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Synfacts 2006(7): 0657-0657  
DOI: 10.1055/s-2006-941839
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Synthesis of cis- or trans-3,4-Disubstituted Piperidines

Contributor(s): Victor Snieckus, Bärbel Wittel
J. T. Williams, P. S. Bahia, B. M. Kariuki, N. Spencer, D. Philp, J. S. Snaith*
The University of Birmingham and University of St. Andrews, UK
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Publication History

Publication Date:
22 June 2006 (online)

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Significance

The synthesis of 3,4-disubstituted piperidines using key carbonyl ene or Prins cyclization reactions is reported. In the former reaction, MeAlCl2 serves as the catalyst to give the kinetic trans isomer with high diastereoselectivity. On the other hand, the corresponding cis isomer is formed at low temperatures with equally high diastereoselectivity by an HCl-catalyzed Prins reaction. Of the several different Lewis and Brøn­sted acids tested for both reactions, MeAlCl2 and HCl were found to be optimal for the two reactions, respectively. The p-toluenesulfonyl protecting group was successfully removed using sodium naphthalenide in THF at -78 °C.

Mechanistic studies including DFT calculations for these reactions are described.