Mechanism of the Ni(0)-catalyzed vinylcyclopropane-cyclopentene rearrangement

Article abstract of DOI:10.1021/jo901525u

(Chemical Equation Presented) A combination of physical organic experiments and quantum chemical calculations were used to construct a detailed mechanistic model for the Ni(0)-N-heterocyclic carbene-catalyzed vinylcyclopropane- cyclopentene rearrangement

Full text of DOI:10.1021/jo901525u

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Mechanism of the Ni(0)-Catalyzed Vinylcyclopropane-Cyclopentene
Rearrangement
Selina C. Wang,† Dawn M. Troast,‡ Martin Conda-Sheridan,‡ Gang Zuo,‡
Donna LaGarde,‡ Janis Louie,*,‡ and Dean J. Tantillo*,†
†Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616,
and ‡Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112
louie@chem.utah.edu; tantillo@chem.ucdavis.edu
Received July 21, 2009
A combination of physical organic experiments and quantum chemical calculations were used to
construct a detailed mechanistic model for the Ni(0)-N-heterocyclic carbene-catalyzed vinylcyclo-
propane-cyclopentene rearrangement that involves a mutistep oxidative addition/haptotropic shift/
reductive elimination pathway. No evidence for the intermediacy of radicals or zwitterions was
found. The roles of substituents on the vinylcyclopropane substrate and variations in the ligands on
Ni were evaluated. It is postulated that bulky carbene ligands facilitate formation of the active
catalyst species.
Introduction
intermediates (Scheme 1).5 Various transition metals (e.g.,
Pd(0),6 Rh(I),7 and Ni(0)8) have been shown to facilitate
vinylcyclopropane-cyclopentene rearrangements, but in
many cases, activating groups on the vinylcyclopropane
appear to be required (see Scheme 2 for representative
examples).
Whereas transition-metal-promoted cycloadditions have
shown tremendous synthetic promise,1 transition-metal-
promoted sigmatropic shifts have not been exploited nearly
as frequently.2-4 However, one sigmatropic shift that has
been shown to be amenable to manipulation by transition
metals is the [1,3] sigmatropic rearrangement of vinylcyclo-
propanes to cyclopentenes.3,4 In the absence of transition
metals, Lewis acids, or activating substituents, vinylcyclo-
propane-cyclopentene rearrangements require high tem-
peratures and tend to produce various byproducts, most
of which are thought to arise from alkyl/allyl diradical
SCHEME 1
(1) For leading references, see: (a) Lautens, M.; Klute, W.; Tam, W.
Chem. Rev. 1996, 96, 49–92. (b) Fruhauf, H.-W. Chem. Rev. 1997, 97, 523–
596.
(2) (a) Siebert, M. R.; Tantillo, D. J. J. Am. Chem. Soc. 2007, 129, 8686–
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3949.
(3) Hudlicky, T.; Kutchan, T. M.; Naqvi, S. M. In Organic Reactions;
Kende, A. S., Ed.; Wiley: New York, 1985; Coll. Vol. 33, Chapter 2.
(4) For a mini-review on metal-promoted vinylcyclopropane-cyclo-
pentene rearrangements, see: Wang, S. C.; Tantillo, D. J. J. Organomet.
Chem. 2006, 691, 4386–4392.
(7) (a) Grigg, R.; Hayes, R.; Sweeney, A. J. Chem. Soc., Chem. Commun.
1971, 1248–1249. (b) Alcock, N. W.; Brown, J. M.; Conneely, J. A.; Williamsom,
D. H. J. Chem. Soc., Chem. Commun. 1975, 792–793. (c) Aris, V.; Brown, J. M.;
Conneely, J. A.; Golding, B. R.; Williamson, D. H. J. Chem. Soc., Perkin Trans.
2 1975, 4–10. (d) Salomon, R. G.; Salomon, M. F.; Kachinski, J. L. C. J. Am.
Chem. Soc. 1977, 99, 1043. (e) Alcock, N. W.; Brown, J. M.; Conneely, J. A.;
Williamsom, D. H. J. Chem. Soc., Perkin Trans. 2 1979, 962–971. (f) Hudlicky,
T.; Koszyk, F. J.; Kutchan, T. M.; Sheth, J. P J. Org. Chem. 1980, 45, 5020–5027.
(g) Hayashi, M.; Ohmatsu, T.; Meng, Y.-P.; Saigo, K. Angew. Chem., Int. Ed.
1998, 37, 837–839. (h) Jun, C.-H.; Kang, J.-B.; Lim, Y.-G. Tetrahedron Lett.
1995, 36, 277–280.
(5) Baldwin, J. E. Chem. Rev. 2003, 1197–1212.
