Mild and efficient nickel-catalyzed heck reactions with electron-rich olefins

Article abstract of DOI:10.1021/ja2084509

A new efficient protocol for the nickel-catalyzed Heck reaction of aryl triflates with vinyl ethers is presented. Mild reaction conditions that equal those of the corresponding palladium-catalyzed Heck reaction are applied, representing a practical and more sustainable alternative to the conventional regioselective arylation of vinyl ethers. A catalytic system comprised of Ni(COD)₂ and 1,1″-bis(diphenylphosphino)ferrocene (DPPF) in combination with the tertiary amine Cy₂NMe proved effective in the olefination of a wide range of aryl triflates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination and base promoted catalyst regeneration. Although these elementary reactions are normally considered challenging, DFT calculations suggested this pathway to be favorable under the applied reaction conditions.

Full text of DOI:10.1021/ja2084509

Article
pubs.acs.org/JACS
Mild and Efficient Nickel-Catalyzed Heck Reactions with
Electron-Rich Olefins
Thomas M. Gøgsig,† Jonatan Kleimark,‡ Sten O. Nilsson Lill,‡ Signe Korsager,† Anders T. Lindhardt,†
Per-Ola Norrby,*,‡ and Troels Skrydstrup*,†
†The Center for Insoluble Protein Structures (inSPIN), Department of Chemistry and the Interdisciplinary Nanoscience Center,
Aarhus University, Langelandsgade 140, 8000 Aarhus, Denmark
‡Department of Chemistry, University of Gothenburg, Kemigarden 4, #8076, SE-412 96 Goteborg, Sweden
̊
̈
S
* Supporting Information
ABSTRACT: A new efficient protocol for the nickel-catalyzed
Heck reaction of aryl triflates with vinyl ethers is presented.
Mild reaction conditions that equal those of the corresponding
palladium-catalyzed Heck reaction are applied, representing a
practical and more sustainable alternative to the conventional
regioselective arylation of vinyl ethers. A catalytic system com-
prised of Ni(COD)2 and 1,1′-bis(diphenylphosphino)ferrocene
(DPPF) in combination with the tertiary amine Cy2NMe
proved effective in the olefination of a wide range of aryl tri-
flates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could
be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the
characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the
intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination and base promoted
catalyst regeneration. Although these elementary reactions are normally considered challenging, DFT calculations suggested this
pathway to be favorable under the applied reaction conditions.
carbamates14 and so forth, have been accessed and utilized in a
INTRODUCTION
■
variety of cross coupling reactions.15 Furthermore, alkyl halides
have been employed with great success in various cross
couplings creating both C(sp3)−C(sp3) and C(sp3)−C(sp2)
σ-bonds under mild reaction conditions.16,17 Alkyl halides
possessing β-hydrogens proved perfectly suitable, and products
arising from the undesired β-hydride elimination were not
observed. This could be accounted for by an inherent reluc-
tance of nickel to undergo β-hydride eliminations, although
procedures relying on such transformations are well established,
including the Shell higher olefin process.18 Nevertheless, in
contrast to other cross coupling reactions, nickel-catalyzed
Heck couplings have only been scarcely described in the
literature. This could indicate that the β-hydride elimination
generating the nickel hydride intermediate, crucial to the Heck
reaction, is in fact problematic.19 Harsh reaction conditions,
such as high temperatures, highly polar solvents, prolonged
reaction times, or metal additives, are usually required for these
reactions to proceed (Scheme 1).20
The Heck reaction represents one of the most important means
for C−C bond formation in organic synthesis for the func-
tionalization of olefins. Not only does this palladium-catalyzed
reaction display an extraordinary functional group tolerance but
due to the required syn-correlation during the β-hydride
elimination, enantioselective variants of this reaction are also
known.1 Its immense applicability and many variations on both
the laboratory and the industrial scale were recently recognized
by the Nobel Prize Committee honoring Richard F. Heck for
his discovery.2 While palladium-based complexes are the most
common catalysts for this reaction, efforts have been made to
replace this metal with less expensive metals, such as nickel or
cobalt.3
In the last 10 years, increasing attention has been directed
toward nickel catalysis. The sustainability and relatively low
prices of nickel precursors are important factors contributing to
the attractiveness when considering transition-metal catalysis.
Numerous reports have been disclosed on a wide variety of
different nickel-catalyzed processes, including cross couplings,4
cycloisomerization,5 cycloadditions,6 multicomponent couplings,7
annulations,8 reductive couplings,9 and others.10 Perhaps one of
the most striking features of nickel catalysis compared to that
of palladium is the broad range of adaptable electrophiles. In
addition to aryl and vinyl halides and their corresponding
sulfonates, functional groups traditionally inert toward oxida-
tive addition, such as ethers,11 metal alkoxides,12 carboxylates,13
An alternative explanation for the observed difficulties in the
Ni-catalyzed Heck reactions could also be the stronger bond
energy of the Ni−H compared to the Pd−H, resulting in a
more difficult reductive elimination step.19 Hence, specific
properties of both the base and the catalyst would be required
Received: September 7, 2011
Published: November 29, 2011
© 2011 American Chemical Society
443
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
In light of the results presented by the group of Jamison and
our own experiences with the regioselective palladium-catalyzed
reaction between aryl and vinyl tosylates and electron-rich
olefins, we set forth to investigate the nickel-catalyzed arylation
of electron-rich olefins in more detail.27,28 In this paper, we
wish to report our discoveries regarding the implementation of
nickel as an efficient catalyst for the regioselective coupling of
aryl triflates and alkyl vinyl ethers. To the best of our know-
ledge this constitutes the first Ni-catalyzed Heck reaction of aryl
substrates proceeding under mild reaction conditions competi-
tive to those of the corresponding Pd-catalyzed Heck reaction.
Furthermore, mechanistic insight is provided based on DFT
calculations supporting the cationic nickel(II) complex as the
key intermediate.
Scheme 1. Examples of Previously Reported Nickel-
Catalyzed Heck Reactions
in order to regenerate the catalyst and complete the catalytic
cycle.
RESULTS AND DISCUSSION
Jamison and co-workers recently reported a protocol
describing the nickel-catalyzed vinylation of allylic ethers and
carbonates producing 1,4-dienes at ambient temperature
(Scheme 2).21 The underlying mechanism was proposed to
proceed through an operational β-hydride elimination reaction
from a cationic nickel(II) complex forming a cationic hydrido-
nickel(II) intermediate. Subsequent base induced reductive
elimination then regenerated the catalyst. Trimethylsilyl
trifluoromethanesulfonate (TESOTf) was added to the reaction
mixture in order to secure the formation of the cationic nickel-
(II) intermediate, abstracting the alkoxylate from the nickel
nucleus and leaving the poorly coordinating triflate counterion
behind. Noteworthy, the reaction proceeded smoothly without
the need of ionic liquids, high temperatures, or strong base,
which could imply that the cationic nickel(II) intermediate is of
utmost importance.
