Ruthenium-catalyzed ortho-selective C-H alkenylation of aromatic compounds with alkenyl esters and ethers

Article abstract of DOI:10.1021/om401204h

A direct, regioselective alkenylation of aromatic C-H bonds of aryl- and heteroarylpyridines and related compounds with alkenyl esters was developed using Ru(cod)(cot) as a catalyst. Aromatic compounds bearing electronically diverse substituents and vario

Full text of DOI:10.1021/om401204h

Article
pubs.acs.org/Organometallics
Ruthenium-Catalyzed Ortho-Selective C−H Alkenylation of Aromatic
Compounds with Alkenyl Esters and Ethers
Yohei Ogiwara,† Masaru Tamura,† Takuya Kochi,† Yusuke Matsuura,‡ Naoto Chatani,‡
and Fumitoshi Kakiuchi*,†
†Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa
223-8522, Japan
‡Department of Applied Chemistry, Faculty of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A direct, regioselective alkenylation of aromatic
C−H bonds of aryl- and heteroarylpyridines and related
compounds with alkenyl esters was developed using Ru(cod)-
(cot) as a catalyst. Aromatic compounds bearing electronically
diverse substituents and various heterocyclic directing groups
are reacted with alkenyl acetates bearing mono- and
disubstituted alkenyl groups with aliphatic and aromatic
substituents to give ortho-alkenylation products in high yields.
The results of deuterium-labeling experiments and competition
reactions using different ratios of the E and Z isomers of β-
styryl acetate suggested that the C−H alkenylation proceeded via a ruthenium−alkene intermediate and the C−O bond of the
alkenyl acetate was cleaved by β-acetoxy elimination. Two types of catalytically relevant species were identified, and the
reactivities of these species, combined with the results of the kinetic studies, suggest that the rate-limiting step is the exchange of
the COD ligand with the alkenyl ester. On the basis of the elucidated mechanism, the first catalytic coupling reaction using
aromatic C−H bonds with C−O bonds of ethers was also developed.
the first catalytic alkenylation of arenes with alkynes via C−H
bond cleavage in 1979.4a Chelation-assisted control of
regioselectivity in C−H functionalization has been applied to
the coupling with alkynes to achieve predominantly ortho-
selective C−C bond formation.10−18 Oxidative arene C−H
alkenylation with alkenes (type 2) can be performed catalyti-
cally using stoichiometric amounts of oxidants.19−24 The first
oxidative coupling was reported by Moritani and co-workers
using a Cu(II) or Ag(I) salt as an oxidizing agent,20a and similar
oxidative C−H alkenylations with various oxidants including
benzoquinone, oxygen, and internal oxidant, such as oxidizing
directing groups, have been reported by several research
groups.19−24 The dehydrogenative alkenylation of arenes (type
3) developed by several groups employed alkenes as both
substrates and hydrogen acceptors, and hydrogenation of
alkenes supervenes as an inevitable side reaction.25,26 The
coupling of aromatic C−H bonds with alkenylmetal reagents
(type 4) is another procedure for direct alkenylation.27,28 This
reaction was considered to take place through transmetalation
at the transition-metal center with alkenylmetal compounds,
such as alkenylboron27 and alkenylsilicon reagents.28 Alkenyl
halides and pseudohalides have also been used as alkenylating
agents (type 5),29−34 and regioselective functionalizations have
been achieved using several directing groups.32−34 These
INTRODUCTION
■
Aromatic alkenes are a highly important class of organic
compounds and have been used as versatile industrial and
laboratory chemicals for the synthesis of various biologically
active compounds and organic materials such as polymers. In
recent years, extended π-conjugated systems such as poly-
arylenes and polyarylenevinylenes have attracted considerable
attention, due to their potential applications as organic optical
and electronic materials.1 The construction of aromatic alkene
moieties by coupling of functionalized aromatic compounds
with alkene derivatives is one of the areas where transition-
metal catalysis plays an invaluable role in modern organic
synthesis.2 As the tremendous potential of catalytic function-
alization of carbon−hydrogen bonds became widely recognized,
considerable efforts have been devoted to the direct
alkenylation of aromatic rings by transition-metal catalysts.3
To date, the following five alkenylation reactions via carbon−
hydrogen bond cleavage by transition-metal catalysts have been
developed: (1) addition of arene C−H bonds to alkynes,4−18
(2) oxidative coupling of arenes with alkenes using a
stoichiometric oxidant,19−24 (3) dehydrogenative coupling
using alkenes as both substrates and hydrogen acceptors,25,26
(4) coupling with alkenylmetal reagents,27,28 and (5) cross-
coupling with alkenyl halides or pseudohalides.29−34
The catalytic addition of C−H bonds to C−C triple bonds
(type 1) is a straightforward and well-studied direct
alkenylation method.4−18 Yamazaki and co-workers reported
Received: December 15, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
alkenylation reactions produce acids as byproducts, and in
general, addition of a base or use of a basic solvent such as
DMF is necessary.
Table 1. Generality of Alkenyl Acetates
We have published a preliminary communication on a new
catalytic C−H alkenylation method employing alkenyl esters as
alkenylating agents.35 This reaction is considered to be a new
entry to the type 5 alkenylation, when carboxylate ions are
regarded as pseudohalides. However, the acidity of the
corresponding conjugate acids, carboxylic acids, is weak and
the reaction mostly does not require the use of an additional
base or a weakly basic solvent. The alkenylation proceeds in the
presence of Ru(cod)(cot) as a catalyst and sp2-nitrogen-
containing heterocycles as directing groups. Therefore, this
alkenylation can be catalytically performed under both
halogen-36 and oxidant-free conditions.
This paper provides a detailed description of our research on
C−H alkenylation using alkenyl esters, including the substrate
scope and a proposed catalytic cycle. In particular, mechanistic
investigations using styryl acetate suggested that the alkenyl C−
O bond of the ester was not cleaved by oxidative addition, as
typically described for catalytic functionalization of carbon−
pseudohalide bonds, but rather by β-acetoxy elimination for
this reaction. Two catalytically relevant ruthenium complexes
were also characterized. In addition, on the basis of the
mechanistic analysis, we extended the scope of the alkenylating
agents to alkenyl aryl ethers, which give phenol derivatives,
acids even weaker than acetic acid, as byproducts. This reaction
represents the first catalytic coupling reaction using aromatic
C−H bonds with C−O bonds of ethers.
RESULTS AND DISCUSSION
■
Optimization and Scope of the C−H Alkenylation
with Alkenyl Esters. Screening of Catalysts for Alkenylation
of 2-(2-Methylphenyl)pyridine (1) with Vinyl Butylate (2).
First, several transition-metal catalysts and additives were
screened for the C−H alkenylation using 2-(2-methylphenyl)-
pyridine (1) and vinyl butylate (bp 115−116 °C)37 (2) as
substrates.38 When the reaction was performed using Ru(cod)-
(cot) (4; COD = 1,5-cyclooctadiene, COT = 1,3,5-cyclo-
octatriene) as a catalyst, which exhibits interesting reactivities
such as cleavage of ortho C−H bonds in 2-phenylpyridine39
and oxidative addition of the C−O bonds in vinyl acetate,40 the
alkenylation product 3 was obtained in 34% GC yield (eq 1).
a
Reaction conditions: 1 (1 mmol), alkenyl acetate (3 mmol),
b
Ru(cod)(cot) (4; 0.05 mmol), toluene (1.5 mL), 120 °C. Isolated
c
d
yield. Determined by 1H NMR spectroscopy. Performed in 1,4-
e
dioxane (1 mL) at 100 °C. 2-Phenylvinyl n-butylate (6d′) was used
instead of 6d. 1 was recovered in 69% yield. Performed with 0.1
mmol of 4 and 0.1 mmol of P(2-furyl)3. 1 was recovered in 68%
yield. 1 was recovered in 42% yield.
f
g
h
i
acetates 6a−d bearing an alkyl or phenyl substituent at the β
carbon (abbreviated as Cβ) reacted with 1 to provide the
corresponding alkenylation products in 82−99% isolated yields
with E selectivity (entries 1−5). β-Alkyl -substituted vinyl
acetates were used as a mixture of E and Z isomers (E:Z =
40:60 to 59:41), and as the steric bulk of the alkyl substituent
increased, the E:Z ratio of the product was improved from 91:9
to 96:4 (entries 1−3). In the alkenylation with 1-hexenyl
acetate (6c), use of 1,4-dioxane as a solvent improved the
product yield to 99% but had apparently no effect on the E:Z
ratio (entry 4). Exclusive formation of the E isomer was
observed for the reaction using 2-phenylvinyl acetate (6d)
(entry 5). In this case, 2-phenylvinyl n-butylate (6d′) was also
tested as an alkenylating agent, but the yield was lower (84%)
than that obtained with 2-phenylvinyl acetate (entry 6). The
On the other hand, the use of additives or other transition-
metal complexes was not effective for the alkenylation. On the
basis of these results, Ru(cod)(cot) (4) was chosen as a catalyst
for the following examinations.
Generality of Alkenyl Acetates. Introduction of a variety of
alkenyl groups to arylpyridine 1 was then investigated. Acetate
was used as a leaving group because of its small size and easy
accisibility to the corresponding alkenyl esters.41 The
alkenylation reactions of 1 with several alkenyl acetates 6
were carried out in toluene in an oil bath with its temperature
adjusted to 120 °C (Table 1). In all cases, C−C bond
formation took place between the ortho carbon of 1 and the α
carbon (abbreviated as Cα) of the alkenyl acetates. Alkenyl
B
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
reaction can be applied to an alkenyl ester containing a
trisubstituted olefin moiety (6e), and the product was obtained
in 90% yield (entry 7). The reaction with β,β-disubstituted
vinyl ester 6f under the standard conditions afforded only 21%
of the corresponding alkenylation product 7f and a large
amount (69% yield) of 1 was recovered (entry 8). Screening of
additives was again examined for the reaction with 6f and
revealed that the use of tri(2-furyl)phosphine (P(2-furyl)3)42
with higher catalyst loading (10 mol %) effectively increased
the yield to 91% (entry 9). 1-Cycloalkenyl acetate (6g) was also
applicable for this reaction (entry 10).
Table 2. Generality of the Directing Groups
It is noteworthy that 7f,g are the types of alkenylation
products simple C−H/alkyne coupling (type 1) cannot provide
mechanistically. The alkenylation of 1 with (E)-1,2-diphenyl-
vinyl acetate ((E)-6h) for 24 h afforded only the E isomer of
the corresponding product ((E)-7h) in 23% yield, and a 68%
yield of 1 was recovered (entry 11). Interestingly, even in the
case of (Z)-1,2-diphenylvinyl acetate ((Z)-6h), complete
inversion of the geometry around the CC bond occurred
and the E isomer (E)-7h was obtained as the sole product in
46% yield (entry 12). The stereoselectivity of the alkenylation is
important for elucidation of the reaction mechanisms, and
detailed analyses are presented in a later section. Due to the
high reactivity of 2-phenylvinyl acetate (6d) among the alkenyl
acetates screened, 6d was used for further examinations.
Generality of Directing Groups. Several sp2-nitrogen-
containing heterocycles function as directing groups for the
C−H alkenylation (Table 2). The reaction of 2-phenyl-
pyrimidine (8) with 6d in refluxing toluene for 30 h gave the
2,6-dialkenylphenylpyrimidine 9 in 90% isolated yield (entry 1).
A variety of five-membered N-heterocyclic rings also served as
directing groups (entries 2−6). When the reactions of 2-
phenyl- and 2-(2-tolyl)oxazolines (10 and 12, respectively)
were carried out under base-free conditions, the corresponding
alkenylation products decomposed during the reactions. For
these reactions, the use of 2,6-lutidine as an additive effectively
suppressed the decomposition to afford products 11 and 13 in
79% and 69% isolated yields, respectively (entries 2 and 3). The
reaction of 1-methyl-5-phenyl-1H-tetrazole (14), which has two
ortho C−H bonds, yielded the monoalkenylation product 15 in
52% yield as a sole product (entry 4). Steric repulsion between
the methyl group on the tetrazole ring and the styryl group
introduced is considered to disturb the second C−H
alkenylation. Thiazole and pyrazole rings also functioned as
directing groups for the alkenylation, and the corresponding
products 17 and 19 were isolated in good yields (entries 5 and
6). In these cases, 1:2 coupling products 17b and 19b were also
formed. Benzo[h]quinoline (20), a fused heteroaromatic
compound, underwent alkenylation selectively at the 10-
position (entry 7).
a
Reaction conditions: aromatic compound (1 mmol), 6d (3 mmol),
b
Ru(cod)(cot) (4; 0.05 mmol), toluene (1.5 mL), 120 °C. Isolated
yield. 2,6-Lutidine (2 equiv) was added. 14 was recoverd in 38%
yield.
c
d
tional groups were tolerated, and the alkenylation products
were mostly obtained in high yields (entries 4−9). An
arylpyridine bearing a methoxy group at the 2-position (26a)
(entry 4) was slightly more reactive than those arylpyridines
bearing electron-withdrawing CF3 and Ac groups (26b,c)
(entries 5 and 6). While acetyl3k and cyano44 groups have been
reported as directing functionalities for a variety of ruthenium-
catalyzed C−C bond formations via aromatic C−H bond
cleavage, the alkenylation of 26c and 28 proceeded only at the
ortho position of the pyridyl group.
Alkenylation of Heteroaromatic Compounds. Introduction
of heteroaromatic rings such as thiophenes and pyrroles into
extended π systems is one of the methods to tune the optical
and electronic properties of the materials.45 Therefore, the
Scope of Arylpyridine Substrates. A variety of arylpyridines
were examined as subtrates for the alkenylation with 6d to
explore the scope and functional group compatibility of the
reaction (Table 3). The reaction of 2-phenylpyridine (22) with
3 equiv of 6d in refluxing toluene for 32 h afforded a 3.3:1
mixture of 1:1 (23a) and 1:2 (23b) coupling products (entry
1). As the amount of 6d was increased to 5 equiv and the
reaction time was extended to 72 h, the 1:2 coupling product
23b was formed exclusively and isolated in 93% yield (entry 2).
The coupling of 3-methyl-2-phenylpyridine (24) with 6d
provided only the monostyrylation product 25 in 93% yield due
to steric repulsion of the methyl group and the styryl group
(entry 3).43 Both electron-donating and -withdrawing func-
C
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 3. Reactions of Arylpyridines with β-Styryl Acetate
(6d)
Table 4. Reactions of Heteroaromatic Compounds with
a
a
Alkenyl Acetates
a
Reaction conditions: heteroaryl compound (0.5−1 mmol), alkenyl
acetate (5 equiv), 4 (0.05 equiv), toluene (0.75−1.5 mL), 120 °C.
b
c
d
e
Isolated yield. 3 equiv of acetate were used. E:Z = 59:41. Only the
f
E isomer was observed. Yields were determined on the basis of the 1H
NMR spectra of 31 isolated as a mixture with a,β-dialkenylated
compound. 2,6-Lutidine (2 equiv) was added. E:Z = 66:34.
g
h
described in Schemes 1 and 2. The ruthenium catalyst may
first react with either an arylpyridine or an alkenyl acetate.
The reaction may start with oxidative addition of an ortho
C−H bond of an arylpyridine to the ruthenium catalyst
(Scheme 1). Chaudret and co-workers reported cleavage of an
ortho C−H bond of 2-phenylpyridine (22) by Ru(cod)(cot)
(4) in the presence of H2 and PiPr3 to form a five-membered
chelate.39 After the oxidative addition to form ruthenacycle 36
proceeds, alkenyl acetates may react in several ways. Insertion
of an alkenyl acetate into the Ru−H bond of 36 may take place,
and depending on the direction of the insertion, two types of
intermediates are formed. If 1,2-insertion occurs (pathway A),
β-acetoxy elimination, followed by a Heck reaction type
sequence, gives the alkenylation product. β-Acetoxy elimination
has been proposed in many transition-metal-mediated
processes.46 2,1-Insertion of an alkenyl acetate to 36 (pathway
B), followed by α-acetoxy elimination, may lead to the
formation of a ruthenium carbene complex, in a way similar
to a reaction reported by Caulton and co-workers,47 and this
intermediate may also give the product by carbene C−H
insertion48 and β-hydride elimination. If 6d is inserted into the
Ru−C bond of 36, the product can be formed via β-acetoxy
elimination (pathway C). As described earlier in this paper,
oxidative addition of vinyl acetate was reported for Ru(cod)-
(cot) in the presence of PEt3,40 and catalytic cycles involving
the oxidative addition of the alkenyl C−O bond of the ester are
also reasonable. In pathway D (Scheme 1), oxidative addition
of the C−O bond after the initial C−H bond cleavage is
involved.
a
Reaction conditions: arylpyridine (1 mmol), 6d (3 mmol), 4 (0.05
b
c
mmol), toluene (1.5 mL), 120 °C. Isolated yield. Products were
isolated as a mixture of 23a and 23b, and the yields were determined
d
on the basis of the 1H NMR spectrum of the mixture. 5 mmol of 6d
e
was used. 29 was obtained as a 94:6 mixture of E and Z isomers.
application of C−H alkenylation to heteroaromatic compounds
was also investigated (Table 4). The reaction of 3-(2-
pyridiyl)thiophene (30) with 6d took place preferentially at
the α C−H bond to give monoalkenylation product 31 and
α,β-dialkenylated product in 89% and 6% yields, respectively
(entry 1). Couplings of N-(2-pyridyl)pyrrole (32) with alkenyl
acetates containing phenyl (6d) and 2-indolyl (6i) groups at Cβ
gave the corresponding 2,5-dialkenylated compounds in
excellent yields (entries 2 and 3). The oxazolyl group also
functioned as a directing group, and C−H bonds at the 2- and
5-positions were both efficiently alkenylated (entry 4).