(6) (a) Morizawa, Y.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982, 23,
2871–2874. (b) Fugami, K.; Morizawa, Y.; Oshima, K.; Nozaki, H. Tetra-
heron Lett 1985, 26, 857–860. (c) Burgess, K. J. Org. Chem. 1987, 52, 2046–
2051. (d) Burgess, K. Tetrahedron Lett. 1985, 26, 3049–3052.
(8) (a) Murakami, M.; Nishida, S. Chem. Lett. 1979, 927–930. (b) Ryu, I.;
Ikura, K.; Tamura, Y.; Maenaka, J.; Ogawa, A.; Sonoda, N. Synlett 1994,
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7822 J. Org. Chem. 2009, 74, 7822–7833
Published on Web 09/25/2009
DOI: 10.1021/jo901525u
r
2009 American Chemical Society

Wang et al.
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FIGURE 1. Possible mechanistic pathways for the isomerization of vinylcyclopropane to cyclopentene.
SCHEME 2
TABLE 1. Nickel-Catalyzed Isomerizationa of Various Vinyl
Cyclopropanes8c
Recently, Louie and co-workers reported that Ni(0)-N-
heterocyclic carbene (NHC) complexes are effective catalysts
for vinylcyclopropane-cyclopentene rearrangements invol-
ving unactivated vinylcyclopropane reactants (Table 1).8c
1,1-Disubstituted substrates underwent facile rearrangement
at room temperature without the aid of activating groups
(entry 1). Trisubstituted substrates required slightly elevated
temperature (60 °C) (entry 2). 1,2-Disubstituted substrates
required both elevated temperature and activation with an
aromatic group (entries 3 and 4).
aPerformed with 1.0 mol % [Ni(COD)2], 2.0 mol % IPr, and 0.10 M
substrate in toluene, benzene, or hexanes. Yields of isolated products
(average of at least two runs). N.R. = no reaction.
b
for asymmetric versions of this metal-promoted sigmatro-
pic shift.
The most likely mechanistic pathways for the metal-
promoted isomerization of vinylcyclopropanes are shown
in Figure 1.4 Both radical and zwitterionic mechanisms
would form an η1-alkyl species through initial addition of
the metal to the alkene (pathway a). Alternatively, oxidative
addition to the cyclopropane would lead to a metallacyclo-
butane intermediate, which could occur with or without
initial complexation of the substrate to the metal
(pathways b and c). Which of these pathways occurs for a
given experimental system depends on the specific metal and
ligands used.4
Herein, we describe quantum chemical calculations and
physical organic experiments on the mechanism of the
Ni(0)-promoted vinylcyclopropane-cyclopentene rearran-
gement. In addition to proposing a detailed mechanism
based on these studies, we also predict the outcome of
reactions with a variety of reactants and explore the poten-
tial of various non-NHC ligands. The transition state
structures we describe in this report should provide impor-
tant points of departure for the rational design of catalysts
Results and Discussion
1. Parent System: Unsubstituted Vinylcyclopropane. Com-
puted Overall Mechanism. We began our theoretical studies
(see Computational Methods for details) by computing
structures involved in the rearrangement of unsubstituted
vinylcyclopropane in the presence of Ni(N,N0-dimethyl-
imidazolylidene). All of the calculations described herein
are based on the assumption that the active catalyst is a Ni(0)
species. The computed intermediates (INT) and transi-
tion state structures (TSq) for this rearrangement are shown
in Figure 2, their relative energies are shown in Figure 3,
and a summary of the overall computed mechanism is shown
in Scheme 3 (note that we do not intend to imply that a
free Ni(N,N0-dimethylimidazolylidene) is generated in
solution).
The computed mechanism first involves rearrangement of
an initially formed η2-vinylcyclopropane complex (INT1;
note that we also located another conformer of INT1 where
the vinylcyclopropane is not oriented appropriately for
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˚
FIGURE 2. Geometries (B3LYP/LANL2DZ; distances in A; see Computational Methods for details) of intermediates and transition state
structures in the Ni(N,N0-dimethylimidazolylidene)-catalyzed rearrangement of vinylcyclopropane to cyclopentene.
oxidative addition; the energy of this conformer is marked
with an INT1b label throughout the paper)9 via oxidative
addition to form a vinylmetallacyclobutane (INT2). This
complex then rearranges to a metallacyclohexene (INT4)
by way of an η1-alkyl/η3-allyl intermediate (INT3). INT4
then undergoes a conformational change (to INT5) that
prepares it for reductive elimination to form a σ-complex
of cyclopentene (INT6). This intermediate then rearranges
with a very small barrier to a π-complex of cyclopentene
(INT7).
