Journal of the American Chemical Society
ARTICLE
here should facilitate the development of further useful pericyclic
cascade reactions.
for graduate fellowships (S.E.S.). C.D.V. acknowledges support
from the National Science Foundation (CAREER Award CHE-
0847061), an Amgen Young Investigator Award, and an Astra-
Zeneca Award for Excellence in Chemistry. C.D.V. is a fellow of
the A. P. Sloan Foundation. Computations were performed using
the UCLA Academic Technology Services Hoffman2 Beowulf
cluster and the San Diego Supercomputer Center Thresher
cluster.
’ COMPUTATIONAL METHODS
All stationary points were fully optimized with Gaussian 0931 using
the CBS-QB3 composite ab initio method, unless otherwise stated.33
The complete basis set (CBS) methods remove error in quantum
mechanical calculations that arise from the truncation of basis sets.
The CBS models extrapolate to an infinite basis set limit by using an N-1
asymptotic convergence of MP2 pair energies calculated from pair
natural orbital expansions. The CBS-QB3 method has a maximum error
of 2.8 kcal/mol for the G2 test set and average and mean absolute errors
of 0.20 and 0.98 kcal/mol. On a B3LYP/6-311G(d,p) geometry, energy
corrections computed at the MP2, MP4(SDQ), and CCSD(T) levels of
theory are used to give a final CBS-QB3 energy. Of particular relevance
to this study, the CBS-QB3 method computes activation energies for a
set of hydrocarbon pericyclic reactions to give a mean absolute error of
2.3 kcal/mol.34 We also performed optimizations with the less demand-
ing B3LYP hybrid density functional in combination with the 6-311þG-
(d,p) basis set.35 A fine grid density was used for numerical integration in
all DFT calculations. Harmonic vibrational frequencies were computed
for all optimized structures to verify that they were either minima or
transition states, possessing zero imaginary frequencies and one ima-
ginary frequency, respectively. This level of DFT calculation has been
shown to compute relative transition-state energies to compute selectiv-
ities that give good quantitative agreement with experiment.36 Single-
point energy calculations were also performed with the more recently
parametrized M06-2X functional,37 which is constructed to include
nonlocal effects of electronic dispersion and is found to give good
estimates for reaction enthalpies in bond-forming reactions. All levels
examined led to the same conclusions, and in particular, the agreement
between M06-2X and the CBS-QB3 results for the barriers and energy
changes shown in Figures 1-3 was quantitatively very close. Therefore,
in our studies on the larger systems which precluded the use of the
demanding CBS-QB3 calculations, we relied on the computed M06-2X
energetics to evaluate the competing mechanisms. A full comparison of
all computed energetics at the different levels of theory is reported in full
in the Supporting Information. Natural bond orbital (NBO) calculations
were performed using NBO version 3.1 in Gaussian 09,38 and principal
delocalizations were quantified from second order pecturbation theory
analysis of the Fock matrix on the basis of the NBOs.
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’ ASSOCIATED CONTENT
S
Supporting Information. Characterization data and ex-
b
perimental procedures for all new compounds, B3LYP/6-
311þG(d,p) and M06-2X/6-311þG(d,p) absolute energies,
CBS-QB3 zero-point inclusive absolute enthalpies, free energies,
and optimized Cartesian coordinates of all stationary points and
imaginary vibrational frequencies where appropriate, and com-
plete ref 32. This material is available free of charge via the
(14) Duncan, J. A.; Calkins, D. E. G.; Chavarha, M. J. Am. Chem. Soc.
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(18) These species were not minima on the potential energy surface
computed with the B3LYP, MP2, and M06-2X level and with MPW1K,
recently recommended for optimizing zwitterions: Wei, Y.; Sateesh, B.;
Maryasin, B.; Sastry, G. N.; Zipse, H. J. Comput. Chem. 2009, 30, 2617–
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Chem. 1966, 699. The value for 1,3-cyclohexadiene is 41 kcal/mol: de
Dobbelaere, J. R.; van Zeeventer, E. L.; de Haan, J. W.; Buck, H. M.
Theor. Chim. Acta 1975, 38, 241.
’ AUTHOR INFORMATION
Corresponding Author
cdv@uci.edu; houk@chem.ucla.edu
’ ACKNOWLEDGMENT
We are grateful to the Royal Commission for the Exhibition
of 1851 for a Research Fellowship (R.S.P.) and the California
Tobacco-Related Disease Research Program and Eastman Chemicals
(20) (a) Jensen, F.; Houk, K. N. J. Am. Chem. Soc. 1987, 109, 3139–
3140. (b) Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Int. Ed. Engl.
3904
dx.doi.org/10.1021/ja107988b |J. Am. Chem. Soc. 2011, 133, 3895–3905