Possible Intermediacy of Ruthenium−Alkene Com-
plex Formed via β-Acetoxy Elimination. The mechanism
of the ruthenium-catalyzed alkenylation has not been obvious,
because alkenyl esters have not been utilized as alkenylating
agents in C−H functionalization reactions except for our
reaction.35 There have been several reports on C−H
alkenylation using alkenyl halides or pseudohalides, but
different types of mechanisms have been proposed for these
reactions.32,33 Several possible mechanisms speculated for the
ruthenium-catalyzed alkenylation with alkenyl esters are
Mechanisms starting with C−O bond cleavage to form
intermediate 37 are also possible and are described in Scheme
D
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 1. Hypothetical Reaction Pathways Starting with Oxidative Addition of a C−H Bond
Scheme 2. Hypothetical Reaction Pathways Starting with Oxidative Addition of a C−O Bond
a
2. While pathway E, containing oxidative addition of the ortho
C−H bond, leads to the same hydrido complex as that in
pathway D, an electrophilic metalation or a concerted
metalation−deprotonation mechanism (so-called CMD mech-
anism)49 provides the product without forming a ruthenium−
hydride intermediate (pathway F).
Table 5. Deuterium-Labeling Experiments
With these several pathways in mind, we carried out
mechanistic studies of the catalytic alkenylation to determine
which pathway is the most plausible.
D incorp, %
Deuterium-Labeling Experiments on the Ruthenium-
Catalyzed Alkenylation of Arylpyridines with 6d. First, we
conducted the alkenylation with the deuterium-labeled
substrate 24-d5. The reaction of 24-d5 with 6d was carried
out at 120 °C. After 1 h, 9% conversion of 24-d5 was observed,
and the alkenylation product 25-dn was isolated in 6% yield
(Table 5, entry 1). The 1H and 2H NMR spectra of the product
revealed that the deuterium content at the alkenyl carbon next
to the pyridylaryl moiety (Cα) was 81%, while less than 1%
introduction of the deuterium was observed at the other alkenyl
carbon (Cβ). However, as the reaction time became longer, the
deuterium content at the Cα position of 25-dn was decreased
and deuterium incorporation at the Cβ position increased
instead (entries 2 and 3). The gradual change in the deuterium
content at both alkenyl carbons is considered to be caused by
entry
time, h
conversion, %
yield, %
Cα
Cβ
1
2
3
1
3
9
38
6
24
98
81
68
45
<1
2
20
100
8
a
Reaction conditions: 24-d5 (0.4 or 0.5 mmol), 6d (E:Z = 59:41, 3
equiv), 4 (5 mol %), toluene-d8 or toluene (0.6 or 0.75 mL), 120 °C,
in a sealed tube.
the ruthenium catalyst and acetic acid released during the
alkenylation, on the basis of the following observation (eq 2).
When coupling product 25 was treated with acetic acid-d under
the same reaction conditions used for the deuterium-labeling
experiments shown in Table 5, 47% and 9% of protons at Cα
and Cβ positions, respectively, were exchanged with deuterium
E
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 7. Alkenylation of 1 with Various Ratios of (E)- and
a
(Z)-6d
atoms. When the reaction of 25 with acetic acid-d was
conducted in the absence of Ru(cod)(cot), no H/D exchange
was observed at any positions.
entry
E:Z ratio
GC yield of 7d, %
1
2
3
59:41
26:74
94:6
95%
96%
13%
The high efficiency (81%) in deuterium incorporation at the
Cα position at low conversion (Table 5, entry 1) indicates that
pathway A in Scheme 1 is the most plausible. In pathway A, 1,2-
insertion of the alkenyl acetate into the Ru−H bond delivers
the ortho hydrogen removed from the substrate onto the
carbon which becomes the Cα carbon in the product. While
pathway B transfers the ortho hydrogen to the other alkenyl
carbon, the other pathways are expected to mainly remove the
ortho hydrogen as acetic acid. Side reactions which allow H/D
scrambling at the Cα position may occur, but the high
deuterium content at the Cα position should be difficult to
achieve simply by the H/D exchange reactions.
Relative Reactivity of (E)- and (Z)-2-Phenylvinyl Acetates
((E)- and (Z)-6d). In the alkenylation reactions described above,
alkenyl acetate 6d was used as a mixture of E and Z isomers.
Because which isomer of 6d participated in the catalytic cycle
should determine if the ortho hydrogen atom is incorporated in
the final product as discussed later, the relative reactivity
between the two stereoisomers is important to provide a
reasonable explanation for the results of the deuterium-labeling
experiments.
a
Reaction conditions: 1 (0.15−0.50 mmol), 6d (3 equiv), 4 (5 mol
%), toluene (0.67 M), 120 °C, 22 h.
The effect of the E:Z ratio of 6d was more significant in the
reaction of 1 (Table 7). The alkenylation of 1 with 59:41 and
26:74 E:Z ratios of 6d again produced the corresponding
product (E)-7d in excellent yields in 22 h with similar reaction
rates (entries 1 and 2). However, the reaction using 6d with a
94:6 E:Z ratio (entry 3) afforded 7d only in 13% yield, and no
improvement of the yield was observed, even when the reaction
was carried out for more than 60 h. The examination of the
relative reactivity of the E and Z isomers of 6d revealed that
(Z)-6d was more reactive and was consumed faster than (E)-
6d.
Proposed Reaction Mechanism for the Alkenylation of
Arylpyridines Using β-Monosubstituted Alkenyl Acetates.
Pathway A in Scheme 1 includes fundamental steps in
organometallic catalysis such as alkene insertion and β-
elimination. In general, both of these processes, alkene
insertion and β-elimination, usually proceed in a cis fashion,
and the stereochemistry of intermediates and products is
strongly affected by that of the substrates.52 If this holds true for
the alkenylation with alkenyl acetate 6d, then the stereo-
chemistry of 6d should determine where the ortho hydrogen
taken off by the initial C−H bond cleavage is located after the
product formation (Figure 1).
For the alkenylation of 24 with three different E:Z ratios of
6d, only the E isomer of 25 was obtained as a product (Table
6). However, monitoring of the reaction revealed that the rate
Table 6. Alkenylation of 24 with Various Ratios of (E)- and
a
(Z)-6d
When (Z)-6d participates in the catalytic cycle (Figure 1a),
after the initial C−H bond cleavage and coordination of (Z)-6d
(A → B), cis hydroruthenation of the coordinating alkenyl
acetate (B → C) provides β-acetoxyalkyl intermediate C. syn-β-
Acetoxy elimination from C leads to the formation of a
complex of styrene bearing the ortho hydrogen (depicted in
red) at the trans position of the phenyl group (C → D).
Following the carboruthenation of the styrene (D → E), β-
hydride elimination (E → A) removes the other terminal
hydrogen of the styrene, which is at the cis position of the
phenyl group in D, from the carbon, and the product formed
contains the ortho hydrogen at the Cα position.
On the other hand, if (E)-6d is used in the catalytic cycle
(Figure 1b), the coordinating styrene in intermediate H
contains the ortho hydrogen at the cis position of the phenyl
group. Therefore, the ortho hydrogen is removed as AcOH and
is not incorporated into the product.
The results of the deuterium-labeling experiments are
consistent with the relative reactivities of the E:Z isomers of
6d. The initially formed product in the alkenylation of 24-d5
with 6d mostly contained a deuterium atom at the Cα position
(Table 5, entry 1), and the alkenylation with (Z)-6d, not (E)-
6d, leads to the deuterium incorporation. The high deuterium
content of the product 25-dn at Cα indicates that (Z)-6d reacts
faster than (E)-6d in the alkenylation, which is also proved by
entry
E:Z ratio
GC yield of 25, %
1
2
3
59:41
20:80
97:3
88
91
43
a
Reaction conditions: 24 (0.5 mmol), 6d (1.5 mmol), 4 (0.025
mmol), toluene (0.75 mL), 120 °C, 24 h.
of the product formation might depend on the E:Z ratio. The
alkenylations of 24 using 6d with E:Z ratios of 59:41 and 20:80
(more than 1 equiv of (Z)-6d was present in the reaction
mixture) provided the product at similar rates (entries 1 and
2),50 but the use of 6d with a low content of the Z isomer
significantly decreased the productivity (entry 3). The reaction
with a 97:3 E:Z ratio of 6d needed more than 60 h to achieve a
GC yield (92% yield, 65 h) comparable to those in entries 1
and 2. The observed low efficiency in entry 3 indicated that the
Z isomer of 6d reacted much faster than the E isomer. The
higher reactivity of the (Z)-alkenes can be explained by their
lower stability and higher coordinating ability toward metal
complexes in general.51
F
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 1. Proposed catalytic cycles of the C−H alkenylation with (a) (Z)-6d and (b) (E)-6d.
the results shown in Tables 6 and 7. In order to investigate this
phenomenon further, the deuterated arylpyridine 24-d5 was
reacted with (E)-6d under the alkenylation conditions, and a
relatively smaller amount of deuterium incorporation at the Cα
position was realized, while it was also indicated that
isomerization of (E)-6d to (Z)-6d occurred, considering the
slight increase of the amount of (Z)-6d in the reaction system
(eq 3).53
diphenylvinyl)-6-methylphenyl)pyridine ((E)-7h) as the sole
product in both cases. The stereochemical outcomes of these
reactions cannot be explained simply by our proposed reaction
mechanisms for the β-monosubstituted alkenyl acetates
described in Figure 1, because alkenylation with (Z)-6h should
give (Z)-7h, not (E)-7h. While β-hydride elimination is
generally considered to proceed in a syn fashion, however, β-
acetoxy elimination via both syn- and anti-periplanar transition
states has been well documented in the literature.46 In
particular, anti elimination may proceed selectively when (E)-
α,β-disubstituted olefins are obtained.46g
The proposed mechanisms of the alkenylation with (E)- and
(Z)-6h are shown in Scheme 3. In the reaction with (E)-6h,
syn-β-acetoxy elimination preferentially takes place from
conformer K-III to give intermediate L, because steric
interactions between the substituents in K-III are smaller
than those in K-II. In contrast, when (Z)-6h is used, syn-
periplanar alignment of the ruthenium and the acetoxy group in
intermediate O-II creates steric repulsion between the two
phenyl groups more severe than for anti alignment. The anti-
acetoxy elimination pathway is more favorable in this case and
Reactions of 1 with E- and Z-1,2-Diphenylvinyl Acetates
((E)- and (Z)-6h). As shown in Table 1, the C−H alkenylation
using (E)- and (Z)-1,2-diphenylvinyl acetates ((E)- and (Z)-
6h) afforded the same coupling product, (E)-2-(2-(1,2-
Scheme 3. Proposed Reaction Pathways for C−H Alkenylation with (Z)- and (E)-1,2-Disubstituted Vinyl Acetates
G
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 4. C−H Alkenylation with a Deuterated 1,2-Diphenylvinyl Acetate
leads to the formation of (E)-stilbene complex L, essentially the
same intermediate as that formed from (E)-6h. Therefore, the
alkenylations with both (E)- and (Z)-6h provided the same
product, (E)-7h, and the conformational requirement for the β-
acetoxy elimination may depend on the structure of the starting
alkenyl acetate.
Although the catalytic cycles described in Figure 1 and
Scheme 3 explain the experimental results, no evidence of the
presence of any intermediate has been obtained by the results
described so far. One of the key intermediates in the
alkenylation is an alkene ruthenium complex (D, H, and L)
generated by β-acetoxy elimination. Olefin insertion may
proceed selectively to form a C−C bond on the less crowded
carbon of the alkene moiety, but if the steric and electronic
environments around the two carbons are similar, the insertion
should operate in both directions.
In order to test the feasibility of the presence of the alkene
ruthenium intermediate, the alkenylation was performed using
(Z)-1-phenyl-2-phenyl-d5-vinyl acetate (6h-d5) (Scheme 4). If
alkene ruthenium intermediate P is formed from 6h-d5,
insertion of the stilbene ligand to the Ru−C bond should
provide both intermediates Q and R, because the C6H5 and
C6D5 groups should not be easily discriminated. Therefore,
both of the corresponding alkenylation products (38 and 39)
should be obtained.
Indeed, when the reaction of 1 with 6h-d5 was carried out at
120 °C for 24 h, a mixture containing a 55:45 ratio of 38 and
39 was obtained in 32% combined isolated yield along with a
54% isolated yield of recovered 1. This result strongly suggests
that an intermediate with a symmetric carbon fragment derived
from 6h-d5, such as alkene ruthenium complex P, is formed in
the catalytic cycle.
dt = kobs) in the concentrations of 24, which decrease as the
reactions progress. The rate constants (kobs) were measured
using various initial concentrations of 24, 6d, and 4 and are
given in Table 8.
Table 8. Kinetic Data in the C−H Alkenylation of 24 with 6d
Using 4 as a Catalyst
entry
[24]0 (M)
[6d]0 (M)
[4]0 (mM)
107kobs (M s−1
)
1
0.1
0.2
0.3
0.1
0.2
0.3
0.1
0.1
0.1
0.1
0.1
0.1
0.1
2.0
2.0
2.0
2.0
2.0
2.0
0.5
1.0
1.5
2.5
2.0
2.0
2.0
10
10
10
20
20
20
20
20
20
20
1
10.4
7.8
2
3
5.4
4
14.5
11.3
8.6
5
6
7
2.9
8
5.8
9
11.3
18.6
2.1
10
11
12
13
3
5.1
5
5.9
As initial concentrations of phenylpyridine 24 ([24]0)
increased from 0.1 to 0.3 M (Table 8, entries 1−3 and 4−6),
the kobs values became smaller (Figure 2). These results mean
that the reaction rate is dependent on [24]0 but not on
decreasing concentrations of 24.
A rational explanation of these results is that the reaction rate
is dependent on the sum of [24] and [25], and the active
species in the catalytic cycle may be in equilibrium with catalyst
resting states, including phenylpyridines 24 or the alkenylation
product 25. The C−H alkenylation was also carried out at
various concentrations of alkenyl ester 6d (entries 4 and 7−10)
Kinetic Studies of the C−H Alkenylation with Alkenyl
Acetate. Kinetic studies were conducted for the C−H
alkenylation of arylpyridine 24 with alkenyl acetate 6d by
catalyst 4. The rate was measured in toluene-d8 at 90 °C by 1H
NMR spectroscopy, and the progress of the reactions with an
excess amount of 6d was monitored by measuring the
concentration of alkenylation product 25. During the reactions,
the rates appear to follow pseudo-zeroth-order kinetics (d[25]/
H
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 9. Effect of Additives
entry
additive, mM
107kobs (M·s−1
)
a
1
2
3
4
5
none
14.5
b
AcOH, 100 mM
―
14.4
15.0
12.2
c
AcOH, 35 mM
c
AcOH, 100 mM
1,5-COD, 24 mM
a
b
The result described in Table 8, entry 4. 25 was not observed.
c
AcOH was added at 200 min after the alkenylation started.
Figure 2. Dependence of [24]0 on the rate constant kobs in the C−H
alkenylation of 24 with 6d. Reaction conditions: [24]0 = 0.1−0.3 M,
■
●
[6d]0 = 2.0 M, [4]0 = 10 mM ( ) or 20 mM ( ) in toluene-d8, at 90
°C.
