Silver-mediated C-H activation: Oxidative coupling/cyclization of N -arylimines and alkynes for the synthesis of quinolines

Article abstract of DOI:10.1021/jo202087j

A silver-mediated tandem protocol for the synthesis of quinolines involving the oxidative coupling/cyclization of N-arylimines and alkynes has been developed. We demonstrated that scenario-dependent metalation could occur either at the ortho C-H bond of an N-arylimine through protonation-driven enhancement of acidity or at the terminal C-H bond of an alkyne by virtue of the carbophilic π-acidity of silver. The diverse set of mechanistic manifolds implemented with a single type of experimental protocol points toward the importance of stringent reactivity analysis of each individual potentially reactive molecular site. Importantly, the direct arene C-H bond activation provides a unique and distinct mechanistic handle for the expansion of reactivity paradigms for silver. As expected, the protocol allows for the incorporation of both internal and terminal alkynes into the products, and in addition, both electron-withdrawing and -donating groups are tolerated on N-arylimines, thus enabling the vast expansion of substituent architectures on quinoline framework. Further, an intriguing phenomenon of structural isomerization and chemical bond cleavage has been observed for aliphatic internal alkynes.

Full text of DOI:10.1021/jo202087j

Article
pubs.acs.org/joc
Silver-Mediated C−H Activation: Oxidative Coupling/Cyclization of
N-Arylimines and Alkynes for the Synthesis of Quinolines
Xu Zhang, Baoqing Liu, Xin Shu, Yang Gao, Haipeng Lv, and Jin Zhu*
Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, State Key Laboratory of
Coordination Chemistry, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093, China
S
* Supporting Information
ABSTRACT: A silver-mediated tandem protocol for the
synthesis of quinolines involving the oxidative coupling/
cyclization of N-arylimines and alkynes has been developed.
We demonstrated that scenario-dependent metalation could
occur either at the ortho C−H bond of an N-arylimine through
protonation-driven enhancement of acidity or at the terminal
C−H bond of an alkyne by virtue of the carbophilic π-acidity
of silver. The diverse set of mechanistic manifolds implemented
with a single type of experimental protocol points toward the
importance of stringent reactivity analysis of each individual
potentially reactive molecular site. Importantly, the direct arene
C−H bond activation provides a unique and distinct mechanistic
handle for the expansion of reactivity paradigms for silver. As expected, the protocol allows for the incorporation of both internal and
terminal alkynes into the products, and in addition, both electron-withdrawing and -donating groups are tolerated on N-arylimines,
thus enabling the vast expansion of substituent architectures on quinoline framework. Further, an intriguing phenomenon of
structural isomerization and chemical bond cleavage has been observed for aliphatic internal alkynes.
chemical bond cleavage has been observed for aliphatic internal
alkynes. Most importantly, the direct arene C−H bond
activation mode provides a unique and distinct mechanistic
handle for the expansion of reactivity paradigms for silver.
INTRODUCTION
■
Silver has received increased attention in the organic synthesis
arena by virtue of its expanding reactivity patterns that have
been discovered recently.1 Indeed, silver-mediated organic
transformations have emerged as an important synthetic tool
for the construction of many architecturally intriguing
molecules.1b In particular, the carbo-, oxo-, and azaphilicity
associated with this precious metal have enabled the generation
of functionally diverse heterocycles.1c The Lewis acidity is
typically exploited to activate the bound functionality for viable
reactivity either through the depletion of electron density,1d or
in the case of terminal alkynes, based on the deprotonation
process.1e In an effort to pursue the diversification of silver
chemistry, we have turned our attention to the possibility of
achieving disparate mechanistic manifolds within a single type
of reaction system. N-arylimines and alkynes are the substrates
of our particular interest for activating and coupling. We
hypothesized that scenario-dependent metalation could occur
either at the ortho C−H bond of an N-arylimine through
protonation-driven enhancement of acidity or at the terminal
C−H bond of an alkyne by virtue of the carbophilic π-acidity of
silver. Herein, we wish to report a silver-mediated tandem
protocol for the synthesis of quinolines involving the oxidative
coupling/cyclization of N-arylimines and alkynes. This protocol
allows for the incorporation of both internal and terminal
alkynes into the products and both electron-withdrawing and
-donating groups are tolerated on N-arylimines. Further, an
intriguing phenomenon of structural isomerization and
RESULTS AND DISCUSSION
■
Our study began with the evaluation on the feasibility of
activating the ortho C−H bond of protonated imine with silver.
