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A Route to 1‐Deoxynojirimycin and 1‐Deoxymannojirimycin Derivatives with Quaternary Centers Adjacent to the Ring Nitrogen from Methyl α‐ d ‐Mannopyranoside
Author(s) -
Chadda Rekha,
Murphy Paul V.
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901875
Subject(s) - chemistry , aziridine , allylic rearrangement , azide , steric effects , stereochemistry , piperidine , epimer , anomer , methyl group , ring (chemistry) , substituent , racemization , medicinal chemistry , organic chemistry , group (periodic table) , catalysis
6‐Alkylated‐8‐azido‐1,6‐octadiene derivatives were prepared from methyl α‐ d ‐mannopyranoside. The sequence to allylic azide precursors included a Horner–Wadsworth‐Emmons reaction with a concomitant epimerization that ultimately enabled synthesis of 1‐deoxynojirimycin as well as 1‐deoxymannojirimycin derivatives. Thermally promoted allylic acid rearrangement followed by triazoline formation, then decomposition to aziridine and finally reaction with acetic acid was used to generate products that have quaternary anomeric centers adjacent to the piperidine ring nitrogen atom (cyclic α‐tertiary amines). The stereoselectivity is accounted for based on minimization of steric interactions in the transition state structure, favoring the product where the methyl substituent is equatorial and the vinyl group prefers to be axial.