M of 24, 2.0 M of 6d, and 20 mM of 4, entry 1), the
alkenylation product 25 was not observed in the presence of
acetic acid (100 mM) (entry 2). Because it is possible that
acetic acid inhibits conversion of 4 to a catalytically active
species, the C−H alkenylation was also conducted by adding
acetic acid 200 min after the reaction was started. The reaction
was examined using both catalytic (35 mM) and stoichiometric
amounts of acetic acid (100 mM), but essentially no effect of
the added acetic acid on the rate was observed (entries 3 and
4). The effect of 1,5-COD, which is released from 4 during the
catalysis, was also investigated. When 24 (0.1 M), 6d (2.0 M),
and 4 (20 mM) were reacted in the presence of a catalytic
amount of 1,5-COD (24 mM) in toluene-d8, the reaction
became slightly slower (entry 5). The retardation of the
reaction in the presence of 1,5-COD may partially explain the
non-first-order dependence of the rate on the catalyst
concentration.
Figure 3. Dependence of [6d]0 on the rate constant kobs in the C−H
alkenylation of 24 with 6d. Reaction conditions: [24]0 = 0.1 M, [6d]0
= 0.5−2.5 M, [4]0 = 20 mM in toluene-d8, at 90 °C.
Isolation of Ortho-Ruthenated Arylpyridines and
Their Relevance to the Catalytic Cycle. Stoichiometric
Reactions of Ruthenium Catalyst 4 with Arylpyridines and
6d. In order to gain a further understanding of the reaction
mechanisms, stoichiometric reactions of substrates with catalyst
4 were investigated. The reaction of 4 with 2 equiv of
arylpyridine 24 and alkenyl acetate 6d in toluene at 120 °C for
3 h gave a mixture of ortho-ruthenated species, including COD
complex 38a and alkenylation-product-containing complex 39a
formed via C−H bond cleavage, which were isolated in 39%
and 12% yields, respectively (eq 4). A similar reaction using
tolylpyridine 1 also led to the formations of the corresponding
1
complexes 38b and 39b, detected by H NMR, and 38b was
isolated in 10% yield (eq 5).
X-ray diffraction analyses of single crystals of 38b and 39a
were performed, and their ORTEP drawings are presented in
Figures 5 and 6, respectively, which clearly shows complexes
38b and 39a have 1,5-COD and alkenylation product 25 as a
chelating ligand, respectively, in addition to pyridylaryl and
acetoxy groups. Identification of the 1,5-COD complexes and
product-containing complexes also indicated that these ortho-
ruthenated species were present when the catalytic C−H
Figure 4. Dependence of [4]0 on the rate constant kobs in the C−H
alkenylation of 24 with 6d. Reaction conditions: [24]0 = 0.1 M, [6d]0
= 2.0 M, [4]0 = 1−20 mM in toluene-d8, at 90 °C.
1
and catalyst 4 (entries 1, 4, and 11−13), and the results showed
that the reaction rate is dependent on the concentrations of
both 6d and 4 and appears to be first order in [6d]0 (Figure 3)
and less than first order in [4]0 (Figure 4).
The effect of other molecules present in the reaction system
on the rate was also investigated (Table 9). Acetic acid is
produced by the alkenylation and may affect the reaction rate.
In comparison with the alkenylation without any additive (0.1
alkenylation was monitored by H NMR.
Reactivities of the Ortho-Ruthenated Species 38 and 39.
The reactions of ortho-ruthenated species 38 and 39 toward
substrates were examined to see if these complexes are
catalytically relevant species. First, the alkenylation of
arylpyridine 1 with styryl acetate (6d) was performed using
38a and 39a as catalysts. The reaction using 10 mol % of COD
complex 38a proceeded to give alkenylation product 7d in 98%
I
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
GC yield, but the product-containing complex 39a showed
lower reactivity, providing a 36% GC yield of 7d for the
catalytic C−H alkenylation (eq 6).54 Conversion of product-
containing complex 39a to the 1,5-COD complex 38a was
1
observed by H NMR (ca. 1:1 ratio of 38a to 39a after 10 h),
on reaction with 1,5-COD and acetic acid (eq 7), suggesting
that complex 39a can be converted to the more reactive 1,5-
COD complex 38a during the reaction of 1 with 6d using 4 as a
catalyst. Therefore, the 1,5-COD complex 38a and product-
containing complex 39a can be considered as relevant
intermediates in the catalytic C−H alkenylation.
The ortho-ruthenated species 38b (0.02 M) was then treated
with styryl acetate (6d; 0.5 M), but the reaction only slowly
gave alkenylation product 7d in 22% GC yield based on 38b
after 7 h (eq 8). In the presence of the same concentration of
6d, on the other hand, the catalytic reaction employing the
corresponding concentrations of 6d and catalyst 4 (0.5 M of 6d
and 0.02 M of 4) with 0.1 M of 1 gave 7d in a 362% GC yield
based on ruthenium catalyst 4 (eq 9). On the basis of these
results, it is indicated that C−C bond formation via direct
carbometalation of 6d by ortho-ruthenated species 38b is not a
major pathway for the catalytic C−H alkenylation.
Possibility of the Ortho-Ruthenated Species Reacting with
Another Arylpyridine Molecule. The possibility of another 1
equiv of an arylpyridine reacting with ortho-ruthenated species
is then examined. The reaction of 38a with 1 equiv of 1 and 6
equiv of 6d afforded alkenylation products 25, originating from
38a, and 7d, originating from 1, in 34% and 47% GC yields,
respectively (eq 10). The reaction of 38b with 24 with 6d also
gave a mixture of the two alkenylation products, and 7d and 25
were obtained in 58% and 41% GC yields (eq 11), respectively.
These results suggest the possibility of ortho-ruthenated species
reacting with another molecule of arylpyridine during the
product formation process.
Figure 5. ORTEP drawing of complex 38b. Hydrogen atoms are
omitted for clarity.
Deuterium-labeling experiments were also carried out using
2-phenyl-3-picoline (24) and 2-(pentadeuteriophenyl)-3-pico-
line (24-d5). The C−H alkenylation of a 1:1 mixture of 24 and
24-d5 with 6d was carried out only for 1 h to see if H/D
exchange between the two substrates occurs at low conversion.
When complex 4 was used as a catalyst, the reaction gave only
2% of the alkenylation products, while 97% of the starting
Figure 6. ORTEP drawings of complex 39a. Hydrogen atoms and a
toluene molecule contained in the unit cell are omitted for clarity.
1
arylpyridines was still present. H and 2H NMR and APCI MS
analyses of the recovered 24-dn showed that intermolecular H/
D scrambling at ortho positions occurred completely (Table 10,
J
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
24-d5 was treated with ruthenium complex 4 or 38a (Table 10,
entries 3 and 4). In both cases, complete H/D exchange at
ortho positions occurred, but only when the reaction was
performed with 4 was deuterium incorporation at the 6-
position of the picoline ring observed. These results indicate
that the ruthenium complex 38a is more relevant to the
catalytic cycle than catalyst 4.
A kinetic experiment was carried out for the reaction of 24-d5
under the conditions used for Table 8, entry 4, and the reaction
rate was similar to that of the alkenylation of 24 (eq 12). The
kinetic isotope effect was not in the range of a primary KIE, and
the C−H bond cleavage should not be considered as the rate-
limiting step in the C−H alkenylation.
Possible Catalytic Cycle of the C−H Alkenylation with
Alkenyl Acetates. On the basis of the mechanistic studies, a
possible catalytic cycle is shown in Figure 7 using 24 and 6d as
substrates. The observation of ortho-ruthenated species and the
kinetic data which suggested the reaction rate is first order in
the alkenyl acetate and zeroth order in the arylpyridine indicate
that the reaction between ortho-ruthenated species and alkenyl
acetate is the turnover-limiting step. However, this step
becomes much slower in the absence of arylpyridines. The
reaction between arylruthenium species with another molecule
of an arylpyridine is very rapid, and it can be considered that
another molecule of the arylpyridine reacts with the ruthenium
center after the turnover-limiting step. Therefore, the turnover-
limiting step may be the substitution of the 1,5-COD ligand of
complex 38a with the alkenyl acetate to form complex S. Then,
the arylpyridine is oxidatively added to complex S to give
hydride complex T, followed by hydrometalation of the alkenyl
acetate and β-acetoxy elimination to form alkene complex V.
Carbometalation of the alkene ligand, β-hydride elimination,
and reductive elimination of acetic acid gave product-containing
complex 39a. Complex 39a can be converted to 1,5-COD
complex 38a, but the amount of 38a is dependent on the
amount of product 25 and substrate 24, which may inhibit the
formation of a 1,5-COD complex through coordination to the
ruthenium center.
Table 10. Intermolecular H−D Scrambling Reaction
a
Catalyzed by Ruthenium Complex 4 and 38a
e
D content of 24-dn
d
entry catalyst yield of 25-dn, %
R1
R1′
R2 and R2′
a
f
f
1
2
3
4
4
2
0.95 D
0.95 D
0.95 D
0.89 D
0.96 D
0.94 D
no D detected
no D detected
b
c
38a
4
<1
f
f
0.13 D
c
f
38a
0.90 D
no D detected
a
Reaction conditions: 24 (0.5 mmol), 24-d5 (0.5 mmol), 6d (E:Z =
b
66:34) (3 mmol), 4 (0.05 mmol), toluene 1.0 mL, 120 °C. Reaction
conditions: 24 (0.25 mmol), 24-d5 (0.25 mmol), 6d (E:Z = 66:34)
(1.5 mmol), 38a (0.025 mmol), toluene 0.5 mL, 120 °C. Reaction
conditions: 24 (0.1 mmol), 24-d5 (0.1 mmol), 4 or 38a (0.025 mmol),
toluene 0.5 mL, 120 °C. GC yield. Determined by APCI MS
analysis. Determined by H and H NMR analysis.
c
Development of C−H Alkenylation with Alkenyl
Ethers Inspired by the Mechanistic Studies. On the
basis of the proposed mechanism of the C−H alkenylation
using alkenyl esters, we postulated that alkenylating agents
other than esters may be used for the alkenylation reaction.
Although the catalyic C−O bond cleavage of the alkenyl esters
seems to be challenging, a mechanistic analysis revealed that the
C−O bond of the alkenyl ester substrate is considered to be
cleaved essentially via β-elimination of the acetoxy group, which
may not be a difficult process, as it is not regarded as a rate-
limiting step. Therefore, we envisioned that alkenylating agents
bearing less effective leaving groups may also be used for the
C−H alkenylation.
d
e
f
1
2
entry 1). A similar reaction was performed using 38a as a
catalyst to show that complete H/D exchange at ortho
positions occurred even at less than 1% conversion (entry 2).
The reaction was also examined using 2-(2-deuteriophenyl)-3-
picoline (24-d1) as a sole substrate to treat with 6d and catalyst
4, and rapid H/D exchange was observed as well.38 Therefore,
H/D exchange and C−H bond cleavage at the ortho positions
of arylpyridines are much faster in the C−H alkenylation than
the product formation.
The deuterium-labeling experiment was also conducted
without using alkenyl acetates, and a 1:1 mixture of 24 and
We chose the alkenyl phenyl ether 40 (E:Z = 96:4) as the
alkenylating agent to examine, because the coupling reactions
K
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 7. Proposed catalytic cycle of the C−H alkenylation of 24 with (Z)-6d.
Table 11. C−H Alkenylation of Arylpyridine 1 with Alkenyl
yield (entry 4). The C−H alkenylation was also conducted
using o-, m-, or p-xylene (entries 5−7), and it turned out that
the use of p-xylene improved the yield to 71%, while the
reaction in o- or m-xylene gave product 7d in a yield
comparable to that obtained for the reaction in a mixture of
xylenes.
a
Ether 40
With the optimized reaction conditions in hand, isolation of
the C−H alkenylation product was investigated. Product 7d
formed by the reaction of 1 with alkenyl ether 40 was isolated
in 62% yield (Table 12, entry 1). The C−H alkenylation were
similarly conducted with 2-aryl-3-picolines. The alkenylation of
2-phenyl-3-picoline (24) with 40 afforded the corresponding
alkenylation product 25 in 76% yield (entry 2), while the
reaction of 2-(p-tolyl)-3-picoline (41) gave a 52% yield of 42
(entry 3). The reaction using an alkenyl ether having a 2-
methoxyphenoxy leaving group (43; E:Z = 94:6) was also
performed to give product 7d in 23% GC yield (entry 4).
entry
solvent
toluene 0.1 mL
temp, °C
GC yield, %
1
2
3
4
5
6
7
120
150
150
150
150
150
150
57
62
50
38
59
66
71
xylenes 0.1 mL
mesitylene 0.1 mL
none
o-xylene 31 μL (0.5 equiv)
m-xylene 31 μL (0.5 equiv)
p-xylene 31 μL (0.5 equiv)
a
Reaction conditions: 1 (0.5 mmol), alkenyl ether 40 (1.5 mmol),
Ru(cod)(cot) (4; 0.025 mmol), solvent.
CONCLUSIONS
■
using alkenyl ethers are still rare,46a,55 while there have been
reported several catalytic46a,55c,56 and stoichiometric57 reactions
proceeding via β-elimination of aryloxy groups. When the
reaction of arylpyridine 1 with alkenyl ether 40 using 5 mol %
of 4 was performed at 120 °C in toluene for 48 h, the desired
ortho-alkenylation product was formed in 57% GC yield (Table
11, entry 1). The alkenylation in xylenes (a mixture of o-, m-,
and p-xylene) at 150 °C gave a slightly higher yield (entry 2),
but the use of mesitylene as a solvent reduced the product yield
(entry 3). The reaction under neat conditions also gave a lower
The use of alkenyl esters for chelation-assisted C−H
alkenylation of arylpyridines and their derivatives was
demonstrated using Ru(cod)(cot) as a catalyst and developed
as a new strategy. Important features of this method are as
follows: (1) the alkenylation can be performed on various aryl-
and heteroarylpyridines and related aromatic compounds
bearing several nitrogen-containing heterocycles such as
pyrimidine, oxazoline, tetrazole, thiazole, and pyrazoles, (2) a
variety of alkenyl esters including 1- and 2-monosubstituted
and 1,2- and 2,2-disubsituted vinyl esters and cyclohexenyl
a
Table 12. C−H Alkenylation of Arylpyridines with Alkenyl Ethers
entry
aryl pyridine
R1
R2
R3
alkenyl ether
Ar
product; isolated yield, %
1
2
3
4
1
H
Me
H
H
40
40
40
43
Ph
Ph
Ph
7d; 62
25; 76
42; 52
24
41
1
Me
Me
H
H
H
Me
H
b
Me
2-MeOC6H4
7d; 23
a
b
Reaction conditions: arylpyridine (0.5 mmol), alkenyl ether (1.5 mmol), Ru(cod)(cot) (4; 0.025 mmol), p-xylene 31 μL, 150 °C, 48 h. GC yield.
L
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
General Procedure B for the Ru(cod)(cot)-Catalyzed
Alkenylation of Aromatic Compounds with Alkenyl Acetates.
An apparatus consisting of a 10 mL two-necked flask equipped with a
reflux condenser and a magnetic stirring bar was oven-dried. In the
flask were placed Ru(cod)(cot) (4; 15.8 mg, 0.05 mmol), aromatic
compound (1 mmol), alkenyl acetate (3 mmol), and 1.5 mL of
toluene. The resulting mixture was refluxed under a nitrogen
atmosphere. After cooling, ca. 0.3 mL of triethylamine (ca. 20
mmol) was added to the reaction mixture. The resulting mixture was
stirred for 5 min at room temperature and analyzed by GC. The
alkenylation product was isolated by silica gel column chromatography
(followed by gel permeation chromatography and/or bulb-to-bulb
distillation, if necessary).
