Experimental determination of the activation parameters and stereoselectivities of the intramolecular Diels-Alder reactions of 1,3,8-nonatriene, 1,3,9-decatriene, and 1,3,10-undecatriene and transition state modeling with the Monte Carlo-Jumping between Wells/molecular dynamics method

Article abstract of DOI:10.1021/ja9643331

Experimental activation parameters for the intramolecular Diels-Alder reactions of 1,3,8-nonatriene, 1,3,9-decatriene, and 1,3,10-undecatriene have been measured, and the Monte Carlo-Jumping between Wells/Stochastic Dynamics [MC(JBW)/SD] method, which gives relative free energies of activation, was tested as a means to predict stereoselectivities. The predictions are compared to experimental results, and to predictions from quantum and molecular mechanics methods.

Full text of DOI:10.1021/ja9643331

VOLUME 119, NUMBER 43
OCTOBER 29, 1997
©
Copyright 1997 by the
American Chemical Society
Experimental Determination of the Activation Parameters and
Stereoselectivities of the Intramolecular Diels-Alder Reactions
of 1,3,8-Nonatriene, 1,3,9-Decatriene, and 1,3,10-Undecatriene
and Transition State Modeling with the Monte Carlo-Jumping
Between Wells/Molecular Dynamics Method
†
,†
‡
,‡
Matthias K. Diedrich, Frank-Gerrit Kl a1 rner,* Brett R. Beno, K. N. Houk,*
§
,§
Hanoch Senderowitz, and W. Clark Still*
Contribution from the Institut f u¨ r Organische Chemie, UniVersit a¨ t GH Essen, D-45117 Essen,
Germany, Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles,
Los Angeles, California 90095, and Department of Chemistry, Columbia UniVersity,
New York, New York 10027
X
ReceiVed December 17, 1996. ReVised Manuscript ReceiVed July 26, 1997
Abstract: Experimental activation parameters for the intramolecular Diels-Alder reactions of 1,3,8-nonatriene, 1,3,9-
decatriene, and 1,3,10-undecatriene have been measured, and the Monte Carlo-Jumping between Wells/Stochastic
Dynamics [MC(JBW)/SD] method, which gives relative free energies of activation, was tested as a means to predict
stereoselectivities. The predictions are compared to experimental results, and to predictions from quantum and
molecular mechanics methods.
Introduction
The new Monte Carlo-Jumping Between Wells/Stochastic
1
Dynamics [MC(JBW)/SD] method has been applied to the
The intramolecular Diels-Alder reaction is not only a
fabulously successful reaction for synthesis, but has become
the testing ground for computational methods which predict
stereoselectivity. This paper reports the first quantitative
measurements of the activation parameters for the intramolecular
Diels-Alder reactions of three trienes which give 5-, 6-, and
2
investigation of the intramolecular Diels-Alder (IDA) reactions
of 1,3,8-nonatriene (1), 1,3,9-decatriene (2), and 1,3,10-unde-
catriene (3) (Scheme 1). In the present study, this method was
used to sample the accessible transition states of the reactions,
and thus provided an extension of previous transition state
3
modeling methods.
7-membered rings fixed to cyclohexene upon cyclization. A
q
q
New experimental measurements of ∆H and ∆S for the IDA
reactions of 1-3 are also reported. In contrast to a previous
new dynamics method that makes it possible to average over
all accessible transition states has been tested for the first time
for modeling organic stereoselectivity. By comparison to
previous “one-state” models, the robustness of the new method
has been demonstrated.
4
study that measured only relative activation parameters for the
cis and trans reaction pathways of 1 and 2, activation parameters
for each of the two pathways for the reactions of 1-3 are
reported here.
†
Universit a¨ t GH Essen.
University of California, Los Angeles.
Columbia University.
Abstract published in AdVance ACS Abstracts, September 15, 1997.
