Kinetic and modeling studies on the nickel-catalyzed Homo-Diels-Alder addition of 7-substituted norbornadienes

Article abstract of DOI:10.1021/jo951849e

Pseudo-first-order rate constants have been determined for several 7-substituted norbornadienes in their nickel-catalyzed homo-Diels-Aider cycloaddition with methyl vinyl ketone. The rate of reaction was slightly influenced by the nature of the substituent. Relative reactivities followed the order 7-Ph > H > 7-OTIPS. The observed activation parameters (ΔH? = 15-18 kcal/mol; ΔS? = -19 to -24 cal/mol K) were also affected by the 7-substituent and are in good agreement with those established for reductive elimination from related nickel phosphine complexes. With regard to regioselectivity, the more reactive norbornadiene was also the less selective. Force field modeling studies of possible organonickel intermediates suggest that the preferred exo selectivity arises from steric interactions between the dienophile substituent and the phosphine ligands. Good qualitative and quantitative agreement with observed exo stereoselectivity was found with three of the five model systems studied. Of these three models, reasonably good agreement with regioselectivity was found with only one of them.

Full text of DOI:10.1021/jo951849e

3490
J . Org. Chem. 1996, 61, 3490-3495
Kin etic a n d Mod elin g Stu d ies on th e Nick el-Ca ta lyzed
Hom o-Diels-Ald er Ad d ition of 7-Su bstitu ted Nor bor n a d ien es
M. M. Gugelchuk* and A. L. Doherty-Kirby
Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
Received October 13, 1995X
Pseudo-first-order rate constants have been determined for several 7-substituted norbornadienes
in their nickel-catalyzed homo-Diels-Alder cycloaddition with methyl vinyl ketone. The rate of
reaction was slightly influenced by the nature of the substituent. Relative reactivities followed
the order 7-Ph > H > 7-OTIPS. The observed activation parameters (∆Hq ) 15-18 kcal/mol; ∆Sq
) -19 to -24 cal/mol K) were also affected by the 7-substituent and are in good agreement with
those established for reductive elimination from related nickel phosphine complexes. With regard
to regioselectivity, the more reactive norbornadiene was also the less selective. Force field modeling
studies of possible organonickel intermediates suggest that the preferred exo selectivity arises from
steric interactions between the dienophile substituent and the phosphine ligands. Good qualitative
and quantitative agreement with observed exo stereoselectivity was found with three of the five
model systems studied. Of these three models, reasonably good agreement with regioselectivity
was found with only one of them.
In tr od u ction
stabilities of proposed intermediates in the nickel-
catalyzed pathway have been reported in an earlier
paper.8 In preparation for an investigation of the rel-
evant DFT-calculated transition state energies, we car-
ried out a kinetic study of selected 7-substituted norbor-
nadienes to obtain relative rates and activation energies
which could be used to test the reliability of the DFT
predictions.
The nickel-catalyzed homo-Diels-Alder reaction of
norbornadienes (NBD) with electron-deficient olefins has
been reported to proceed with high degrees of stereo- and
even some enantioselectivity.1,2 In contrast to the un-
catalyzed process,1c,3 the catalytic reaction affords the exo
isomer predominantly, and exo/endo isomerization of the
products is negligible under the reaction conditions. This
stereoselectivity is influenced by the steric nature of an
added phosphorus ligand1b and the steric bulk of the
olefin substituent.1c,4c
More recently, the effect of 7-norbornadienyl substit-
uents on regioselectivity in the deltacyclane product has
been examined with encouraging results.4a,b The extent
of regioselectivity is dependent upon the nature of the
norbornadiene substituent and ranges from negligible (in
the case of alkyl and phenyl) to extremely high (in the
case of alkyl and silyl ethers). Experimental studies
suggest a dominant electronic influence on the regio-
chemical outcome with a lesser contribution from steric
factors.4 Determination of these substituent effects is
necessary to provide further insight into the control of
regiochemistry and expand the scope of synthetic ap-
plications for this chemistry.
This paper reports the details of our examination of
substituent-induced perturbation on the rate and activa-
tion parameters, along with related molecular mechanics
calculations which attempt to assess the importance of
proposed intermediate complexes to the observed regio-
and stereochemical behavior of the molecule in nickel-
catalyzed homo-Diels-Alder reactions. As the following
results will show, steric interactions in several organo-
nickel intermediates successfully reproduce quantita-
tively the observed exo/endo diastereoselectivities, but
reasonable correlation with the observed anti/syn regio-
selectivities was found with only one of the complexes.