Traditionally, aryl and vinyl triflates have been used in the
regioselective palladium-catalyzed Heck reaction of electron-
rich olefins, facilitated by a cationic pathway, forming the α-
substituted alkenes.22 In this regard, bidentate ligands, such as
bisphosphines, are typically employed in order to secure an
effective generation of the cationic palladium(II) center responsible
for the formation of the branched α-substituted olefins. On the
other hand, monodentate phosphines tend to produce mixtures
of both isomers as the competing neutral pathway then will
operate.23 The generation of the central cationic palladium(II)
intermediate is, on the other hand, considerably hampered when
introducing the halide equivalents. Consequently, mixtures of
both regioisomers are often encountered, and certain require-
ments to the catalytic system are therefore needed.24 Besides
employing bidentate phosphine ligands, the choice of solvent
may induce a dramatic impact on the regioselective outcome of
the reaction. Hence, highly polar solvents or ionic liquids favor-
ing the cationic pathway have efficiently been applied in the
α-arylation of electron-rich olefins using aryl halides, as reported
by the groups of Xiao, Larhed, and Hallberg.25 Alternatively,
silver- or thallium-based halide scavengers can be used.26
■
A catalytic system derived from Ni(COD)2 and a bidentate
phosphine ligand in combination with a tertiary amine base
(Cy2NMe) was envisioned to be a suitable starting point in
the coupling of 4-biphenyl triflate 1 and butyl vinyl ether.29
Preliminry screenings revealed that this was indeed possible
(Table 1). Conducting the reaction in dioxane at 100 °C for
approximately 20 h resulted in a 21% conversion using 1,2-
bis(diphenylphosphino)ethane (DPPE) as the ligand (entry 1).
Increasing the bite angle of the bisphosphine facilitated the
desired reaction to a greater extent (entries 2 and 3).30 Gratify-
ingly, full conversion was obtained when 1,1′-bis(diphenylphos-
phino)ferrocene (DPPF) was employed, and a 90% isolated
yield of 4-phenylacetophenone 2 could be secured after hydro-
lysis of the initially formed α-arylated butyl vinyl ether (entry 4).
Changing to solvents such as toluene or THF proved less
effective compared to dioxane (entries 5 and 6). However,
applying diglyme as the solvent restored the high catalytic
outcome forming the α-substituted vinyl ether selectively in
a 90% isolated yield (entry 7). Catalytic systems carrying
more bulky and electron-donating ligands did not provide any
detectable amounts of the desired product (entries 8―11).
Applying monodentate phosphine ligands, which have demon-
strated to be of high value in other coupling reactions, turned
out to be nonproductive (entries 12 and 13).31 Different amine
bases were then evaluated. Diisopropylethylamine (DIPEA)
and triethylamine, often used in palladium-catalyzed Heck reac-
tion, were inferior compared to Cy2NMe (entries 14 and 15).
On the other hand, no reaction was observed when changing
the base to pyridine or increasing the basicity, as in the case of
DBU (entries 16 and 17). A significant drop in the reaction
turnover was observed when lowering the reaction temperature
to 80 °C. Moreover, changing the catalyst precursor to Ni-
(acac)2 resulted in no reaction (results not shown).
With these optimized conditions in hand, we set forth to
investigate the generality of this reaction. A variety of aryl tri-
flates were synthesized using standard procedures and evaluated
Scheme 2. Nickel Catalyzed Allylic Substitutions of Simple Alkenes
444
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
a
Table 1. Screening the Nickel-Catalyzed Heck Reaction of 4-Biphenyl Triflate and Butyl Vinyl Ether
b
entry
ligand (mol %)
base
conversion (%)
1
2
DPPE (5)
DPPP (5)
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
DIPEA
21
46
3
BINAP (5)
DPPF (5)
42
4
100 (90)
c
5
DPPF (5)
66
d
6
DPPF (5)
80
e
7
DPPF (5)
100 (90)
8
PPF-tBu (5)
DiPrPF (5)
DtBuPF (5)
Xantphos (5)
PCy3HBF4 (10)
PPh3 (10)
<5
<5
<5
<5
<5
<5
76
69
<5
9
10
11
12
13
14
15
16
17
DPPF (5)
DPPF (5)
Et3N
DPPF (5)
pyridine
DBU
DPPF (5)
<5
a
b
c
Aryl triflate (0.15 mmol), butyl vinyl ether (0.6 mmol), base (0.45 mmol), and dioxane 1 mL at 100 °C for 20 h. Isolated yields. Toluene as
d
e
f
solvent. THF as solvent. Diglyme as solvent. (2R)-1-[(1R)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene.
g
h
1,1′-bis(diisopropylphosphino)ferrocene. 1,1′-Bis(di-tert-butylphosphino)ferrocene.
with butyl vinyl ether (Table 2).32 In general, good to excellent
yields of the desired aryl methyl ketones were obtained after
treating the resulting aryl vinyl ether with 6 M HCl at room
temperature for approximately 1 h. Aryl triflates containing
both electron-withdrawing and -donating groups performed
well under the applied reaction conditions. Functionalities, such
as esters, amides, cyano, diazo, and acetals, and trifluoromethyl
groups were allowed, paralleling the functional group tolerance
observed in the analogous palladium-catalyzed Heck reaction
(entries 4−13). Furthermore, acetylation of biological relevant
structures represented by carbazole,33 eugenol,34 isoeugenol,34
and coumarin35 were successfully achieved attaining near quan-
titative yields (entries 14−17). Interestingly, isomerization of
the allyl double bond in the coupling of eugenol triflate was
identified generating mixtures of the conjugated cis- and trans-
adducts along with the nonisomerized ketone product (entry 16).