5
Subtle conformational effects which result in low to modest
‡
§
stereoselectivities make 1-3 stringent test systems for compu-
tational methods directed toward prediction of stereoselectivity,
X
S0002-7863(96)04333-8 CCC: $14.00 © 1997 American Chemical Society

10256 J. Am. Chem. Soc., Vol. 119, No. 43, 1997
Diedrich et al.
Scheme 1. IDA Reactions of 1,3,n-Trienes
vinyl halides as a key step.7 Mesylation of the alcohols 7 and
1
3 and subsequent reaction with lithium acetylide led to the
alkenynes 15 and 16 which underwent reaction with DIBAL in
a highly specific cis-addition leading to (E)-vinylalanes 17 and
8
1
8. The coupling of 17 and 18 with vinyl bromide in the
presence of catalytic amounts of tetrakis(triphenylphosphine)-
9
palladium(0) proceeded with retention of configuration afford-
ing the dienes (E)-2 and (E)-3.
cis- and trans-bicyclo[5.4.0]undec-8-enes (cis- and trans-6),
the products expected from the intramolecular Diels-Alder
reaction of (E)-3, were independently prepared according to
Scheme 2. Synthesis of (E)-Nonatriene (1)
10
procedures reported by Christol, Mousseron, et al. and by
1
1
McKenna et al. (Scheme 4).
Upon gas-phase thermolysis at temperatures between 200 and
2
80 °C under carefully controlled conditions excluding acid
catalysis, nonatriene (1) and decatriene (2) underwent clean IDA
reactions leading to mixtures of cis- and trans-bicyclononene
(4) and cis- and trans-bicyclodecene (5), respectively, which
could be separated by preparative GC in each case. The
corresponding rearrangement of undecatriene (3) required higher
temperatures and proceeded with comparable rates of reaction
only above 250 °C. In this case the bicyclic products cis- and
and they have been used as test cases in several previous
1
2
studies.3a,5,6
trans-6 formed at 294 °C were assigned by GC comparison
with authentic samples prepared by the procedure depicted in
Scheme 4. The temperature dependence of the rates of
formation of cis and trans cycloadducts was determined from
the disappearance of trienes 1, 2, or 3, and the cis/trans product
The stereoselectivities predicted by the MC(JBW)/
SD calculations are compared to the new experimental results
as well as to stereoselectivities predicted by previous ab initio
and molecular mechanics methods.
q
q
ratios. Arrhenius parameters and ∆H and ∆S values for each
system at 250 °C are given in Table 1.
Results and Discussion
The IDA reactions of trienes 1 and 2 have activation barriers
close to that of the intermolecular Diels-Alder reaction of
Experimental Results. Most of the IDA reactions studied
experimentally involve substituted systems. Only one experi-
mental stereochemical study of IDA reactions of unsubstituted
trienes has been reported. Lin and Houk determined relative
activation parameters for the formation of the cis and trans fused
unsaturated hydrindane (4) and decalin (5) systems from 1,3,8-
nonatriene (1) and 1,3,9-decatriene (2, Scheme 1).4 Preferences
of 1.0 and 0.3 kcal/mol for the formation of cis-4 and cis-5,
respectively, were found.
1
3
butadiene and ethylene, while the barrier for the reaction of 3
is a few kilocalories per mole higher. The primary effect of
q
intramolecularity is to increase the ∆S by 11-14 eu relative
q
to the reaction of butadiene with ethylene; this change in ∆S
lowers ∆G by 6 to 9 kcal/mol.
q
At 250 °C, the IDA reaction of 1,3,8-nonatriene (1) is
q
moderately cis stereoselective with a ∆∆G (cis-trans) of -0.82
kcal/mol. This corresponds to a cis:trans product ratio of 69:
We have synthesized trienes (E)-1-3, and have measured
the activation parameters for intramolecular Diels-Alder reac-
tions of these structures to give both cis and trans adducts in
the gas phase.