Resu lts a n d Discu ssion
Hom o-Diels-Ald er Rea ction w ith Meth yl Vin yl
Keton e. Three norbornadienes (NBD) were chosen as
representative examples for neutral (Z ) H), weakly
regioselective (Z ) Ph), and strongly regioselective (Z )
OTIPS) substituents. The kinetic runs were studied in
benzene-d6 at 30-70 °C and followed to 70-94% comple-
Due to the complexity of this reaction mechanism5-7
and the current scarcity of detailed information concern-
ing the actual nickel-bonded intermediates, we started
a theoretical investigation to provide some clues for a
greater understanding of this transformation. Our re-
sults of a density functional (DFT) study into the relative
(5) (a) Schrauzer, G. N. Adv. Catal. Rel. Subj. 1968, 18, 373. (b)
Schrauzer, G. N. Adv. Organomet. Chem. 1964, 2, 1. (c) Schrauzer, G.
N.; Glockner, P. Chem. Ber. 1964, 97, 2451. (d) Schrauzer, G. N.;
Eichler, S. Chem. Ber. 1962, 95, 2764.
(6) Cassar, L.; Halpern, J . J . Chem. Soc., Chem. Commun. 1970,
1082.
X Abstract published in Advance ACS Abstracts, April 15, 1996.
(1) (a) Yoshikawa, S.; Kiji, J .; Furukawa, J . Bull. Chem. Soc. J pn.
1976, 49, 1093. (b) Yoshikawa, S.; Aoki, K.; Kiji, J .; Furukawa, J . Bull.
Chem. Soc. J pn. 1975, 48, 3239. (c) Noyori, R.; Umeda, I.; Kawauchi,
H.; Takaya, H. J . Am. Chem. Soc. 1975, 97, 812.
(2) Brunner, H.; Muschiol, M.; Prester, F. Angew. Chem., Int. Ed.
Engl. 1990, 29, 652.
(3) (a) Kobuke, Y.; Sugimoto, T.; Furukawa, J .; Fueno, T. J . Am.
Chem. Soc. 1972, 94, 3633. (b) Cookson, R. C.; Dance, J .; Hudec, J . J .
Chem. Soc. 1964, 5416.
(4) (a) Lautens, M.; Edwards, L. G.; Tam, W.; Lough, A. J . J . Am.
Chem. Soc. 1995, 117, 10276. (b) Lautens, M.; Tam, W.; Edwards, L.
G. J . Chem. Soc., Perkin Trans. 1 1994, 2143. (c) Lautens, M.; Edwards,
L. G. J . Org. Chem. 1991, 56, 3761. (d) Lautens, M.; Edwards, L. G.
Tetrahedron Lett. 1989, 30, 6813.
(7) (a) Pardigon, O.; Buono, G. Tetrahedron: Asymmetry 1993, 4,
1977. (b) Duan, I.-F.; Cheng, C.-H.; Shaw, J .-S.; Cheng, S.-S.; Liou, K.
F. J . Chem. Soc., Chem. Commun. 1991, 1347. (c) Brunner, H.; Prester,
F. J . Organomet. Chem. 1991, 414, 401. (d) Lautens, M.; Lautens, J .
C.; Smith, A. C. J . Am. Chem. Soc. 1990, 112, 5627. (e) Lautens, M.;
Crudden, C. M. Organometallics 1989, 8, 2733. (f) Lyons, J . E.; Myers,
H. K.; Schneider, A. Ann. N.Y. Acad. Sci. 1980, 333, 273. (g) Lyons, J .
E.; Myers, H. K.; Schneider, A. J . Chem. Soc., Chem. Commun. 1978,
636.
(8) Gugelchuk, M. M.; Wisner, J . Organometallics 1995, 14, 1834.