Indeed, a rapid H/D exchange between an N-arylimine and
D2O could be observed with the participation of AgNTf2 and
HOTf (eqs S1, Supporting Information, and 1). The process
became extremely sluggish in the absence of either AgNTf2 or
HOTf. The requisite use of HOTf and selective C−H
activation at N-aryl carbon argues against either chelation-
assisted or proximal site mechanism.2 Indeed, typical chelation-
based C−H activation would occur with the formation of a
stable five-membered metalacycle and preferred coordination of
AgI with the imine nitrogen should be translated to the C-aryl
C−H bond activation.1b,3 In addition, protonation at the imine
Received: October 11, 2011
Published: December 5, 2011
© 2011 American Chemical Society
501
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
Table 1. Optimization of Reaction Conditions
isolated yield
entry
catalyst
solvent
temp (°C)
4b
4p
1
AgNTf2/HOTf
AgNTf2
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
DMF
80
80
80
80
80
50
120
60
76
60
60
78%
23%
NR
96%
40%
10%
70%
75%
NR
2
3
HOTf
4
AgNTf2/AlMe3
AgNTf2/CF3COOH
AgNTf2/HOTf
AgNTf2/HOTf
AgNTf2/HOTf
AgNTf2/HOTf
AgNTf2/HOTf
HOTf
65%
68%
12%
NR
5
6
7
NR
8
THF
32%
NR
NR
9
CCl4
NR
10
11
Toluene
Toluene
68%
NR
75%
NR
nitrogen would render the functional group highly electron
deficient and a less likely coordination site for AgI. Further,
acidic conditions have been postulated to be beneficial to the
enhancement of electrophicility of cationic metals.4 However, it
HOTf (entry 1). The lack of substantial reaction in the
exclusive presence of HOTf (entry 3) suggests that AgI is an
indispensable species driving the catalytic coupling/cyclization
process. The ability to generate quinoline derivative from the
internal alkyne is consistent with a pathway involving the initial
carbometalation of alkyne and a subsequent cyclization of
carbometalated product with the iminium unit (Scheme 1).
Since alkyne could be activated by AgI, and migratory insertion
is not a common process in coinage metal-mediated reactions,
the carbometalation should be achieved through the
nucleophilic attack of AgI-linked N-aryl carbon on AgI-activated
alkyne. It should be noted that the proposed transformation
from dihydroquinoline to quinoline is a commonly observed
process,7 which presumably proceeds through the oxidation by
air during the postreaction workup step. The electron-deficient
nature of the iminium group allows the cyclization process to
proceed through nucleophilic attack of AgI-attached alkenyl
bond on the partially positively charged iminium carbon.
Further evidence for the protonation-enabled C−H acidity
enhancement mechanism comes from the observation that an
increased product yield could be obtained through the
assistance of a main-group Lewis acid (entry 4). Indeed, such
a Lewis acid-based C−H acidity enhancement has been
employed previously on a site-selective alkenylation/alkylation
of heterocycles.8 Toluene is the solvent of choice for the
oxidative coupling/cyclization tandem sequence and the
reaction can be carried out at a relatively low temperature
(80 °C). Other reaction media tested, including CH2Cl2, DMF,
THF, and CCl4 (entries 6−9), could not effect the desired
transformation with a yield comparable to that in toluene.