3
1. Increasing the length of the methylene chain connecting
the diene to the dienophile results in a decrease in cis
stereoselectivity. The 1,3,9-decatriene (2) and 1,3,10-undec-
atriene (3) IDA reactions are essentially unstereoselective, with
cis:trans product ratios of 51:49 and 53:47, respectively. The
results presented here are similar to those of Lin and Houk,4
who obtained cis:trans product ratios (252 °C) of 73:27 and
(
E)-Nonatriene (1) was synthesized in five steps by a
4
procedure adapted from Lin and Houk (7-11, Scheme 2). To
avoid the tedious separation of isomers, an alternative route to
prepare (E)-2 and (E)-3 was developed (Scheme 3). This
approach utilized palladium-catalyzed coupling of alkynes with
5
2:48 for the IDA reactions of 1 and 2, respectively.
Theoretical Results. Several theoretical models including
3
a,6
3
ab initio,
molecular mechanics, and combined ab initio/
6
(
1) (a) Senderowitz, H.; Guarnieri, F.; Still, W. C. J. Am. Chem. Soc.
995, 117, 8211. (b) Senderowitz, H.; Parish, C.; Still, W. C. J. Am. Chem.
Soc. 1996, 118, 2078.
2) (a) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1977, 16, 10. (b)
molecular mechanics calculations have been used to predict
1
(7) (a) Ratoveloma, V.; Linstrumelle, G. Synth.Commun. 1981, 11, 917.
(b) Crombie, L.; Horsham, M. A.; Blade, R. J. Tetrahedron Lett. 1987, 28,
4879. (c) Just, G.; O’Connor, B. Tetrahedron Lett. 1988, 29, 753. (d)
Guillerm, D.; Linstrumelle, G. Tetrahedron Lett. 1986, 27, 5857.
(8) Wilke, G.; M u¨ ller, H. Chem. Ber. 1956, 89, 444.
(
Oppolzer, W. Synthesis 1978, 793. (c) Funk, R. L.; Vollhardt, K. P. C.
Chem. Soc. ReV. 1980, 9, 41. (d) Brieger, G.; Bennett, J. N. Chem. ReV.
1
980, 80, 63. (e) Fallis, A. G. Can. J. Chem. 1984, 62, 183. (f) Ciganek, E.
Org. React. 1984, 32, 1. (g) Taber, D. F. Intramolecular Diels-Alder and
Alder Ene Reactions; Springer-Verlag: Berlin, 1984. (h) Craig, D. Chem.
Soc. ReV. 1987, 16, 187. (i) Roush, W. R. In AdVances in Cycloaddition;
Curran, D. P., Ed.; JAI Press: Greenwich, 1990; Vol. 2, p 91. (j) Okamura,
W. H.; Curtin, M. L. Synlett 1990, 1, 1. (k) Thomas, E. J. Acc. Chem. Res.
(9) Negishi, E.; Takahashi, T.; Baba, S.; van Horn, D. E.; Okukado, N.
J. Am. Chem. Soc. 1987, 109, 2393.
(10) (a) Mousseron, M.; Jacquier, R.; Christol, H. Bull. Soc. Chim. Fr.
1957, 346. (b) Christol, H.; Jacquier, R.; Mousseron, M. Bull. Soc. Chim.
Fr. 1957, 1027.
(11) McKenna, J.; Norymberski, J. K.; Stubbs, R. D. J. Chem. Soc. 1959,
2502.
1
991, 24, 229. (l) Martin, S. F. J. Heterocyclic Chem. 1994, 31, 679.
3) (a) Raimondi, L.; Brown, F. K.; Gonzalez, J.; Houk, K. N. J. Am.
(
Chem. Soc. 1992, 114, 4796. (b) For a review of transition state modeling
with empirical force fields see: Eksterowicz, J. E.; Houk, K. N. Chem.
ReV. 1993, 93, 2439.
