Aminophosphonic acids, resolution

Stereoselective hydrolysis of racemic l-(//-phenylacetylamino) alkanephos-phonic acids performed in the presence of penicillin acylase under the kinetic resolution conditions gave both the unreacted substrates and the products - the corresponding 1-aminophosphonic acids in high yields and with full enantioselec-tivity. The unreacted A -acyl derivatives were hydrolysed chemically and in this way each enantiomer of the free acid was obtained (Scheme 5). ... 

Chromatographic resolutions of aminophosphonic acids are a relatively recent innovation. The resolution of phaclofen, [3-amino-2-(4-chlorophenyl)propyl]phosphonic acid... 

Heisler A, Rabiller C, Douillard R, Goalou N, Hagele G, Levayer F (1993) Enzyme catalysed resolution of aminophosphonic acids-I—serine and isoserine analogues. Tetrahedron Asym 4 959-960... 

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... 

Thus, in 2008, List and coworkers published the first enantioselective version of Kabachnik-Fields reaction [214a]. They found that chiral binol-derived phosphoric acids were efficient in inducing chirality under dynamic kinetic resolution conditions when bulky a-branched aldehydes (isopropyl, cyclopentyl and cyclohexyl) were used as substrate in their reaction with p-anisidine and di(3-pentyl) phosphite (Scheme 12.28). In particular, 3,3 -bis(4-anthracenyl-2,6-diisopropylphenyl)-l,l -8-binaphtyl-2, 2 -diyl hydrogenphosphate 80 allowed the synthesis of the corresponding p,p-disubstituted-a-aminophosphonates 84 in high yields with very good stereocontrol (dr up to 28 1 and er up to 97 3). 

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