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Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study

Hannelore Goossens UGent, Karel Vervisch UGent, Saron Catak UGent, Sonja Stanković UGent, Matthias D'hooghe UGent, Frank De Proft, Paul Geerlings, Norbert De Kimpe UGent, Michel Waroquier UGent and Veronique Van Speybroeck UGent (2011) JOURNAL OF ORGANIC CHEMISTRY. 76(21). p.8698-8709
abstract
The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
RING-OPENING REACTIONS, THEORETICAL RATIONALIZATION, NUCLEOPHILIC-SUBSTITUTION, DENSITY-FUNCTIONAL THEORY, CONTINUUM SOLVENT CALCULATIONS, THERMOCHEMICAL KINETICS, ASYMMETRIC-SYNTHESIS, CHEMICAL-REACTIONS, CHIRAL AZIRIDINES, FREE-ENERGY
journal title
JOURNAL OF ORGANIC CHEMISTRY
J. Org. Chem.
volume
76
issue
21
pages
8698 - 8709
Web of Science type
Article
Web of Science id
000296206400012
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/jo201255z
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
1943629
handle
http://hdl.handle.net/1854/LU-1943629
date created
2011-11-18 08:24:28
date last changed
2013-09-17 10:46:06
@article{1943629,
  abstract     = {The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.},
  author       = {Goossens, Hannelore and Vervisch, Karel and Catak, Saron and Stankovi\'{c}, Sonja and D'hooghe, Matthias and De Proft, Frank and Geerlings, Paul and De Kimpe, Norbert and Waroquier, Michel and Van Speybroeck, Veronique},
  issn         = {0022-3263},
  journal      = {JOURNAL OF ORGANIC CHEMISTRY},
  keyword      = {RING-OPENING REACTIONS,THEORETICAL RATIONALIZATION,NUCLEOPHILIC-SUBSTITUTION,DENSITY-FUNCTIONAL THEORY,CONTINUUM SOLVENT CALCULATIONS,THERMOCHEMICAL KINETICS,ASYMMETRIC-SYNTHESIS,CHEMICAL-REACTIONS,CHIRAL AZIRIDINES,FREE-ENERGY},
  language     = {eng},
  number       = {21},
  pages        = {8698--8709},
  title        = {Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study},
  url          = {http://dx.doi.org/10.1021/jo201255z},
  volume       = {76},
  year         = {2011},
}

Chicago
Goossens, Hannelore, Karel Vervisch, Saron Catak, Sonja Stanković, Matthias D’hooghe, Frank De Proft, Paul Geerlings, Norbert De Kimpe, Michel Waroquier, and Veronique Van Speybroeck. 2011. “Reactivity of Activated Versus Nonactivated 2-(bromomethyl)aziridines with Respect to Sodium Methoxide: a Combined Computational and Experimental Study.” Journal of Organic Chemistry 76 (21): 8698–8709.
APA
Goossens, Hannelore, Vervisch, K., Catak, S., Stanković, S., D’hooghe, M., De Proft, F., Geerlings, P., et al. (2011). Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study. JOURNAL OF ORGANIC CHEMISTRY, 76(21), 8698–8709.
Vancouver
1.
Goossens H, Vervisch K, Catak S, Stanković S, D’hooghe M, De Proft F, et al. Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study. JOURNAL OF ORGANIC CHEMISTRY. 2011;76(21):8698–709.
MLA
Goossens, Hannelore, Karel Vervisch, Saron Catak, et al. “Reactivity of Activated Versus Nonactivated 2-(bromomethyl)aziridines with Respect to Sodium Methoxide: a Combined Computational and Experimental Study.” JOURNAL OF ORGANIC CHEMISTRY 76.21 (2011): 8698–8709. Print.