(12) A conclusive stereochemical assignment of the two products cis-6
and trans-6 could not be achieved from the spectroscopic data and relies
on the comparison of GC retention times with those of cis-4/trans-4 and
cis-5/trans-5. In agreement with this assignment, the retention time of each
cis bicyclic compound is larger than that of the corresponding trans isomer.
(13) Goldstein, E.; Beno, B.; Houk, K. N. J. Am. Chem. Soc. 1996, 118,
6036 and references therein.
(
(
(
4) Lin, Y.-T.; Houk, K. N. Tetrahedron Lett. 1985, 26, 2269.
5) Brown, F. K.; Houk, K. N. Tetrahedron Lett. 1985, 26, 2297.
6) Brown, F. K.; Singh, U. C.; Kollman, P. A.; Raimondi, L.; Houk, K.
N.; Bock, C. W. J. Org. Chem. 1992, 57, 4862.

Reactions of Nona-, Deca-, and Undecatrienes
J. Am. Chem. Soc., Vol. 119, No. 43, 1997 10257
Scheme 3. Synthesis of (E)-Decatriene (2) and (E)-Undecatriene (3)
Scheme 4. Synthesis of cis- and trans-6
Table 1. Activation Parameters for the Intramolecular
Diels-Alder Reactions of (E)-1,3,n-Trienes 1-3a
of sampling minima separated by substantial barriers. We used
this method to calculate ∆∆G (cis-trans) values for the IDA
reactions of 1-3 for comparison with experimental results and
with previous computational results.
q
q
∆
Ea
∆H
q
reaction
(kcal/mol)
log A
(kcal/mol)
∆S (eu)
1
1
2
2
3
3
f cis-4
26.32 ( 0.10 7.96 ( 0.04 25.28 ( 0.10 -25.21 ( 0.19
Monte Carlo searches predict that each triene has multiple
cis and trans transition structure conformations within 5 kcal/
mol of the lowest energy one. Each corresponds to a minimum
f trans-4 27.79 ( 0.09 8.23 ( 0.04 26.75 ( 0.09 -23.97 ( 0.19
f cis-5 25.41 ( 0.33 7.06 ( 0.14 24.37 ( 0.33 -29.32 ( 0.65
f trans-5 25.56 ( 0.33 7.11 ( 0.15 24.52 ( 0.33 -29.10 ( 0.66
1
4,15
b
on its respective MM2*
potential surface and is separated
f cis-6
30.95 ( 0.61 7.17 ( 0.23 29.91 ( 0.61 -28.82 ( 1.07
b
f trans-6 31.01 ( 0.52 7.15 ( 0.20 29.97 ( 0.52 -28.91 ( 0.92
from the other minima by large energy barriers. Such PES
features often result in slow convergence during standard
molecular dynamics (MD) or stochastic dynamics (SD) simula-
tions, since transitions between minima occur infrequently, or
a
Enthalpies and entropies of activation given for reaction at 250
C. b Extrapolated from an Arrhenius plot for the temperature range
°
2
67.2-325.5 °C.
1
6
not at all. To address convergence difficulties of the type
described above, Still and Guarnieri developed the hybrid MC/
Table 2. Relative Activation Parameters for the Intramolecular
Diels-Alder Reactions of Trienes 1-3 at 250 °C
SD method which alternates between MC and SD steps during
q
q
q
∆
H
∆∆S
∆∆G
product
ratio
cis:trans
17
a simulation.
The MC steps increase the probability of
(
cis-trans)
(kcal/mol)
(cis-trans)
(cis-trans)
(kcal/mol)
transition between conformational wells, while SD provides
good sampling of each individual well. This method was found
to converge several orders of magnitude more rapidly than SD
for n-pentane.
reaction
(eu)
1
2
3
f 4
f 5
f 6
-1.47
-0.15
-0.06
-1.24
-0.22
0.09
-0.82
-0.03
-0.11
69:31
51:49
53:47
The additional problem of small acceptance rates in Monte
Carlo simulations, and consequently slow convergence, was later
addressed by Senderowitz and co-workers. Their approach,
stereoselectivities of IDA reactions. All of these studies have
utilized 1,3,8-nonatriene (1) and 1,3,9-decatriene (2, Scheme
1
termed Jumping Between Wells (JBW), uses a conformational
1
) as test systems. Using the MM2 force field,14 Lin and Houk
search to locate all low-energy conformers for a system. A
series of transformations based on bond and dihedral angles
which allows the interconversion of all pairs is then defined.
