3
carboxyl group is considerably less electron-withdrawing owing
to the electron-donating resonance characteristics of the amide
nitrogen. The reductive debrominations observed in a few cases
are not discussed further here since in our previous report on
similar reactions with anisidines we had offered a reasonable
mechanism for these reactions.
of the α-hydrogen than with esters 6 or 8 (pKa values of α-CH
in ethyl acetate and N,N-dimethylacetamide are 25 and 30,
respectively).8
Acknowledgments
This investigation was partly supported by the National
Institutes of Health, United States [Grant No. SC1 GM095419
(W.W.) and Grant No. SC1 GM082340 (I.E.)]. The NMR
facility was funded by the National Science Foundation, United
States (DUE-9451624 and DBI 0521342).
3. Conclusions.
After having uncovered a new reductive debromination of
non-activated 1,2-dibromides with o- and m-anisidines, and in an
effort to shed light on the types of interaction of vicinal
dibromides with tertiary amines, we studied the corresponding
reactions of 1,2-dibromides derived from non-activated
arylalkenes as well their activated counterparts, α,β-unsaturated
carboxyl derivatives, with NEt3. The reactions were conducted in
two different solvents (THF and DMF, respectively) at different
temperatures, and based on the product distribution under the
conditions applied, the outcome of the NEt3 promoted reactions
turned out to be quite different from that achieved with o- and m-
anisidine, respectively. With the latter weak aromatic bases that
are easily oxidizable, exclusive reductive debromination was
observed in activated and non-activated 1,2-dibromides (pKa of
the conjugate acids, respectively, of o-anisidine 4.52, m-anisidine
4.23).7 On the other hand, with a much stronger base like NEt3
(pKa of conjugate acid 10.75), and in particular with activated
dibromides, the dehydrobromination by an E1cB dominates,
except for the N,N-dimethyl amide 12, where in either solvent
only the reductive debromination product 13 was isolated. With
the ester 8, the reductive debromination product 11 was absent in
References and Notes
1. McGraw, K. M.; Bowler, J. T.; Ly, V. T.; Erden, I.; Wu, W.
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(b) Heasley, G. E.; Bower, T. R.; Dougharty, K. W.; Easton, J. C.;
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T.; Shellhamer, D. F. J. Org. Chem. 1980, 45, 5150-5155.
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Stenzel, O.; Shipman, J. L.; Khan, M. A.; Dechert, S.;
Schuhmann, H. Organometallics, 2000, 19, 5464-5470. (b)
Usanov, D. L.; Yamamoto, H. Org. Lett. 2012, 14, 414-417.
4. Von Braun, J.; Ostermayer, H. Chem. Ber. 1937, 70, 1006-1008.
5. Keeffe, J. R.; Jenks, W. P. J. Am. Chem. Soc. 1983, 105, 265-269,
and references cited therein.
6. E2 Eliminations require strong bases. Triethylamine is not a
common E2 base due to its relatively low basicity (pKa of the
conjugate acid 10.75) as compared to, e.g., 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU), a popular E2 base (pKa of
conjugate acid 12): Srivastava, R. J. Mol. Catal A: Chem. 2007,
264, 146-152.
o
THF at 66 C, but its proportion relative to the E1cB products
7. (a) Perrin, D. D., Dissociation Constants of Organic Bases
Aqueous Solution, Butterwoths, London, 1965; Supplement, 1972.
(b) Serjeant, E. P.; Dempsey, B., Ionization Constants of Organic
Acids in Aqueous Solution, Pergamon, Oxford, 1979.
9+10 was ca. 36%. Apparently, the reductive debromination
pathway requires higher temperatures than the E1cB reaction.
Thus, with the deactived dibromide 4, the E1cB pathway is
precluded, but the reductive debromination pathway still requires
8. These pKa values were taken from a Table in J. G. Smith Organic
Chemistry, 4th ed.; McGraw-Hill: New York, 2014; p A2.
°
90 C in DMF. The question why the debromination dominates
with the N,N-dimethyl amide 12 can be traced to the fact that the
E1cB in this case is much less preferred due the decreased acidity