Several of the intermediates and transition state structures
involved in this process have interesting features. First, it
is somewhat unusual that the vinylmetallacyclobutane,
η1-alkyl/η3-allyl, and metallacyclohexene structures are all
found as minima. Even though the barrier for conversion of
the vinylmetallacyclobutane (INT2) to the η1-alkyl/η3-allyl
(INT3) is small enough to be of little chemical consequence
(in other words, this portion of the energy surface is
rather flat), the barrier for conversion of INT3 to INT4 is
substantial (greater than 10 kcal/mol; see Figure 3). Note
q
˚
that the Ni-CNHC distance in TS34 (1.85 A) is shorter
than the corresponding distance in all of the other struc-
tures (except the weakly bound σ-complex (INT6) and the
transition structure (TS67q) for its conversion to INT7),
hinting that Ni-allyl bonding in this structure is weaker
(9) Geometries of INT1b complexes are available in the Supporting
Information. For the unsubstituted vinylcyclopropane system, INT1b is
1.2 kcal/mol lower in energy than INT1 (B3LYP/DZVP2þ//B3LYP/
LANL2DZ þ ZPE(B3LYP/LANL2DZ)).
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FIGURE 3. Relative energies (B3LYP/LANL2DZ, kcal/mol in normal text; B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/
LANL2DZ) in underlined text; see Computational Methods for details) of structures shown in Figure 1.
While our calculations suggest that the formation of
vinylmetallacyclobutane INT2 is the rate-determining step,
energies of the transition state structures for formation of
metallacyclohexene INT4 (TS34q) and σ-complex INT6
(TS56q) are only very slightly lower in energy, respectively.
All of the intermediates that we located (INT1-INT6) have
similar energies (spanning only a few kcal/mol), while the
product π-complex INT7 is much lower in energy, reflecting
the energy difference between σ- and π-complexation of
cyclopentene; interestingly, throughout the reaction there
appears to be a balance of strain and Ni-carbon bonding.
Likelihood of Diradical or Zwitterionic Intermediates. Sev-
eral additional mechanistic possibilities were also explored.
First, we considered the possibility that diradical species
might be involved (e.g., Figure 1, path a). Using a system
with a 2-methyl group (for additional details on this parti-
cular system, see below), the triplet diradical counterpart
of INT1 was located as a minimum (using UB3LYP/
LANL2DZ), and this structure is ∼23 kcal/mol higher in
energy than INT1. Similarly, the triplet diradical analogue of
INT4 was 6 kcal/mol higher in energy than INT4 (see
Supporting Information for details). On the basis of these
results, we did not pursue further calculations on diradicals.
Second, we explored the possibility of zwitterionic inter-
mediates. Here we assessed the energies of species such as A
(below) by performing constrained optimizations with the
indicated bond angle fixed to a value of 109.5°. The energies
of the resulting structures (for substrates with alkyl substit-
uents in various positions; see Supporting Information
for further details) were generally 15-20 kcal/mol above
that of the corresponding INT1 complexes, i.e., they were
generally similar in energy to TS12q. Thus, we think that
mechanisms involving such intermediates are unlikely
(note that although these are gas phase calculations, the
SCHEME 3
than in the other allyl complexes INT2-INT5. Second, a
crankshaft rotation of the ethylene group in metallacyclo-
hexene INT4 (dashed box in Figure 2) is necessary to bring
the two methylenes attached directly to Ni closer together
so that reductive elimination can occur readily. Third,
formation of the σ-complex (INT6) is also noteworthy.
Note that both of the C-H bonds near to the Ni are elon-
gated.
(10) Since the internal and terminal monoalkyl systems are isomers of
each other, all of the energies are on the same scale, relative to the energy of
the internal substituted h2-vinylcyclopropane INT1 complex.
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FIGURE 4. Relative energies (B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/LANL2DZ), kcal/mol; see Computational Methods
for details) of analogues of structures shown in Figure 1 with monomethyl-substituted vinylcyclopropanes.10
experimental reactions were carried out in nonpolar aromatic
and aliphatic solvents).8c
from the lower energy INT1b in these cases9). Note also that
the absolute energies of the transition state structures are
lower for the internally substituted system. Moreover, this
difference in reactivity is likely to be underestimated in our
calculations, given that a small NHC was used in the model-
ing; given the geometries of the transition structures involved
(e.g., Figure 1), we expect steric repulsions to be greater for
1-substitution. The internally substituted system also leads
to a trisubstituted alkene, rather than a disubstituted alkene,
providing a greater driving force for rearrangement of the
internally substituted systems. An internal methyl group is
also predicted to accelerate the rearrangement as compared
to the unsubstituted system (vide supra), whose overall
barrier (from INT1b) is computed to be 16.8 kcal/mol.
