Page 952 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

936 the TS for the Claisen rearrangement by hydroxy substituents has been probed using
both HF/6-31G and B3LYP/6-31G calculations. 298 The effect of cyano, amino, and
∗
∗
CHAPTER 10 trifluoromethyl groups has also been calculated. 299 The effect of methoxy groups has
Concerted Pericyclic been examined using a combination AM1-MM method. The predicted changes in E ,
Reactions a
as summarized in Table 10.8, are in qualitative agreement with experimental results.
These substituent effects can be analyzed by considering the effect on reactants,
products, and the TS. For example, the large accelerating effect of 2-alkoxy and
2-amino substituents is due in substantial part to the amide and ester resonance stabi-
lization that develops in the products.

NR 2 NR 2 OR OR
O O O O

The analysis can be done in terms of the Marcus theory by considering the effect on
‡
overall reaction energy E rxn and E , the intrinsic barrier, using a version of the
0
Marcus equation. 300 (See Section 3.3.2.3 to review the Marcus equation.)
‡
2
‡
‡
1
E = E + / 2 E rxn + E /16 E
0
0
rxn
For the HF/6-31G* calculations, the barriers were separated into effects owing to
changes in reaction energy and changes in TS energy. 299b Changes in TS energy
can be analyzed in terms of radical stabilization effects, as was done for the Cope
rearrangement. (see p. 924ff). In addition, there may be variation in the extent of
the polar character at the TS. The TS for the Claisen rearrangement has some ionic
character, resembling an enolate for C(1), C(2), and O(3) and allyl cation for C(4),
C(5), C(6). For the parent reaction, charge transfer is calculated to be 0.21e. The
stabilizing effect of the 4- and 6-oxy substituents may be due to stabilization of the
cationic fragment, as indicated by the charge distribution below.
OR O R – + –
+
– + – O
O O O OR O R
+
Table 10.8. Calculated Substituent Effects on E in kcal/mol
a
for Claisen Rearrangement
Position OH a CN b NH 2 b CF 3 b OCH 3 c
1 −2 7 +0 1 −5 5 +1 1
2 −9 1 −3 8 −6 7 −3 8 −9 1
4 −1 0 −4 8 −8 6 −1 2 −4 7
5 +5 0 −2 4 +4 5 −1 8 +4 0
6 −0 6 +2 6 −2 3 +1 6 −1 2
a. HF/6-31G : H. Y. Yoo and K. N. Houk, J. Am. Chem. Soc., 119, 2877 (1997);
∗
∗
b. B3LYP/6-31G : V. Aviyente and K. N. Houk, J. Phys. Chem. A, 105, 383 (2001).
c. AM1-MM: A. Sehgal, L. Shao, and J. Gao, J. Am. Chem. Soc., 117, 11337 (1995).
298
H. Y. Yoo and K. N. Houk, J. Am. Chem. Soc., 119, 2877 (1997).
299 (a) V. Aviyente, H. Y. Yoo, and K. N. Houk, J. Org. Chem., 62, 6121 (1997); (b) V. Aviyente and
K. N. Houk, J. Phys. Chem. A, 105, 383 (2001).
300
M. Y. Chen and J. R. Murdoch, J. Am. Chem. Soc., 106, 4735 (1984).