Ghent University Academic Bibliography

Advanced

Stereoselective synthesis of cis-3,4-disubstituted piperidines through ring transformation of 2-(2-mesyloxyethyl)azetidines

Karen Mollet UGent, Saron Catak UGent, Michel Waroquier UGent, Veronique Van Speybroeck UGent, Matthias D'hooghe UGent and Norbert De Kimpe UGent (2011) JOURNAL OF ORGANIC CHEMISTRY. 76(20). p.8364-8375
abstract
The reactivity of 2-(2-mesyloxyethyl)azetidines, obtained through monochloroalane reduction and mesylation of the corresponding beta-lactams, with regard to different nucleophiles was evaluated for the first time, resulting in the stereoselective preparation of a variety of new 4-acetoxy-, 4-hydroxy-, 4-bromo-, and 4-formyloxypiperidines. During these reactions, transient 1-azoniabicyclo[2.2.0]hexanes were prone to undergo an S(N)2-type ring opening to afford the final azaheterocycles, which was rationalized by means of a detailed computational analysis. This approach constitutes a convenient alternative for the known preparation of 3,4-disubstituted 5,5-dimethylpiperidines, providing an easy access to the 5,5-nor-dimethyl analogues as valuable templates in medicinal chemistry. Furthermore, cis-4-bromo-3-(phenoxy or benzyloxy)piperidines were elaborated into the piperidin-3-one framework via dehydrobromination followed by acid hydrolysis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SUBSTITUTED PIPERIDINES, THERMOCHEMICAL KINETICS, DENSITY FUNCTIONALS, THEORETICAL RATIONALIZATION, MOLECULAR-ORBITAL METHODS, CONTINUUM SOLVENT CALCULATIONS, AZETIDINES, PYRROLIDINES, BETA-LACTAMS, BUILDING-BLOCKS
journal title
JOURNAL OF ORGANIC CHEMISTRY
J. Org. Chem.
volume
76
issue
20
pages
8364 - 8375
Web of Science type
Article
Web of Science id
000295816700024
JCR category
CHEMISTRY, ORGANIC
JCR impact factor
4.45 (2011)
JCR rank
9/56 (2011)
JCR quartile
1 (2011)
ISSN
0022-3263
DOI
10.1021/jo201556t
project
HPC-UGent: the central High Performance Computing infrastructure of Ghent University
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1943641
handle
http://hdl.handle.net/1854/LU-1943641
date created
2011-11-18 08:24:39
date last changed
2013-09-17 10:46:11
@article{1943641,
  abstract     = {The reactivity of 2-(2-mesyloxyethyl)azetidines, obtained through monochloroalane reduction and mesylation of the corresponding beta-lactams, with regard to different nucleophiles was evaluated for the first time, resulting in the stereoselective preparation of a variety of new 4-acetoxy-, 4-hydroxy-, 4-bromo-, and 4-formyloxypiperidines. During these reactions, transient 1-azoniabicyclo[2.2.0]hexanes were prone to undergo an S(N)2-type ring opening to afford the final azaheterocycles, which was rationalized by means of a detailed computational analysis. This approach constitutes a convenient alternative for the known preparation of 3,4-disubstituted 5,5-dimethylpiperidines, providing an easy access to the 5,5-nor-dimethyl analogues as valuable templates in medicinal chemistry. Furthermore, cis-4-bromo-3-(phenoxy or benzyloxy)piperidines were elaborated into the piperidin-3-one framework via dehydrobromination followed by acid hydrolysis.},
  author       = {Mollet, Karen and Catak, Saron and Waroquier, Michel and Van Speybroeck, Veronique and D'hooghe, Matthias and De Kimpe, Norbert},
  issn         = {0022-3263},
  journal      = {JOURNAL OF ORGANIC CHEMISTRY},
  keyword      = {SUBSTITUTED PIPERIDINES,THERMOCHEMICAL KINETICS,DENSITY FUNCTIONALS,THEORETICAL RATIONALIZATION,MOLECULAR-ORBITAL METHODS,CONTINUUM SOLVENT CALCULATIONS,AZETIDINES,PYRROLIDINES,BETA-LACTAMS,BUILDING-BLOCKS},
  language     = {eng},
  number       = {20},
  pages        = {8364--8375},
  title        = {Stereoselective synthesis of cis-3,4-disubstituted piperidines through ring transformation of 2-(2-mesyloxyethyl)azetidines},
  url          = {http://dx.doi.org/10.1021/jo201556t},
  volume       = {76},
  year         = {2011},
}

Chicago
Mollet, Karen, Saron Catak, Michel Waroquier, Veronique Van Speybroeck, Matthias D’hooghe, and Norbert De Kimpe. 2011. “Stereoselective Synthesis of Cis-3,4-disubstituted Piperidines Through Ring Transformation of 2-(2-mesyloxyethyl)azetidines.” Journal of Organic Chemistry 76 (20): 8364–8375.
APA
Mollet, K., Catak, S., Waroquier, M., Van Speybroeck, V., D’hooghe, M., & De Kimpe, N. (2011). Stereoselective synthesis of cis-3,4-disubstituted piperidines through ring transformation of 2-(2-mesyloxyethyl)azetidines. JOURNAL OF ORGANIC CHEMISTRY, 76(20), 8364–8375.
Vancouver
1.
Mollet K, Catak S, Waroquier M, Van Speybroeck V, D’hooghe M, De Kimpe N. Stereoselective synthesis of cis-3,4-disubstituted piperidines through ring transformation of 2-(2-mesyloxyethyl)azetidines. JOURNAL OF ORGANIC CHEMISTRY. 2011;76(20):8364–75.
MLA
Mollet, Karen, Saron Catak, Michel Waroquier, et al. “Stereoselective Synthesis of Cis-3,4-disubstituted Piperidines Through Ring Transformation of 2-(2-mesyloxyethyl)azetidines.” JOURNAL OF ORGANIC CHEMISTRY 76.20 (2011): 8364–8375. Print.