2-trifluoro-l-(9-anthryl)ethanol. Independently, an asymmetric synthesis of ot-aminophosphonic acids was reported using the chiral ferrocenylamine catalyst (R)-(S)-(3) (eq 13). ... 

Laschat, S, Kunz, H, Carbohydrates as chiral templates stereoselective s3mthesis of (R)- and (5)-a-aminophosphonic acid derivatives. Synthesis, 90-95, 1992. 

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