Potentially, this could be explained by a long-lived nickel
hydride complex responsible for a consecutive hydronickelation
and β-hydride elimination forming the thermodynamically
more stable styrene derivative.36 Somewhat lower yields were
obtained in some cases, when electron-donating groups were
positioned para to the triflate or ortho-substituents were intro-
duced on the aromatic ring (entries 3 and 7−9). However, a
slight increase in the catalytic loading restored the high levels of
the synthetically useful outcome. Even heteroaromatic systems,
such as quinolines, turned out to be adaptable to the optimized
reaction conditions resulting in a 56% isolated yield of the hete-
roaryl ketone after hydrolysis (entry 18). Finally, an example
with a vinyl triflate (entry 19) proved also effective for these
Ni-catalyzed transformations. The coupling yield for this sub-
strate was nevertheless lower than that obtained for the corres-
ponding aromatic counterpart (entry 2).
in-depth study of the mechanistic details was desired. In order
to investigate the role of the leaving group, aryl sulfonates with
different electronic properties were prepared from 2-naphthol
and various arylsulfonyl chloride derivatives using known pro-
cedures (Table 3).28 Relying on the optimized reaction condi-
tions, the coupling between 2-naphthyl benzenesulfonate and
butyl vinyl ether resulted in a 68% conversion (entry 1). Mixtures
of regioisomers were obtained, suggesting that both the neutral
and the cationic pathway are operating (entry 1). A slight increase
in the electron density impeded the reaction, as illustrated by the
reaction of 2-naphthyl tosylate (entry 2). In contrast, electron-
withdrawing substituents, such as the trifluoromethyl group,
favored the nickel-catalyzed Heck coupling although mixtures
of regioisomers were again observed (entries 3 and 4). On the
other hand, employing pentafluorophenyl sulfonate as the leaving
group provided a clean reaction, generating the α-substituted
butyl vinyl ether selectively, and a 91% yield of the corresponding
2-acetonaphthone 3 could be secured (entry 5). Reduced catalytic
activity was observed, when a nitro group was introduced on the
arylsulfonate (entries 6 and 7).
Furthermore, halide additives, such as LiCl and TBAB, com-
pletely inhibited the reaction presumably due to the trapping of
the cationic nickel(II) complex, hence occupying the vacant site
on the nickel nucleus and thereby preventing the β-hydride
elimination step (results not shown).25a,37,38
Next, different olefins were tested in the coupling of 4-
biphenyl triflate (Table 4). Introducing an isobutyl side chain
on the vinyl ether did not affect the catalytic efficiency forming
the 4-phenyl acetophenone in excellent yields after hydrolysis
(entry 1). Employing a sterically encumbered vinyl ether or the
cyclic olefin 2,3-dihydrofuran, traditionally used in the enantio-
selective Heck reaction, lowered the yield dramatically (entries
2 and 3). Moreover, essentially no reaction was obtained in the
coupling of N-vinyl acetamide, N-vinyl 2-pyrrolidone, and vinyl
Having established an efficient catalytic system for the nickel-
catalyzed Heck reaction with an electron-rich olefin, a more
445
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
a
Table 2. Nickel-Catalyzed Heck Reaction of Aryl Triflates and Butyl Vinyl Ether
a
Aryl triflate (0.5 mmol), butyl vinyl ether (2.0 mmol), Cy2NMe (1.5 mmol), DPPF (5 mol %), and Ni(COD)2 (5 mol %) in dioxane 3 mL at
b
c
d
100 °C for 20 h. Isolated yields. DPPF (7 mol %) and Ni(COD)2 (7 mol %). A 7:10:2 mixture (E:Z:allyl) was obtained.
acetate (entries 4−6). Possibly, coordination of the amide/ester
carbonyl group to the empty site on the metal center could
potentially account for the lack of reactivity.39 The cationic
alkylnickel(II) complex formed after the olefin insertion, which
is electron deficient and unsaturated, could therefore be stabi-
lized and thus become reluctant to undergo β-hydride elimina-
tion (Scheme 3).
Finally, the couplings of ethyl vinyl sulfide and allyltrime-
thylsilane failed most likely due to catalyst poisoning by the
sulfide and lack of nucleophilicity displayed by the less electron-
rich allyltrimethylsilane (entries 7 and 8).25a,40
These results clearly demonstrate vinyl ethers to be the most
suitable olefins in the nickel-catalyzed Heck reaction, con-
trasting the results obtained in the palladium-catalyzed Heck
reactions of 2-pyridyl tosylates, in which N-vinyl acetamides
were found to be considerably more reactive.28 Hence, a com-
petition experiment was set up adding a 1:1 mixture of butyl
vinyl ether and N-vinyl acetamide to a mixture of 4-biphenyl
triflate and the DPPF ligated nickel catalyst in combination
with Cy2NMe (Scheme 4). Only traces of the two possible
1,1-disubstituted alkenes were detected, implying that the
nickel catalyst is truly obstructed by N-vinyl acetamide.
The results presented in Tables 2−4 suggest an unsaturated
cationic nickel(II) intermediate to be essential in order to achieve
successful coupling. In particular, the reductive elimination in
transition metal catalysis has been shown to be influenced by a
number of factors, including the electronic properties of the metal
center and the steric effects of the chelating ligands.1a For
instance, electron poor transition-metal complexes tend to be
more prone to facilitate the reductive elimination in contrast to
metal complexes with high electron densities.41 Furthermore,
Brown and co-workers have demonstrated that the bite angle of
bidentate ligands has a great impact on this catalyst recovering
step, whereby an increase in the rate of reductive elimination is
observed with increasing bite angles of the ligand.42 Thus, the
electron deficient nature of the cationic hydridonickel inter-
mediate and the bite angle of the bidentate ligand could possibly
account for a more favorable β-hydride elimination and reductive
elimination observed in this work, thereby representing a new
strategy in the nickel-catalyzed Heck reaction.
446
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
Scheme 3. Nickel-Catalyzed Allylic Substitutions of Simple
Alkenes
Table 3. Nickel-Catalyzed Heck Reaction of 2-Naphthyl
Sulfonates and Butyl Vinyl Ether
a
Experimentally, DPPF is better, but the difference is not large
enough to motivate the substantial computational resources needed
to add a ferrocene moiety to the already large computational
model. Phenyl triflate and ethyl vinyl ether were used as model
substrates (Figure 1). The bisphosphine nickel(0) complex
coordinating to the phenyl triflate prior to the oxidative addition
(complex I) was selected as the starting point of the computa-
tional cycle. Reaction profiles are calculated from free energies,
with dotted lines representing alternative paths that are excluded
because of high barriers and dotted curves represent ligand
exchange that could be either dissociative or associative, where
the former can be monotonous processes on the potential energy
surface (see Computational Details for further information).
