A-Aminophosphonic acid esters

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

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.

Startg. iminoester salt in benzene added with stirring to a soln. of Na-diethyl phosphite in the same solvent at 10° product. Y 72%. F.e. inch pyrrole and azepine derivs., and cyclic a-aminophosphonic acid esters, s. V.Y. Mavrin et al., Zh. Obshch. Khim. 58, 1668-9 (1988). 

Hydrogen chloride a-Aminophosphonic acid esters from dialkyl phosphites and azomethines... 

Aminoperoxides, review 21,161 suppl. 29 -, cyclic s. 1,2,4-Dioxazoles a-Aminophosphonic acid esters... 

Without additional reagents a-Aminophosphonic acid esters from aldehydes and amines... 

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

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from a-amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the a-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The a-allyl-a-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+)-AV-dicycIohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ee[72]. 

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). ... 

Compounds which have been studied in the phosphonic group included an a-aminophosphonic acid and ester, a thiamin betaine, a cyclopropane-phosphonate, a cyclic ester (82), and two phosphazenes. ... 

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

One of the very first methods for the preparation of a-aminophosphonic acids appears to be the one described by Kabachnik and Medved [8]. The Kabachnik-Fields reaction is still very useful, especially for the preparation of dialkyl 1-aminoalkanephosphonates. According to this method, a-aminophosphonates were obtained reacting ammonia, carbonyl compounds (aldehydes and ketones), and dialkyl H-phosphonate. A little later. Fields [9] presented a method of synthesis of 1-aminoalkylphosphonic acids by replacing ammonia with amine—reacting both (aldehydes and ketones) with ammonia, or amine and dialkyl H-phosphonate to give dialkyl esters of 1-aminoalkylphosphonic acid (see Appendix). Hydrolysis of the esters produced free aminoalkylphosphonic acids. Yields of aminophosphonates vary from 40 to 47%. 

Selke, R., Holz, J. and Riepe, A., Impressive enhancement of the enantioselectivity for a hydroxy-containing rhodium(I) bisphosphine catalyst in aqueous solution by micelle-forming amphiphiles, Chem. Eur. J., 1998, 4, 769, and references cited therein. For a recent application, see Grassert, I., Schmidt, U., Ziegler, S., Fischer, C. and Oehme, G., Use of rhodium complexes with amphiphilic and nonamphiphilic Ugands for the preparation of chiral of-aminophosphonic acid esters by hydrogenation in micellar media. Tetrahedron Asymmetry, 1998, 9, 4193. 

Di- and oligo-peptides with a terminalo-aminophosphonous acid residue have been prepared by coupling with N-hydroxy succinimide esters of N-benzyloxycarbonylamino acids or peptides. 

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