The actual MC(JBW) simulation starts by determining which
conformation the initial structure most closely resembles. The
initial structure is then transformed to a new conformation which
is randomly chosen from the conformer list. After random
variations in the geometry of this new structure, its energy is
compared to that of the initial structure, and it is then accepted
or rejected based on the Metropolis criterion. This procedure
results in a much higher step acceptance rate. The combination
of this MC(JBW) method with the hybrid MC/SD technique of
Guarnieri and Still results in a rapidly convergent dynamics
technique that works efficiently for systems with conformations
separated by large energy barriers.
determined that relative product stabilities could not account
for the observed stereoselectivities in the IDA reactions of the
unactivated trienes.4 On the basis of simple model calculations,
Brown and Houk later attributed the cis selectivity in the reaction
of 1 to unfavorable steric interactions and rationalized the low
stereoselectivity of the IDA reaction of 2.5 Raimondi and co-
workers developed molecular mechanics transition state models
for activated and unactivated Diels-Alder reactions based on
ab initio transition structures of intermolecular Diels-Alder
reactions,3 and Brown and co-workers have studied the IDA
reactions of 1,3,8-nonatriene (1) and 1,3,9-decatriene (2) using
both ab initio methods and a hybrid ab initio/force-field
approach that is implemented in the program QUEST. All of
these previous models predicted stereoselectivities in good
agreement with available experimental results.
We have studied the IDA reactions of 1-3 with transition
state dynamics using the force field based Monte Carlo-Jumping
Between Wells/Stochastic Dynamics method.1 This approach
has the advantage of including contributions of all conforma-
tionally distinct transition structures to the calculated relative
free energy. The technique provides a solution to the problem
a
6
This method holds considerable promise for the study of
relative rates using transition state modeling techniques since
(15) MacroModel V5.0: Mohamadi, F.; Richards, N. G. J.; Guida, W.
C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.;
Still, W. C. J. Comput. Chem. 1990, 11, 440.
(16) (a) Mitchell, M. J.; McCammon, J. A. J. Comput. Chem. 1991, 12,
271. (b) Straatsma, T. P.; McCammon, J. A. J. Chem. Phys. 1989, 91, 3631.
(c) Straatsma, T. P.; McCammon, A. J. J. Chem. Phys. 1989, 90, 3300.
(14) Allinger, N. L. J. Am. Chem. Soc. 1977, 99, 8127.
(17) Guarnieri, F.; Still, W. C. J. Comput. Chem. 1994, 15, 1302.

10258 J. Am. Chem. Soc., Vol. 119, No. 43, 1997
Diedrich et al.
Table 3. Relative Energetics of the Cis and Trans Pathways of the
a
IDA Reactions of (E)-1,3,n-Trienes 1-3
b
b,c
MC(JBW)/SDb
exptl.
QM
MM
q
q
q
q
q
d
∆∆Gq
triene ∆∆H /∆∆G ∆∆H /∆∆S /∆∆G
∆E
1
2
3
f 4 -1.47/-0.82 -0.96/-0.74/-0.57 -1.20 (-0.83)
0.33 (0.25)
f 6 -0.06/-0.11 -0.12/ 0.68/-0.48 -0.04 (0.25)
-0.96
0.51
0.57
f 5 -0.15/-0.03 0.05/-0.80/ 0.47
a
All differences are E(cis) - E(trans) and are in kcal/mol. Entropy
Figure 1. Transition structures sampled during the first 500 ps (10-ps
intervals) of the MC(JBW)/SD simulation of the Diels-Alder reaction
of 1.
b
c
differences are in eu. Determined at 523 K. RHF/3-21G with
vibrational frequencies scaled by 0.8929. [Pople, J. A.; Schlegel, H.