S0022-3263(95)01849-4 CCC: $12.00 © 1996 American Chemical Society

Diels-Alder Addition of 7-Substituted Norbornadienes
J . Org. Chem., Vol. 61, No. 10, 1996 3491
Sch em e 1
Ta ble 1. Rea ctivity a n d Regioselectivity Da ta a ,b
Z
T (°C)
103kobs (min-1
)
t1/2 (min)
A/Sc
OTIPS
30
40
50
60
70
2.59 ( 0.04
7.77 ( 0.09
14.1 ( 0.4
40.3 ( 1.9
71.0 ( 3.0
268
89
49
17
10
93:7 ( 0.6
91:9 ( 0.7
87:13 ( 1
90:10 ( 1
88:12 ( 4
F igu r e 1. Plot of ln k versus 1/T. Straight lines are from the
least-squares regression.
Ta ble 2. Ar r h en iu s a n d Eyr in g Activa tion P a r a m eter s.a
H
30
40
50
55
60
3.48 ( 0.01
9.29 ( 0.03
20.2 ( 1.0
41.3 ( 1.1
53.8 ( 1.3
199
75
35
17
13
Z
Ea
A
∆Hq
∆Sq
∆∆Hq
∆∆Sq
H
Ph
OTIPS
18.6
15.2
17.1
844 × 108
7.87 × 108
60.3 × 108
17.9
14.6
16.5
-18.8
-20.0
-24.1
2.6b
-3.6b
Ph
a
Energies are given in kcal/mol. Entropies are given in cal/
The estimated
30
40
50
60
70
6.79 ( 0.2
18.4 ( 1.1
47.7 ( 3.2
76.6 ( 1.0
131 ( 5.0
102
38
15
9
mol K. Arrhenius A factors are given in min-1
.
uncertainty is (1 kcal/mol in energy terms and (2 eu in entropy
terms. b The values given were determined from the intercepts and
slopes of plots of ln (kA/kS) vs 1/T using the following equations:
∆∆Hq ) ∆Hq - ∆Hq ) Ea(S) - Ea(A) and ∆∆Sq ) ∆Sq - ∆Sq
5
S
A
A
S
a
Pseudo-first-order rate constants and anti/syn ratios were
) R ln (AA/AS).
obtained from the averages of multiple kinetic runs over 2-4 half-
b
lives in C6D6. [MVK]o ) 3.5[NBD]o. Standard deviations are of
the averages. c Kinetic anti:syn ratios (A/S).
slight increase in the rate of reaction whereas replace-
ment by a 7-OTIPS group slightly decreased the rate. The
relative reactivity is 7-Ph (1.93) > H (1.0) >7-OTIPS
(0.75). With regard to regioselectivity, the limited data
indicate that the more reactive norbornadiene is also the
less selective. Nickel-catalyzed homo-Diels-Alder cy-
cloadditions of norbornadienes are known to be irrevers-
ible; consequently, the observed regio- and stereoselection
is a result of kinetically-controlled dienophile capture.
We investigated the influence of temperature on the
reactivity to examine the substituent effect on the cor-
responding activation parameters. Analysis of the Ar-
rhenius and Eyring plots (Figure 1) provided the activa-
tion parameters that appear in Table 2. By assuming
the kinetic anti:syn product ratio (A/S) is equal to the
ratio of the rate constants (kA/kS), the differences in
activation parameters for syn and anti addition in the
7-OTIPS case were obtained by plots of ln (kA/kS) vs 1/T.
In proposed mechanisms for this reaction, a final,
irreversible reductive elimination to yield the deltacy-
clane product is thought to be the rate-limiting step. The
relatively small enthalpies of activation and the large
negative entropies of activation are of similar magnitude
to those reported for reductive elimination from related
nickel phosphine complexes (∆Hq ) 14-23 kcal/mol; ∆Sq
) -8 to -21 eu).9 Compared to norbornadiene, a
substituent in the 7-position leads to a stronger interac-
tion between reactants (decreasing ∆Hq) accompanied by
tighter binding in the transition state (more negative
∆Sq). Concerning the differences in the anti/syn activa-
tion parameters for the formation of OTIPS-substituted
adducts, enthalpy changes favor the anti TS while
entropy changes favor the syn TS.
1
tion by H NMR analysis of the disappearing norborna-
diene 1 and the appearing cycloadducts (see Experimen-
tal Section for details). When heated with methyl vinyl
ketone (MVK), 20 mol % Ni(COD)2, and 40 mol % PPh3
in benzene, the norbornadienes 1 proceeded to give 2, the
isomer arising from exo addition (Scheme 1).
