Asymmetric synthesis of intermediates for otamixaban and premafloxacin by the chiral ligand-controlled asymmetric conjugate addition of a lithium amide.
A chiral ligand-controlled conjugate addition reaction of lithium benzyl(trimethylsilyl)amide with tert-butyl enoates gave the corresponding lithium enolates that were then treated with electrophiles, giving anti-alkylation products with high ee up to 98%. The benzyl group on the amino nitrogen was removed by the oxidation of secondary amines to imines and subsequent transoximation to give 3-aminoalkanoates in good yields. The products are the possible key intermediates of otamixaban and premafloxacin.
Sakai
Takeo
T
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Kawamoto
Yoshito
Y
Tomioka
Kiyoshi
K
D000577:Amides; D003497:Cyclic N-Oxides / Q000138:chemical synthesis*; D024841:Fluoroquinolones / Q000138:chemical synthesis*; D008024:Ligands; D008094:Lithium; D011725:Pyridines / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*; D015363:Quinolones / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000577:Amides; D003497:Cyclic N-Oxides; D024841:Fluoroquinolones; D008024:Ligands; D011725:Pyridines; D011758:Pyrroles; D015363:Quinolones; D008094:Lithium; C435830:otamixaban; C105016:premafloxacin