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Title: A General Strategy for N-(Hetero)arylpiperidine Synthesis Using Zincke Imine Intermediates
Methods to synthesize diverse collections of sub- stituted piperidines are valuable due to the prevalence of this heterocycle in pharmaceutical compounds. Here, we present a general strategy to access N-(hetero)arylpiperidines using a pyridine ring-opening and ring-closing approach via Zincke imine inter- mediates. This process generates pyridinium salts from a wide variety of substituted pyridines and (heteroaryl)anilines; hydro- genation reactions and nucleophilic additions then access the N- (hetero)arylpiperidine derivatives. We successfully applied high- throughput experimentation (HTE) using pharmaceutically relevant pyridines and (heteroaryl)anilines as inputs and developed a one-pot process using anilines as nucleophiles in the pyridinium salt-forming processes. This strategy is viable for generating piperidine libraries and applications such as the convergent coupling of complex fragments.  more » « less
Award ID(s):
2155215
PAR ID:
10516680
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Corporate Creator(s):
Editor(s):
Lloyd-Jones, Guy
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
Journal of the American Chemical Society
Edition / Version:
1
Volume:
146
Issue:
1
ISSN:
0002-7863
Page Range / eLocation ID:
936 to 945
Subject(s) / Keyword(s):
Synthetic organic chemistry piperidines, pyridinium salts, NTf-pyridinium, Zincke, high-throughput experimentation, HTE, asymmetric hydrogenation
Format(s):
Medium: X Size: 3.3MB Other: pdf
Size(s):
3.3MB
Sponsoring Org:
National Science Foundation
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