Dialkylvinylcyclopropanes. Disubstituted vinylcyclopro-
panes are predicted to behave much like the monosubstituted
systems described above (Figure 5). One key difference,
however, is observed for the gem-dimethyl case. Unlike the
trans monomethyl case described above, no simple change in
conformation can lead to a reductive elimination transition
structure where the Ni is not near to a methyl group, and a
high energy reductive elimination transition structure is
therefore observed (Figure 6, left); again, this steric problem
is likely to greater in the experimental system, which involves
a bulky NHC. Note also that TS67q for this system involves
migration of the Ni “the long way around” the five-mem-
bered ring in order to avoid the methyl group (Figure 6,
right).
2. Alkyl-Substituted Systems. Monoalkylvinylcyclopro-
panes. We also examined the effects of alkyl substitution
on the rearrangement. As shown in Figure 4, the overall
mechanism does not change upon alkyl substitution,
although which of the three highest transition state struc-
tures is the absolute highest does vary. Interestingly, the
reaction coordinates for the cis- and trans-methylvinylcyclo-
propane systems actually intersect at INT5, and both systems
undergo reductive elimination through the same TS56q
(actually, the two paths involve enantiomeric versions of
INT5 and TS56q). This is a result of a conformational change
for the trans system that allows the Ni to avoid being in close
proximity to the methyl group in the last few intermediates
and transition state structures.
The experimental results of Zuo and Louie indicate that
systems with internal alkyl groups rearrange readily, whereas
systems with terminal alkyl groups do not (Table 1; compare
entries 1 and 4).8c Our calculations are consistent with these
observations. The overall barrier for rearrangement of the
vinylcyclopropane with an internal methyl group is predicted
to be 15.5 kcal/mol, while the barriers for the systems with a
terminal methyl group are higher (19.6 and 17.9 kcal/mol,
Although experimental results on gem-dialkyl substrates
have not been reported (we would predict that the proble-
matic reductive elimination described above in such systems
would hinder rearrangements on the basis of our
computations), rearrangements of vicinal dialkyl systems
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FIGURE 5. Relative energies (B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/LANL2DZ), kcal/mol; see Computational Methods
section for details) of analogues of structures shown in Figure 1 with dimethyl-substituted vinylcyclopropanes (note that, again, the cis and
trans pathways converge).10
Trialkylvinylcyclopropanes. The trimethyl-substituted vinyl-
cyclopropane shown in Figure 7 behaves very much like the
gem-dimethyl-substituted system described above. Again, we
predict that this sort of system will not rearrange efficiently;
however, we do predict that the internal alkyl group will lower
the overall barrier compared to that for the gem-dimethyl-
substituted system (23.9 vs 28.0 kcal/mol).
3. Aryl-Substituted Systems. Louie and co-workers
showed that phenyl-substituted vinylcyclopropanes rear-
range more easily than do related alkyl-substituted cases,
for both internal and terminal substituted cases (Tables 1
and 2).8c Our calculations do not predict a significant
increase in reactivity for the phenyl-substituted systems,
however (compare Figure 8 with Figure 4). This discrepancy
between experiment and theory perhaps suggests that the
main difference between aryl and alkyl substituents in these
reactions, in terms of their effects on the overall rearrange-
ment barriers, is predominantly steric rather than electronic
in nature, since our calculations capture electronic effects but
underestimate steric effects due to the size of our model
FIGURE 6. Computed geometries (B3LYP/LANL2DZ, distances
ligand.
˚
in A; see Computational Methods for details) of unusual transition
structures from Figure 5.
In the case of the cis-phenyl-substituted vinylcyclopro-
pane (Figure 8b), we observed a shorter version of our
proposed mechanism (Scheme 3). We were unable to locate
the vinylmetallacyclobutane complex (INT2) and instead
have been reported.8c These systems are observed to rear-
range more sluggishly than do monoalkyl-substituted sys-
found a transition state structure (TS13q, Figure 9a) that
tems with internal alkyl groups, but more readily than do
monoalkyl-substituted systems with terminal alkyl groups.
Our predicted barriers for the vicinal dimethyl systems
(Figure 5) are 17.3 (here, TS12q is the highest energy
structure) and 16.0 kcal/mol (here, TS34‡ is the highest
energy structure), respectively; interestingly, these barriers
are between those computed for systems with internal and
terminal methyl groups (vide supra).
connects the η2-vinylcyclopropane (INT1) and η1-alkyl/η3-
allyl intermediate (INT3). Thus, in this case, the very shallow
minimum associated with INT2 disappears. Additionally, it
appears that no conformational changes are required before
formation of the σ-complex INT6.
