Stereocontrolled synthesis of orthogonally protected 2-substituted 4-aminopiperidines?

Organic & Biomolecular Chemistry Pub Date: 2009-05-27 DOI: 10.1039/B904948G

Abstract

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.

Graphical abstract: Stereocontrolled synthesis of orthogonally protected 2-substituted 4-aminopiperidines
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