Stereocontrolled synthesis of orthogonally protected 2-substituted 4-aminopiperidines.
Expedient and highly stereoselective routes to orthogonally protected chiral 2-substituted 4-aminopiperidines have been developed. Diastereoselective nucleophilic substitution of the hydroxy group of (2R,4S)-2-[(S)-1,2-dibenzyloxyethyl]-4-hydroxy-1-[(S)-1-phenylethyl]piperidine using sodium azide afforded the corresponding azido derivative, which could be reduced and selectively protected to give (2R,4R)-1-tert-butoxycarbonyl-2-[(S)-1,2-dibenzyloxyethyl]-4-acetylaminopiperidine. This compound was easily converted into optically active 2-substituted 4-aminopiperidines using different synthetic methodologies such as epoxide nucleophilic ring opening reactions and Wittig olefination reactions among others.
Badorrey
Ramón
R
Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, E-50009, Zaragoza, Spain.
Portaña
Elsa
E
Díaz-de-Villegas
María D
MD
Gálvez
José A
JA
D000081:Acetamides / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
D000081:Acetamides; D010880:Piperidines; D011728:Pyridones; C030686:acetamide