Asymmetric Synthesis of 1-Aminoalkylphosphonic Acids

Cyclic tri- and Pentavalent Amidoesters and Diamides with a Stereogenic Phosphorus Atom in Asymmetric Synthesis: Part I: Stoichiometric Reagents

“…Their hydrolysis afforded enantiomerically pure 1-aminoalkylphosphonic acids 65a,b with (S)-or (R)-configuration, respectively (Scheme 19) [51]. Later on, a protocol for asymmetric synthesis of this type of aminophosphonic acids was reported in which chloromethylphosphonic dichloride was used instead of N-benzoylaminomethylphosphonic dichloride and an amino functionality was introduced by a nucleophilic substitution reaction in the formed diastereomerically pure 2-chloromethyl-1,3,2-oxazaphospholanes derived from L-ephedrine 2 [52].…”

The Kabachnik–Fields reaction: synthetic potential and the problem of the mechanism

“…Subsequent hydrolysis of compounds 6a and 6b resulted in the APA (S)-7 and (R)-7, respectively. Later, 80 this strategy was used for the synthesis of APA 7 from enantiomeric oxazaphospholanes with the exocyclic chloromethyl group.…”

Synthetic Applications of Dialkyl (Chloromethyl)phosphonates and N,N,N‘,N‘-Tetraalkyl(chloromethyl)phosphonic Diamides

“…The 3 / 1 mixture of the two diastereomers is separated by silica gel column chromatography to afford enantiomerically pure samples of 97a (mp 85 °C; NMR 31 potassium phthalimide in toluene at 50 °C under sonication conditions gives the corresponding N-phthalimido oxazaphospholanes which are converted into (R) and (S) aminoalkylphosphonic acids 99a and 99b after acidic hydrolysis followed by treatment with ethanolic hydrazine (Scheme 54). 123 Scheme 54.…”

“…The 3/1 mixture of the two diastereomers is separated by silica gel column chromatography to afford enantiomerically pure samples of 97a (mp 85 °C; 31 P NMR (CDCl 3 ) δ ) +35.84 ppm) and 97b (mp 80 °C; 31 P NMR (CDCl 3 ) δ ) +34.47 ppm), respectively (Scheme 53). 123 Deprotonation of each diastereomer with n-BuLi in THF at low temperature followed by alkylation at the same temperature results in formation of the corresponding R-substituted oxazaphospholanes 98a and 98b in moderate yield (40-65%). Reaction of each isomer with potassium phthalimide in toluene at 50 °C under sonication conditions gives the corresponding N-phthalimido oxazaphospholanes which are converted into (R)-and (S)-(aminoalkyl)phosphonic acids 99a and 99b after acidic hydrolysis followed by treatment with ethanolic hydrazine (Scheme 54).…”

“…A mixture of diastereomeric (2 S ,4 S ,5 R )- and (2 R ,4 S ,5 R )-2-(chloromethyl)-3,4-dimethyl-2-oxo-5-phenyl-1,3,2-oxazaphospholanes ( 97a and 97b ) is obtained in 60% yield from the reaction of (−)-ephedrine with 2 in THF in the presence of triethylamine at room temperature. The 3/1 mixture of the two diastereomers is separated by silica gel column chromatography to afford enantiomerically pure samples of 97a (mp 85 °C; 31 P NMR (CDCl 3 ) δ = +35.84 ppm) and 97b (mp 80 °C; 31 P NMR (CDCl 3 ) δ = +34.47 ppm), respectively (Scheme ) 53 …”