Page 873 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

the diene as a net electron acceptor; that is, the reactions are diene LUMO-controlled 857
inverse electron demand reactions. The size of the stabilization and the charge transfer
correlated reasonably well with a combination of the polar and resonance substituent SECTION 10.2
constants. A polarization effect was also noted in several series. In each instance, the The Diels-Alder Reaction
stabilization increased with substituent size and polarizability (F < Cl < Br; CH <
3
CF < CCl < CBr ; OCH < SCH < SeCH .
3
3
3
3
3
3
Computation on TS structure may be useful in predicting and interpreting trends
in reactivity, regioselectivity, and stereoselectivity. To the extent observed trends are
in agreement with the computations, the validity of the TS structure is supported.
One experimental measurement that can be directly connected to TS structure is
the kinetic isotope effect (review Section 3.5), which can be measured with good
experimental accuracy as well as calculated from the TS structure. 58 Comparisons
can be used to examine TS structure at a very fine level of detail. The computed
TS for the (CH AlCl-catalyzed reaction of isoprene with acrolein, ethyl acrylate,
3 2
and but-3-en-2-one indicated highly asynchronous TSs and gave calculated isotope
effects in agreement with experiment. 59 For example, the study of the (CH AlCl-
3 2
catalyzed D-A reaction of isoprene with propenal found good agreement between
observed and computed isotope effects, except at one position. A later study located an
60
alternative TS that gave better agreement with the isotope effect at this position. This
structure incorporates a formyl H bond, as postulated in other Lewis acid–catalyzed
reactions of aldehydes. 61 Although this structure was computed to be slightly higher
in energy, it was favored when a PCM solvent model was used. The TSs are shown in
Figure 10.10.
Several studies have looked at the TS of D-A reactions in which the extent of
aromaticity increases or decreases in going from reactants to products. For example,
aromaticity is enhanced with o-quinodimethanes, where a new benzene ring is formed.
The benzo[c] fused heterocycles contain an o-quinoid structure. The aromaticity of
the heterocyclic ring is lost, but a new benzenoid ring is formed by cycloaddition.
When polycyclic aromatic compounds undergo D-A reactions, the aromaticity of the
reacting central ring is lost, but the peripheral rings have increased aromaticity per
carbon.
Calculated E ’s in several cases are in accord with the experimental trends. 62
a
Quinodimethanes are more reactive than benzo[c]heterocycles and the reactivity of
the linear polycyclic hydrocarbons increases with the number of rings. The changes
in the NICS values for the rings is consistent with the changing aromaticity. In the
case of polycyclic hydrocarbons, the aromaticity in the peripheral rings increases. The
aromaticity of the center ring is transformed to the aromaticity of the TS and then
diminishes as the reaction is completed. 63

58 B. R. Beno, K. N. Houk, and D. A. Singleton, J. Am. Chem. Soc., 118, 9984 (1996); E. Goldstein,
B. Beno, and K. N. Houk, J. Am. Chem. Soc., 118, 6036 (1996).
59
D. A. Singleton, S. R. Merrigan, B. R. Beno, and K. N. Houk, Tetrahedron Lett., 40, 5817 (1999).
60
O. Acevedo and J. D. Evanseck, Org. Lett., 5, 649 (2003).
61 E. J. Acevedo Corey, J. J. Rohde, A. Fischer, and M. D. Alimiora, Tetrahedron Lett., 38,33
(1997).
62 C. Di Valentin, M. Freccero, M. Sarzi-Amade, and R. Zanaletti, Tetrahedron, 56, 2547 (2000).
63
M. Manoharan, F. De Proft, and P. Geerlings, J. Chem. Soc., Perkin Trans. 2, 1767 (2000); M.-F. Cheng
and W.-K. Li, Chem. Phys. Lett., 368, 630 (2003).