Page 965 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

Equations (10.4) and (10.5) is the fact that the more remote positions (4 and 2 ) 949
change less than the substituted positions. Local softness parameters have also been
calculated by a bond electronegativity equalization approach. 345 All the computations TOPIC 10.1
reported to date refer to diene (HOMO)-dienophile (LUMO) combination pairs, so it Application of DFT
Concepts to Reactivity
is not possible to see if this approach successfully predicts the case in which both the and Regiochemistry of
diene and the dienophile carry EWG substituents. Cycloaddition Reactions
By comparing the FMO and DFT analyses, we see that most combinations of
diene and dienophiles lead to the same prediction. The underlying physical basis of
the predictions is also quite similar. In FMO theory it is the closeness in energy of
the FMOs that is considered to be the origin of relative reactivity. Regioselectivity is
attributed to maximum orbital overlap, as judged by the FMO coefficients. In the DFT
approach, the extent of charge transfer (as measured by the global electrophilicity and
nucleophilicity parameters) is considered to be the indicator of reactivity and local
softness is considered to govern regioselectivity. The physical picture of the D-A
reaction that emerges is one of complementary electronic interactions between the
diene and dienophile that reduce the electron-electron repulsions that are otherwise
dominant in the early stages of the reaction. Although both approaches can provide
predictive relationships for a range of diene-dienophile combinations, neither has yet
developed quantitative predictions of relative rates over a wide range of reactant
combinations. This, of course, would be inherently difficult for combinations in which
steric effects are significant, since neither FMO coefficients nor the DFT parameters
take account of steric effects directly. It would be interesting to know, however, perhaps
with cyanoethenes and cyanoethynes, if some combination of the local electrophilicity
and softness parameters could account for relative reactivity.
Domingo and co-workers applied the DFT concepts of electrophilicity and
softness in a study of all the possible cyanoethenes in reaction with cyclopentadiene,
calculating the TS geometries, energies, and charge transfer at the B3LYP/6-31G ∗
level. 346 Both gas phase and benzene solution E values were calculated. The geome-
a
tries indicated that the TS is slightly earlier in benzene. For symmetrically substituted
ethenes, the reactions are nearly synchronous, whereas for unsymmetrical dienophiles
they are asynchronous. The global and local parameters were determined and the
local electrophilicity parameter was found to correlate with the number of cyano
2
substituents, as would be expected.

Substitution 1 f + 1 2 f + 2
1-CN 1.74 0.46 0.266 0.82 0.469
1,1-diCN 2.82 0.59 0.209 1.41 0.499
E-1,2-diCN 3.08 0.92 0.300 0.92 0.300
Z-1,2-diCN 3.01 0.92 0.306 0.92 0.306
1,1,2-triCN 4.38 1.03 0.236 1.46 0.333
1,1,2,2-tetraCN 5.96 1.53 0.257 1.53 0.257

The calculated E decreased with the value of , whereas the extent of charge
a
transfer at the TS increased.
345 Y. Cong, Z. Z. Yang, C. S. Wang, X. C. Liu, and Y. H. Bao, Chem. Phys. Lett., 357, 59 (2002).
346
L. R. Domingo, M. J. Aurell, P. Perez, and R. Contreras, J. Org. Chem., 68, 3884 (2003).