Reaction of 1 with 6e. General procedure B was followed with 2-
(2-methylphenyl)pyridine (1; 84.6 mg, 0.5 mmol) and (E)-3,7-
dimethylocta-1,6-dienyl acetate (6e; 294.4 mg, 1.5 mmol), except that
the reaction was performed on a half scale (4, 7.9 mg, 0.025 mmol;
toluene, 0.75 mL). Column chromatography (5/1 hexane/EtOAc)
afforded 7e (137.5 mg, 0.45 mmol) as a pale yellow oil in 90% yield:
1H NMR (E isomer, CDCl3, 400.1 MHz) δ 0.91 (d, J = 6.7 Hz, 3H,
CH3), 1.27 (q, J = 7.5 Hz, 2H, CH2), 1.54 (s, 3H, CH3), 1.65 (s, 3H,
CH3), 1.78−2.00 (m, 2H, CH2), 2.02−2.10 (m, 4H, CH3 and CH),
5.02 (t, J = 7.1 Hz, 1H, −CHCMe2), 5.85 (dd, J = 15.7, 7.3 Hz, 1H,
ArCHCHCH), 5.92 (d, J = 15.7 Hz, 1H, ArCHCHCH), 7.13 (d,
J = 7.4 Hz, 1H, ArH), 7.20−7.26 (m, 3H, ArH), 7.41 (d, J = 7.8 Hz,
1H, ArH), 7.72 (ddd, J = 7.7, 7.7, 1.8 Hz, 1H, ArH), 8.70−8.72 (m,
1H, ArH); 13C NMR (E isomer, CDCl3, 100.5 MHz) δ 17.7, 20.1,
20.6, 25.6, 25.7, 36.9, 37.0, 121.6, 123.1, 124.6, 125.2, 126.7, 127.9,
128.5, 131.1, 135.9, 136.0, 136.6, 138.0, 138.7, 149.4, 159.4; LRMS
(EI) m/z (% relative intensity) 305 (M+, 21), 248 (10), 222 (28), 195
(17), 194 (100), 182 (10), 181 (25), 180 (10); IR (KBr) 2963 m,
2921 m, 1584 m, 1563 m, 1455 s, 1377 m, 1147 w, 1090 w, 1053 w,
1024 m, 988 w, 970 s, 777 s, 749 s, 634 w, 620 m, 571 w, 527 w cm−1;
HRMS (ESI) calcd for [M + H]+ (C22H28N) m/z 306.2222, found
306.2228.
Reaction of 1 with (Z)-6h. General procedure A was followed
with 2-(2-methylphenyl)pyridine (1; 84.6 mg, 0.5 mmol) and (Z)-1,2-
diphenylethenyl acetate ((Z)-6h; 357.4 mg, 1.5 mmol), except that the
reaction was performed on a half scale (4, 7.9 mg, 0.025 mmol;
toluene, 0.75 mL). Column chromatography (gradient elution, 20/1−
10/1 hexane/EtOAc) afforded (E)-7h (79.9 mg, 0.23 mmol) as a pale
yellow powder in 46% yield: 1H NMR (CDCl3, 270.1 MHz) δ 2.06 (s,
3H, CH3), 6.61 (s, 1H, PhCHCArPh), 6.70−6.74 (m, 2H, ArH),
6.91−7.09 (m, 10H, ArH), 7.22−7.28 (m, 1H, ArH), 7.30−7.41 (m,
3H, ArH), 8.38 (ddd, J = 4.8, 1.8, 1.0 Hz, 1H, ArH); 13C NMR
(CDCl3, 100.4 MHz) δ 20.3, 120.9, 125.0, 126.3, 126.4, 127.6, 127.7,
127.7, 127.9, 129.1, 129.5, 129.6, 130.8, 135.1, 136.3, 137.4, 139.7,
140.4, 142.7, 143.8, 148.6, 159.2; LRMS (EI) m/z (% relative
intensity) 348 (14), 347 (M+, 50), 346 (13), 271 (23), 272 (100), 254
(13); IR (KBr) 3079 m, 3048 s, 3022 s, 2922 m, 1945 w, 1884 w, 1805
w, 1585 s, 1563 s, 1492 s, 1474 s, 1444 s, 1422 s, 1379 m, 1275 w,
1184 w, 1173 w, 1152 m, 1092 w, 1075 m, 1054 w, 1026 m, 988 m,
969 w, 921 m, 881 m, 844 w, 807 m, 792 s, 774 s, 745 s, 712 s, 695 s,
658 m, 623 m, 606 w, 557 m, 527 m, 518 s, 484 w cm−1; HRMS (ESI)
calcd for [M + H]+ (C26H22N) m/z 348.1752, found 348.1759.
Reaction of 8 with 6d. General procedure B was followed with 2-
phenylpyrimidine (8) (156.2 mg, 1 mmol) and styryl acetate (6d;
811.0 mg, 5 mmol), except that 5 mmol, not 3 mmol, of 6d was used.
Column chromatography (10/1/0.1 hexane/EtOAc/Et3N) afforded 9
(324.4 mg, 0.9 mmol) as a white solid in 90% yield: 1H NMR (CDCl3,
270.1 MHz) δ 6.74 (d, J = 15.9 Hz, 2H, ArCHCHAr), 6.98 (d, J =
15.9 Hz, 2H, ArCHCHAr), 7.16−7.28 (m, 10H, ArH), 7.35 (t, J =
4.8 Hz, 1H, ArH), 7.46 (t, J = 7.8 Hz, 1H, ArH), 7.69 (d, J = 8.1 Hz,
2H, ArH), 8.94 (d, J = 4.8 Hz, 2H, ArH); 13C NMR (CDCl3, 67.8
MHz) δ 119.2, 125.1, 126.6, 126.6, 127.6, 128.5, 128.5, 129.1, 130.8,
136.4, 137.4, 157.2, 167.5; LRMS (EI) m/z (% relative intensity) 361
(13), 360 (M+, 47), 359 (19), 284 (23), 283 (100), 206 (10), 140
(50), 133 (175); IR (KBr) 3021 m, 1596 w, 1556 s, 1492 m, 1444 m,
1403 s, 1322 w, 1155 w, 1072 w, 1031 w, 981 w, 960 s, 833 w, 792 m,
acetate can be used for the reaction, (3) the alkenylation takes
place selectively at the γ-C−H bond to the sp2 nitrogen atom in
the directing functionality, and (4) in most cases, addition of a
base is unnecessary to achieve high yields of the products.
The mechanistic investigation was also conducted for the
alkenylation. For example, the reaction of 24-d5 with styryl
acetate 6d revealed that the ortho hydrogen atom cleaved off is
transferred to the Cα position of product 25 at the early stage of
the reaction. The competition reactions using different ratios of
E and Z isomers of 6d indicated that the reactivity of (Z)-6d
was higher than that of (E)-6d.
The reaction mechanisms of the C−H alkenylation using
alkenyl acetates were elucidated on the basis of the results of
the deuterium labeling experiments, competition reactions,
kinetic studies, and structural determination of relevant
intermediates. The C−H alkenylation with 6d is considered
to proceed through the following steps: (1) rate-limiting
exchange of the COD ligand with the alkenyl ester, (2)
oxidative addition of the aromatic C−H bond to the ruthenium
center, (3) hydroruthenation of the alkenyl acetate, (4) β-
acetoxy elimination leading to the ruthenium alkene complex,
(5) carboruthenation of the coordinating alkene, and (6) β-
hydride elimination to yield the alkenylation product. The
deuterium labeling experiment using 6h-d5 strongly suggests
the presence of the ruthenium−alkene intermediate generated
by β-acetoxy elimination.
On the basis of the elucidated mechanism, we extended the
scope of the alkenylating agents and found that alkenyl aryl
ethers can also be used as the alkenylating agents in catalytic
C−H functionalization.
The acetoxy and aryloxy groups are not excellent leaving
groups, and the direct cleavage of the alkenyl C−O bond in
alkenyl esters and ethers has rarely been observed. However,
conversion of the alkenyl ester or ether to the β-acetoxy- or β-
aryloxyalkylmetal species by hydrometalation would make the
C−O bond much easier to cleave. Therefore, if this strategy can
be applied, the cross-coupling type C−H functionalization may
not have to rely on the use of excellent leaving groups such as
halides and sulfonates.
EXPERIMENTAL SECTION
■
General Information. 1H, 13C{1H}, 2H{1H}, and 2D NMR
spectra were recorded on a 270 or 400 MHz spectrometer. Chemical
1
shifts in H and 13C{1H} NMR spectra were reported in ppm relative
1
to residual solvent peaks such as chloroform (δ 7.26 for H, and δ
77.00 for 13C), benzene (δ 7.16 for H, and δ 128.00 for 13C), and
1
1
toluene (δ 2.09 for H), or the internal reference tetramethylsilane (δ
0.00 for both 1H and 13C). The temperature for both GC and GCMS
analyses was programmed from 70 to 250 °C at a 10 °C/min ramp
with a final hold time of 30 min (injection temperature, 250 °C;
detector temperature, 250 °C). Benzene, toluene, and hexane were
distilled from Na/benzophenone ketyl. Dry CH2Cl2 was purchased
and used without further purification. Ru(cod)(cot) was prepared by a
modified literature method.58
General Procedure A for the Ru(cod)(cot)-Catalyzed
Alkenylation of Aromatic Compounds with Alkenyl Acetates.
In a glovebox, Ru(cod)(cot) (4; 15.8 mg, 0.05 mmol), aromatic
compound (1 mmol), alkenyl acetate (3 mmol), toluene (1.5 mL), and
a magnetic stirring bar were placed in a 10 mL Schlenk flask. The
resulting solution was heated at 120 °C. After cooling, ca. 0.3 mL of
triethylamine (ca. 20 mmol) was added to the reaction mixture. The
resulting mixture was stirred for 5 min at room temperature and
analyzed by GC. The alkenylation product was isolated by silica gel
column chromatography (followed by gel permeation chromatography
and/or bulb-to-bulb distillation, if necessary).
M
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
736 s, 690 s, 659 w, 632 w, 532 w, 505 w cm−1. Anal. Calcd for
C26H20N2: C, 86.64; H, 5.59; N, 7.77. Found: 86.42; H, 5.70; N, 7.70.
Reaction of 10 with 6d. General procedure B was followed with
4,5-dihydro-4,4-dimethyl-2-phenyloxazole (10; 175.2 mg, 1.0 mmol)
and styryl acetate (6d; 486.6 mg, 3 mmol), except that 2 mmol of 2,6-
lutidine (214.3 mg) was used as an additive. Column chromatography
(10/1 hexane/EtOAc) afforded 11 (299.8 mg, 0.79 mmol) as a pale
yellow powder in 79% yield: 1H NMR (CDCl3, 399.7 MHz) δ 1.54 (s,
6H, CH3), 4.20 (s, 2H, CH2), 7.10 (d, J = 16.6 Hz, 2H, ArH), 7.29 (t, J
= 7.3 Hz, 2H, ArH), 7.35 (d, J = 16.6 Hz, 2H, ArH), 7.38 (t, J = 7.3
Hz, 4H, ArH), 7.43 (t, J = 7.8 Hz, 1H, ArH), 7.50 (d, J = 7.3 Hz, 4H,
ArH), 7.64 (d, J = 7.8 Hz, 2H, ArH); 13C NMR (CDCl3, 100.4 MHz)
δ 28.7, 68.4, 79.2, 124.3, 125.7, 126.5, 127.0, 127.7, 128.6, 129.7, 131.0,
137.0, 137.2, 161.1; IR (KBr) 2966 w, 1666 s, 1598 w, 1495 m, 1453
m, 1437 w, 1364 w, 1346 w, 1289 s, 1250 w, 1210 m, 1096 m, 1075 w,
1029 s, 977 m, 961 s, 918 w, 873 w, 791 m, 738 s, 726 m, 693 s, 617 w,
526 m, 506 m cm−1; HRMS (ESI) calcd for [M + H]+ (C27H26NO)
m/z 380.2014, found 380.2003.
Reaction of 16 with 6d. General procedure B was followed with
2-methyl-4-phenylthiazole (16; 175.3 mg, 1 mmol) and styryl acetate
(6d; 486.6 mg, 3 mmol). Column chromatography (10/1/0.1 hexane/
EtOAc/Et3N), followed by gel permeation chromatography (GPC)
and bulb-to-bulb distillation, afforded 17a (61.0 mg, 0.22 mmol) as a
white solid in 22% yield: 1H NMR (CDCl3, 270.1 MHz) δ 2.81 (s, 3H,
CH3), 7.04 (d, J = 16.2 Hz, 1H, ArCHCHAr), 7.11 (s, 1H, ArH),
7.22−7.47 (m, 8H, ArH and ArCHCHAr), 7.70 (t, J = 7.0 Hz, 2H,
ArH); 13C NMR (CDCl3, 67.8 MHz) δ 19.3, 116.9, 126.5, 126.6,
127.5, 127.6, 128.1, 128.2, 128.6, 129.9, 130.0, 133.8, 136.0, 137.6,
154.0, 165.2.; LRMS (EI) m/z (% relative intensity) 277 (M+, 27), 236
(13), 235 (11), 203 (10), 202 (24), 201 (17), 200 (100), 186 (48),
115 (14), 101 (11), 59 (11), 51 (10); IR (neat) 3052 s, 3023 s, 2919
m, 1598 m, 1494 s, 1448 s, 1434 s, 1307 m, 1214 w, 1170 s, 1101 w,
1027 s, 962 s, 856 w, 790 w, 759 s, 728 m, 692 s, 647 w, 547 m, 512 m
cm−1. Anal. Calcd for C18H15NS: C, 77.94; H, 5.45; N, 5.05. Found:
77.87; H, 5.42; N, 4.99. Distyrylation product 17b (227.7 mg, 0.6
mmol) was also isolated in 60% yield from the crude material, as
described previously.35
Reaction of 30 with 6d. General procedure B was followed with
2-(3-thienyl)pyridine (30; 161.22 mg, 1 mmol) and styryl acetate (6d;
486.6 mg, 3 mmol). Column chromatography (9/1/0.1 hexane/
EtOAc/Et3N), followed by gel permeation chromatography (GPC)
and bulb-to-bulb distillation, afforded a mixture of 31 (259.5 mg) and
α,β-dialkenylated compound as a colorless oil in 89% yield of 31,
which was determined on the basis of H NMR spectra: H NMR
(CDCl3, 270.1 MHz) δ 7.07 (d, J = 16.5 Hz, 1H, ArCHCHAr),
7.19−7.60 (m, 10H, ArH and ArCHCHAr), 7.74 (td, J = 7.6 Hz, 1.9
Hz, 1H, ArH), 8.69 (d, J = 4.9 Hz, 1H, ArH); 13C NMR (CDCl3, 67.8
MHz) δ 121.6, 122.4, 122.9, 126.1, 126.3, 126.7, 127.4, 128.5, 130.6,
136.3, 136.7, 137.2, 139.2, 149.6, 152.8; LRMS (EI) m/z (% relative
intensity) 263 (M+, 8), 187 (12), 186 (100), 51 (13); IR (neat) 3077
s, 3054 s, 3025 s, 1596 s, 1581 s, 1563 s, 1523 s, 1492 s, 1467 s, 1438 s,
1423 s, 1288 m, 1247 m, 1220 m, 1153 s, 997 m, 960 s, 836 s, 782 s,
754 s, 692 s, 646 s, 619 m, 551 s, 503 m cm−1. Anal. Calcd for
C17H13NS: C, 77.53; H, 4.98; N, 5.32. Found: C, 77.26; H, 4.92; N,
5.21.
1
1
Reaction of 32 with 6i. General procedure B was followed with 2-
(1H-pyrrol-1-yl)pyridine (32; 72.1 mg, 0.5 mmol) and 2-(1,3-
dimethyl-1H-indol-2-yl)ethenyl acetate (6i; 573.2 mg, 2.5 mmol),
except that the reaction was performed on a half scale (4, 7.9 mg,
0.025 mmol; toluene, 0.75 mL), 2.5 mmol, not 1.5 mmol, of the
alkenyl acetate was used, and 1 mmol of 2,6-lutidine (107.15 mg) was
also employed as an additive. Column chromatography (gradient
elution, 10/1−6/1 hexane/EtOAc) afforded 33b (193.0 mg, 0.4
mmol) as an orange solid in 80% yield: 1H NMR (CDCl3, 400.1
MHz) δ 2.27 (s, 6H, CCH3), 3.67 (s, 6H, NCH3), 6.58 (d, J = 16.3 Hz,
2H, ArCHCHAr), 6.78 (s, 2H, ArH), 6.90 (d, J = 16.3 Hz, 2H,
ArCHCHAr), 7.06 (ddd, J = 7.9, 6.8, 1.3 Hz, 2H, ArH), 7.14−7.22
(m, 4H, ArH), 7.38−7.43 (m, 2H, ArH), 7.48 (apparent br d, J = 7.8
Hz, 2H, ArH), 7.89 (ddd, J = 7.8, 7.6, 1.9 Hz, 1H, ArH), 8.72 (ddd, J =
4.8, 1.9, 0.7 Hz, 1H, ArH); 13C NMR (CDCl3, 100.5 MHz) δ 10.2,
30.4, 108.5, 108.7, 109.2, 115.2, 118.4, 119.0, 121.0, 121.9, 123.3,
123.5, 128.6, 134.6, 134.6, 137.3, 138.3, 149.7, 151.1; IR (KBr) 2927
w, 1585 w, 1469 s, 1438 m, 1356 m, 945 w, 735 s cm−1; HRMS (ESI)
calcd for [M + Na]+ (C33H30N4Na1) m/z 505.2368, found 505.2374.