The oxidative addition of phenyl triflate to the nickel(0)
complex resulting in the bisphosphine phenylnickel(II) triflate
complex II was found to be highly exergonic (−131 kJ mol−1)
with an activation barrier of 15 kJ mol−1 (Figure 1). The ex-
change of the weakly coordinating triflate anion forming the
cationic nickel(II) complex III coordinated by the ethyl vinyl
ether revealed itself slightly more stable than the parent neutral
nickel(II) complex II. The regioselective outcome of the reac-
tion is determined in the subsequent carbonickelation of the
olefin forming the α- or β-substituted alkene via TS-b and TS-c,
respectively (Figure 2). However, under the applied reaction
conditions the primary alkylnickel(II) complex TS-b leading to
the branched α-arylated alkene was strongly favored over the
secondary alkylnickel(II) species TS-c by 20 kJ mol−1, resulting
in less than 0.1% of the linear product, in good agreement with
the results observed experimentally.
a
Aryl sulfonate (0.15 mmol), butyl vinyl ether (0.60 mmol), Cy2NMe
(0.45 mmol), DPPF (5 mol %), and Ni(COD)2 (5 mol %) dioxane 1
mL at 100 °C for 20 h. Isolated yields. Mixtures of regioisomers
were observed.
b
c
Table 4. Nickel Catalyzed Heck Reaction of 4-Biphenyl
Triflate and Various Olefins
a
Displacement of the coordinated phenyl group in complex
IV with the oxygen moiety via a rotation of the C−C bond
was found to proceed with a barrier of 18 kJ mol−1 compared to
31 kJ mol−1, leading to the agostic complex through TS-e. The
generation of the kinetically favored oxygen coordinated cationic
alkylnickel(II) complex V represents the most stable complex
obtained after olefin insertion with a free energy 37 kJ mol−1
below that of complex IV. The formation of the agostic nickel-
(II) complex VI by a consecutive rotation of the C−C bond in
V proved to be a demanding process, with a barrier of 68 kJ
mol−1 (Figure 3). Interestingly, this C−C bond rotation TS-f
demonstrated to be of higher energy than the following β-hydride
elimination via TS-g in accordance to the observations reported by
Norrby and co-workers in the palladium-catalyzed Heck reaction.43
The cationic nickel(II) hydride complex VII then undergoes a
base induced reductive elimination TS-h regenerating the nickel(0)
catalyst coordinated by the α-arylated vinyl ether product VIII.
The barrier for this process was calculated to be 47 kJ mol−1
using the computationally more simplistic trimethyl amine as a
model base compared to Cy2NMe. Several different base promoted
hydrogen abstractions were investigated, including the reductive
elimination from an amine coordinated hydridonickel(II) com-
plex.29 However, none of these were found to be more efficient
than the bimolecular process depicted as TS-h in Figure 3.
Endergonic ligand exchange (30 kJ mol−1) substituting the olefinic
product with another phenyl triflate completes the catalytic cycle.
a
Aryl triflate (0.5 mmol), olefin (2.0 mmol), Cy2NMe (1.5 mmol),
DPPF (5 mol %), and Ni(COD)2 (5 mol %) dioxane 3 mL at 100 °C
for 20 h. Isolated yields.
b
DFT STUDIES
■
In order to examine the influence of the intermediary cationic
nickel(II) complexes on the elementary reactions constituting
the catalytic cycle, a DFT study was performed. For compu-
tational efficiency, the catalytically competent ligand 1,3-bis-
(diphenylphosphino)propane (DPPP) was used in the calculations.
447
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
Scheme 4. Competition Experiment Between Butyl Vinyl Ether and N-Vinyl Acetamide
Figure 1. Oxidative addition and ligand exchange.
Figure 3. β-Hydride elimination and reductive elimination.
sible since TS-c is higher in energy than TS-h.44 On the other
hand, the β-hydride elimination and catalyst regeneration were
both found to be endergonic and thus constitute the most
demanding step with an overall barrier of 87 kJ mol−1 through
TS-h. These findings parallel the calculations performed by
Guo and co-workers suggesting the reductive elimination to be
the rate-determining step in the nickel-catalyzed Heck reaction.19
The highly exergonic oxidative addition ensures the total lower-
ing in the energy facilitating the consecutive catalytic cycle.
On the other hand, impeded reaction rates could possibly be
encountered if any of the other potential resting states includ-
ing complex II obtained after the oxidative addition were signi-
ficantly stabilized (Figure 1). During the investigations on the
influence of the leaving group, a detrimental effect of added
halides to the reaction mixture was observed. This effect was
proposed to originate from the trapping of the crucial cationic
nickel(II) intermediate blocking the vacant site mandatory in
order to facilitate the olefin coordination.38 Consequently, calcu-
lations regarding the dissociation of a bromide anion from the
nickel(II) center were conducted (Scheme 5).
The presence of bromide anions proved to stabilize the
neutral nickel(II) complex considerably by a free energy of
69 kJ mol−1 compared to complex II which would result in a
carbonickelation barrier corresponding to 132 kJ mol−1, essen-
tially preventing further reaction.
Performing the nickel-catalyzed Heck reaction with olefins
containing carbonyl groups, such as N-vinylacetamide, afforded
the desired product only to a limited extent (Table 4). The
potential coordination of the carbonyl oxygen to the electron
deficient cationic nickel(II) intermediate was suggested to ob-
struct the β-hydride elimination. Hence, DFT calculations were
Figure 2. Carbonickelation and chelation.
From the simplified overall catalytic cycle depicted in Figure 4,
two transition states can be identified as effectively irreversible
(TS-a and TS-h), as they are higher than any subsequent point
on the global free energy surface. The resting state of the
nickel-catalyzed Heck reaction can be identified as the alkyl-
nickel(II) complex V generated after the migratory insertion,
which would imply that the migratory insertion can be rever-
sible. However, the alternative reaction pathway forming a
terminal alkylnickel(II) complex is still energetically inacces-
448
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
Figure 4. Simplified free energy surface of two sequential catalytic cycles.
Scheme 5. Nickel(II) Bromide and Triflate Complexes
calculations supported this assumption, revealing the cationic
nickel intermediates to be of utmost importance.45
EXPERIMENTAL SECTION
■
General Methods. All reactions were carried out in 7.0 mL
sample vials with a Teflon-sealed screwcap in a glovebox under an
argon atmosphere. All purchased chemicals were used as received
without further purification. Solvents were dried according to standard
procedures, reactions were monitored by thin-layer chromatography
analysis, and flash chromatography was carried out on silica gel 60
(230−400 mesh). The chemical shifts are reported in ppm relative to
solvent residual peak.46 The 1H NMR spectra were recorded at
400 MHz, 13C NMR spectra were recorded at 100 MHz, and 19F
NMR spectra were recorded at 376 MHz on a Varian Mercury 400
spectrometer (see Supporting Information). MS spectra were recorded
on a LC TOF (ES) apparatus. The aryl triflates were synthesized
according to known procedures.47 The aryl sulfonates depicted in
Table 3 were prepared using known procedures.48
Scheme 6. Coordination of Carbonyl Oxygen
commissioned in order to evaluate the coordinating abilities of
the carbonyl moiety (Scheme 6).
