Communications
DOI: 10.1002/anie.200903293
Dynamic Effects
Recrossing and Dynamic Matching Effects on Selectivity in a
Diels–Alder Reaction**
Zhihong Wang, Jennifer S. Hirschi,* and Daniel A. Singleton*
The products and selectivities of some organic reactions
cannot be explained within the normal framework of reaction
barriers and transition state theory. In these cases, explicit
consideration of the detailed motions and momenta of the
atoms can often rationalize the experimental results.[1] Such
reactions may be described as involving “dynamic effects”.
The recognition of the breadth of reactions involving dynamic
effects and the detailed understanding of experimental
observations in these reactions remains a substantial chal-
lenge in chemistry.
dynamic factors affecting the selectivity and have proven
highly successful in predicting product ratios,[3b,c,6b,7,8c,9] but
provide little direct guidance to intuitive understanding.
We describe here a combined experimental and theoret-
ical study of diene/dienophile role selectivity in a synthetically
useful hetero-Diels–Alder reaction. The results demonstrate
the importance of dynamic factors, particularly non-statistical
recrossing and a new form of dynamic matching, in control-
ling the selectivity of Diels–Alder reactions involving bifur-
cating surfaces.
Dynamic effects can arise in several ways. In reactions
involving “dynamic matching”, the selectivity after passing
through a shallow intermediate is related to the momentum of
atoms crossing an initial transition state.[2–4] Other reactions
involve “bifurcating energy surfaces”, in which reactions that
pass through a rate-limiting transition state can proceed
downhill to two or more products.[5–11] A third dynamic effect
involves the recrossing of barriers; much recrossing is
predictable and handled well by variational transition state
theory, but some recrossing is not readily predictable statisti-
cally,[12] and such “non-statistical recrossing” can affect
observations in organic reactions.[9] Reactions can involve a
complex combination of dynamic effects.[9–13]
The simple hetero-Diels–Alder reaction of acrolein (1)
with methyl vinyl ketone (2) has found synthetic application
including the total synthesis of brevicomin.[14,15] Aside from
homodimers, this cycloaddition affords two cross products: 3,
in which methyl vinyl ketone has acted as the dienophile, and
4, in which acrolein has acted as the dienophile. The 3:4 ratio
was previously reported as 10:1, but the product ratio changes
with time as these isomers interconvert by what was proposed
to be a Cope-type rearrangement.[14,16]
A number of cycloadditions involve bifurcating energy
surfaces,[7–10] and the understanding of selectivity in unsym-
metrical examples is a difficult problem. In general terms, the
effects influencing the selectivity between products on a
bifurcating surface may be artificially divided into “static
factors”, i.e., the geometry of the initial transition state and
the shape of the energy surface beyond the transition state,
and “dynamic factors”, i.e., effects associated specifically with
the momenta of atoms. The latter category would include
both dynamic matching and non-statistical recrossing. Pre-
vious studies of Diels–Alder reactions have focused on static
factors,[7,10] and this has provided qualitative guidance in
rationalizing the major products and which reactions are
highly selective versus unselective. The role of dynamic
factors is much less easily assessed, even with the aid of
trajectory studies. Trajectory studies inherently incorporate
The formation of mixtures of products complicates the
direct determination of the reaction kinetics, so we opted for
an indirect process. Looking at the simple Diels–Alder
dimerization of 1, the activation energy was 21.9 Æ 1.2 kcal
molÀ1, based on initial rates over a temperature range from
100–1808C. In the mixed reaction of 1 with 2 at 808C, the
cross products 3 and 4 are formed in sum with a rate constant
5.1 Æ 0.5 times greater than the rate constant for dimerization
of 1. Assuming that this difference is due to activation energy,
the barrier for the cross reaction is 20.8 kcalmolÀ1
.
The 3:4 ratio varies at a significant rate even at 808C. On
prolonged heating, ketone 3 is favored and less than 2% of 4
was observed. Pyrolyses of the Diels–Alder cycloadducts did
not afford observable monomers up to 1808C. From the rate
of the slow decomposition of 3 in a pyrolysis at 1808C in
dibenzyl ether, an upper limit for the rate of the retro-Diels–
Alder reaction of 2.5 ꢀ 10À6 sÀ1 could be estimated. This is at
least 10 times slower than the loss of 4 at this temperature.
The complete reaction composition versus time was kineti-
cally modeled in a series of experiments up to 1608C (see the
Supporting Information) assuming bimolecular kinetics for
the Diels–Alder reactions, unimolecular isomerization of 4 to
3, and negligible rates for conversion of 3 to 4 and retro-
[*] Dr. Z. Wang, Dr. J. S. Hirschi, Prof. D. A. Singleton
Department of Chemistry, Texas A&M University
College Station, Texas 77842-3012 (USA)
Fax: (+1)979-845-0653
E-mail: singleton@mail.chem.tamu.edu
[**] We thank NIH grant no GM-45617, NSF-CRIF CHE-0541587, and
The Robert A. Welch Foundation for financial support.
Supporting information for this article is available on the WWW
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 9156 –9159