For the trans-phenyl-substituted vinylcyclopropane
(Figure 8c), an additional interesting transition state
q
structure was also located (TS57b , Figure 9b, left). This
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FIGURE 7. Relative energies (B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/LANL2DZ), kcal/mol; see Computational Methods
for details) of analogues of structures shown in Figure 1 with trisubstituted vinylcyclopropanes.
transition structure leads to a product complex in which the
nickel interacts with the π-system of the phenyl group
(INT7b, Figure 9b, right), rather than the σ-framework of
the cyclopentene (INT6). TS57b is more than 1 kcal/mol
higher in energy than TS46q, however.
the unsubstituted substrate (entry 4), and substrates bearing
electron-donating groups (entries 5 and 6) rearranged more
slowly. The Hammett plot (Figure 10)11,12 constructed from
this data had a F value of 0.11. A F value greater than 0.2 is
typically considered to indicate a significant substituent
effect.11 Therefore, although substituents on the aryl ring
have an effect on the rate of the reaction, this effect is small,
consistent with zwitterionic (or radical) mechanisms not
contributing significantly. The effect of varying the electron
density of the aromatic group was also explored by theore-
tical calculations, and as shown in Table 3 (last column), the
experimentally determined order of reactivity is reflected in
the computed rearrangement barriers for processes not in-
volving zwitterionic or diradical intermediates.
4. Other Ligands on Ni. The effect of the structure of the
carbene ligand on the rearangement was also examined by
measuring the first-order rate constants for rearrangement
with a variety of ligands (Table 4). The rearrangement
of (E)-(2-cyclopropylvinyl)benzene (2) in the presence of
1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene
q
The reactivity of several phenyl-substituted vinylcyclopro-
panes was investigated experimentally by determining
their rearrangement rates (Table 2). The isomerization of
(1-cyclopropylvinyl)benzene (1) was significantly faster than
that of (E)-(2-cyclopropylvinyl)benzene (2); note that the
rate for 2 (entry 2) was determined at 60 °C, whereas the rate
for 1 (entry 1) was determined at 27 °C because the rate of
rearrangement for 1 was too fast to measure at 60 °C. This
reactivity difference was borne out in our calculations as
well (Figure 8). (Z)-(1-Cyclopropylprop-1,2-yl)benzene (3)
isomerizes to the (E)-substrate (2) before rearrangement
(entry 3), so a rearrangement rate was not determined for
this specific substrate. When (E)-(1-cyclopropylprop-1,2-yl)-
benzene (4) was subjected to the isomerization conditions, no
reaction was observed, even at higher temperatures
(60 °C, entry 4). These results are consistent with the unwill-
ingness of gem-disubstituted vinylcyclopropanes to rear-
range (vide supra).
The initial cis-trans isomerization of 3 could be explained
by a diradical mechanism, but our calculations (vide supra)
suggest that this is unlikely. In an attempt to settle this issue,
the reaction of 3 was carried out in the presence of TEMPO
and BHT (2,6-di-tert-butyl-p-cresol) in an effort to trap any
radical intermediates. Under these conditions, no decrease in
conversion or yield was observed, consistent with the ab-
sence of radical intermediates.
(11) For leading references, see: Hansch, C.; Leo, A.; Taft, R. W. Chem.
Rev. 1991, 91, 165–195.
(12) The activation energy for (E)-1-(2-cyclopropylvinyl)-4-fluoroben-
zene was determined by measuring the first-order rate constant at various
temperatures (see below). Application of the Eyring equation led to an
activation energy of 27 kcal/mol, which is consistent with the need for
elevated temperatures to promote rearrangements of 1,2-disubstituted sub-
strates.
Substituent Effects. The effect of substituents on the
phenyl ring on the rate of rearrangement was also examined
(Table 3). Substrates bearing electron-withdrawing groups
(entries 1 and 2) were found to rearrange more quickly than
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FIGURE 8. Relative energies (B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/LANL2DZ), kcal/mol; see Computational Methods
for details) of analogues of structures shown in Figure 1 with (a) internal phenyl-substituted vinylcyclopropane, (b) terminal cis-phenyl-
substituted vinylcyclopropane, and (c) terminal trans-phenyl-substituted vinylcyclopropane.
(SIPr) is 3.2 times faster than the rearrangement of 2 in the
presence of 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-yli-
dene (IPr) (entries 1 and 2). Rearrangement is not observed
electronically similar IPr, SIPr, and IMes ligands suggests
that steric factors play a significant role in the rear-
rangement, in that the NHCs with bulky isopropyl groups
near the carbene center promoted reaction, whereas the one
with only methyl groups near the carbene center (IMes)
did not.