Signals due to endo isomers (3) were not readily
apparent in the H NMR spectra. If endo isomers are
1
present, their concentrations are less than 3% and could
not be distinguished from noise in the base line. Anti:
syn ratios could be determined only for the 7-OTIPS
adduct. In the 7-phenyl adducts, all useful diagnostic
signals overlapped, but it appears that the syn-exo and
anti-exo 7-phenyl adducts were formed in similar amounts
with slightly more of the anti-exo isomer. These results
compare favorably with those earlier reported by Lautens
and co-workers.4a
A large excess (3.5 equiv) of methyl vinyl ketone was
used, and the reactions all showed clean pseudo-first-
order kinetics over ca. 2-4 half-lives. Each run was
carried out in duplicate or triplicate trials. The pseudo-
first-order rate constants given in Table 1 were deter-
mined by linear least-squares regression of a plot of ln
([NBD]o/[NBD]t) versus time. Close scrutiny of the NMR
data indicated that possible side reactions were not
competitive under the conditions except at 70 °C with
the unsubstituted norbornadiene. In this case, a new
signal at δ 4.1 began to appear along with the expected
ones; thus, the reaction rates were monitored at 60 °C
or lower where this side reaction did not occur. At higher
temperatures, there may be competition from the [2 +
2] cycloaddition manifold which is also known to be
catalyzed by nickel.1,5
(9) (a) Kurosawa, H.; Ohnishi, H.; Emoto, M.; Chatani, N.; Ka-
wasaki, Y.; Murai, S.; Ikeda, I. Organometallics 1990, 9, 3038. (b)
Kurosawa, H.; Ohnishi, H.; Emoto, M.; Kawasaki, Y.; Murai, S. J . Am.
Chem. Soc. 1988, 110, 6272.
On the basis of this study, replacement of hydrogen
by a 7-phenyl substituent on norbornadiene results in a

3492 J . Org. Chem., Vol. 61, No. 10, 1996
Gugelchuk and Doherty-Kirby
Ta ble 3. Rela tive MM2 En er gies a n d Ca lcu la ted Regio-/Ster eoselectivities of Delta cycla n e Mod ela
calcd rel energies
calcd ratio
(anti:syn)
calcd ratio
(exo:endo)
obsd ratio
(anti:syn)
obsd ratio
(exo:endo)
G
AX
SX
AN
SN
n-hexyl
0.06
(32)
0.03
(31)
0.00
(40)
0.30
(27)
0.00
(74)
0.02
(35)
0.00
(36)
0.00
(34)
0.28
(25)
0.00
(43)
3.38
(0)
0.49
(14)
0.44
(15)
0.57
(16)
0.69
(18)
0.61
(26)
0.55
(14)
0.36
(18)
0.27
(20)
0.49
(19)
0.55
(12)
3.49
(0)
46:54
46:54
56:44
45:55
100:0
49:51
68:32
65:35
65:35
70:30
74:26
72:28
42:58
55:45
72:28
80:20
91:9
98:2
99:1
Ph
Cl
99:1
O2CPh
OTIPS
OBu-t
100:0
99:1
0.00
(37)
0.55
(14)
95:5
100:0
a
Relative energies given in kcal/mol. The numbers in parentheses are the predicted Boltzmann distributions of the various isomers
calculated at 25 °C.
Mod elin g Stu d ies. In an attempt to better under-
stand the origins of the regio- and stereoselectivity, we
first conducted MM2 calculations on the isomeric delta-
cyclane products. We determined the global minimum
energy conformations for all reasonable isomers which
included exploring all possible rotors of the particular
substituent. The more thermodynamically stable exo
diastereomers (according to MM2) were the major prod-
ucts of reaction, but there was no correlation between
the steric energy differences and the observed product
ratios (Table 3). Experimental results suggest a pre-
dominant electronic factor may be involved in the anti/
syn regioselectivity of this reaction. The molecular
mechanics models which lack explicit electronic consid-
erations yield nearly identical energies for syn and anti
isomers (except for Z ) OTIPS) and as expected fail to
provide any satisfactory explanation for the anti/syn
regioselectivity exhibited by the 7-norbornadienyl group.