Further lowering the temperature to more benign 60 °C still
enables the product formation with a reasonably high yield
(entry 10). The reaction gets completely suppressed in the
absence of AgNTf2 at such a temperature (entry 11). Without
the participation of silver, no product was observed for the
internal alkyne even at higher temperatures (e.g., 110 °C), while
the corresponding quinoline derivative could be obtained for
the terminal alkyne. Therefore, AgI is absolutely essential for the
transformation involving internal alkynes and it can also
contribute to the quinoline formation for terminal alkynes
under more benign settings. Interestingly, under the experimental
−
is unlikely to be operative here since NTf2 is already a highly
noncoordinating anionic species. Taking into account above
considerations and acidity enhancement of ortho C−H bond
upon imine protonation, the activation process therefore favors
a mechanistic interpretation by the concerted metalation-
deprotonation (CMD) mechanism.5 Transition metal-mediated
C−H functionalization has become an active research area due
to the ability to achieve conceptually distinct reaction modes.2
For arene type of substrates, the C−H bond functionalization is
most successfully achieved via electrophilic aromatic substitu-
tion (EAS), which entails the requisite use of an electrophilic
metal catalyst and an electron-rich aromatic structure. As an
alternative pathway, CMD mechanism has been recently
proposed to account for the unusual reactivity of electron-
deficient, C−H acidic aromatic rings.5 The positive correlation
between the acidity and reactivity is furnished by the initial
agostic interaction of C−H bond with metal and subsequent
facile deprotonation by the counterion (through either σ-bond
metathesis or base assistance), thus complementing the
reaction pattern through the Wheland intermediate. For such
a CMD-based strategy, the research is directed largely toward
the exploitation of high-valent cationic species and only
recently has the direct evidence for a low-valent AuI-mediated
stoichiometric C−H activation been identified.6 We envisioned
that the novel reactivity mode could be imparted on silver with
otherwise unattainable C−H activation-driven, synthetically
useful reaction patterns. With the encouraging C−H activation
result in hand, we theorized that the carbon nucleophile
generated thereof could be used for the attack on a AgI-
activated alkyne. Gratifyingly, reaction of an N-arylimine and an
internal alkyne allows for the generation of a quinoline deriv-
ative. Further screening of the reaction conditions indicates that
an amine/aldehyde/alkyne combination (Table 1) is as
effective as an imine/alkyne mix for the transformation,
offering evidence that the product formation proceeds through
the same reaction pathway. Notably, the desired product is
formed in high yield only in the presence of both AgNTf2 and
502
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
Scheme 1. Proposed Transformation Mechanisms for Conjugated Internal Alkynes and Terminal Alkynes
conditions employed herein, terminal alkynes generally offer better
yields than those from internal alkynes (entries 1, 4, 5, and 10).
However, in spite of similarity in the frameworks of end products,
the reactions with internal and terminal alkynes most likely proceed
through distinctly different mechanistic pathways (vide infra).
To further probe the reaction mechanism and explore the
substrate scope, a range of substituted amines, aldehydes, and
alkynes were examined under the optimized conditions (Table 2).
For internal aryl-substituted alkynes, good yields are obtainable
irrespective of the electronic property of the N-aryl ring sub-
stituent (4a−4f). Specifically, the efficient product formation
from aniline with an electron-withdrawing group (4e and 4f)
favors an acidic C−H bond activation mechanism and argues
against ring closure through the EAS pathway. In further sup-
port of this, a competition experiment carried out with anilines
bearing electron-withdrawing and -donating groups indicates
that the electron-withdrawing aniline slightly dominates the
product formation (eq 2). Since a group meta to the C−H
bond is expected to exert less electronic influence on the activ-
ation process, an additional competition experiment was carried
out on two substrates with substituents on the para positions of
the C−H bonds (eq 3). A much more pronounced electronic
effect has indeed been observed for an N-arylimine containing
such a substitution pattern, with product formation substan-
tially dominated by the electron-withdrawing structure.
Notably, the reaction is not sensitive to steric hindrance, as
the transformation can be effected for an alkyne with two
phenyl substituents (4g). The alkyne scope is manifested by a
high-yield product formation for electron-poor substrates
(bearing two electron-withdrawing ester groups) (4h−4l).
Under this circumstance, quinoline derivatives with both the
retention of ester groups and the loss of one ester group could
be observed, depending on the imine substrate. The loss of
ester group in the quinoline derivative is speculated to occur
after the C−H activation step and before the cyclization pro-
cess. Although the exact mechanism has yet to be elucidated,
acidic conditions likely contribute to the destabilization of the
ester group. It should be noted that no product of 4j−4l was
observed in the absence of AgI, confirming the essential role
played by the metal species. To examine the feasibility of
C−H bond activation pathway, an imine substrate with bulky,
cyclization-blocking C-substituents was challenged with an
internal alkyne (eq 4). Indeed an intermediate product with the
503
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
imine substrates employed herein, proto-demetalation reaction
does not take place at this stage (vide infra). On a final note, no
reaction occurs between an internal alkyne and a C−H
activation-blocking imine substrate (bearing two o-methyl
groups on N-aryl ring) (eq 5), indicating that the trans-
formation might not be initiated through such an alkyne/imine
coupling step.