Reaction of 34 with 6d. General procedure B was followed with
4,5-dihydro-4,4-dimethyl-2-(1H-pyrrol-1-yl)oxazole (34; 98.1 mg, 0.5
mmol) and styryl acetate (6d; 405.5 mg, 2.5 mmol), except that the
reaction was performed on a half scale (4, 7.9 mg, 0.025 mmol;
toluene, 0.75 mL), 2.5 mmol, not 1.5 mmol, of styryl acetate was used,
and 1 mmol of 2,6-lutidine (107.15 mg) was also employed as an
additive. Column chromatography (10/1 hexane/EtOAc) afforded 35
Reaction of 18 with 6d. General procedure B was followed with
1-phenyl-1H-pyrazole (18; 144.2 mg, 1 mmol) and styryl acetate (6d;
486.6 mg, 3 mmol). Column chromatography (9/1/0.1 hexane/
EtOAc/Et3N), followed by gel permeation chromatography (GPC)
and bulb-to-bulb distillation, afforded 19a (137.9 mg, 0.56 mmol) as a
1
colorless oil in 56% yield: H NMR (CDCl3, 270.1 MHz) δ 6.47 (s,
1H, ArH), 6.94 (d, J = 16.5 Hz, 1H, ArCHCHAr), 7.06 (d, J = 16.5
Hz, 1H, ArCHCHAr), 7.26−7.46 (m, 8H, ArH), 7.66 (d, J = 2.2 Hz,
1H, ArH), 7.75−7.78 (m, 2H, ArH); 13C NMR (CDCl3, 67.8 MHz) δ
106.5, 123.8, 126.2, 126.4, 126.6, 127.8, 128.0, 128.3, 128.5, 131.1,
131.4, 132.8, 136.8, 138.6, 140.6; LRMS (EI) m/z (% relative
intensity) 246 (M+, 35), 245 (41), 218 (12), 217 (14), 170 (11), 169
(100), 168 (13), 89 (11), 77 (10), 76 (13), 51 (14); IR (neat) 3027 m,
1598 w, 1573 w, 1515 s, 1496 s, 1461 s, 1415 w, 1394 s, 1328 m, 1191
w, 1095 w, 1045 m, 1020 w, 964 m, 937 m, 755 s, 728 m, 692 s, 622 w,
551 w, 522 m cm−1. Anal. Calcd for C17H14N2: C, 82.90; H, 5.73; N,
11.37. Found: C, 82.70; H, 5.67; N, 11.27. The synthetic procedure
also provided distyrylation product 19b (52.3 mg, 0.15 mmol), which
was similarly isolated as a white solid in 15% yield: 1H NMR (CDCl3,
270.1 MHz) δ 6.49 (d, J = 16.4 Hz, 2H, ArCHCHAr), 6.54 (d, J =
2.2 Hz, 1H, ArH), 7.02 (d, J = 15.9 Hz, 2H, ArCHCHAr), 7.21−
7.31 (m, 10H, ArH), 7.48 (t, J = 7.6 Hz, 1H, ArH), 7.55 (d, J = 1.9 Hz,
1H, ArH), 7.71 (d, J = 7.8 Hz, 2H, ArH), 7.87 (d, J = 1.6 Hz, 1H,
ArH); 13C NMR (CDCl3, 67.8 MHz) δ 106.5, 123.1, 124.7, 126.7,
128.0, 128.6, 129.4, 131.5, 132.9, 136.2, 136.6, 136.9, 140.7; LRMS
(EI) m/z (% relative intensity) 349 (22), 348 (M+, 98), 347 (100),
272 (19), 271 (84), 268 (10), 254 (12), 241 (13), 193 (13), 165 (10),
152 (11), 135 (24), 134 (10), 115 (10), 77 (17), 51 (15); IR (KBr)
3133 m, 3079 w, 3043 m, 1625 m, 1581 m, 1511 m, 1492 m, 1461 s,
1415 m, 1390 m, 1328 m, 1213 m, 1072 m, 1054 m, 1022 m, 962 s,
941 m, 854 w, 796 s, 775 s, 736 s, 690 s, 624 w, 553 w, 526 m, 505 m
cm−1. Anal. Calcd for C25H20N2: C, 86.17; H, 5.79; N, 8.04. Found: C,
85.93; H, 5.72; N, 8.03.
1
(172.2 mg, 0.43 mmol) as a pale yellow powder in 85% yield: H
NMR (CDCl3, 270.1 MHz) δ 1.51 (s, 6H, CH3), 4.27 (s, 2H, CH2),
6.62 (s, 2H, ArH), 6.91 (d, J = 16.2 Hz, 2H, ArCHCHAr), 7.21 (t, J
= 7.3 Hz, 2H, ArH), 7.30 (d, J = 16.2 Hz, 2H, ArCHCHAr), 7.33
(dd, J = 7.8, 7.3 Hz, 4H, ArH), 7.44 (d, J = 7.8 Hz, 4H, ArH); 13C
NMR (CDCl3, 100.5 MHz) δ 28.2, 66.8, 79.4, 109.9, 117.8, 126.1,
127.2, 127.3, 128.6, 134.6, 137.6, 152.8; IR (KBr) 3056 w, 3030 w,
2974 m, 2964 m, 2927 w, 1726 w, 1663 s, 1622 m, 1596 m, 1573 w,
1547 w, 1495 m, 1463 m, 1447 m, 1415 s, 1367 s, 1333 m, 1285 w,
1259 m, 1231 m, 1201 m, 1180 m, 1076 s, 1031 m, 1011 w, 949 s, 839
w, 817 w, 774 s, 747 s, 723 w, 693 s, 647 w, 619 w, 549 w, 507 w cm−1;
HRMS (ESI) calcd for [M + Na]+ (C25H24N2NaO) m/z 391.1786,
found 391.1769.
Preparation of 6i. The literature procedure59 was followed with
2.03 g of 2-(1,3-dimethyl-1H-indol-2-yl)acetaldehyde (10.8 mmol),
and the reaction was carried out for 16.5 h. Column chromatography
(15/1 hexane/EtOAc) afforded 6i (1.77 g, 7.7 mmol) as an orange
1
solid in 71% yield (E:Z = 66:34): H NMR (CDCl3, 270.1 MHz) δ
2.16 (s, 3H, CH3 (Z isomer)), 2.23 (s, 3H, CH3 (E isomer)), 2.26 (s,
3H, CH3 (Z isomer)), 2.38 (s, 3H, CH3 (E isomer)), 3.65 (s, 3H,
NCH3 (Z isomer)), 3.70 (s, 3H, NCH3 (E isomer)), 5.85 (d, J = 7.2
Hz, 1H, OCHCHAr (Z isomer)), 6.47 (d, J = 12.8 Hz, 1H, OCH
CHAr (E isomer)), 7.06−7.14 (m, 1H, ArH), 7.16−7.29 (m, 2H,
ArH), 7.43 (d, J = 7.2 Hz, 1H, OCHCHAr (Z isomer)), 7.52−7.58
(m, 1H, ArH), 7.65 (d, J = 12.8 Hz, 1H, OCHCHAr (E isomer));
13C NMR (E isomer, CDCl3, 100.5 MHz) δ 9.90, 20.6, 30.2, 104.8,
N
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
108.7, 109.2, 118.6, 119.0, 121.9, 128.3, 130.0, 137.2, 138.4, 167.7; IR
(KBr) 3118 m, 3059 m, 2937 m, 2857 m, 1742 s, 1658 m, 1541 w,
1471 m, 1412 w, 1371 s, 1333 w, 1297 w, 1218 s, 1097 s, 1017 m, 928
s, 866 w, 823 w, 733 s, 658 m, 618 w, 597 m, 552 m cm−1; HRMS
(ESI) calcd for [2M + AcOH + H]+ (C30H35N2O6) m/z 519.2495,
found 519.2500.
was heated in an oil bath at 120 °C for 3 h. The reaction mixture was
cooled to room temperature, and hexane (20 mL) was added at −78
°C. A mixture of 38a and 39a as a brown precipitate was collected by
filtration and washed twice with hexane (10 mL, 5 mL) at −78 °C. To
the 38a/39a mixture was added toluene (2 mL) at room temperature
to give 39a as a red precipitate, which was collected by filtration and
washed three times with hexane (2 mL each) at room temperature.
The filtrate of 38a was carried out by further purification shown below.
Red crystals of 39a (36.5 mg, 0.06 mmol) were obtained by
recrystallization from toluene (2.8 mL) at 120 °C to room
temperature in 12% yield. The filtrate of 38a was concentrated in
vacuo and extracted with toluene (1 mL) and twice with hexane (2 mL
each) at room temperature to remove the remaining 39a. The filtrate
was concentrated, and toluene (3 mL) and hexane (14 mL) were
added to the residue and then cooled to −78 °C. The yellow powder
38a (86.1 mg, 0.195 mmol) was obtained by filtration at −78 °C in
39% yield.
Mechanistic Studies of the C−H Alkenylation with Alkenyl
Esters. For the mechanistic studies (Tables 5−7, eq 3, and Scheme 4),
the alkenylation reactions were performed in a Schlenk flask or an
NMR tube by following general procedure A using appropriate
reagents. For the reactions analyzed by GC, after the addition of
triethylamine, tetracosane (internal standard) was also introduced to
the reaction mixture, which was then subjected to GC analysis. The
1
1
deuterium contents were determined by H NMR analysis. H NMR
chemical shifts of the protons at the Cα and Cβ positions of 25 were
determined on the basis of 1H,1H COSY, HMQC, and HMBC
analyses. The stereochemistry of product 7h prepared by the reaction
of 1 with 6h (Table 1, entries 11 and 12) was assigned on the basis of
1H,1H COSY and NOESY analyses.
1
Characterization data for 38a: mp 174−175 °C dec; H NMR
(C6D6, 391.8 MHz) δ 1.50 (dd, J = 7.2, 7.2 Hz, 1 H, cod), 1.56−1.73
(m, 2 H, cod), 1.75 (s, 3 H, −OCH(O)CH3), 2.05−2.13 (m, 1 H,
cod), 2.16 (s, 3 H, ArCH3), 2.20−2.19 (m, 2 H, cod), 2.30−2.41 (m, 2
H, cod), 3.01 (ddd, J = 8.1, 8.1, 5.4 Hz, 1 H, cod), 3.25 (dddd, J =
14.4, 10.1, 10.1, 6.5 Hz, 1 H, cod), 4.07 (dd, J = 7.3, 7.3 Hz, 1 H, cod),
4.59 (ddd, J = 8.5, 8.5, 5.2 Hz, 1 H, cod), 6.34 (dd, J = 7.6, 5.6 Hz, 1 H,
ArH), 6.63 (d, J = 7.6 Hz, 1 H, ArH), 7.23 (dd, J = 7.5, 7.5 Hz, 1 H,
ArH), 7.39 (dd, J = 7.5, 7.5 Hz, 1 H, ArH), 7.85 (d, J = 7.9 Hz, 1 H,
ArH), 8.49 (d, J = 7.2 Hz, 1 H, ArH), 8.92 (dd, J = 5.6, 1.1 Hz, 1 H,
ArH); 13C NMR (C6D6, 98.5 MHz) δ 23.0, 24.7, 28.7, 28.9, 29.0, 34.3,
72.8, 77.9, 88.8, 96.0, 119.5, 122.6, 127.9, 128.7, 130.2, 137.4, 139.5,
145.4, 148.1, 163.1, 181.0, 186.0; IR (KBr) 3036 w, 2972 w, 2909 w,
2871 w, 2829 w, 1574 w, 1525 m, 1456 s, 1422 s, 1380 w, 1252 w,
1122 w, 1011 w, 940 w, 877 w, 781 w, 738 m, 676 m, 503 w cm−1.
Anal. Calcd for C22H25NO2Ru: C, 60.53; H, 5.77; N, 3.21. Found: C,
60.36; H, 5.72; N, 3.11.
General Procedure for Determination of the Reaction Rate
Constant of the Regioselective Alkenylation of 3-Methyl-2-
phenylpyridine (24) Using β-Styryl Acetate (6d) Catalyzed by
Ru(cod)(cot) (4). In a glovebox, 1,3,5-trimethoxybenzene as an
internal standard and a catalytic amount of Ru(cod)(cot) (4) were
placed in a NMR tube, and then toluene-d8, 3-methyl-2-phenylpyridine
(24), and an excess amount of β-styryl acetate (6d) were added in that
order. The tube was sealed and heated in an oil bath at 90 °C. The
reaction mixture was monitored by measuring the concentration of the
alkenylation product 25 by 1H NMR. For all experiments, the
concentration of 25 was considered to be nearly proportinal to the
reaction time, which means these reactions follow zeroth-order
kinetics. Thus, the rate constants kobs were calculated from the slope
of the change in the concentration of 25 with time (d[25]/dt):
d[25]/dt = k[24]0[6d]b[4]c = kobs kobs = k[6d]b[4]c
1
Characterization data for 39a: mp 189−190 °C dec; H NMR
(CDCl3, 391.8 MHz) δ 1.75 (s, 3 H, −OCH(O)CH3), 2.36 (s, 1.5
H, toluene), 2.40 (s, 3 H, ArCH3), 2.64 (s, 3 H, ArCH3), 3.46 (d, J =
10.5 Hz, 1 H, vinyl H), 4.82 (d, J = 10.5 Hz, 1 H, vinyl H), 5.65 (s, 1
H, ArH), 5.67 (s, 1 H, ArH), 6.37 (d, J = 7.9 Hz, 1 H, ArH), 6.40 (d, J
= 7.6 Hz, 1 H, ArH), 6.56−6.60 (m, 1 H, ArH), 6.72−6.77 (m, 1 H,
ArH), 6.91(ddd, J = 7.3, 7.3, 1.3 Hz, 1 H, ArH), 6.95−6.99 (m, 2 H,
ArH), 7.03 (dd, J = 7.6 Hz, 5.6 Hz, 1 H, ArH), 7.16−7.28 (m, 3 H,
ArH), 7.41 (ddd, J = 7.3 Hz, 7.3 Hz, 1.8 Hz, 1 H, ArH), 7.46 (d, J = 8.1
Hz, 1 H, ArH), 7.65 (d, J = 7.6 Hz, 1 H, ArH), 7.87 (d, J = 7.9 Hz, 1 H,
ArH), 8.77 (dd, J = 5.4, 1.3 Hz, 1 H, ArH), 8.84 (dd, J = 5.4, 1.3 Hz, 1
H, ArH); 13C NMR (CDCl3, 98.5 MHz) δ 21.5 (toluene), 22.3
(ArCH3), 23.1 (ArCH3), 24.2 (COCH3), 70.3 (CC), 72.7 (C
C), 118.9, 119.2, 120.6, 123.3, 124.1, 124.3, 125.3 (toluene), 126.2,
126.4, 128.0, 128.2 (toluene), 129.0 (toluene), 129.2, 129.9, 130.6,
131.2, 131.8, 133.8, 134.6, 138.3, 139.1, 142.3, 142.8, 145.0, 149.5,
153.3, 160.8, 165.2, 184.1 (RuC), 185.8 (CO); IR (KBr) 3045 w,
2980 w, 2925 w, 2869 w, 1917 w, 1727 w, 1594 w, 1575 m, 1537 m,
1448 s, 1416 s, 1379 w, 1344 w, 1302 w, 1259 w, 1232 w, 1160 w,
1119 w, 1077 w, 1028 w, 1001 w, 937 w, 790 m, 762 m, 736 s, 695 m,
675 m, 546 m cm−1. Anal. Calcd for C75H68N4O4Ru2 (39a·
2(toluene)): C, 69.75; H, 5.31; N, 4.34. Found: C, 69.87; H, 5.27;
N, 4.23.