7-Acetyl-2H-chromen-2-one (Table 2, entry 17). In dioxane
(3 mL), 2-Oxo-2H-chromen-7-yl triflate (0.5 mmol), DPPF (5 mol %),
Cy2NMe (1.5 mmol), vinyl ether (2.0 mmol), and Ni(COD)2
(5 mol %) were dissolved, and the sample vial was fitted with a
Teflon-sealed screwcap and removed from the glovebox. The reaction
mixture was stirred at 100 °C for 20 h. Hydrolysis was performed adding 6
M HCl (3 mL) to the reaction mixture and stirred at room temperature
for 1 h. Diethyl ether was added, and the crude reaction mixture was
washed twice with water and once with brine, dried over anhydrous
MgSO4, and filtrated. Flash chromatography using diethyl ether:-
pentane:CH2Cl2 2:2:1 as eluent resulting in 73.0 mg (78% yield) of the
title product obtained as a colorless solid. 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.82−7.79 (m, 2H), 7.73 (d, 1H, J = 9.5 Hz), 7.56 (d, 1H, J = 7.9
Hz), 6.48 (d, 1H, J = 9.5 Hz), 2.61 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ (ppm) 196.5, 160.1, 153.9, 142.5, 139.3, 128.3, 122.2, 118.9, 116.7, 26.9.
HRMS C11H18O3 [M + Na+]: calculated 211.0371; found 211.0366.
The transition state for the β-hydride elimination from the
cyclic cationic alkylnickel(II) complex X was located with a free
energy barrier of 94 kJ mol−1 compared to 68 kJ mol−1 (from
V−VII, Figure 4), accounting for the poor catalytic outcome
observed using carbonyl containing olefins.
CONCLUSION
■
In summary, a new efficient strategy for the nickel-catalyzed
Heck reaction of aryl triflates and vinyl ethers has been pre-
sented. The mild reaction conditions applied allow the presence
of a wide range of functional groups complementing the palla-
dium based analogous. This approach represents a more sus-
tainable and less costly alternative for the vinylation of aromatic
compounds. The high catalytic activity was attributed to the
formation of a crucial cationic nickel complex formed during
the catalytic cycle being responsible for a favorable β-hydride
elimination step and subsequent reductive elimination. DFT
COMPUTATIONAL DETAILS
■
The calculations were performed using Jaguar, version 7.6,49
employing the B3LYP hybrid functional50 with the LACVP* basis
449
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
set, which uses an effective core potential51 for Pd and 6-31G* for
all other atoms. All geometries were optimized in the gas phase with
a subsequent single-point energy calculation in the solution phase,
utilizing the PBF solvation model52 with parameters suitable for THF
(ε = 7.6, probe radius =2.52 Å), which is a competent solvent for the
title reaction and computationally more feasible than the experimen-
tally preferred dioxane. Vibrational analysis was performed for the
optimized geometries in the gas phase, and the free energies for the
geometries were calculated by adding the thermodynamic contribution
at 298.15 K to the solution phase energy. Dispersion corrections were
calculated using the DFT-D3 program53 and added to obtain the final
energies. The transition states in the lowest free energy path on the
potential energy surface were determined to be connected to their
corresponding reactants and products via geometry optimization in the
forward and backward direction from the transition state. All transition
states presented have exactly one imaginary frequency, and the sta-
tionary minima have no imaginary frequencies.
M. J. Am. Chem. Soc. 2009, 131, 11949. (d) Ishizuka, K.; Seike, H.;
Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2010, 132, 13117.
(e) Lohre, C.; Droge, T.; Wang, C.; Glorius, F. Chem.Eur. J. 2011,
̈
17, 6052. (f) Molander, G. A.; Beaumard, F. Org. Lett. 2010, 12, 4022.
(g) Ackermann, L.; Sandmann, R.; Song, W. Org. Lett. 2011, 13, 1784.
(h) Joshi-Pangu, A.; Ganesh, M.; Biscoe, M. R. Org. Lett. 2011, 13,
1218. (i) Molander, G. A.; Argintaru, O. A.; Aron, I.; Dreher, S. D.
Org. Lett. 2010, 12, 5783. For reviews see: (j) Rudolph, A.; Lautens,
M. Angew. Chem., Int. Ed. 2009, 48, 2656. (k) Jana, R.; Pathak, T. P.;
Sigman, M. S. Chem. Rev. 2011, 111, 1417.
(5) For some selected papers on nickel-catalyzed cycloisomerizations
see: (a) Takachi, M.; Kita, Y.; Tobisu, M.; Fukumoto, Y.; Chatani, N.
Angew. Chem., Int. Ed. 2010, 49, 8717. (b) Phillips, J. H.; Montgomery,
J. Org. Lett. 2010, 12, 4556. (c) Takachi, M.; Chatani, N. Org. Lett.
2010, 12, 5132. (d) Chen, M.; Weng, Y.; Guo, M.; Zhang, H.; Lei, A.
Angew. Chem., Int. Ed. 2008, 47, 2279. (e) Boing, C.; Hahne, J.;
̈
́
Francio, G.; Leitner, W. Adv. Synth. Catal. 2008, 350, 1073. For a review
see: Montgomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890.
ASSOCIATED CONTENT
(6) For some selected papers on nickel-catalyzed cycloadditions see:
(a) Koyama, I.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2009,
131, 1350. (b) Kumr, P.; Troast, D. M.; Cella, R.; Louie, J. J. Am.
Chem. Soc. 2011, 133, 7719. (c) Ogoshi, S.; Nishimura, A.; Ohashi, M.
Org. Lett. 2010, 12, 3450. (d) Qui, Z.; Wang, S. R.; Xie, Z. Angew.
Chem., Int. Ed. 2010, 49, 4649. (e) Saya, L.; Bhargava, G.; Navarro,
■
S
* Supporting Information
Experimental details and copies of H NMR and 13C NMR
1
spectra for all the coupling products. This material is available
free of charge via the Internet at http://pubs.acs.org.
́ ́
M. A.; Gulías, M.; Lopez, F.; Fernandez, I.; Castedo, L.; Mascarenas,
̃
AUTHOR INFORMATION
Corresponding Author
pon@chem.gu.se; ts@chem.au.dk
■
J. L. Angew. Chem., Int. Ed. 2010, 49, 9886. Miura, T.; Morimoto, M.;
Murakami, M. J. Am. Chem. Soc. 2010, 132, 15836.
(7) For some selected papers on nickel-catalyzed multicomponent
reactions see: (a) Yang, C. −M.; Jeganmohan, M.; Parthasarathy, K.;
Cheng, C.-H. Org. Lett. 2010, 12, 3610. (b) Ogata, K.; Atsuumi, Y.;
Fukuzawa, S. Org. Lett. 2010, 12, 4536. (c) Ogata, K.; Sugasawa, J.;
Atsuumi, Y.; Fukuzawa, S. Org. Lett. 2010, 12, 148. (d) Namitharan,
K.; Pitchumani, K. Eur. J. Org. Chem. 2010, 411.
(8) For some selected papers on nickel-catalyzed annulations see:
(a) Auvinet, A.-L.; Harrity, J. P. A Angew. Chem., Int. Ed. 2011, 50,
2769. (b) Kajita, Y.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc.
2008, 130, 17226. (c) Yoshino, Y.; Kurahashi, T.; Matsubara, S. J. Am.
