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Download fileApplications and Limitations of the I2‑Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation
journal contribution
posted on 2013-10-04, 00:00 authored by Hilary
M. Corkran, Stefan Munneke, Emma M. Dangerfield, Bridget L. Stocker, Mattie S. M. TimmerA protecting-group-free
synthetic strategy for the synthesis of
piperidines has been explored. Key in the synthesis is an I2-mediated carbamate annulation, which allows for the cyclization
of hydroxy-substituted alkenylamines into piperidines, pyrrolidines,
and furans. In this work, four chiral scaffolds were compared and
contrasted, and it was observed that with both d-galactose
and 2-deoxy-d-galactose as starting materials, the transformations
into the piperidines 1-deoxygalactonorjirimycin (DGJ) and 4-epi-fagomine, respectively, could be achieved in few steps
and good overall yields. When d-glucose was used as a starting
material, only the furan product was formed, whereas the use of 2-deoxy-d-glucose resulted in reduced chemo- and stereoselectivity and
the formation of four products. A mechanistic explanation for the
formation of each annulation product could be provided, which has
improved our understanding of the scope and limitations of the carbamate
annulation for piperidine synthesis.