Preparation of 38b and 39b (Eq 5). In a glovebox, Ru(cod)(cot)
(4; 157.7 mg, 0.5 mmol), 2-(2-methylphenyl)pyridine (1; 169.2 mg,
1.0 mmol), β-styryl acetate (6d; 162.2 mg, 1.0 mmol, E:Z = 66:34),
and toluene (1 mL) were placed in a 50 mL Schlenk tube. The mixture
was heated in an oil bath at 120 °C for 3 h. The reaction mixture was
cooled to room temperature, and hexane (40 mL) was added at −78
°C. A mixture of 38b and 39b as a brown precipitate was collected by
filtration and washed twice with hexane (10 mL each) at −78 °C. To
the 38b/39b mixture were added CH2Cl2 (1 mL) and hexane (30 mL)
at −78 °C. A brown precipitate containing 39b was removed by
filtration. The filtrate of 38b was concentrated in vacuo, and
recrystallization from toluene (4.5 mL) and hexane (50 mL) afforded
38b (21.7 mg, 0.05 mmol) as yellow crystals in 10% yield: mp 181−
Determination of the Effect of Acetic Acid (Table 9, Entries 3
and 4). In a glovebox, 1,3,5-trimethoxybenzene (16.8 mg, 0.1 mmol)
as an internal standard and Ru(cod)(cot) (4; 6.3 mg, 20 μmol) were
placed in a NMR tube, and then toluene-d8, 3-methyl-2-phenylpyridine
(24; 16 μL, 0.1 mmol), and β-styryl acetate (6d; 309 μL, 2.0 mmol, E/
Z = 66:34) were added in that order. The tube was sealed and heated
in an oil bath at 90 °C for 200 min. Acetic acid was added, and the
mixture was heated and monitored by measuring the concentration of
the alkenylation product 25 by 1H NMR. The concentrations of acetic
acid and the rates were as follows; 35 mM (2 μL, 35 μmol, toluene-d8
673 μL, kobs = 14.4 × 10−7 M s−1), 0.1 M (6 μL, 0.1 mmol, toluene-d8
669 μL, kobs = 15.0 × 10−7 M s−1).
Determination of the Effect of 1,5-COD (Table 9, Entry 5). In
a glovebox, 1,3,5-trimethoxybenzene (16.8 mg, 0.1 mmol) as an
internal standard and Ru(cod)(cot) (4; 6.3 mg, 20 μmol) were placed
in a NMR tube, and then toluene-d8 (672 μL), 1,5-COD (3 μL, 24
μmol), 3-methyl-2-phenylpyridine (24; 16 μL, 0.1 mmol), and β-styryl
acetate (6d; 309 μL, 2.0 mmol, E:Z = 66:34) were added in that order.
The tube was sealed and heated in an oil bath at 90 °C. The reaction
mixture was monitored by measuring the concentration of the
1
alkenylation product 25 by H NMR (kobs = 12.2 × 10−7 M s−1).
Determination of the Kinetic Isotope Effect (Eq 12). In a
glovebox, 1,3,5-trimethoxybenzene (16.8 mg, 0.1 mmol) as an internal
standard and Ru(cod)(cot) (4; 6.3 mg, 20 μmol) were placed in a
NMR tube, and then toluene-d8 (675 μL), 3-methyl-2-phenylpyridine
(24; 16 μL, 0.1 mmol) or 2-(pentadeuteriophenyl)-3-picoline (24-d5;
16 μL, 0.1 mmol), and β-styryl acetate (6d; 309 μL, 2.0 mmol, E:Z =
66:34) were added in that order. The tube was sealed and heated in an
oil bath at 90 °C. The reaction mixture was monitored by measuring
1
the concentration of the alkenylation product (25-dn) by H NMR
(kobs(25) = 14.5 × 10−7 M s−1, kobs(25-d5) = 14.6 × 10−7 M s−1).
Preparation of 38a and 39a (Eq 4). In a glovebox, Ru(cod)(cot)
(4; 157.7 mg, 0.5 mmol), 3-methyl-2-phenylpyridine (24; 169.2 mg,
1.0 mmol), β-styryl acetate (6d; 162.2 mg, 1.0 mmol, E:Z = 66:34),
and toluene (1 mL) were placed in a 50 mL Schlenk tube. The mixture
O
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
182 °C dec; 1H NMR (C6D6, 391.8 MHz) δ 1.44 (dd, J = 6.7 Hz, 6.7
Hz, 1 H, cod), 1.60−1.71 (m, 2 H, cod), 1.74 (s, 3 H, -C(O)CH3),
2.08−2.14 (m, 1 H, cod), 2.22−2.37 (m, 4 H, cod), 2.37 (s, 3 H,
ArCH3), 2.95 (ddd, J = 7.9, 7.9, 5.6 Hz, 1 H, cod), 3.27 (dddd, 14.4,
10.3, 10.3, 6.3 Hz, 1 H, cod), 4.10 (dd, J = 7.6, 7.6 Hz, 1 H, cod),
4.55−4.61 (m, 1 H, cod), 6.38 (ddd, J = 7.3, 5.8, 1.3 Hz, 1 H, ArH),
6.80 (ddd, J = 8.3, 7.4, 1.8 Hz, 1 H, ArH), 7.01 (d, J = 7.2 Hz, 1 H,
ArH), 7.29 (dd, J = 7.6, 7.6 Hz, 1 H, ArH), 7.49 (d, J = 8.5 Hz, 1 H,
ArH), 8.34 (d, J = 8.1 Hz, 1 H, ArH), 8.98 (dd, J = 5.8, 1.8 Hz, 1 H,
ArH); 13C NMR (C6D6, 98.5 MHz) δ 24.6, 24.7, 28.6, 28.9, 29.1, 34.5,
72.4, 77.3, 89.4, 97.1, 119.7, 122.1, 128.6, 134.5, 135.5, 135.7, 136.9,
142.5, 150.6, 165.2, 180.9, 186.1; IR (KBr) 3042 w, 2973 m, 2911 m,
2867 m, 2823 m, 1595 m, 1561 s, 1525 s, 1454 s, 1300 m, 1247 m,
1181 w, 1130 w, 1088 w, 1009 w, 940 m, 835 m, 763 s, 724 m, 676 s
cm−1. Anal. Calcd for C22H25NO2Ru: C, 60.53; H, 5.77; N, 3.21.
Found: C, 60.56; H, 5.57; N, 3.22.
Catalytic Activities of 38a and 39a (Eq 6). In a glovebox, 1,5-
COD coordinated complex 38a (4.4 mg, 0.01 mmol) or alkenylation
product coordinated complex 39a (6.0 mg, 0.01 mmol) and a
magnetic stirring bar were placed in a 20 mL pressure tube, and then
toluene (0.5 mL), 2-(2-methylphenyl)pyridine (1; 16.9 mg, 0.1
mmol), and β-styryl acetate (6d; 48.7 mg, 0.3 mmol, E/Z = 66:34)
were added in that order. The tube was sealed and heated in an oil
bath at 120 °C for 24 h. After it was cooled, the resulting mixture was
diluted with dichloromethane (2 mL), and triethylamine (ca. 0.1 mL)
and n-tetracosane as an internal standard were added. The resulting
mixture was analyzed by GC.
tetracosane as an internal standard were added. The resulting mixture
was analyzed by GC.
Observation of Intermolecular H−D Scrambling at the
Ortho Positions of 24 and 24-d5 with 6d Catalyzed by 4
(Table 10, Entry 1). In a glovebox, Ru(cod)(cot) (4; 15.8 mg, 0.05
mmol) and a magnetic stirring bar were placed in a 20 mL pressure
tube. Then toluene (1.0 mL), 3-methyl-2-phenylpyridine (24; 84.6
mg, 0.5 mmol), 2-(pentadeuteriophenyl)-3-picoline (24-d5; 87.1 mg,
0.5 mmol), and β-styryl acetate (6d; 486.6 mg, 3.0 mmol, E:Z =
66:34) were added to the tube in that order. The tube was sealed and
heated in an oil bath at 120 °C for 1 h. After it was cooled, the
resulting mixture was diluted with dichloromethane (2 mL), and
triethylamine (ca. 0.1 mL) and n-tetracosane as an internal standard
were added. GC analysis of the reaction mixture revealed that 24-dn
and 25-dn were obtained in 97% and 2% yields, respectively. After
removal of the volatile materials by rotary evaporation, the starting
material and alkenylation product were isolated by silica gel column
chromatography (10/1 hexane/EtOAc), followed by Kugelrohr
distillation, to afford 24-dn (Mw = 171.7) as a pale yellow oil (153.0
1
mg, 89%) and 25-dn (Mw = 273.9) as a yellow oil (7.0 mg, 3%). H
2
and H NMR analysis of the isolated 24-dn showed 1.03 H (0.97 D)
content at the ortho positions (δ 7.61 in C6D6 and C6H6), and APCI
MS spectrometry indicated that the intermolecular H−D scrambling
reaction at the ortho positions had completely occurred.
Observation of Intermolecular H−D Scrambling at the
Ortho Positions of 24 and 24-d5 with 6d Catalyzed by 38a
(Table 10, Entry 2). In a glovebox, 1,5-COD coordinated complex
38a (10.9 mg, 0.025 mmol) and a magnetic stirring bar were placed in
a 20 mL pressure tube, and then toluene (0.5 mL), 3-methyl-2-
phenylpyridine (24; 42.3 mg, 0.25 mmol), 2-(pentadeuteriophenyl)-3-
picoline (24-d5; 43.6 mg, 0.25 mmol), and β-styryl acetate (6d; 243.3
mg, 1.5 mmol, E:Z = 66:34) were added in that order. The tube was
sealed and heated in an oil bath at 120 °C for 1 h. After it was cooled,
the resulting mixture was diluted with dichloromethane (2 mL), and
triethylamine (ca. 0.1 mL) and n-tetracosane as an internal standard
were added. GC analysis of the reaction mixture revealed that 24-dn
and 25-dn were obtained in 99% and <1% yields, respectively. After
removal of the volatile materials by rotary evaporation, the starting
material and alkenylation product were isolated by silica gel column
chromatography (9/1 hexane/EtOAc), followed by Kugelrohr
distillation, to afford 24-dn (Mw = 171.7) as a pale yellow oil (84.8
mg, 99%). 1H and 2H NMR analysis of the isolated 24-dn showed 1.04
H (0.96 D) content at the ortho positions (δ 7.61 in C6D6 and C6H6),
and APCI MS spectrometry indicated that the intermolecular H−D
scrambling reaction at the ortho positions had completely occurred.
Observation of Intermolecular H−D Scrambling of 24 and
24-d5 Catalyzed by 4 (Table 10, Entry 3). In a glovebox,
Ru(cod)(cot) (4; 3.2 mg, 0.01 mmol) and a magnetic stirring bar were
placed in a 20 mL pressure tube, and then toluene (0.2 mL), 3-methyl-
2-phenylpyridine (24; 16.9 mg, 0.1 mmol), and 2-(pentadeuter-
iophenyl)-3-picoline (24-d5; 17.4 mg, 0.1 mmol) were added in that
order. The tube was sealed and heated in an oil bath at 120 °C for 1 h.
After removal of the volatile materials by rotary evaporation, the
resulting mixture was purified through silica gel column chromatog-
raphy (hexane), to afford 24-dn (Mw = 171.7) as a pale yellow oil (36.0
Formation of 38a from 39a (Eq 7). In a glovebox, alkenylation
product coordinated complex 39a (3.0 mg, 5 μmol) was placed in a
NMR tube, and then toluene-d8 (0.6 mL) and 1,5-COD (1 μL, 8
μmol) were added in that order. The tube was sealed and heated in an
oil bath at 100 °C for 1 h. Acetic acid (1 μL, 17 μmol) was added, and
the mixture was heated at 100 °C. The progress of the reaction was
1
monitored by H NMR.
Stoichiometric Reactions of 38b with 6d (Eq 8). In a glovebox,
1,5-COD coordinated complex 38b (8.7 mg, 0.02 mmol) was placed
in a NMR tube, and then toluene-d8 (922 μL) and β-styryl acetate (6d;
78 μL, 0.5 mmol, E:Z = 66:34) were added in that order. The tube was
sealed and heated in an oil bath at 120 °C. After it was cooled, the
reaction mixture was diluted with dichloromethane (2 mL), and
triethylamine (ca. 0.1 mL) and n-tetracosane as an internal standard
were added. The resulting mixture was analyzed by GC.
Alkenylation of 1 with 6d Catalyzed by 4 (Eq 9). In a glovebox,
Ru(cod)(cot) (4; 6.3 mg, 0.02 mmol) was placed in a NMR tube, and
then toluene-d8 (906 μL), 2-(2-methylphenyl)pyridine (1; 16 μL, 0.1
mmol), and β-styryl acetate (6d; 78 μL, 0.5 mmol, E:Z = 66:34) were
added in that order. The tube was sealed and heated in an oil bath at
120 °C. After it was cooled, the reaction mixture was diluted with
dichloromethane (2 mL), and triethylamine (ca. 0.1 mL) and n-
tetracosane as an internal standard were added. The resulting mixture
was analyzed by GC.
Stoichiometric Reaction of 38a with 1 and 6d (Eq 10). In a
glovebox, 1,5-COD coordinated complex 38a (8.7 mg, 20 μmol) and a
magnetic stirring bar were placed in a 20 mL pressure tube, and then
toluene (0.1 mL), 2-(2-methylphenyl)pyridine (1; 3.4 mg, 20 μmol),
and β-styryl acetate (6d; 19.5 mg, 120 μmol, E:Z = 66:34) were added
in that order. The tube was sealed and heated in an oil bath at 120 °C
for 24 h. After it was cooled, the resulting mixture was diluted with
dichloromethane (2 mL), and triethylamine (ca. 0.1 mL) and n-
tetracosane as an internal standard were added. The resulting mixture
was analyzed by GC.
Stoichiometric Reaction of 38b with 24 and 6d (Eq 11). In a
glovebox, 1,5-COD coordinated complex 38b (8.7 mg, 20 μmol) and a
magnetic stirring bar were placed in a 20 mL pressure tube, and then
toluene (0.1 mL), 3-methyl-2-phenylpyridine (24; 3.4 mg, 20 μmol),
and β-styryl acetate (6d; 19.5 mg, 120 μmol, E:Z = 66:34) were added
in that order. The tube was sealed and heated in an oil bath at 120 °C
for 24 h. After it was cooled, the resulting mixture was diluted with
dichloromethane (2 mL), and triethylamine (ca. 0.1 mL) and n-
1
2
mg, quant). H and H NMR analysis of the isolated 24-dn showed
1.05 H (0.95 D) content at the ortho positions (δ 7.61 in C6D6 and
C6H6) and 0.87 H (0.13 D) content at the 2- positions on the pyridine
ring (δ 8.53 in C6D6 and 8.52 in C6H6).
Observation of Intermolecular H−D Scrambling at the
Ortho Positions of 24 and 24-d5 Catalyzed by 38a (Table 10,
Entry 4). In a glovebox, 1,5-COD coordinated complex 38a (4.4 mg,
0.01 mmol) and a magnetic stirring bar were placed in a 20 mL
pressure tube, and then toluene (0.2 mL), 3-methyl-2-phenylpyridine
(24; 16.9 mg, 0.1 mmol), and 2-(pentadeuteriophenyl)-3-picoline (24-
d5; 17.4 mg, 0.1 mmol) were added in that order. The tube was sealed
and heated in an oil bath at 120 °C for 1 h. After removal of the
volatile materials by rotary evaporation, the resulting mixture was
purified through silica gel column chromatography (hexane), to afford
1
2
24-dn (Mw = 171.7) as a pale yellow oil (36.4 mg, quant). H and H
P
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
NMR analysis of the isolated 24-dn showed 1.07 H (0.93 D) content at
the ortho positions (δ 7.61 in C6D6 and C6H6), and APCI MS
spectrometry indicated that the intermolecular H−D scrambling
reaction at the ortho positions had completely occurred.
Synthesis 2008, 3013−3039. (l) Godula, K.; Sames, D. Science 2006,
312, 67−72. (m) Park, Y. J.; Jun, C.-H. Bull. Korean Chem. Soc. 2005,
26, 871−877. (n) Kakiuchi, F.; Chatani, N. In Ruthenium in Organic
Synthesis; Murahashi, S.-I., Ed.; Wiley-VCH: Weinheim, Germany,
2004; pp 219−255. (o) Kakiuchi, F.; Chatani, N. Top. Organomet.
Chem. 2004, 11, 45−79. (p) Kakiuchi, F.; Chatani, N. Adv. Synth.
Catal. 2003, 345, 1077−1101. (q) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. Rev. 2002, 102, 1731−1769. (r) Kakiuchi, F.; Murai, S. Top.
Organomet. Chem. 1999, 3, 47−79. (s) Dyker, G. Angew. Chem., Int. Ed.
1999, 38, 1698−1712.
(4) (a) Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1979, 339−
342. (b) Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1980, 9, 507−
510. (c) Hong, P.; Yamazaki, H. J. Mol. Catal. 1983, 21, 133−150.