Chem. Soc. 2009, 131, 7494. (d) Yamauchi, M.; Morimoto, M.; Miura,
T.; Murakami, M. J. Am. Chem. Soc. 2010, 132, 54. (e) Inami, T.; Baba,
Y.; Kurahashi, T.; Matsubara, M. Org. Lett. 2011, 13, 1912.
(9) For some selected papers on nickel-catalyzed reductive couplings
see: (a) Molinaro, C.; Montgomery, T. F. J. Am. Chem. Soc. 2003, 125,
8076. (b) Zhou, C.−Y.; Zhu, S.−F.; Wang, L.−X.; Zhou, X.−L. J. Am.
Chem. Soc. 2010, 132, 10955. (c) Li, W.; Chen, N.; Montgomery, J.
Angew. Chem., Int. Ed. 2010, 49, 8712. (d) Yang, Y.; Zhu, S.-F.; Duan,
H.-F.; Zhou, C.-Y.; Wang, L.-X.; Zhou, X.-L. J. Am. Chem. Soc. 2007,
129, 2248. (e) Moslin, R. M.; Jamison, T. F. Org. Lett. 2006, 8, 455.
(10) For some recent miscellaneous papers on nickel-catalyzed
reactions see: (a) Everson, D. A.; Shrestha, R.; Weix, D. J. J. Am.
Chem. Soc. 2010, 132, 920. (b) Hirata, Y.; Yada, A.; Morita, E.; Nakao,
Y.; Hiyama, T.; Ohashi, M.; Ogoshi, S. J. Am. Chem. Soc. 2010, 132,
10070. (c) Taniguchi, H.; Ohmura, T.; Suginome, M. J. Am. Chem. Soc.
2009, 131, 11298. (d) Mukai, T.; Hirano, K.; Satoh, T.; Miura, M.
J. Org. Chem. 2009, 74, 6410. (e) Nakao, Y.; Kashihara, N.; Kanyiva, K.
S.; Hiyama, T. Angew. Chem., Int. Ed. 2010, 49, 4451. (f) Nakao, Y.;
Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am. Chem. Soc. 2010, 132,
13666. (g) Tsai, C.-C.; Shih, W.-C.; Fang, C.-H.; Li, C.-Y.; Ong,
T. −G.; Yap, G. P. A J. Am. Chem. Soc. 2010, 132, 11887.
ACKNOWLEDGMENTS
■
We thank the Danish National Research Foundation, the
Lundbeck Foundation, the Carlsberg Foundation, the iNANO
and OChem Graduate Schools, and Aarhus University for
generous financial support of this work
REFERENCES
■
(1) (a) Hartwig, J. F. In Organotransition Metal Chemistry: From
Bonding to Catalysis; University Science Books: Herndon, VA , 2010.
(b) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
(c) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. 1994, 33, 2379.
(d) Loiseleur, O.; Meier, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1996, 35,
200. (e) Drury, W. J. III; Zimmermann, N.; Keenan, M.; Hayashi, M.;
Kaiser, S.; Goddard, R.; Pfaltz, A. Angew. Chem., Int. Ed. 2004, 43, 70.
́ ́
(f) Mata, Y.; Dieguez, M.; Pamies, O.; Claver, C. Org. Lett. 2005, 7,
5597. (g) Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54,
4738. (h) Carpenter, N. E.; Kucera, D. J; Overman, L. E. J. Org. Chem.
1989, 54, 5846. (i) Wu, W.−Q.; Peng, Q.; Dong, D.−X.; Hou, X.−L.;
Wu, Y.−D J. Am. Chem. Soc. 2008, 130, 9717.
(2) For some recent papers on applications and mechanistic studies
regarding the palladium catalyzed Heck reaction see: (a) Carrow,
B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 79. (b) Wu, X.−F.;
Neumann, H.; Spannenberg, A.; Schulz, T.; Jiao, H.; Beller, M. J. Am.
Chem. Soc. 2010, 132, 14596. (c) Hermange, P.; Gøgsig, T. M.;
Lindhardt, A. T.; Taaning, R. H.; Skrydstrup, T. Org. Lett. 2011, 13,
2444. (d) Stone, M. T. Org. Lett. 2011, 13, 2326. (e) Delcamp, J. H.;
Brucks, A. P.; White, M. C. J. Am. Chem. Soc. 2008, 130, 11270.
(f) Surawatanawong, P.; Hall, M. B. Organometallics 2008, 27, 6222.
(3) For selected papers on cobalt-catalyzed Heck reactions see:
(a) Shukla, P.; Hsu, Y.−C.; Cheng, C.−H. J. Org. Chem. 2006, 71, 655.
(b) Affo, W.; Ohmiya, H.; Fujioka, T.; Ikeda, Y.; Nakamura, T.;
Yorimitsu, H.; Oshima, K.; Imamura, Y.; Mizuta, T.; Miyoshi, K. J. Am.
Chem. Soc. 2006, 128, 8068. (c) Ikeda, Y.; Nakamura, T.; Yorimitsu,
H.; Oshima, K. J. Am. Chem. Soc. 2002, 124, 6514. (d) Fujioka, T.;
Nakamura, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4, 2257.
(4) For some recent papers on nickel-catalyzed cross couplings see:
(a) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2009,
131, 9590. (b) Xie, L.−G.; Wang, Z.−X. Angew. Chem, Int, Ed. 2011,
50, 4901. (c) Hatakeyama, T.; Hashimoto, S.; Ishizuka, K.; Nakamura,
(11) For some selected papers on ethers as coupling partners see:
(a) Sergeev, A. G.; Hartwig, J. F. Science 2011, 332, 439. (b) Taylor, B.
L. H.; Swift, E. C.; Waetzig, J. D.; Jarvo, E. R. J. Am. Chem. Soc. 2011,
133, 389. (c) Shimasaki, T.; Konno, Y.; Tobisu, M.; Chatani, N. Org.
Lett. 2009, 11, 4890. (d) Guan, B. −T.; Xiang, S. −K.; Wang, B. −Q.;
Sun, Z. −P.; Wang, Y.; Zhao, K. −Q.; Shi, Z. −J. J. Am. Chem. Soc.
2008, 130, 3268. (e) Tobisu, M.; Shimasaki, T.; Chatani, N. Angew.
́
Chem., Int. Ed. 2008, 47, 4866. (f) Alvarez-Bercedo, P.; Martin, R.
J. Am. Chem. Soc. 2010, 132, 17352.
(12) Yu, D.-G.; Li, B.-J.; Zheng, S.-F.; Guan, B.-T.; Wang, B.−Q.; Shi,
Z.-J. Angew. Chem., Int. Ed. 2010, 49, 4566.