Table 2. Reaction Scope for Conjugated Internal Alkynes
and Terminal Alkynes
For aliphatic internal alkynes, an interesting C−C bond
cleavage reaction was observed, furnishing quinoline products
with shortened carbon skeletons (Table 3, 4y). One striking
Table 3. Reaction Scope for Aliphatic Internal Alkynes
a
Trace amount of 4y was observed.
feature of the reaction is that the two carbon atoms
incorporated into the heterocycle might not come from those
of the initial triple bond, as indicated by the bond-shifted
product (4z) and 13C labeling experiment (eq 6). Further
evidence for the triple bond shift comes from several deuterium
labeling studies. Reaction of aliphatic internal alkynes with an
imine bearing an o-deuterated N-aryl ring, or a nondeuterated
imine in the presence of deuterated acid or deuterated water
(eqs 7 and 8), afforded the quinoline product with apparent
deuterium incorporation. The internal alkyne is therefore
proposed to be isomerized to a terminal alkyne before the
carbometalation step (Scheme 2), at which stage the deuterium
exchange is achieved on the acidic C−H bond. To test whether
C−C bond cleavage occurs after the initial proto-demetalation
formation of alkenylated imine and during the cyclization
process, two independently synthesized substrates with an alkyl
substituent on the alkene group were examined (eq 9). No C−C
bond-cleaved product was observed, offering evidence that
attachment of AgI to the alkenyl group might be required for
the C−C bond cleavage following the cyclization step (Scheme 2).
Aromatization resulting from the AgI-mediated β-alkyl elimi-
nation9 could be potentially responsible for the occurrence of
C−C bond cleavage reaction. Several observations for the
reactions with aliphatic internal alkynes deserve comments: (1)
Spheres with bright metallic luster were observed after the re-
action, indicating the reduction of AgI to Ag0. (2) An attempted
stabilization of AgI with a coordinating ligand (e.g., PPh3 and
a
The alkyne substrate: R3 = R4 = COOEt. The quinoline products:
R3 = H, R4 = COOEt.
alkenylation of imine N-aryl ring was trapped, offering evidence
for the possibility of alkyne carbometalation-initiated reaction
sequence. It should be noted however that, when a subsequent
ring closure reaction is possible as in the case of less hindered
504
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
transformation. (5) A fluorescent product other than the target
compound (e.g., 4y), with polarity similar to aliphatic internal
alkynes according to thin layer chromatography, could be
consistently observed in either the absence or presence of an
N-arylimine. The low product yield of quinoline for an aliphatic
internal alkyne is therefore derived from two factors: a
speculated high-yield competing side reaction and reduction
of AgI to Ag0 metal by β-eliminated alkyl group (the proto-
demetalation release of active AgI species apparently did not
occur, Scheme 2). In spite of the unsatisfactory performance of
aliphatic internal alkynes, the intriguing phenomenon observed
herein provides important insight into the potentially new
reaction patterns for AgI and might serve as the basis for the
exploration of mechanistically distinct synthetic possibilities. A
slight kinetic isotope effect10 is identified (kH/kD = 1.12 and
1.10) (eq S2, Supporting Information), indicating that C−H
bond activation is not a kinetically significant event in the
reaction. It should be noted that, however, kinetic isotope effect
depends on a variety of factors, with possibly consistently low
values under certain circumstances (e.g., for sufficiently non-
linear transition-state configurations10c).