On the premise that steric interactions among one (or
more) of the various proposed ground state nickel com-
plexes might influence the exo/endo diastereoinduction
of these nickel-catalyzed cycloadditions, and having no
a priori reason to draw conclusions about the product-
determining species, we chose to investigate the geo-
metrical and conformational characteristics of all feasible
nickel species (Chart 1). However any analysis is subject
to the usual caveat that the catalytically active species
may not be the most stable form of these complexes, but
may be a less stable, more reactive form. With regard
to exo/endo stereoselectivity, it is obvious that for steric
reasons orientation of an olefin substituent away from
the phosphine ligand would be more favorable in any of
the complexes. The choice to test the possible models
first for predictions of exo/endo stereoselectivity was
based on the expectation that the exo/endo preference
would be largely governed by steric interactions for which
such molecular mechanics models are well suited. Thus,
it was hoped that evaluating the complexes in this
manner would clearly eliminate some of the possible
structures and reduce the number of working models to
be examined in the further investigations into effects of
the 7-substituent.
Ch a r t 1
Using a modified MM2 force field,10 molecular mechan-
ics calculations were performed on model complexes 4-8
with three different phosphine ligands (PH3, PMe3, and
PPh3) to examine how the steric bulk of the phosphorus
ligand effects the predicted exo/endo stereoselectivity. To
evaluate these models, the relative energies of stereo-
isomeric intermediates were compared to the observed
stereochemical ratios. Only the global conformational
minima were used to determine relative energies. The
calculated differences in steric energy were taken to be
an approximation of the free energy differences for these
complexes and used to predict the expected ratios. In
complex 7, there was some conformational flexibility
found in the ethano-linkage (arising from the original
dienophile carbons). The alternate staggered conforma-
tion was predicted to be 2 kcal/mol higher in energy than
the global minimum.
In models containing a triphenylphosphine ligand, the
energetically preferred rotor conformations of the three
phenyl rings for each type of complex were determined.
The method used was to drive the dihedral angles of the
individual phenyl-phosphorus bonds and the nickel-
phosphorus bond through 180° (in 15° increments) to
(10) Gugelchuk, M. M.; Houk, K. N. J . Am. Chem. Soc. 1994, 116,
330.

Diels-Alder Addition of 7-Substituted Norbornadienes
J . Org. Chem., Vol. 61, No. 10, 1996 3493
F igu r e 2. MM2-optimized structures of the lowest energy conformations for complexes 4-6.
Ta ble 4. Rela tive MM2 En er gies of Tr ip h en ylp h osp h in e
Con for m a tion s.
rel energy
(kcal/mol)
model
rotor
4
CCW
CW
CW
CCW
CW
CCW
CW-CW
CCW-CW
CW-CCW
CCW-CCW
CW-CW
CW-CCW
CCW-CCW
0.0
0.7
0.0
0.7
0.0
0.5
0.0
0.5
1.4
1.7
0.0
0.4
1.7
5
6
7
8
Ta ble 5. Rela tive MM2 En er gies a n d Ca lcu la ted Exo/
F igu r e 3. MM2-optimized structure of the lowest energy
conformation for complex 7.
En d o Selectivities of Mod el Com p lexes 4-8a
∆Es
(endo-exo)
calc ratio
(exo:endo)
complex
PR3
4
5
6
7
8
PH3
PH3
PH3
PH3
PH3
0.46
-2.6
-1.6
3.3
67:33
1:99
6:94
99.6:0.4
52:48
0.06
4
5
6
7
8
PMe3
PMe3
PMe3
PMe3
PMe3
1.0
-8.1
-6.0
3.1
83:17
0:100
0:100
99.5:0.5
83:17
1.0
4
5
6
7
8
PPh3
PPh3
PPh3
PPh3
PPh3
1.5
-5.4
-3.9
5.2
93:7
0:100
0.1:99.9
100:0
100:0
7.2
F igu r e 4. MM2-optimized structure of the lowest energy
conformation for complex 8.
a
Steric energy differences given in kcal/mol. Calculated ratios
are at 25 °C. Experimental exo:endo ratio is 93:7 (25 °C, PPh3).
ensure we located the lowest possible conformation of the
ligand for the various complexes.