450
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
(13) For some selected papers on carboxylates as coupling partners
see: (a) Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008,
130, 14422. (b) Li, B.-J.; Li, Y.-Z.; Lu, X.-Y.; Liu, J.; Guan, B.-T.; Shi,
Z.-J. Angew. Chem., Int. Ed. 2008, 47, 10124. (c) Shimasaki, T.; Tobisu,
M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929.
(14) For some selected papers on carbamates as coupling partners
see: (a) Antoft-Finch, A.; Blackburn, T.; Snieckus, V. J. Am. Chem. Soc.
2009, 131, 17750. (b) Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.;
Silberstein, A. L.; Komaromi, A.; Blackburn, T.; Ramgren, S. D.; Houk,
K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352.
(c) Huang, K.; Yu, D.−G.; Zheng, S.−F.; Wu, Z.−H.; Shi, Z.−J.
Chem.Eur. J. 2011, 17, 786. (d) Baghbanzadeh, M.; Pilger, C.;
Kappe, C. O. J. Org. Chem. 2011, 76, 1507. (e) Xu, L.; Li, B.−J.; Wu,
Z.−H.; Lu, X.−Y.; Guan, B.−T.; Wang, B.−Q.; Zhao, K.−Q.; Shi,
Z.−J. Org. Lett. 2010, 12, 884.
(15) Reviews on C−O coupling partners see: (a) Li, B.−J.; Yu,
D.−G.; Sun, C.−L.; Shi, Z.−J. Chem.Eur. J. 2011, 17, 1728.
(b) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.−M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346.
(16) For some selected papers see: (a) Zhou, J.; Fu, G. C. J. Am.
Chem. Soc. 2004, 126, 1340. (b) Strotman, N. A.; Sommer, S.; Fu,
G. C. Angew. Chem., Int. Ed. 2007, 46, 3556. (c) Terao, J.; Watanabe,
H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2002, 124,
4222. (d) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem.
Soc. 2003, 125, 5646. (e) Jensen, A. E.; Knochel, P. J. Org. Chem. 2002,
67, 79. For a review see: Frisch, A. C.; Beller, M. Angew. Chem., Int.
Ed. 2005, 44, 674.
(17) For some recent enantioselective protocols see: (a) Lu, Z.;
Wilsily, A; Fu, G. C. J. Am. Chem. Soc. 2011, 133, 8154. (b) Owston,
N. A.; Fu, G. C. J. Am. Chem. Soc. 2010, 132, 11908. (c) Lou, S.; Fu,
G. C. J. Am. Chem. Soc. 2010, 132, 5010. (d) Smith, S. W.; Fu, G. C.
J. Am. Chem. Soc. 2008, 130, 12645. (e) Saito, B.; Fu, G. C. J. Am.
Chem. Soc. 2008, 130, 6694. For a review see: Glorius, F. Angew.
Chem., Int. Ed. 2008, 47, 8347.
495. (d) Datta, G. K.; von Schenk, H.; Hallberg, A.; Larhed, M. J. Org.
Chem. 2006, 71, 3896. (e) Carrow, B. P.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 79. (f) Amatore, C.; Godin, B.; Jutand, A.; Lemaître, F.
Organometallics 2007, 26, 1757. (g) Nilsson Lill, S. O.; Ryberg, P.;
Rein, T.; Bennstrom, E.; Norrby, P.-O. Chem.Eur. J. 2011, in press.
̈
(25) (a) Mo, J.; Xu, L.; Xiao, J. J. Am. Chem. Soc. 2005, 127, 751.
(b) Ruan, J.; Iggo, J. A.; Berry, N. G.; Xiao, J. J. Am. Chem. Soc. 2010,
132, 16689. (c) Arvela, R. K.; Pasquini, S.; Larhed, M. J. Org. Chem.
2007, 72, 6390. (d) Vallin, K. S. A.; Larhed, M.; Hallberg, A. J. Org.
Chem. 2001, 66, 4340.
(26) (a) Sonesson, C.; Larhed, M.; Nyqvist, C.; Hallberg, A. J. Org.
Chem. 1996, 61, 4756. (b) Vallin, K. S. A.; Larhed, M.; Johansson, K.;
Hallberg, A. J. Org. Chem. 2000, 65, 4537.
(27) Hansen, A. L.; Skrydstrup, T. Org. Lett. 2005, 7, 5585.
(28) Gøgsig, T. M.; Lindhardt, A. T.; Dekhane, M.; Grouleff, J.;
Skrydstrup, T. Chem.Eur. J. 2009, 15, 5950.
(29) (a) Gurtler, C.; Buchwald, S. L. Chem. Eur. J. 1999, 5, 3107.
̈
(b) Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 13178.
́
(30) For a review on bite angle effects see: Birkholz (nee Gensow,
M.-N.; Freixa, Z.; van Leeuwen, P. W. N. M. Chem. Soc. Rev. 2009, 38,
1099.
(31) PCy3 has been employed with great success in a variety of cross
couplings see refs 10−15.
(32) (a) Jutand, A.; Mosleh, A. J. Org. Chem. 1997, 62, 261.
(b) Kwong, F. K.; Lai, C. W.; Chan, K. S. J. Am. Chem. Soc. 2001, 123,
8864.
(33) (a) Cho, S. H.; Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011, 133,
5996. (b) Tsvelikhovsky, D.; Buchwald, S. L. J. Am. Chem. Soc. 2010,
132, 14048. (c) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. J. Org.
Chem. 2009, 74, 4720.
(34) (a) Unno, T.; Kim, S.−J.; Kanaly, R. A.; Ahn, J.−H.; Kang,
S.−I.; Hur, H.−G. J. Agri. Food Chem. 2007, 55, 8556. (b) Bertrand, F.;
Basketter, D. A.; Roberts, D. W.; Lepoittevin, J.−P. Chem. Res. Toxicol.
1997, 10, 335.
(35) (a) Sarpietro, M. G.; Giuffrida, M. C.; Ottimo, S.; Micieli, D.;
Castelli, F. J. Nat. Prod. 2011, 74, 790. (b) Arango, V.; Robledo, S.;
Seon-Meniel, B.; Figadere, B.; Cardona, W.; Saez, J.; Otalvaro, F.
́ ́ ́ ́ ́
J. Nat. Prod. 2010, 73, 1012. (c) Jana, R.; Trivedi, R.; Tunge, J. A. Org.
Lett. 2009, 11, 3434.
(18) For Shell higher olefin process see: Weissermel, K.; Arpe, H.-J.
In Industrial Organic Chemistry, 3rd ed.; J. Wiley & Sons: Hoboken, NJ,
1997. For other Ni(II) facilitated β-hydride elimination: (a) Herath,
A.; Li, W.; Montgomery, J. J. Am. Chem. Soc. 2008, 130, 469. (b) Ng,
S.−S.; Ho, C.−Y.; Jamison, T. F. J. Am. Chem. Soc. 2006, 128, 11513.