(d) Tokunaga, Y.; Sakakura, T.; Tanaka, M. J. Mol. Catal. 1989, 56,
305−314. (e) Boese, W. T.; Goldman, A. S. Organometallics 1991, 10,
782−786. (f) Schipper, D. J.; Hutchinson, M.; Fagnou, K. J. Am. Chem.
Soc. 2010, 132, 6910−6911.
(5) (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara,
Y. Science 2000, 287, 1992−1995. (b) Jia, C.; Lu, W.; Oyamada, J.;
Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc.
2000, 122, 7252−7263. (c) Tsukada, N.; Mitsuboshi, T.; Setoguchi,
H.; Inoue, Y. J. Am. Chem. Soc. 2003, 125, 12102−12103. (d) Tsukada,
N.; Murata, K.; Inoue, Y. Tetrahedron Lett. 2005, 46, 7515−7517.
(6) (a) Nakao, Y.; Kanyiva, K. S.; Oda, S.; Hiyama, T. J. Am. Chem.
Soc. 2006, 128, 8146−8147. (b) Nakao, Y.; Kanyiva, K. S.; Hiyama, T.
J. Am. Chem. Soc. 2008, 130, 2448−2449. (c) Nakao, Y.; Kashihara, N.;
Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 16170−16171.
(d) Mukai, T.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74,
6410−6413. (e) Kanyiva, K. S.; Kashihara, N.; Nakao, Y.; Hiyama, T.;
Ohashi, M.; Ogoshi, S. Dalton Trans. 2010, 39, 10483−10494.
(f) Nakao, Y. Chem. Rec. 2011, 11, 242−251. (g) Liu, S.; Sawicki, J.;
Driver, T. G. Org. Lett. 2012, 14, 3744−3747.
Observation of Intramolecular H−D Scrambling at the
Ortho Positions of 24-d1 with 6d Catalyzed by 4. In a glovebox,
Ru(cod)(cot) (4; 7.9 mg, 0.025 mmol) and a magnetic stirring bar
were placed in a 20 mL pressure tube, and then toluene (0.5 mL), 2-
(2-deuteriophenyl)-3-methylpyridine (24-d1; 85.1 mg, 0.5 mmol), and
β-styryl acetate (6d; 243.3 mg, 1.5 mmol, E:Z = 66:34) were added in
that order. The tube was sealed and heated in an oil bath at 120 °C for
1 h. After it was cooled, the resulting mixture was diluted with
dichloromethane (2 mL), and triethylamine (ca. 0.1 mL) and n-
tetracosane as an internal standard were added. GC analysis of the
reaction mixture revealed that 24-dn and 25-dn were obtained in 96%
and 2% yields, respectively. After removal of the volatile materials by
rotary evaporation, the starting material and alkenylation product were
isolated by silica gel column chromatography (10/1 hexane/EtOAc),
followed by Kugelrohr distillation, to afford 24-dn (Mw = 170.2) as a
pale yellow oil (75.0 mg, 88%) and 25-dn (Mw = 272.4) as a yellow oil
1
2
(2.4 mg, 2%). H and H NMR analysis of the isolated 24-dn showed
0.95 H (1.05 D) content at the ortho positions (δ 7.61 in C6D6 and
C6H6), and APCI MS spectrometry indicated that the intramolecular
H−D scrambling reaction at ortho positions had completely occurred.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, tables, figures, and CIF files giving experimental details,
characterization data, and crystallographic data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for F.K.: kakiuchi@chem.keio.ac.jp.
■
(7) (a) Ding, Z.; Yoshikai, N. Org. Lett. 2010, 12, 4180−4183.
(b) Ding, Z.; Yoshikai, N. Synthesis 2011, 2561−2566.
(8) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2011, 13,
3076−3079.
Notes
The authors declare no competing financial interest.
(9) (a) Yoon, M. Y.; Kim, J. H.; Choi, D. S.; Shin, U. S.; Lee, J. Y.;
Song, C. E. Adv. Synth. Catal. 2007, 349, 1725−1737. (b) Yadav, J. S.;
Reddy, B. V. S.; Sengupta, S.; Biswas, S. K. Synthesis 2009, 1301−1304.
(c) de Mendoza, P.; Echavarren, A. M. Pure Appl. Chem. 2010, 82,
801−820. (d) Qiu, Y.; Kong, W.; Fu, C.; Ma, S. Org. Lett. 2012, 14,
6198−6201. (e) Rao, V. K.; Shelke, G. M.; Tiwari, R.; Parang, K.;
Kumar, A. Org. Lett. 2013, 15, 2190−2193.
ACKNOWLEDGMENTS
■
This work was supported, in part, by a Grant-in-Aid for
Scientific Research (21350056) from MEXT and by a Grant for
Private Education Institute Aid from MEXT. Y.O. acknowl-
edges a Research Fellowship of JSPS for Young Scientists
(4259).
(10) (a) Halbritter, G.; Knoch, F.; Wolski, A.; Kisch, H. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1603−1605. (b) Durr, U.; Kisch, H.
̈
Synlett 1997, 1335−1341. (c) Gao, K.; Lee, P.-S.; Fujita, T.; Yoshikai,
N. J. Am. Chem. Soc. 2010, 132, 12249−12251. (d) Yoshikai, N. Synlett
2011, 1047−1051. (e) Lee, P.-S.; Fujita, T.; Yoshikai, N. J. Am. Chem.
Soc. 2011, 133, 17283−17295.
REFERENCES
■
(1) (a) Grimsdale, A. C.; Chan, K. L.; Martin, R. E.; Jokisz, P. G.;
Holmes, A. B. Chem. Rev. 2009, 109, 897−1091. (b) Murphy, A. R.;
́
Frechet, J. M. J. Chem. Rev. 2007, 107, 1066−1096. (c) Yamamoto, T.
(11) (a) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem.
Lett. 1995, 24, 681−682. (b) Harris, P. W. R.; Rickard, C. E. F.;
Woodgate, P. D. J. Organomet. Chem. 1999, 589, 168−179. (c) Cheng,
K.; Yao, B.; Zhao, J.; Zhang, Y. Org. Lett. 2008, 10, 5309−5312.
(d) Ackermann, L.; Lygin, A. V.; Hofmann, N. Angew. Chem., Int. Ed.
2011, 50, 6379−6382. (e) Li, B.; Feng, H.; Xu, S.; Wang, B. Chem. Eur.
J. 2011, 17, 12573−12577. (f) Hashimoto, Y.; Hirano, K.; Satoh, T.;
Kakiuchi, F.; Miura, M. Org. Lett. 2012, 14, 2058−2061.
(g) Hashimoto, Y.; Hirano, K.; Satoh, T.; Kakiuchi, F.; Miura, M. J.
Org. Chem. 2013, 78, 638−646. (h) Itoh, M.; Hashimoto, Y.; Hirano,
K.; Satoh, T.; Miura, M. J. Org. Chem. 2013, 78, 8098−8104.
(12) (a) Aulwurm, U. R.; Melchinger, J. U.; Kisch, H. Organometallics
1995, 14, 3385−3395. (b) Lim, Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-
B. Tetrahedron Lett. 2001, 42, 7609−7612. (c) Lim, S.-G.; Lee, J.-H.;
Moon, C. W.; Hong, J.-B.; Jun, C.-H. Org. Lett. 2003, 5, 2759−2761.
(d) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407−1409.
(e) Satoh, T.; Ueura, K.; Miura, M. Pure Appl. Chem. 2008, 80, 1127−
1134. (f) Katagiri, T.; Mukai, T.; Satoh, T.; Hirano, K.; Miura, M.
Chem. Lett. 2009, 38, 118−119. (g) Shibata, Y.; Otake, Y.; Hirano, M.;
Macromol. Rapid Commun. 2002, 23, 583−606. (d) Scherf, U. Top.
Curr. Chem. 1999, 201, 163−222. (e) Friend, R. H.; Gymer, R. W.;
Holmes, A. B.; Burroughes, J. H.; Marks, R. N.; Taliani, C.; Bradley, D.
D. C.; Dos Santos, D. A.; Bred
Nature 1999, 397, 121−128.
(2) (a) The Mizoroki-Heck Reaction; Oestreich, M., Ed.; Wiley:
Chichester, U.K., 2009. (b) Farina, V. Adv. Synth. Catal. 2004, 346,
1553−1582. (c) Heck, R. F. Org. React. 1982, 27, 345−390.
(3) (a) Ackermann, L. Acc. Chem. Res. 2013, DOI: 10.1021/
ar3002798. (b) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem.
Rev. 2012, 112, 5879−5918. (c) Yeung, C. S.; Dong, V. M. Chem. Rev.
2011, 112, 1215−1292. (d) Satoh, T.; Miura, M. Chem. Eur. J. 2010,
16, 11212−11222. (e) Messaoudi, S.; Brion, J.-D.; Alami, M. Eur. J.
Org. Chem. 2010, 6495−6516. (f) Lyons, T. W.; Sanford, M. S. Chem.
Rev. 2010, 110, 1147−1169. (g) Colby, D. A.; Bergman, R. G.; Ellman,
J. A. Chem. Rev. 2010, 110, 624−655. (h) Chen, X.; Engle, K. M.;
Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094−5115.
(i) Kitamura, T. Eur. J. Org. Chem. 2009, 1111−1125. (j) Vasil’ev, A. V.
Russ. J. Org. Chem. 2009, 45, 1−17. (k) Kakiuchi, F.; Kochi, T.
́
as, J. L.; Logdlund, M.; Salaneck, W. R.
̈
Q
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Tanaka, K. Org. Lett. 2009, 11, 689−692. (h) Liu, G.; Shen, Y.; Zhou,
Z.; Lu, X. Angew. Chem., Int. Ed. 2013, 52, 6033−6037.
Miura, M. J. Org. Chem. 2009, 74, 7094−7099. (d) Patureau, F. W.;
Glorius, F. J. Am. Chem. Soc. 2010, 132, 9982−9983. (e) Patureau, F.
W.; Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 1064−1067.
(f) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc.
2011, 133, 2350−2353. (g) Tsai, A. S.; Brasse, M.; Bergman, R. G.;
Ellman, J. A. Org. Lett. 2011, 13, 540−542. (h) Park, S. H.; Kim, J. Y.;
Chang, S. Org. Lett. 2011, 13, 2372−2375. (i) Mochida, S.; Hirano, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2011, 76, 3024−3033. (j) Feng, C.;
Loh, T.-P. Chem. Commun. 2011, 47, 10458−10460. (k) Patureau, F.
W.; Nimphius, C.; Glorius, F. Org. Lett. 2011, 13, 6346−6349.
(l) Zheng, L.; Wang, J. Chem. Eur. J. 2012, 18, 9699−9704. (m) Wang,
C.; Chen, H.; Wang, Z.; Chen, J.; Huang, Y. Angew. Chem., Int. Ed.
2012, 51, 7242−7245. (n) Zhao, P.; Niu, R.; Wang, F.; Han, K.; Li, X.
Org. Lett. 2012, 14, 4166−4169. (o) Shen, Y.; Liu, G.; Zhou, Z.; Lu, X.
Org. Lett. 2013, 15, 3366−3369.
(22) (a) Weissman, H.; Song, X.; Milstein, D. J. Am. Chem. Soc. 2001,
123, 337−338. (b) Ueyama, T.; Mochida, S.; Fukutani, T.; Hirano, K.;
Satoh, T.; Miura, M. Org. Lett. 2011, 13, 706−708. (c) Arockiam, P.
B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Green Chem. 2011,
13, 3075−3078. (d) Hashimoto, Y.; Ueyama, T.; Fukutani, T.; Hirano,
K.; Satoh, T.; Miura, M. Chem. Lett. 2011, 40, 1165−1166. (e) Padala,
K.; Jeganmohan, M. Org. Lett. 2011, 13, 6144−6147. (f) Hashimoto,
Y.; Ortloff, T.; Hirano, K.; Satoh, T.; Bolm, C.; Miura, M. Chem. Lett.
2012, 41, 151−153. (g) Ackermann, L.; Wang, L.; Wolfram, R.; Lygin,
A. V. Org. Lett. 2012, 14, 728−731. (h) Li, B.; Ma, J.; Wang, N.; Feng,
H.; Xu, S.; Wang, B. Org. Lett. 2012, 14, 736−739. (i) Padala, K.;
Jeganmohan, M. Org. Lett. 2012, 14, 1134−1137. (j) Graczyk, K.; Ma,
W.; Ackermann, L. Org. Lett. 2012, 14, 4110−4113. (k) Li, B.; Ma, J.;
Liang, Y.; Wang, N.; Xu, S.; Song, H.; Wang, B. Eur. J. Org. Chem.
2013, 1950−1962. (l) Kozhushkov, S. I.; Ackermann, L. Chem. Sci.
2013, 4, 886−896.
(13) (a) Satoh, T.; Nishinaka, Y.; Miura, M.; Nomura, M. Chem. Lett.
1999, 28, 615−616. (b) Tsuchikama, K.; Kasagawa, M.; Hashimoto,
Y.; Endo, K.; Shibata, T. J. Organomet. Chem. 2008, 693, 3939−3942.
(c) Takebayashi, S.; Shibata, T. Organometallics 2012, 31, 4114−4117.
(14) (a) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2005,
127, 13498−13499. (b) Kuninobu, K.; Tokunaga, Y.; Kawata, A.;
Takai, K. J. Am. Chem. Soc. 2006, 128, 202−209. (c) Kuninobu, Y.;
Kikuchi, K.; Tokunaga, Y.; Nishina, Y.; Takai, K. Tetrahedron 2008, 64,
5974−5981. (d) Tang, Q.; Xia, D.; Jin, X.; Zhang, Q.; Sun, X.-Q.;
Wang, C. J. Am. Chem. Soc. 2013, 135, 4628−4631.
(15) (a) Tang, S.; Peng, P.; Pi, S.-F.; Liang, Y.; Wang, N.-X.; Li, J.-H.
Org. Lett. 2008, 10, 1179−1182. (b) Wang, C.; Rakshit, S.; Glorius, F.
J. Am. Chem. Soc. 2010, 132, 14006−14008. (c) Wang, L.; Huang, J.;
Peng, S.; Liu, H.; Jiang, X.; Wang, J. Angew. Chem., Int. Ed. 2013, 52,
1768−1772. (d) Kuran, M. R.; Bhanuchandra, M.; Sahoo, A. K. Angew.
Chem., Int. Ed. 2013, 52, 4607−4612.
(16) Shiota, H.; Ano, Y.; Aihara, Y.; Fukumoto, Y.; Chatani, N. J. Am.
Chem. Soc. 2011, 133, 14952−14955.
(17) (a) Gehrmann, T.; Fillol, J. L.; Scholl, S. A.; Wadepohl, H.;
Gade, L. H. Angew. Chem., Int. Ed. 2011, 50, 5757−5761.
(b) Gehrmann, T.; Scholl, S. A.; Fillol, J. L.; Wadepohl, H.; Gade,
L. H. Chem. Eur. J. 2012, 18, 3925−3941. (c) Scholl, S. A.; Wadepohl,
H.; Gade, L. H. Organometallics 2013, 32, 937−940.
(18) Zhou, B.; Chen, H.; Wang, C. J. Am. Chem. Soc. 2013, 135,
1264−1267.
(19) (a) Fujiwara, Y.; Kitamura, T. In Handbook of C−H
Transformations; Dyker, G., Ed.; Wiley-VCH: Weinheim, Germany,
2005; Vol. 1, pp 194−202. (b) Fujiwara, Y. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.;
Wiley: Hoboken, NJ, 2002; Vol. 2, pp 2863−2871.
(20) (a) Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S.
J. Am. Chem. Soc. 1969, 91, 7166−7169. (b) Tsuji, J.; Nagashima, H.
Tetrahedron 1984, 40, 2699−2702. (c) Miura, M.; Tsuda, T.; Satoh,
T.; Nomura, M. Chem. Lett. 1997, 26, 1103−1104. (d) Miura, M.;
Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63,
5211−5215. (e) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett.
1999, 1, 2097−2100. (f) Boele, M. D. K.; van Strijdonck, G. P. F.; de
Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N.
M. J. Am. Chem. Soc. 2002, 124, 1586−1587. (g) Yokota, T.; Tani, M.;
Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2003, 125, 1476−1477.
(h) Dams, M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew. Chem.,
Int. Ed. 2003, 42, 3512−3515. (i) Tani, M.; Sakaguchi, S.; Ishii, Y. J.
Org. Chem. 2004, 69, 1221−1226. (j) Grimster, N. P.; Gauntlett, C.;
Godfrey, C. R. A.; Gaunt, M. J. Angew. Chem., Int. Ed. 2005, 44, 3125−
3129. (k) Beck, E. M.; Grimster, N. P.; Hatley, R.; Gaunt, M. J. J. Am.