B.; Krishnan, R.; DeFrees, D. J.; Binkley, J. S.; Frisch, M. J.; Whiteside,
R. A.; Hout, R. F. Int. J. Quantum Chem. Symp. 1981, 15, 269.] d ∆E
values based on Boltzmann averages for all conformationally distinct
transition structures for each triene are in parentheses.
q
Table 4. ∆∆G (cis-trans) Values for the IDA Reactions of 1-3
from MC(JBW)/SD Simulationsa
simulation
time (ns)
it incorporates entropic effects. However, since transition state
parameters are determined, in Houk’s method, from the lowest
energy transition state, there was no guarantee a priori that this
method would be able to deal with conformational flexibility
in transition states. This study was undertaken on a relatively
well-understood system to determine how it behaved.
1
2
3
3
1
5
0
-0.96
-0.96
0.60
0.50
0.54
0.54
1
-0.96 ( 0.04
0.51 ( 0.07
0.57 ( 0.05
a
Energies are in kcal/mol. Standard deviations were calculated by
the method of block averages.
We explored the use of the MC(JBW)/SD method to calculate
q
the ∆∆G (cis-trans) (523 K) for the IDA reactions 1-3. The
Diels-Alder force field of Houk and Raimondi3a was used in
The largest deviation between experiment and prediction was
less than 0.7 kcal/mol. A MC(JBW)/SD simulation of another
test system, 3,9-dimethyl-1,3,9-decatriene, predicted a ∆∆G -
cis-trans) (463 K) of 2.4 ( 0.1 kcal/mol, in excellent
agreement with the experimental result of 2.7 kcal/mol.
all cases. Relative free energies of activation were determined
from:
q
(
G ) -RT ln K
18
For comparison, both ab initio and molecular mechanics
methods were also used to predict the stereoselectivities of the
IDA reactions of 1-3. Monte Carlo conformational searches19
using the MM2* force field and the Diels-Alder transition state
where K is the cis/trans population ratio. This ratio was found
by monitoring the H-C4-C8-H, H-C4-C9-H, and H-C4-
C10-H torsional angles (cis 0 ( 90°; trans 180 ( 90°) in 1, 2,
and 3, respectively, during the simulations.
3
a
force field parameters of Raimondi et al., as implemented in
6
6
7
15
the MacroModel/BatchMin 5.0 software package, were carried
5
4
7
8
5
6
5
8
out to obtain all possible transition structures for the IDA
reactions of trienes 1-3. The Monte Carlo searches for 1, 2,
and 3 were carried out for 10 000, 20 000, and 20 000 steps,
4
1
7
4
9
3
2
3
2
3
2
8
9
10
11
20
9
10
respectively. For each system, all minima found were within
1
1
5
kcal/mol of the lowest energy structure.
1
2
3
The differences in steric energies between the lowest energy
Monte Carlo conformational searches using the Diels-Alder
force field were carried out first to determine all low-energy
transition structures for each triene. Thus, the input for the MC-
cis and trans transition structures are given in Table 3. For the
IDA reactions of 1 and 3, the transition state models predict
cis preferences of 1.20 and 0.04 kcal/mol, respectively, while a
(JBW)/SD simulations of 1, 2, and 3 included 5, 8, and 16
0
.33 kcal/mol trans preference is predicted for 2. Boltzmann
conformations, respectively.
averaged energies over all conformers at the experimental
All MC(JBW)/SD simulations were run for 10 ns with time
steps of 0.5 fs at the experimental temperature of 523 K. To
prevent isomerization of the double bonds and to maintain the
s-cis conformation of the butadiene moieties, appropriate flat-
bottom constraining potentials were used.
temperature (523 K) give a cis preference of 0.83 kcal/mol for
1
2
, and predict slight trans preferences of 0.25 kcal/mol for both
and 3.