A variety of ligand/additive combinations were also ex-
amined in order to assess the composition of the active
catalyst (Table 5). Interestingly, Ni(IPr)2 without any addi-
tional additives promoted the rearrangement, although with
a much lower yield and rate (entry 4, 32% yield and 14.2 ꢀ
10-3 s-1 first-order rate constant) than Ni(COD)2 with IPr
with
1,3-bis(1,3,5-trimethylphenyl)-imidazol-2-ylidene
(IMes) even under more forcing conditions (80 or 100 °C)
and longer reaction times (16 h, entry 3). These results
are consistent with previously reported vinylcyclopropane
rearrangements in which use of the IMes ligand resulted
in a dramatic decrease in yield.8c Rearrangement in the
presence of IPrCl2 is slightly faster than with the parent
IPr ligand (entry 4, perhaps because IPrCl2 is more robust
than IPr). The difference in reactivity between the
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˚
FIGURE 9. Computed geometries (B3LYP/LANL2DZ; distances in A; see Computational Methods for details) of selected structures from (a)
Figure 8b and (b) Figure 8c.
TABLE 2. Nickel-Catalyzed Isomerization of Various Vinyl
Cyclopropanes
TABLE 3. Ni-Catalyzed Isomerization with Various Substratesa
rate (k)b s-1 yield computed barrier
entry X (compound no.)
(10-3 c
)
(%)d
(kcal/mol)e,f
1
2
3
4
5
6
CO2Me (5)
CF3 (6)
F (7)
H (2)
Me (8)
OMe (9)
98.6
85.1
32.7
26.2
23.1
11.7
93
83
82
92
92
72g
18.1
19.1
19.3
19.7
19.9
20.9
aConditions: 5.0 mol % [Ni(IPr)2], 10 mol % COD, and 0.20 M
substrate in deuterated benzene. bFirst-order rate constant (average of at
c
least three runs). Determined by NMR with ferrocene as an internal
standard (average of at least two runs). dIsolated yields, performed with
2.0 mol % [Ni(COD)2], 4.0 mol % IPr, and 0.10 M substrate in hexanes.
eBased on INT1; see Supporting Information for details. fThe X = CN,
NO2 and NH2 systems were also examined, and their computed barriers
are 18.4, 18.5, and 20.8 kcal/mol, respectively; see Supporting Informa-
tion for details. gGC yield.
aFirst-order rate constant (average of at least three runs). bDeter-
mined by NMR with ferrocene as an internal standard (average of at
least three runs). N.R. = no reaction.
additive (entry 1, 81% yield and 26.2 ꢀ 10-3 s-1 first-order
rate constant). Ni(IPr)2 with cyclooctadiene additive gave
results (entry 2, 79% yield and 19.0 ꢀ 10-3 s-1 first-order
rate constant) comparable to those of Ni(COD)2 with IPr.
When excess IPr was added to the Ni(IPr)2 catalyst, the yield
and rate (entry 3, 28% yield and 14.7 ꢀ 10-3 s-1 first-order
rate constant) were comparable to those of Ni(IPr)2 without
an additive. Styrene and 1,5-dimethyl-cycloocta-1,5-diene
were also examined as additives, and these led to slower
reactions and lower yields than did Ni(IPr)2 with COD
additive. In addition, the optimized ratio of IPr to COD
was determined to be 1:2. These results suggest that COD
plays an important role in the formation (or stabilization) of
the active catalyst.
In addition, calculations were performed on the rearran-
gement of the parent vinylcyclopropane system with
other heterocyclic carbenes. Adding two chlorines to the
imidazolylidene (Figure 11) seems to have only a very small
effect on the rearrangement (the predicted overall barrier
only changes from 16.8 to 16.5 kcal/mol), consistent with the
experimental results in Table 4 (entries 2 and 4). Replacing
one NR group of the imidazolylidene with an O or S is also
predicted to have only small effects (Figure 11). These two
ligands are sterically smaller than the corresponding imida-
zolylidenes, however, which could present a problem, as
described above (also, vide infra). Overall, these results
indicate that the rearrangement mechanism, from INT1 to
INT7, is not very sensitive to the electronic nature of the
heterocyclic carbene ligand on Ni.
Rearrangement of the parent vinylcyclopropane system
was also examined with trimethylphosphine as a simple
model of alkyl phosphines (Figure 11). Although tricyclo-
hexylphosphine was shown experimentally to be an ineffective
ligand for promoting the rearrangement of unactivated
vinylcyclopropanes,8c the computed mechanism and ener-
getics for the trimethylphosphine-promoted rearrange-
ment (Figure 11) are similar to those for the reaction with
N,N0-dimethylimidazolylidene. Although the transition
state structure for conversion of the η1-alkyl/η3-allyl inter-
mediate to the metallacyclohexene intermediate becomes the
rate-determining transition state structure in the phosphine
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Wang et al.
JOCArticle
FIGURE 10. Hammett plot constructed from data in Table 3.11
TABLE 4. Ni-Catalyzed Isomerization with Various Ligandsa
TABLE 5. Ni-Catalyzed Isomerization with Different Nickel Ligands
(L) and Various Additivesa
aConditions: 5.0 mol % [Ni(L)2], 10.0 mol % additive, and 0.20 M
substrate in deuterated benzene. bFirst-order rate constant (average of at
least two runs). cDetermined by NMR with ferrocene as an internal
standard after three half-lives (average of at least two runs).