Chem. Soc. 2006, 128, 2528−2529. (l) Cai, G.; Fu, Y.; Li, Y.; Wan, X.;
Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666−7673. (m) Maehara, A.;
Satoh, T.; Miura, M. Tetrahedron 2008, 64, 5982−5986. (n) Maehara,
A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159−1162.
(23) Bernini, R.; Fabrizi, G.; Sferrazza, A.; Cacchi, S. Angew. Chem.,
Int. Ed. 2009, 48, 8078−8081.
(24) Guan, Z.-H.; Yan, Z.-Y.; Ren, Z.-H.; Liu, X.-Y.; Liang, Y.-M.
Chem. Commun. 2010, 46, 2823−2825.
(25) (a) Sasaki, K.; Sakakura, T.; Tokunaga, Y.; Wada, K.; Tanaka, M.
Chem. Lett. 1988, 17, 685−688. (b) Kakiuchi, F.; Sato, T.; Yamauchi,
M.; Chatani, N.; Murai, S. Chem. Lett. 1999, 28, 19−20. (c) Kwon, K.-
H.; Lee, D. W.; Yi, C. S. Organometallics 2010, 29, 5748−5750.
(26) Dehydrogenative alkenylation using an aldimine directing group
as a hydrogen acceptor has also been reported: Kuninobu, Y.;
Nakahara, T.; Yu, P.; Takai, K. J. Organomet. Chem. 2011, 696, 348−
351.
(27) (a) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Org. Chem. 2007, 72,
3600−3602. (b) Ueno, S.; Kochi, T.; Chatani, N.; Kakiuchi, F. Org.
Lett. 2009, 11, 855−858. (c) Wasa, M.; Chan, K. S. L.; Yu, J.-Q. Chem.
Lett. 2011, 40, 1004−1006. (d) Wasa, M.; Engle, K. M.; Lin, D. W.;
Yoo, E. J.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 19598−19601.
(e) Chinnagolla, R. K.; Jeganmohan, M. Org. Lett. 2012, 14, 5246−
5249.
́
(o) García-Rubia, A.; Arrayas, R. G.; Carretero, J. C. Angew. Chem., Int.
(28) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2009, 48, 6511−6515. (p) Yang, Y.; Cheng, K.; Zhang, Y. Org. Lett.
2009, 11, 5606−5609. (q) Wang, D.-H.; Engle, K. M.; Shi, B.-F.; Yu,
J.-Q. Science 2010, 327, 315−319. (r) Lu, Y.; Wang, D.-H.; Engle, K.
M.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 5916−5921. (s) Baxter, R.
D.; Sale, D.; Engle, K. M.; Yu, J.-Q.; Blackmond, D. G. J. Am. Chem.
Soc. 2012, 134, 4600−4606. (t) Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q.
Nature 2012, 486, 518−522. (u) Kubota, A.; Emmert, M. H.; Sanford,
M. S. Org. Lett. 2012, 14, 1760−1763. (v) Shao, J.; Chen, W.;
Giulianotti, M. A.; Houghten, R. A.; Yu, Y. Org. Lett. 2012, 14, 5452−
5455. (w) Li, G.; Leow, D.; Wan, L.; Yu, J.-Q. Angew. Chem., Int. Ed.
Ed. 2010, 49, 2202−2205.
(29) (a) Hughes, C. C.; Trauner, D. Angew. Chem., Int. Ed. 2002, 41,
1569−1572. (b) Hughes, C. C.; Trauner, D. Tetrahedron 2004, 60,
9675−9686. (c) Cruz, A. C. F.; Miller, N. D.; Willis, M. C. Org. Lett.
2007, 9, 4391−4393. (d) Gottumukkala, A. L.; Derridj, F.; Djebbar, S.;
Doucet, H. Tetrahedron Lett. 2008, 49, 2926−2930. (e) Koubachi, J.;
Kazzouli, S. E.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G.
Synthesis 2008, 2537−2542. (f) Ackermann, L.; Althammer, A.;
Fenner, S. Angew. Chem., Int. Ed. 2009, 48, 201−204. (g) Verrier, C.;
Hoarau, C.; Marsais, F. Org. Biomol. Chem. 2009, 7, 647−650.
(h) Mousseau, J. J.; Fortier, A.; Charette, A. B. Org. Lett. 2010, 12,
2013, 52, 1245−1247. (x) Babu, B. P.; Meng, X.; Backvall, J.-E. Chem.
̈
Eur. J. 2013, 19, 4140−4145. (y) Dai, H.-X.; Li, G.; Zhang, X.-G.;
Stepan, A. F.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 7567−7571.
(z) Meng, X.; Kim, S. Org. Lett. 2013, 15, 1910−1913.
516−519. (i) Ackermann, L.; Barfusser, S.; Pospech, J. Org. Lett. 2010,
̈
12, 724−726. (j) Ackermann, L.; Fenner, S. Chem. Commun. 2011, 47,
430−432. (k) Schneider, C.; Masi, D.; Couve-Bonnaire, S.;
Pannecoucke, X.; Hoarau, C. Angew. Chem., Int. Ed. 2013, 52,
3246−3249.
(21) (a) Matsumoto, T.; Yoshida, H. Chem. Lett. 2000, 29, 1064−
1065. (b) Matsumoto, T.; Periana, R. A.; Taube, D. J.; Yoshida, H. J.
Catal. 2002, 206, 272−280. (c) Umeda, N.; Hirano, K.; Satoh, T.;
R
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(30) (a) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 1128−
B. S.; Leatherman, M. D.; White, P. S.; Brookhart, M. J. Am. Chem. Soc.
2005, 127, 5132−5146. (j) Mariampillai, B.; Herse, C.; Lautens, M.
Org. Lett. 2005, 7, 4745−4747. (k) Zhao, H.; Ariafard, A.; Lin, Z.
Organometallics 2006, 25, 812−819. (l) Ohmiya, H.; Makida, Y.;
Tanaka, T.; Sawamura, M. J. Am. Chem. Soc. 2008, 130, 17276−17277.
̀
1129. (b) Besselievre, F.; Piguel, S.; Mahuteau-Betzer, F.; Grierson, D.
S. Org. Lett. 2008, 10, 4029−4032.
(31) C−H alkenylation using allyl halides or pseudohalides through
olefin isomerization has also been reported: (a) Oi, S.; Tanaka, Y.;
Inoue, Y. Organometallics 2006, 25, 4773−4778. (b) Goriya, Y.;
Ramana, C. V. Chem. Eur. J. 2012, 18, 13288−13292. See also ref 11c.
(32) (a) Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.;
Inoue, Y. Org. Lett. 2001, 3, 2579−2581. (b) Oi, S.; Ogino, Y.; Fukita,
S.; Inoue, Y. Org. Lett. 2002, 4, 1783−1785. (c) Oi, S.; Aizawa, E.;
Ogino, Y.; Inoue, Y. J. Org. Chem. 2005, 70, 3113−3119.
(33) (a) Zaitsev, V. G.; Daugulis, O. J. Am. Chem. Soc. 2005, 127,
4156−4157. (b) Takeda, D.; Yamashita, M.; Hirano, K.; Satoh, T.;
Miura, M. Chem. Lett. 2011, 40, 1015−1017. (c) Zhao, Y.; He, G.;
Nack, W. A.; Chen, G. Org. Lett. 2012, 14, 2948−2951.
(34) (a) Zhao, X.; Yu, Z. J. Am. Chem. Soc. 2008, 130, 8136−8137.
(b) Jin, W.; Yu, Z.; He, W.; Ye, W.; Xiao, W.-J. Org. Lett. 2009, 11,
1317−1320. (c) Ye, W.; Luo, N.; Yu, Z. Organometallics 2010, 29,
1049−1052.
(m) Lindh, J.; Savmarker, J.; Nilsson, P.; Sjoberg, P. J. R.; Larhed, M.
̈
̈
Chem. Eur. J. 2009, 15, 4630−4636. (n) Yu, J.-Y.; Kuwano, R. Angew.
Chem., Int. Ed. 2009, 48, 7217−7220. (o) Yu, J.-Y.; Shimizu, R.;
Kuwano, R. Angew. Chem., Int. Ed. 2010, 49, 6396−6399.
́
(47) Ferrando, G.; Coalter, J. N., III; Gerard, H.; Huang, D.;
Eisenstein, O.; Caulton, K. G. New. J. Chem. 2003, 27, 1451−1462.
(48) (a) Hoover, J. F.; Stryker, J. M. J. Am. Chem. Soc. 1990, 112,
464−465. (b) Trace, R. L.; Sanchez, J.; Yang, J.; Yin, J.; Jones, W. M.
Organometallics 1992, 11, 1440−1442. (c) Bergamini, P.; Costa, E.
Organometallics 1994, 13, 1058−1060. (d) Zhang, J.; Barakat, K. A.;
Cundari, T. R.; Gunnoe, T. B.; Boyle, P. D.; Petersen, J. L.; Day, C. S.
Inorg. Chem. 2005, 44, 8379−8390.
(49) (a) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc.
2008, 130, 10848−10849. CMD with ruthenium-catalyzed arylations:
̈
(b) Ozdemir, I.; Demir, S.; Çetinkaya, B.; Gourlaouen, C.; Maseras, F.;
(35) Matsuura, Y.; Tamura, M.; Kochi, T.; Sato, M.; Chatani, N.;
Kakiuchi, F. J. Am. Chem. Soc. 2007, 129, 9858−9859.
Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc. 2008, 130, 1156−1157.
(c) Ackermann, L.; Vicente, R.; Althammer. Org. Lett. 2008, 10, 2299−
2302. (d) Flegeau, E. F.; Bruneau, C.; Dixneuf, P. H.; Jutand, A. J. Am.
Chem. Soc. 2011, 133, 10161−10170.
(36) Development of alternatives to halogenated compounds may
offer more environmentally benign chemical processes. In addition,
several patents describe that the reduction of halogen impurities is
important to achieve the desired properties for organic semi-
conductors: (a) Shigehara, K.; Nakacho, Y.; Tada, Y.; Inoue, T.;
Nakaya, K. JP 3560259B, 1996; Chem. Abstr 1996, 126, 118346;
(b) Higashi, H.; Sakai, T.; Hosokawa, C. WO 2000041443A1, 2000;
Chem. Abstr. 2000, 133, 96613;(c) Spreitzer, H.; Falcou, A.; Scheurich,
R.; Schulte, N.; Buesing, A.; Stoessel, P. WO 2006037458 A1; 2006;
Chem. Abstr. 2006, 144, 391623.
(50) When the reaction was monitored by GC analysis, the efficiency
of the reaction was slightly lowered, probably due to the occasional
sampling of the reaction mixture.
(51) (a) Hartley, F. R. Chem. Rev. 1973, 73, 163−190. (b) Brown, T.
J.; Dickens, M. G.; Widenhoefer, R. A. J. Am. Chem. Soc. 2009, 131,
6350−6351.
̀
(52) Espinet, P.; Albeniz, A. C. In Fundamentals of Molecular
Catalysis; Kurosawa, H., Yamamoto, A., Eds.; Elsevier: Amsterdam,
2003; pp 293−372.
(37) Sasin, R.; Olszewski, W. F.; Russell, J. R.; Swern, D. J. Am. Chem.
Soc. 1959, 81, 6275−6277.
(38) See the Experimental Section and Supporting Information for
details.
(53) Ru(cod)(cot)-catalyzed olefin coupling through hydrometala-
tion and β-hydride elimination has also been reported: (a) Yamamoto,
Y.; Ohkoshi, N.; Kameda, M.; Itoh, K. J. Org. Chem. 1999, 64, 2178−
2179. (b) Tsujita, H.; Ura, Y.; Wada, K.; Kondo, T.; Mitsudo, T. Chem.
Commun. 2005, 5100−5102.
(39) Guari, Y.; Sabo-Etienne, S.; Chaudret, B. J. Am. Chem. Soc. 1998,
120, 4228−4229.
(40) Planas, J. G.; Marumo, T.; Ichikawa, Y.; Hirano, M.; Komiya, S.
Dalton Trans. 2000, 2613−2625.
(54) In these cases, the corresponding alkenylation product 25
originating from the catalysts 38a and 39a were also obtained in 50%
or 110% GC yields based on ruthenium complexes, respectively.
(55) (a) Wenkert, E.; Michelotti, E. L.; Swindell, C. S. J. Am. Chem.
Soc. 1979, 101, 2246−2247. (b) Wenkert, E.; Michelotti, E. L.;
Swindell, C. S.; Tingoli, M. J. Org. Chem. 1984, 49, 4894−4899.
(c) Andersson, C.-M.; Hallberg, A. J. Org. Chem. 1988, 53, 235−239.
(56) (a) Nguefack, J.-F.; Bolitt, V.; Sinou, D. J. Org. Chem. 1997, 62,
1341−1347. (b) Ohashi, M.; Taniguchi, T.; Ogishi, S. J. Am. Chem.
Soc. 2011, 133, 14900−14903.
(57) (a) Strazisar, S. A.; Wolczanski, P. T. J. Am. Chem. Soc. 2001,
123, 4728−4740. (b) Luo, S.; Jordan, R. F. J. Am. Chem. Soc. 2006,
128, 12072−12073. (c) Chen, C.; Luo, S.; Jordan, R. F. J. Am. Chem.
Soc. 2010, 132, 5273−5284.
(41) Cousineau, T. J.; Cook, S. L.; Secrist, J. A., III Synth. Commun.
1979, 9, 157−163.
(42) Andersen, N. G.; Keay, B. A. Chem. Rev. 2001, 101, 997−1030.
(43) (a) Lim, Y.-G.; Kang, J.-B.; Kim, Y. H. J. Chem. Soc., Perkin
Trans. 1 1996, 2201−2206. (b) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai,
S. J. Org. Chem. 1997, 62, 2604−2610.
(44) Kakiuchi, F.; Sonoda, M.; Tsujimoto, T.; Chatani, N.; Murai, S.
Chem. Lett. 1999, 1083−1084.
(45) Introduction of pyrrole rings into the backbones of poly- and
oligo(phenylenevinylenes): (a) Van Der Looy, J. F. A.; Thys, G. J. H.;
Dieltiens, P. E. M.; De Schrijver, D.; Van Alsenoy, C.; Geise, H. J.
Tetrahedron 1997, 53, 15069−15084. (b) Kim, I. T.; Elsenbaumer, R.
L. Chem. Commun. 1998, 327−328. (c) Kim, I. T.; Elsenbaumer, R. L.
Macromolecules 2000, 33, 6407−6411. (d) Tietze, L. T.; Nordmann, G.
Synlett 2001, 337−340. (e) Zheng, S.; Beverina, L.; Barlow, S.; Zojer,
E.; Fu, J.; Padilha, L. A.; Fink, C.; Kwon, O.; Yi, Y.; Shuai, Z.; Van
Stryland, E. W.; Hagan, D. J.; Bredas, J.-L.; Marder, S. R. Chem.
Commun. 2007, 1372−1374. (f) Biswas, A. K.; Ashish, A.; Tripathi, A.
K.; Mohapatra, Y. N.; Ajayaghosh, A. Macromolecules 2007, 40, 2657−
2665. (g) Ajayaghosh, A.; Praveen, V. K.; Vijayakumar, C.; George, S.
J. Angew. Chem., Int. Ed. 2007, 46, 6260−6265.
(58) Itoh, K.; Nagashima, H.; Ohshima, T.; Oshima, N.; Nishiyama,
H. J. Organomet. Chem. 1984, 272, 179−188.
(59) Cousineau, T. J.; Cook, S. L.; Secrist, J. A., III Synth. Commun.
1979, 9, 157−163.
(46) (a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5535−5538.
(b) Komiya, S.; Yamamoto, A. J. Chem. Soc., Chem. Commun. 1974,
523−524. (c) Komiya, S.; Yamamoto, A. J. Organomet. Chem. 1975,
87, 333−339. (d) Cheng, J. C.-Y.; Daves, G. D., Jr. Organometallics
1986, 5, 1753−1755. (e) Andersson, C.-M.; Hallberg, A. J. Org. Chem.
1988, 53, 235−239. (f) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R.
J. Org. Chem. 1992, 57, 3558−3563. (g) Zhu, G.; Lu, X.
Organometallics 1995, 14, 4899−4904. (h) Zhang, Z.; Lu, X.; Xu, Z.;
Zhang, Q.; Han, X. Organometallics 2001, 20, 3724−3728. (i) Williams,
S
dx.doi.org/10.1021/om401204h | Organometallics XXXX, XXX, XXX−XXX