The stereoselectivities predicted by MC(JBW)/SD are very
similar to those predicted by either simple energy minimization
or by Boltzmann averaged energies, the largest deviation
between the methods being 0.6 and 0.3 kcal/mol, respectively.
Transition structures for the concerted cis (endo) and trans (exo)
pathways of the IDA reactions of 1-3 were also located with
q
The ∆∆G (cis-trans) values for each system are listed in
q
Table 3. For the IDA reaction of 1, the predicted ∆∆G (cis-
trans) is -0.96 kcal/mol, in excellent agreement with the
experimental result of -0.82 kcal/mol. For this system, 10-ns
simulations with either SD or MC/SD were also performed. Each
simulation was initiated from a cis conformer, and no transitions
to trans conformers were observed during either simulation.
During the MC(JBW)/SD simulation, all conformationally
distinct transition structures were sampled, and 2.6% of the
interconversion attempts were successful (Figure 1). Thus MC-
21
quantum mechanics at the RHF/3-21G level. Endo (20) and
exo (21) transition structures for the reaction of 3 are shown in
Figure 2. Geometries of the lowest energy endo and exo
(
18) Wilson, S. R.; Mao, D. T. J. Am. Chem. Soc. 1978, 100, 6289.
(19) (a) Saunders, M.; Houk, K. N.; Wu, Y.-D.; Still, W. C.; Lipton,
M.; Chang, G.; Guida, W. C. J. Am. Chem. Soc. 1990, 112, 1419. (b) Chang,
G.; Guida, W. C.; Still, W. C. J. Am. Chem. Soc. 1989, 111, 4379.
(
JBW)/SD samples the conformational spaces for these systems
far more effectively than either SD or MC/SD. In fact, the MC-
JBW)/SD simulations for each triene were essentially converged
(20) While true transition states are defined as first order saddle points
on potential energy surfaces, they are most often parametrized as minima
with empirical force field models: see ref 3b. Two cis and three trans
minima were found for nonatriene (1). Eight minima, four cis and four
trans, were found for the decatriene (2) system. A total of 16 minima were
located for undecatriene (3). Of these, eight corresponded to cis, and eight
to trans transition structures.
(
within 1 ns (Table 4).
Trans preferences of approximately 0.5 kcal/mol are predicted
for 2 and 3. Experimentally, the two reactions are practically
unstereoselective, with cis preferences of less than 0.2 kcal/
mol.
(21) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.

Reactions of Nona-, Deca-, and Undecatrienes
J. Am. Chem. Soc., Vol. 119, No. 43, 1997 10259
slight trans stereoselectivity of about 0.5 kcal/mol. For 3, a
0
.6 kcal/mol preference for trans products is predicted. For
this system, simple molecular mechanics provides the best
agreement with experiment.
The transition state dynamics method performed well. It
q
converged rapidly, and predicted ∆∆G (cis-trans) values within
(
0.7 kcal/mol of experimental values. In addition, it success-
fully sampled all conformationally distinct transition structures
while both SD and MC/SD simulations failed to interconvert
cis and trans transition structures. This technique should be
particularly effective for systems with large entropy differences
between transition structures or substantial differences in the
shapes of their potential energy surfaces.
Figure 2. Cis and trans transition structures for the intramolecular
Diels-Alder reaction of 3. RHF/3-21G bond lengths are in plain text,
and MM2* bond lengths are in square brackets. All bond lengths are
in Å.
transition structures for each triene obtained from the Monte
Carlo conformational searches were used as initial guesses for
ab initio transition structure searches using Gaussian 94.