(c) Ref 5b.
(36) Palladium catalyzed double bond isomerization has been re-
ported see: Gauthier, D.; Lindhardt, A. T.; Olsen, E. P. K.; Overgaard,
J.; Skrydstrup, T. J. Am. Chem. Soc. 2010, 132, 7998 and references
herein.
(37) It has been shown that ionic liquids in combination with high
temperatures and prolonged reaction times are mandatory in the
nickel-catalyzed Heck coupling of aryl bromides and butyl vinyl ether.
See ref 20g.
(38) Similar observations have been made by Xiao and coworkers in
the palladium-catalyzed Heck reaction of aryl bromides in ionic liquids
with added halides. See: Ruan, J.; Xiao, J. Acc. Chem. Res. 2011, 44,
614.
(39) Carbonyl ligated cationic palladium(II) and nickel(II)
complexes have been isolated and characterized see: (a) Curley, J.
J.; Kitiachvili, K. D.; Waterman, R.; Hillhouse, G. L. Organometallics
(19) DFT calculations have indicated that the β-hydride elimination
from nickel(II) complexes is slower compared to the palladium
analogue. In addition, the reductive elimination from the Ni−H
complex was found to be considerably more difficult than from the
corresponding Pd−H complex. See: Lin, B.−L.; Liu, L.; Fu, Y.; Luo,
S.−W.; Chen, Q.; Guo, Q.−X. Organometallics 2004, 23, 2114.
(20) For nickel-catalyzed Heck reactions see: (a) Wang, Z.-X.; Chai,
Z.-Y. Eur. J. Inorg. Chem. 2007, 4492. (b) Ma, S.; Wang, H.; Gao, K.;
Zhao, F. J. Mol. Catal. A Chem. 2006, 248, 17. (c) Bhanage, B. M.;
Zhao, F.; Shirai, M.; Arai, M. Catal. Lett. 1998, 54, 195. (d) Inamoto,
K.; Kuroda, J.; Hiroya, K.; Noda, Y.; Watanabe, M.; Sakamoto, T.
Organometallics 2006, 25, 3095. (e) Lin, P.−S.; Jeganmohan, M.;
Cheng, C.-H. Chem. Asian. J. 2007, 2, 1409. (f) Inamoto, K.; Kuroda,
J.; Danjo, T.; Sakamoto, T. Synlett 2005, 1624. (g) Sun, L.; Pei, W.;
Shen, C. J. Chem. Res. 2006, 388.
(21) Matsubara, R.; Jamison, T. F. J. Am. Chem. Soc. 2010, 132, 6880.
(22) (a) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
(b) Vallin, K. S. A.; Zhang, Q.; Larhed, M.; Curran, D. P.; Hallberg, A.
J. Org. Chem. 2003, 68, 6639. (c) Tu, T.; Hou, X.-L.; Dai, L.-X. Org.
Lett. 2003, 5, 3651. (d) Bengtson, A.; Larhed, M.; Hallberg, A. J. Org.
Chem. 2002, 67, 5854. (e) Hansen, A. L.; Skrydstrup, T. J. Org. Chem.
2005, 70, 5997.
2009, 28, 2568. (b) Vicente, J.; Abad, J. A.; Lop
́ ́
ez-Saez, M.-J. Organo-
metallics 2010, 29, 409.
(40) For regioselective Heck reactions employing allyltrimethylsilane
see: Olofsson, K.; Larhed, M.; Hallberg, A. J. Org. Chem. 1998, 63,
5076.
(41) (a) Hartwig., J. F. Inorg. Chem. 2007, 46, 1936. (b) Lanci, M. P.;
Remy, M. S.; Kaminsky, W.; Mayer, J. M.; Sanford, M. S. J. Am. Chem.
Soc. 2009, 131, 15618. (c) Furuya, T.; Benitez, D.; Tkatchouk, E.;
Strom, A. E.; Tang, P.; Goddard, W. A. III; Ritter, T. J. Am. Chem. Soc.
2010, 132, 3793.
(23) Cabri, W.; Candiani, I.; Bedeschi, A. J. Org. Chem. 1990, 55,
3655.
(24) For selected papers regarding the regioselectivity in Heck
reactions with electron-rich olefins, see: (a) Littke, A. F.; Fu, G. C.
J. Am. Chem. Soc. 2001, 123, 6989. (b) Littke, A. F.; Fu, G. C. Angew.
Chem., Int. Ed. 2002, 41, 4176. (c) Schnyder, A.; Aemmer, T.;
Indolese, A. F.; Pittelkow, U.; Studer, M. Adv. Synth. Catal. 2002, 344,
(42) Brown, J. M.; Guiry, P. J. Inorg. Chim. Acta 1994, 220, 249.
(43) Ambrogio, I.; Fabrizi, G.; Cacchi, S.; Henriksen, S. T.; Fristrup,
P.; Tanner, D.; Norrby, P.-O. Organometallics 2008, 27, 3187−3195.
(44) For a mathematically more complete analysis of free energy
profiles, see: Shaik, K. S. Acc. Chem. Res. 2011, 44, 101.
451
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452

Journal of the American Chemical Society
Article
(45) Jamison and coworkers have recently published their work on
the regioselective Ni-catalyzed Heck reaction of benzyl chlorides with
simple alkenes. As in their earlier work (ref 21), the addition of
triethylsilyl triflate is mandatory, suggesting the intermediacy of a
Ni(II) cationic intermediate. Matsubara, R.; Gutierrez, A. C.; Jamison,
T. F. J. Am. Chem. Soc. 2011, 133, 19020.
(46) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997,
62, 7512.
(47) Seganish, W. M.; DeShong, P. J. Org. Chem. 2004, 69, 1137.
(48) Kubota, Y.; Nakada, S.; Sugi, Y. Synlett 1998, 183.
(49) Jaguar, version 7.6; Schrodinger, LLC: New York, 2009.
̈
(50) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 1372. (b) Becke, A. D.
J. Chem. Phys. 1993, 98, 5648. (c) Lee, C.; Yang, W.; Parr, R. G. Phys.
Rev. B 1988, 37, 785.
(51) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
(52) (a) Marten, B.; Kim, K.; Cortis, C.; Friesner, R. A.; Murphy,
R. B.; Ringnalda, M. N.; Sitkoff, D.; Honig, B. J. Phys. Chem. 1996, 100,
11775. (b) Tannor, D. J.; Marten, B.; Murphy, R.; Friesner, R. A.;
Sitkoff, D.; Nicholls, A.; V, B.; Ringnalda, M.; Goddard, W. A. J. Am.
Chem. Soc. 1994, 116, 11875.
(53) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys.
2010, 132, 154104.
452
dx.doi.org/10.1021/ja2084509 | J. Am. Chem.Soc. 2012, 134, 443−452