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Organic & Biomolecular Chemistry
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COMMUNICATION
Only a modest barrier (21.7 kcal/mol, relative to the energy coumarins reported herein are of potential bioloVgieicwaAlrtiicnleteOrnelinset
DOI: 10.1039/C7OB02335A
of 7) was calculated for the [1,5]-hydrogen shift from 7 ([1,5]- to medicinal chemists.
H-shift TS8). Thus, both the lower barriers for the sequential
pathway (i.e. [3,5]-rearrangement followed by [1,5]-H shift)
and the thermodynamic stability of 8 are in agreement with
Conflicts of interest
our experimental observation of the selective formation of 8.
Similar to the acetate ([3,3]-TS1 and [3,3]-TS3), the
transition state for [3,3]-rearrangement of imidate 3 ([3,3]-
TS5) also has a flattened boat geometry. The [3,5]-TS6 and
[1,3]-TS7 would be orbital symmetry-forbidden as pericyclic
reactions. As expected both these transition state geometries
are purely pseudopericyclic, i.e. planar on the imidate moiety
(Figure 4).
There are no conflicts to declare.
Acknowledgements
This research was supported by Robert A. Welch Foundation
Grant D-1239. We are grateful for the use of a 400 MHz NMR
spectrometer made available through the NSF CRIF MU Grant
CHE-1048553.
In principle, a stepwise biradical mechanism via 11 is
possible for the [3,5]-sigmatropic rearrangement from 3 to 7.
This is arguably unlikely for two reasons: first, the radical
pathway for the [3,5]-rearrangement in 1,3,7-octatriene is
calculated to have a much higher barrier than the pericyclic
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[3,3]-rearrangement.21B,C
If
rearrangement of 3 is assumed to be concerted, and the
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the
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[3,3]-
2
3
3
rearrangement observed, this argues that the latter does not
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intermediates by stabilizing the radicals by conjugation.21B,C
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Conclusions
A
substituted coumarin imidate (3) has been shown
experimentally to selectively undergo thermal [3,5]-
a
sigmatropic rearrangement that would be forbidden by the
Woodward-Hoffmann rules, yielding the rearrangement
product 8. Calculations suggest the energetically favorable
pathway is a sequential one, in which a pseudopericyclic [3,5]-
rearrangement gives the amide 7, for which the modest
decrease in the aromaticity of the coumarin system is offset by
the increased stability of the amide functionality. This is
followed by a facile [1,5]-hydrogen shift to yield the observed
product 8. The [3,3]-rearrangement of 3 is energetically
disfavored because the stability of the amide is insufficient to
overcome the loss of aromaticity in 6. Attempted pyrolysis of
the isoelectronic acetate 2 gave only unreacted 2. DFT
calculations (B3LYP/6-31G(d,p)) suggest that the [3,3]- and
[3,5]-rearrangements of acetate 2 are not expected to occur
because the expected products 4 and 5 are less stable.
Moreover, the functionalized and structurally diverse
23 Sharma, S.; Rajale, T.; Unruh, D. K.; Birney, D. M. J. Org.
Chem. 2015, 80, 11734-11743.
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