Experimental Section
2
2
Kinetic Measurements. Thermolyses of 1-3. Portions (250-
3
00 mL each) of the solution of 1, 2, and 3, respectively, and n-nonane,
RHF/3-21G relative free energies (250 °C) for the IDA
n-decane, and n-undecane as internal standards in n-hexane or n-heptane
were injected into a thermostated and evacuated 20 l Pyrex flask. At
each temperature the specific rate constants (Tables 1, 2, and 3,
Supporting Information) were calculated from the time dependence of
the disappearance of the triene versus the internal standard and the
ratio of the forming bicyclic products by the use of the kinetic law for
first-order irreversible reactions.
reactions of 1-3 are listed in Table 3. For 1 and 2, the predicted
q
∆
∆G values fall within 0.5 kcal/mol of the MC(JBW)/SD
results, while the difference is larger (∼1 kcal/mol) for 3.
Conclusions
Activation parameters for the formation of cis and trans
products in the intramolecular Diels-Alder reactions of non-
atriene (1), decatriene (2), and undecatriene (3) have been
determined. The activation enthalpies for the reactions of 1
and 2 are similar to that of the butadiene/ethylene intermolecular
Diels-Alder reaction, while the barrier for 3 is a few kilocalories
per mole higher. These IDA reactions are favored entropically
by 11-17 eu over the parent Diels-Alder reaction. At 250
1
. 1 (50 mg) and n-nonane (50 mg) in 5 mL of n-hexane: GC
column A, 50 °C); t
(n-nonane) ) 6.1 min, t (1) ) 9.3 min, t (trans-
) ) 12.1 min, t (cis-4) ) 12.6 min).
. 2 (50 mg) and n-decane (50 mg) in 5 mL of n-heptane: GC
column A, 120 °C); t (n-decane) ) 4.4 min, t (2) ) 5.7 min, t (trans-
5) ) 8.5 min, t (cis-5) ) 10.0 min).
(
R
R
R
4
R
2
(
R
R
R
R
3. 3 (15 mg) and n-undecane (15 mg) in 5 mL of n-heptane: GC
(column A, 120 °C); t (n-undecane) ) 5.1 min, t (3) ) 6.7 min, t
trans-6) ) 13.2 min, t (cis-6) ) 14.2 min).
R
R
R
-
(
R
°
C, the IDA reaction of 1 is moderately cis selective, forming
a 69:31 ratio of cis:trans products. The IDA reactions of trienes
and 3 are essentially unstereoselective, with only a few percent
Acknowledgment. We are grateful to the National Science
2
Foundation for financial support of this research. F.-G.K. and
M.K.D. are grateful to Mrs. Heike W o¨ ll for performing major
parts of the preperative work and to Mr. Heinz Bandmann for
measuring the 300-MHz NMR spectra. F.-G.K. and M.K.D.
thank the Deutsche Forschungsgemeinschaft, Fonds der Che-
mischen Industrie, and the Ministerium f u¨ r Wissenschaft und
Forschung des Landes Nordrhein-Westfalen for support. B.R.B.
and K.N.H. thank the UCLA Office of Academic Computing
for computer time.
excess cis product formed in each case.
The stereoselectivity of each reaction was predicted by using
transition state dynamics which gives ∆∆G (cis-trans) values
including contributions from all low-energy cis and trans
q
q
transition structures. The predicted ∆∆G (cis-trans) for the
IDA reaction of 1 is within 0.2 kcal/mol of the experimental
value. Experimentally, almost no stereoselectivity is observed
for the decatriene (2) reaction, while MC(JBW)/SD predicted
(
22) Gaussian 94 (Revision D.2), Frisch, M. J.; Trucks, G. W.; Schlegel,
H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.;
Keith, T. A.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-
Latham, M. A.; Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski,
J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart,
J. J. P.; Head-Gordon, M.; Gonzalez, C.; Pople, J. A.; Gaussian, Inc.:
Pittsburgh, PA, 1995.
Supporting Information Available: Experimental proce-
dures, tables of kinetic data for the IDA reactions of 1-3, and
Cartesian coordinates for RHF/3-21G transition structures 20
and 21 (14 pages). See any current masthead page for ordering
and Internet access instructions.
JA9643331