higher in energy, and the CCW-CCW conformations
were 1.7 kcal/mol higher than the global minimum (Table
4). The calculated energy differences between the right-
hand and left-hand rotors were all less than 1-2 kcal/
mol which is consistent with experimental values. The
right-hand and left-hand screw configurations in orga-
nometallic complexes typically differ by less than 1 kcal/
mol, and the helicity reversal process has a low energy
barrier.11
Generally, the MM2-calculated barrier to rotation
about the phenyl-phosphorus bond was around 2-3 kcal/
mol and that about the nickel-phosphorus bond ap-
proximately 3-5 kcal/mol. For the monophosphine com-
plexes 5 and 6, the clockwise (CW) rotor was slightly
favored over the counterclockwise (CCW) rotor, but for
complex 4 the counterclockwise rotor was favored (see
Figures 2-4). In the case of the bisphosphine complexes
7 and 8, the conformation having both triphenylphos-
phine ligands in clockwise orientations was the most
stable. Mixed CW-CCW conformations were slightly
With acrylonitrile as dienophile, steric properties of the
phosphorous ligand have been shown to strongly influ-
ence the exo/endo selectivity, whereas the electronic

3494 J . Org. Chem., Vol. 61, No. 10, 1996
Gugelchuk and Doherty-Kirby
Ta ble 6. Rela tive MM2 En er gies a n d Ca lcu la ted Regio-/Ster eoselectivities of Mod el Com p lexes 4, 7, a n d 8a
calcd rel energies
calcd ratio
(anti:syn)
calcd ratio
(exo:endo)
obsd ratio
(anti:syn)
obsd ratio
(exo:endo)
G
AX
SX
AN
SN
complex 4
n-hexyl
Cl
0.05
(46)
0.16
(41)
0.20
(39)
0.00
(49)
0.00
(54)
0.00
(55)
1.67
(3)
1.95
(2)
1.78
(3)
1.96
(2)
1.63
(3)
1.67
(3)
49:51
43:57
42:58
95:5
95:5
94:6
42:58
72:28
95:5
98:2
99:1
OBu-t
100:0
complex 7
n-hexyl
Cl
1.74
(32)
0.12
(40)
1.07
(35)
0.00
(36)
0.00
(25)
0.00
(37)
9.62
(14)
8.15
(16)
9.33
(14)
7.57
(18)
7.23
(19)
7.79
(14)
5:95
45:55
14:86
100:0
100:0
100:0
42:58
72:28
95:5
98:2
99:1
OBu-t
100:0
complex 8
n-hexyl
Cl
0.003
(49.6)
0.00
(62.4)
0.00
0.000
(49.9)
0.31
(37)
0.32
3.26
(0.2)
3.01
(0.4)
2.89
(0.5)
3.05
(0.3)
3.31
(0.2)
3.36
(0.2)
49.8:50.2
62.8:37.2
63:37
99.5:0.5
99.4:0.6
99.3:0.7
42:58
72:28
95:5
98:2
99:1
OBu-t
100:0
(62.5)
(36.8)
a
Relative energies given in kcal/mol. The numbers in parentheses are the predicted Boltzmann distributions of the various isomers
calculated at 25 °C.
character had no appreciable effect.1a Assuming that
bond formation occurs with retention of configuration,
the modeling results indicate that complexes 4, 7, and 8
consistently give good quantitative agreement with the
observed exo stereoselectivity (Table 5). Complexes 4 and
8 best reproduced the trend of increasing exo selectivity
with increasing cone angle of the phosphorous ligand
(PH3 ) 87, PMe3 ) 118, PPh3 ) 145).12 The endo isomer
was predicted to be the energetically more stable isomer
with model complexes 5 and 6.
to correlate well with both the extent and direction of
the observed regioselectivity. The quantitative agree-
ment with regioselectivity, while good, was still less than
perfect. This was not entirely unexpected due to the
likelihood that significant electronic factors, which are
absent in the force field models, play a role in the
regiochemical outcome. Yet a closer inspection of the
various interaction energies did reveal that for the Cl and
t-BuO cases the main energy difference between the syn
and anti orientations was a result of dipole interactions
between the C-Cl bond with the CdO bond of the acetyl
group, whereas for the n-hexyl substituent the energy
differences were largely due to van der Waals interac-
tions between the substituent and the rest of the complex.
Although we have not proven the origins of regiocontrol
lie within complex 8, our study does suggest that similar
interactions may be involved in the stereodiscriminating
step and provides a direction for further study of this
complex reaction.
