Journal of the American Chemical Society
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’ AUTHOR INFORMATION
Corresponding Author
’ ACKNOWLEDGMENT
We gratefully acknowledge the support of the National Science
Foundation (CHE-0749907 and CHE-0840504) and the NIH-
National Institute of General Medical Sciences (GM085736-
01A1). We thank Profs. Peter R. Schreiner and Thomas M. Gilbert
for helpful discussions.
’ REFERENCES
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Figure 2. MP2 6-311G(d,p)-calculated NBO charges for carbon atoms
in diprotonated N-heterocycles 34À38 and the types of addition
chemistry observed (CA, conjugate addition; MA, Markovnikov addi-
tion; B3LYP 6-311G(d,p)-calculated NBO charges in parentheses).
carbocation (from protonation of the vinyl group), and it
should also increase the tendency for CA with the arene
nucleophile. Thus, CA is observed with 2- and 4-vinylpyrimidines
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nazoline and quinoxaline systems 37 and 38 showed the same
trend as the pyrimidine series. These N-heterocyclic systems give
MA products at electron-rich positions and CA products at electron-
deficient positions.
ꢀ
These studies demonstrate the importance of charge distribu-
tions in controlling the chemistry of N-heterocycles. Diproto-
nated N-heterocycles (pyrazines, pyrimidines, quinoxalines, and
quinazolines) are shown to exert very powerful regioelectronic
effects at certain ring positions. NMR experiments have shown
that these effects drastically influence the basicity of substituent
styryl groups. The relatively high amount of positive charge leads
to CA with the weak nucleophile benzene, making this chemistry
analogous to that of the superelectrophiles described by Olah.13
Other ring positions are clearly not as electron deficient, and this
leads to a completely different reaction course. The olefinic
groups at these sites tend to undergo FriedelÀCrafts-type chem-
istry via carbocationic intermediates. Functionalized N-hetero-
cycles are often prepared by synthetic reactions at side chains
or substituent groups. Our results have shown that such chemis-
try may be significantly impacted by localized charges within the
N-heterocycles.
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(13) Olah, G. A.; Klumpp, D. A. Superelectrophiles and Their Chem-
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’ ASSOCIATED CONTENT
S
Supporting Information. Detailed experimental proce-
b
dures, characterization data, H and 13C NMR spectra for new
1
compounds, 13C NMR spectra for ions 29 and 31, computational
methods and results, and complete ref 11. This material is
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dx.doi.org/10.1021/ja202557z |J. Am. Chem. Soc. 2011, 133, 8467–8469