Phosphonic amides, diastereomeric

More recently, the chiral phosphonate 85 has been used as a CDA with chiral amines to form diastereomeric phosphonic amides (86)79 which are analyzed by 31P-NMR spectroscopy for the determination of enantiomeric ratios. The reagent is readily prepared from (5)-2-butanol and phosphorous trichloride, and all a-amino acids and amines thus far examined react quantitatively in a few hours at room temperature in aqueous ethanol79. 

Phosphonate groups also provided regiochemical control in the aza-annulation reaction. Condensation of 409 with BnNH2, followed by reaction with acryloyl chloride gave 410 in good yield (eq. 83).57 59 Catalytic hydrogenation of 410 was less efficient than the corresponding ester and amide derivatives and resulted in the formation of a mixture of diastereomeric products 411. 

As mentioned in Volume 13 of these Reports, 4-oxoazetidin-2-yl phosphonates and phosphinates (19) can be prepared by Arbusov-like reactions between P compounds and 4-acetoxyazetidin-2-one (20). Acid hydrolysis of (19) yields phosphono- and phosphino-aspartic acids (21) which can be converted into peptides with antibacterial activity. Diastereomeric mixtures of phosphono-dipeptides, which can be prepared from racemic dialkyl 1 -aminoalkylphosphonates, can be separated by ion-exchange chromatography. It appears that it is easier to synthesize phosphonodipeptides from these phosphonates as their P-dialkyl esters rather than as the free phosphonic acids. Phosphonic acid analogues of A-Cbz-alanine and -phenylalanine can be converted into ester and amide fluoridates, e.g., (22, R = OMe or NHCHMeg). These fluoridates are the most potent inhibitors of elastase and chymotrypsin yet reported and seem to mimic the natural substrates of these enzymes. ... 

Ubukata s synthesis [51] started with ammonolysis followed by Swern oxidation of ( )-55 [52] to give nitrile aldehyde 56. Wittig-Horner reaction of 56 with phosphonate 58 derived from glutarimide acetic acid 57 [27] gave 59. The nitrile was converted to amide 60, which was subjected to selenolac-tamization [53] to afford 61. Oxidation-elimination of the selenenide moiety gave 48 a diastereomeric mixture. 

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