Efficient Solution-Phase Parallel Synthesis of 4-Substituted N-Protected Piperidines
2003 (English)In: European Journal of Organic Chemistry, Vol. 23, 4586-92 p.Article in journal (Refereed) Published
Practical conditions for the synthesis of 4-substituted N-protected piperidines through CuCN·2LiBr-catalyzed organozinc additions to 1-acylpyridinium salts and subsequent hydrogen-transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4-substituted N-protected piperidines in excellent overall yields without the isolation of intermediate dihydropyridines. In those cases in which the organozinc addition results in mixtures of 2- and 4-substituted dihydropyridines, the 2-substituted isomers are efficiently scavenged with maleic anhydride and subsequently removed by a mild extractive workup with NaHCO3 (sat.). The N-acyl group can conveniently be exchanged from N-phenoxycarbonyl to N-tBoc, thus allowing orthogonal deprotection strategies.
Place, publisher, year, edition, pages
2003. Vol. 23, 4586-92 p.
Copper, Hydrogenations, Nitrogen heterocycles, Zinc, Parallel synthesis
IdentifiersURN: urn:nbn:se:umu:diva-9942DOI: doi:10.1002/ejoc.200300387OAI: oai:DiVA.org:umu-9942DiVA: diva2:149613