A-aminophosphonate

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. ... 

During the asymmetric synthesis of a-aminophosphonates (14 in Fig. 4.4), numerous attempts to cleave the benzylic C—N bond, involving catalytic or transfer hydrogenolysis, resulted in epimerization at the a-carbon.319... 

Symmetrical cyclic triazines (masked imines) have been used in reaction with diethyl trimethylsilyl phosphite to provide phosphonates bearing silyl-substituted a-aminophosphonates.349... 

Campbell, M.M. and Carruthers, N., Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones, Chem. Commun., 730, 1980. 

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. 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

Several methods have been devised for the preparation of racemic a-aminophosphonates in 1972 the first optically active example was synthesized.8... 

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). 

Scheme 40 Formation of a-aminophosphonates by a three-component (a) or a two-component (b) route [97]...

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). 

Fluorinated a-aminophosphonates containing two pendent alkene chains with catalyst la led to six- or seven-membered cyclic phosphonates as potential antibacterial reagents [36] (Sciieme 8.4). 

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]. 

The use ofTaddol as an asymmetric phase-transfer catalyst has been adopted by other research groups. For example, Jaszay has used Taddol for Michael additions to a-aminophosphonate derivative 20, as shown Scheme 8.10 [22]. A range ofTaddol derivatives was investigated, but the best results were again obtained with the same catalyst employed by Belokon and Kagan. Thus, phosphoglutamic acid derivative 21 was obtained in 95% yield and with 72% ee when tert-butyl acrylate was employed as the Michael acceptor. 

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