We also carried out a preliminary study of the anti/
syn energy differences in the 7-substituted complexes
with various substituents for the more promising models
4, 7, and 8 (see Table 6). Three substituents were chosen
as representative examples for weakly syn regioselective
(Z ) n-hexyl), modestly anti regioselective (Z ) Cl), and
strongly anti regioselective (Z ) OBu-t) substituents. The
lowest energy conformers of the various triphenylphos-
phine complexes were used to derive the corresponding
7-substituted complexes. We determined the global
minimum energy conformations for all reasonable iso-
mers which included exploring all possible rotors of the
particular substituent. Only the global conformational
minima were used to determine relative energies.
There is still a need to more carefully address the
electronic influences of the 7-substituent and how they
may translate into a regiochemical preference in these
systems, but at this early stage we prefer not to speculate
on this matter. Extensive work on the transmission of
stereoelectronic substituent effects through norbornene
and similar systems has been carried out by many groups
and many different viewpoints abound, such as transi-
tion-state hyperconjugation, through-bond and through-
space electrostatic effects, σ-π orbital mixing, torsional
strain, and steric interactions.13 Our ongoing investiga-
tion involves a systematic study using molecular orbital
methods which may shed further insight into the anti/
syn selectivity issue and provide evidence for or against
the previously suggested hypotheses.
Using complex 4, nearly identical energies were found
for the syn and anti isomers of a given endo or exo
complex with the syn isomers being favored. In the case
of complex 7, there was more sensitivity to the orientation
of the substituent (except for Cl) but again with the syn
isomer being the lower energy form. The most viable
predictive model was complex 8. We found this model
(11) (a) Davies, S. G.; Derome, A. E., McNally, J . P. J . Am. Chem.
Soc. 1991, 113, 2854-2861. (b) Hunter, G.; Weakley, T. J . R.;
Weissensteiner, W. J . Chem. Soc., Dalton Trans. 1987 1545-1550. (c)
J ones, W. D.; Feher, F. J . Inorg. Chem. 1984, 23, 2376-2388. (d)
Docherty, J . B.; Rycroft, D. S.; Sharp, D. W. A.; Webb, G. A. J . Chem.
Soc., Chem. Commun. 1979, 336-337. (e) Faller, J . W.; J ohnson, B.
V. J . Organomet. Chem. 1975, 95, 99-113. (f) Stanley, K.; Zelonka, R.
A.; Thomson, J .; Fiess, P.; Baird, M. C. Can. J . Chem. 1974, 52, 1781-
1786. (g) Brown, J . M.; Mertis, K. J . Organomet. Chem. 1973, 47, C5-
C7 and references therein.
(13) (a) Li, H.; Silver, J . E.; Watson, W. H.; Kashyap, R. P.; le Noble,
W. J . J . Org. Chem. 1991, 56, 5932. (b) Houk, K. N.; Wu, Y.-D.; Mueller,
P. H.; Caramella, P.; Paddon-Row, M. N.; Nagase, S.; Mazzocchi, P.
H. Tetrahedron Lett. 1990, 31, 7289. (c) Mazzocchi, P. H.; Stahly, B.;
Dodd, J .; Rondan, N. G.; Domelsmith, L. N.; Rozeboom, M. D.;
Caramella, P.; Houk, K. N. J . Am. Chem. Soc. 1980, 102, 6482 and
references therein.
(12) Tolman, C. A. Chem. Rev. 1977, 77, 313.

Diels-Alder Addition of 7-Substituted Norbornadienes
J . Org. Chem., Vol. 61, No. 10, 1996 3495
Ta ble 7. Dia gn ostic 1H NMR Sign a ls Used a n d In itia l Con cen tr a tion s of Rea cta n ts
Z
reactant
product
2.55 (1H)
[NBD]o
[MVK]o
[Ni(COD)2]o
[PPh3]o
H
3.38 (2H)
3.31 (2H)
0.401
0.260
1.397
0.917
0.0800
0.0520
0.1597
0.1040
OTIPS
2.79 (1H, SX)
2.36 (1H, AX)
Ph
3.7-3.5 (3H)
3.10 (1H, AX + SX)
0.305
1.068
0.0609
0.1220
a
Chemical shifts are given in ppm and concentrations in mol/L.
diene)nickel(0) was purchased from Alfa AESAR and used
without further purification. Standard solutions (0.095 M) of
Ni(COD)2 in benzene-d6 were carefully prepared in a glovebox
under a nitrogen atmosphere prior to the kinetic runs to aid
in the measurement and transfer of such small quantities.