Taken together, this experimental and theoretical data
hints that the most important difference between NHCs that
promote rearrangement and NHCs and phosphines that do
not may be their bulkiness. Our calculations indicate that in
the absence of bulky groups, all of the ligand frameworks
should allow for rearrangement. Our calculations also
suggest, however, that two full-sized IPr ligands are unable
to bind simultaneously to Ni when a vinylcyclopropane
substrate is bound (i.e., optimization of such structures leads
to dissociation of one IPr; see Supporting Information for
details). Interestingly, a complex with two tricyclohexyl-
phoshine ligands and a vinylcyclopropane substrate all
bound to Ni could be located as a minimum. Thus, we
suggest that the key role of bulky groups on IPr (and the
related SIPr and IPrCl2) is to promote dissociation of one
NHC, allowing INT1 to form; the smaller IMes and differ-
ently shaped phosphine ligands are less inclined to dissociate.
The effectiveness of adding COD is also likely due to its
ability to facilitate NHC dissociation.
aConditions: 5.0 mol % [Ni(L)2], 10 mol % COD, and 0.20 M
substrate in deuterated benzene. bFirst-order rate constant (average of
at least three runs). cDetermined by NMR with ferrocene as an internal
standard (average of at least two runs). N.R. = No reaction.
system, the overall barrier predicted for rearrangement with
trimethylphosphine is comparable to that predicted for
rearrangement with N,N0-dimethylimidazolylidene. This
suggests that the problem with phosphine ligands observed
experimentally8 may be related to initial formation of INT1
rather than the subsequent rearrangement steps.
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Wang et al.
JOCArticle
FIGURE 11. Relative energies (B3LYP/DZVP2þ//B3LYP/LANL2DZ þ ZPE(B3LYP/LANL2DZ), kcal/mol; see Computational Methods
for details) of analogues of structures shown in Figure 1 with alternative ligands on Ni (trimethylphosphine in normal text, dichloro-N,N0-
dimethylimidazolylidene in underlined text, N-methyloxazolylidene in bold text, N-methylthiazolylidene in italic text).9
Conclusion
computed and experimental geometries were observed (see
Supporting Information for details). The vibrational frequen-
cies of all stationary points were analyzed to characterize
structures as minima or transition state structures. Intrinsic
reaction coordinate (IRC) calculations15 were used to further
characterize the nature of some transition state structures by
mapping out the portions of the reaction coordinates near to
them (see Supporting Information for details). Geometries for
the parent system (Figure 3) were also reoptimized using
B3LYP/DZVP2þ,16 and no significant changes were observed
(see Supporting Information for coordinates). Single point
energies were calculated for all structures at the B3LYP/
DZVP2þ level,16 and these B3LYP/DZVP2þ//B3LYP/
LANL2DZ þ ZPE(B3LYP/LANL2DZ) energies are reported
throughout the text. (The corresponding energies from B3LYP/
LANL2DZ þ ZPE(B3LYP/LANL2DZ) calculations can be
found in the Supporting Information). This theoretical ap-
proach has been used previously to characterize the chemistry
of various organometallic complexes involving metals from the
first transition series;17 additional tests on the validity of this
We have proposed a catalytic cycle (Scheme 3) for the Ni(0)-
catalyzed isomerization of vinylcyclopropanes to cyclopen-
tenes based on physical organic experiments and theoretical
calculations. Which step in this process is rate-determining
appears to depend on the exact nature of the substrate used. In
addition, the importance of generating a catalyst species with
only one bound NHC was revealed, pointing to the importance
of bulky groups on the NHC and the utility of COD as an
additive. These results should aid the rational design of
catalysts for additional substrates and asymmetric versions
of this useful metal-promoted sigmatropic shift.
Experimental Section
Computational Methods. GAUSSIAN0313 was used for all
calculations. All geometries were optimized without symmetry
constraints using B3LYP/LANL2DZ.14 As a test, the B3LYP/
LANL2DZ level was used to optimize the geometries of several
Ni-allyl and Ni-NHC complexes for which X-ray structures
have been reported, and no significant deviations between the
(14) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652. (b) Becke, A. D.
J. Chem. Phys. 1993, 98, 1372–1377. (c) Lee, C.; Yang, W.; Parr, R. G. Phys.
Rev. B 1988, 37, 785–789. (d) Stephens, P. J.; Devlin, F. J.; Chabalowski, C.
F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623–11627. (e) Hay, P. J.; Wadt,
W. R. J. Chem. Phys. 1985, 82, 270–283.
(13) GAUSSIAN03, revision B.04; Frisch, M. J.; Trucks, G. W.; Schlegel,
H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.,
Jr., Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Lyengar, S. S.;
Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petresson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda,
R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.;
Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; R.,
Cammi; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; G. A,
VothSalvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.;
Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M.
