Concise, enantiospecific synthesis of (3 S,4 R)-3-amino-4-ethylpiperidine as partner to a non-fluoroquinolone nucleus

Abstract

An enantiospecific, eight-step synthesis of (3 S,4 R)-3-amino-4-ethylpiperidine 3 starting from readily available ( S)-(−)-α-methyl-4-pyridinemethanol 6 has been achieved utilizing an Overman rearrangement of a chiral allylic trichloroacetimidate 13 as the key step. A diastereoselective hydrogenation of the resulting chiral allylic amine 15 afforded predominantly the desired trans-substituted piperidine. The conformation of the piperidine along with the directing nature of the amino function are implicated in the selectivity observed.