As mentioned above, our synthetic scheme has been
demonstrated on a terminal alkyne. Previous methods for the
preparation of quinolines are generally restricted to this type of
substrates, although distinct mechanistic hypotheses have been
proposed (e.g., initial attack of imine carbon by alkyne, direct
Diels−Alder reaction).7a,11 Gratifyingly, the versatility of our
silver-based system is manifested by the broad terminal alkyne
substrate scope, with the formation of desired quinoline
derivatives regardless of electron-donating or -withdrawing
character of the functionality on aniline (Table 2, 4m-4w). Also
noteworthy is the achievement of a relatively high yield for an
aliphatic terminal alkyne (4x), in marked contrast with the
reactivity pattern for aliphatic internal alkynes. Two mechanis-
tically relevant phenomena deserve special attention for the
terminal alkyne substrates: (1) A reaction carried out with an
imine substrate bearing two o-methyl groups on N-aryl ring
indicates that an initial attack of terminal alkyne on iminium
carbon is possible (eq 5). (2) A competition experiment
with electron-withdrawing and -donating imines provides
the dominant product from the electron-donating imine
(eqs 10 and 11). Therefore, although an arene C−H bond
PCy3) during the transformation proved unsuccessful. (3)
Reaction in the presence of air or 1 equivalent of oxidant (e.g.,
1,2-dibromoethane), which should presumably enable the
reoxidation of Ag0 back to AgI and furnish a conceptually
valid catalytic cycle, did not result in the improvement of yield.
(4) The addition of 1 equivalent of either AgNTf2 or acid (e.g.,
HOTf) was not effective for the achievement of a quantitative
Scheme 2. Proposed Transformation Mechanism for Aliphatic Internal Alkynes
505
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
Na2SO4. After evaporation of the solvent, the residue was purified by
silica gel chromatography (dichloromethane/petroleum ether = 1/1,
v/v) to afford 0.236 g of 2,4-diphenyl-3-methylquinoline (4a, yield
80%). All other compounds are synthesized in a similar manner, with
the yields calculated from the isolated, pure products.
activation mechanism might still be operative here, an alter-
native reaction sequence involving the initial addition of AgI-
activated terminal alkynes to iminium ions and a subsequent
Procedure for Demonstrating ortho C−H Bond Activation of
an N-Arylimine. N-(4-methylbenzylidene)aniline (0.098 g, 0.5 mmol)
was dissolved in D2O/DMSO-d6 (D2O/DMSO-d6 = 1/1, v/v). The
solution was added to a NMR tube. Then the catalyst AgNTf2 (0.01 g,
0.025 mmol) and HOTf (0.0038 g, 0.025 mmol) was added. The
reaction mixture was heated at 80 °C for 3 h. The H/D molar ratio
1
was measured by H NMR, see eq S1, Supporting Information.
4-Methyl-N-(4-methylbenzylidene)aniline (0.104 g, 0.5 mmol) was
dissolved in D2O/DMSO-d6 (D2O/DMSO-d6 = 1/1, v/v). The
solution was added to a NMR tube. Then the catalyst AgNTf2 (0.01 g,
0.025 mmol) and HOTf (0.0038 g, 0.025 mmol) was added. The
reaction mixture was heated at 80 °C for 3 h. The H/D molar ratio
1
was measured by H NMR, see eq 1.
The analysis of the H/D exchange ratio was described as follows. In
the case of N-(4-methylbenzylidene)aniline, the quantitative NMR
integration of the H signal area at the ortho position of N-arylimine
(with the para Me group on the C-aryl moiety as the internal
reference) equals 3.58 for pure N-(4-methylbenzylidene)aniline. The
area is decreased to 0.93 + 1.78 (2.71) after the reaction is performed
in the presence of both AgNTf2 and D2O/DMSO-d6. Assuming that
the H with a signal area of 0.93 is assigned as the para H on the N-aryl
moiety and that the integration value corresponds to 1 H, the decrease
from 3.58 to 2.71 is derived from the D incorporation into the ortho
position. Therefore D% = (3.58−0.93−1.78)/(3.58−0.93) × 100% =
33%. However, since the exact integration area for the para H in the
original total of 3.58 is not clear, and there is a partial overlap between
the signals with areas of 0.93 and 1.78, we cannot strictly exclude the
possibility of H/D exchange at the para H on the N-aryl moiety. The
ortho H/D exchange can be unambiguously observed with the
substitution of the para position with a Me group. In the case of 4-
methyl-N-(4-methylbenzylidene)aniline, the quantitative NMR inte-
gration of the H signal area at the ortho position of N-arylimine (with
the para Me group on the C-aryl moiety as the internal reference,
which exhibits a signal area of 3.00) equals 1.84 for pure 4-methyl-N-
(4-methylbenzylidene)aniline. The area is decreased to 0.80 after the
reaction is performed in the presence of both AgNTf2 and D2O/
DMSO-d6. Therefore D% = (1.84−0.80)/1.84 × 100% = 57%.