W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
Gaussian, Inc.: Pittsburgh, PA, 2003.
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(b) Fukui, K. Acc. Chem. Res. 1981, 14, 363–368.
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(17) (a) Tantillo, D. J.; Hoffmann, R. Helv. Chim. Acta 2001, 84, 1396–
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9859. (c) Tantillo, D. J.; Carpenter, B. K.; Hoffmann, R. Organometallics
2001, 20, 4562–4564. (d) Tantillo, D. J.; Hietbrink, B. N.; Merlic, C. A.;
Houk, K. N. J. Am. Chem. Soc. 2000, 122, 7136–7137. (Additional note: J.
Am. Chem. Soc. 2001, 123, 5851). (e) Merlic, C. A.; Walsh, J. C.; Tantillo, D.
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theoretical approach for the Ni(0) systems explored herein are
described below. In general, in order to reduce computational
cost, the diisopropylphenyl groups of the IPr ligands were
replaced by methyl groups (see Scheme 3). However, tests on
the validity of this approximation were also performed using
ONIOM(B3LYP/LANL2DZ:UFF) calculations18 with full-
sized carbene ligands. In these calculations, the quantum me-
chanics layer (treated with B3LYP/LANL2DZ) consisted of the
vinylcyclopropane system, the Ni atom, and the heterocycle,
while the molecular mechanics layer (treated with the Universal
Force Field [UFF]) included the diisopropylphenyl groups. For
the subset of structures from Figure 2 examined using this
method, no significant changes to relative energies were ob-
served (see Supporting Information for details), although we
were not able to locate transition state structures for reductive
elimination, where steric effects may be largest (vide infra).
Structural drawings were produced using Ball & Stick.19
General Procedure for Rearrangement of Vinyl Cyclopro-
panes. In the drybox, vinyl cyclopropane was weighed directly
into an oven-dried screw cap vial equipped with a magnetic stir
bar and dissolved in hexane (0.1 M). A solution of Ni(COD)2/
IPr (2 mol %) (Ni(COD)2 (1.0 equiv) and IPr (2.0 equiv) were
dissolved in benzene and allowed to equilibrate at room tem-
perature for 3 h) was added, and the vial was sealed with a
PTFE-lined cap. The vial was removed from the drybox and
the dark greenish-black reaction was stirred at 60 °C. After
complete consumption of the substrate, the solvent was re-
moved in vacuo, and the products were purified by silica gel
chromatography. See Supporting Information for additional
details.
General Procedure for Kinetic Experiments. A stock solution
of vinyl cyclopropane and ferrocene (10 mol %) was prepared in
deuterated benzene. A stock solution of Ni(COD)2 (1.0 equiv)
and IPr (2.0 equiv) was prepared in deuterated benzene and
stirred for 4 h. The solution of vinyl cyclopropane (0.104 mmol)
and ferrocene (0.0104 mmol) was syringed into an NMR with a
screw cap. Deuterated benzene was added to give an overall
solution of 0.2 M. The solution was then frozen in the glovebox
before the Ni(COD)2/IPr (0.00520 mmol) was added to prevent
mixing. The NMR tube was frozen again after addition of the
Ni(COD)2/IPr solution and removed from the drybox. The
NMR tube was warmed just before being placed in the NMR.
1
The reaction was monitored by H NMR, taking data points
every minute. Reaction monitored for at least three half-lives.
See Supporting Information for additional details.
Acknowledgment. We gratefully acknowledge the Univer-
sity of California-Davis, the National Science Foundation’s
CAREER and Partnership for Advanced Computational
Infrastructure (PSC) programs, the American Chemical
Society’s Petroleum Research Fund (S.C.W. and D.J.T.),
and the National Institutes of Health (all authors) for support.
(18) (a) Maseras, F.; Morokuma, K. J. Comput. Chem. 1995, 16, 1170–
€
1179. (b) Vreven, T.; Morokuma, K.; Farkas, O.; Schlegel, H. B.; Frisch, M.
J. J. Comput. Chem. 2003, 24, 760–769. (c) Svensson, M.; Humbel, S.;
Morokuma, K. J. Chem. Phys. 1996, 105, 3654–3661.
Supporting Information Available: Coordinates and ener-
gies for all structures, IRC plots, additional computational data,
and experimental details. This material is available free of
charge via the Internet at http://pubs.acs.org.
€
(19) N. Muller Falk, A. Ball & Stick V.3.7.6, molecular graphics applica-
tion for MacOS computers, Johannes Kepler University: Linz, 2000.
J. Org. Chem. Vol. 74, No. 20, 2009 7833