Communications
DOI: 10.1002/anie.201103998
Cycloaddition
Experimental Diels–Alder Reactivities of Cycloalkenones and Cyclic
Dienes Explained through Transition-State Distortion Energies**
Robert S. Paton,* Seonah Kim, Audrey G. Ross, Samuel J. Danishefsky, and K. N. Houk*
The power of the Diels–Alder reaction was expanded recently
through the discovery by Li and Danishefsky that cyclo-
butenone is an unusually reactive dienophile; importantly, the
adducts can be converted to products that are formally the
[
1]
Diels–Alder adducts of unreactive dienophiles. We have
determined the origin of the special reactivity of cyclobute-
none and quantitate the origins of the unusually high
reactivity of strained enones. Cyclopropenones, the Diels–
Alder reactions of which were studied earlier by Breslow and
[2]
co-workers, are also highly reactive dienophiles. We show
that the ease of out-of-plane distortion of strained cyclo-
alkenones contributes to their high reactivity.
Ross and Danishefsky have compared the reactivity of
four-, five-, and six-membered cycloalkenones with cyclo-
[
3]
Scheme 1. Reactivities of cycloalkenones with cyclopentadiene.
pentadiene and other dienes. New experimental results (see
the Supporting Information) are summarized in Scheme 1.
The reactivities of different dienes with cyclobutenone
have been measured as well. Scheme 2 gives results of
standard reaction conditions. Experimental details for these
and other conditions are given in the Supporting Information.
The reactions of pent-3-en-2-one, cyclohex-2-enone,
cyclopent-2-enone, cyclobutenone, and cyclopropenone with
three cyclic dienes have been explored with M06-2X, a
density functional that we have shown to give relatively
[
4]
accurate activation and reaction energies for cycloadditions.
[5]
B3LYP and CBS-QB3, a high-accuracy composite method,
were also used (see the Supporting Information for a full
Scheme 2. Reactivities of cyclic dienes with cyclobutenone.
[
*] Dr. S. Kim, Prof. K. N. Houk
[
6]
comparison) and gave the same trends as discussed here.
Department of Chemistry and Biochemistry
University of California, Los Angeles
Los Angeles, CA 90095-1569 (USA)
E-mail: houk@chem.ucla.edu
Herein, we interpret the activation barriers of these reactions
by using the distortion/interaction model (or activation
strain model). This model relates the activation energy to
[7]
[8]
Dr. R. S. Paton
Chemistry Research Laboratory
University of Oxford
Mansfield Road, Oxford OX1 3TA (UK)
E-mail: robert.paton@chem.ox.ac.uk
the energy required for the geometrical deformation to
achieve the transition structure, and to the favorable inter-
actions between the two distorted reactants.
Figure 1 shows the transition structures for reactions of
cyclopentadiene with these dienophiles. The endo transition
states are favored, except with cyclopropenone. The predicted
relative rates are given below each structure. Cyclobutenone
and cyclopropenone are 1000 to 100000 times more reactive
A. G. Ross, Prof. S. J. Danishefsky
Department of Chemistry, Columbia University
Havemeyer Hall, 3000 Broadway, New York, NY 10027 (USA)
[
**] We are grateful to the John Fell Oxford University Press Research
Fund (R.S.P) and the National Science Foundation (CHE-0548209
and Graduate Fellowship to A.G.R.) for financial support of this
research. Computer time was provided in part by the UCLA Institute
for Digital Research and Education (IDRE), by the Shared Research
Computing Services Pilot (ShaRCS) project for the University of
California Systems, and by the National Center for Supercomputing
Applications on Cobalt, TG-CHE050044N, and Abe, TG-
CHE090070.
[
9]
than cyclohexenone at room temperature.
These reactions are asynchronous concerted processes,
except that of the symmetrical cyclopropenone. Cyclohexe-
none and cyclopentenone have high activation barriers and
low predicted rate constants, approximately like those of the
acyclic analogue. By contrast, cyclobutenone has a consid-
erably lower activation barrier and, accordingly, higher rate
constants for reaction. Cyclopropenone is predicted to be
even more reactive.
1
0366
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 10366 –10368