Syringe techniques were employed in the transfer all liquid
reactants. 1H NMR spectra for kinetic runs were recorded on
a 200 MHz FT-NMR with a variable-temperature probe rated
at (1 °C and calibrated prior to the kinetic study. Preliminary
1H NMR spectra of the individual reactants and products were
recorded on a 250 MHz FT-NMR in both benzene-d6 and
chloroform-d3.
Kin etics. Rate constants for the nickel-catalyzed reaction
of 1 with methyl vinyl ketone in C6D6 were determined at
various temperatures in the NMR. NMR tubes (5 mm)
equipped with rubber septa and containing a solution of 1, Ni-
(COD)2 (20 mol %), and PPh3 (40 mol %) in C6D6 under
nitrogen were heated in the probe of the machine. The tube
was removed, and methyl vinyl ketone (3.5 equiv) was added.
After the tube was returned to the probe, the machine was
shimmed to constant values (ca. 2.5 min total). Data (eight
scans) were collected at 5 min to 1 h time intervals depending
on the 7-substituent and reaction temperature. Relative
concentrations of 1 and the isomeric exo adducts (2) were
determined by comparison of the integrations of characteristic
proton resonances for 1 and 2, normalized to 100% (sum-
marized in Table 7).
Con clu sion s
The rate of nickel-catalyzed homo-Diels-Alder cy-
cloaddition of 7-substituted norbornadienes with MVK
was found to be slightly influenced by the nature of the
substituent. Relative reactivities followed the order: 7-Ph
> H > 7-OTIPS. The observed activation parameters
(∆Hq ) 15-18 kcal/mol; ∆Sq ) -19 to -24 cal/mol K)
are also affected by the 7-substituent and are in good
agreement with those established for reductive elimina-
tion from related nickel phosphine complexes. Force field
modeling studies of possible organonickel intermediates
suggest that the preferred exo selectivity arises from
steric interactions between the dienophile substituent
and the phosphine ligands. The anti/syn preferences are
most likely a blend of steric and electronic factors and
were not as well predicted by force field models. How-
ever, good qualitative and quantitative agreement with
both the observed exo/endo stereoselectivity and anti/syn
regioselectivity was found with only one complex. More
detailed studies are needed to test its viability as a
predictive model for this chemistry.
We are currently examining the influence of substit-
uents on the stabilities of these organonickel intermedi-
ates, using a combined electronic structure/molecular
mechanics approach. We are also undertaking an inves-
tigation into possible transition structures for the forma-
tion and collapse of these intermediate complexes using
density functional methods. As more experimental and
theoretical data is gathered, more stringent tests and
further refinement of these models will be possible and
presented in due course.
Pseudo-first-order rate constants were obtained by linear
regression from slopes of plots of ln ([NBD]o/[NBD]t) vs time.
These plots were linear (r > 0.99) over ca. 2-4 half-lives at
which time the reactions were g70% complete. Variable-
temperature results (30-70 °C) were used to obtain the linear
Arrhenius and Eyring plots (r > 0.99) for these reactions.
Activation parameters were determined from least-squares
analyses of ln k and ln (k/T) vs 1/T plots.
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council (NSERC)
of Canada for financial support in the form of an
Undergraduate Research Scholarship (A.L.D.-K.) and
Research Grant (M.M.G.). We thank Professor Mark
Lautens (University of Toronto) for supplying the nor-
bornadienes. We also thank Professors W. P. Power and
S. Collins (University of Waterloo) for use of their
glovebox and Professor Power for use of his WIN-NMR
software to process the NMR spectra.
Exp er im en ta l Section
Gen er a l. Triphenylphosphine was purified by recrystalli-
zation from hexane and dried in a vacuum oven. Methyl vinyl
ketone was distilled under nitrogen prior to use. Benzene-d6
was dried and degassed by standard procedures. Norborna-
diene, 7-phenylnorbornadiene, and 7-(tert-butyldimethylsi-
loxy)norbornadiene were used as received.14 Bis(cycloocta-1,5-
(14) Courtesy of Professor Lautens. For synthesis see: (a) Story, P.
R. J . Org. Chem. 1961, 26, 287. (b) Story, P. R.; Fahrenholtz, S. R. J .
Org. Chem. 1963, 28, 1716.
J O951849E