Procedure for Competition Experiments Involving an
Internal Alkyne. AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g,
0.05 mmol), 1-phenyl-1-propyne (0.058 g, 0.5 mmol), and imine sub-
strates of 4-fluoro-N-(4-methylbenzylidene)aniline (0.105 g, 0.5 mmol),
4-methoxy-N-(4-methylbenzyli dene)aniline (0.113 g, 0.5 mmol) were
added to a Schlenk flask containing 5 mL of toluene. The reaction
mixture was stirred at 80 °C for 6 h, then cooled down to room
temperature, diluted with 10 mL of dichloromethane and washed with
10 mL of H2O. The aqueous layer was extracted twice with dichloro-
methane (10 mL) and the combined organic phase was dried over
anhydrous Na2SO4. After evaporation of the solvent, the residue was
purified by silica gel chromatography (dichloromethane/petroleum
ether = 3/2, v/v) to afford the product, see eq 2.
nucleophilic cyclization attack of N-aryl ring on alkyne-AgI
complex (Scheme 1) is more likely occurring. Such a distinct
mechanism is warranted by the preferred deprotonation of
terminal alkyne C−H bond over ortho C−H bond of proto-
nated N-arylimine due to the difference in acidity.
CONCLUSION
■
In conclusion, a silver-based system for the synthesis of
quinolines via oxidative coupling/cyclization of N-arylimines
and alkynes has been uncovered. The transformation is effective
for a broad range of substrates, thus enabling the expansion of
substituent architectures on the heterocyclic framework. The
acidity enhancement-based C−H activation strategy reported
herein should be generally applicable to the coupling chemistry
with other functional partners. The diverse set of mechanistic
manifolds implemented with a single type of experimental
protocol points toward the importance of stringent reactivity
analysis of each individual potentially reactive molecular site.
EXPERIMENTAL SECTION
■
General Information. NMR (1H and 13C) spectra were recorded
in CDCl3 or DMSO-d6 solutions on a 500 MHz NMR spectrometer.
High resolution mass spectra were obtained on a mass spectrometry
facility. AgNTf2 was prepared according to the literature procedure.12
All other reagents were facilely prepared or used as received from
commercial sources except that toluene, THF, CCl4, DMF and
CH2Cl2 were distilled to the dry and oxygen-free state under the
protection of nitrogen. All the reactions were performed with the
standard Schlenk technique.
AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g, 0.05 mmol), 1-
phenyl-1-propyne (0.058 g, 0.5 mmol), and imine substrates of 3-
fluoro-N-(4-methylbenzylidene)aniline (0.105 g, 0.5 mmol), 3-
methoxy-N-(4-methylbenzylidene)aniline (0.113 g, 0.5 mmol) were
added to a Schlenk flask containing 5 mL of toluene. The reaction
mixture was stirred at 80 °C for 6 h, then cooled down to room
temperature, diluted with 10 mL of dichloromethane and washed
with 10 mL of H2O. The aqueous layer was extracted twice with
dichloromethane (10 mL) and the combined organic phase was dried
over anhydrous Na2SO4. After evaporation of the solvent, the residue
was purified by silica gel chromatography (dichloromethane/
petroleum ether = 3/2, v/v) to afford the product, see eq 3.
General Catalytic Procedure. Aniline (0.093 g, 1 mmol) and
benzaldehyde (0.106 g, 1 mmol) were added to a Schlenk flask. After
stirring for 10 min, AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g,
0.05 mmol), and 1-phenyl-1-propyne (0.128 g, 1.1 mmol) were further
added to the Schlenk flask containing 5 mL of toluene. The mixture
was stirred at 80 °C for 24 h, then cooled down to room temperature,
diluted with 10 mL of dichloromethane, and washed with 10 mL
of H2O. The aqueous layer was extracted twice with dichloromethane
(10 mL) and the combined organic phase was dried over anhydrous
Procedure for Trapping an Alkenylation Product on a Bulky
N-Arylimine. p-Toluidine (0.75 g, 7 mmol) and diphenylketone
(1.82 g, 10 mmol) was dissolved in benzene, to which zinc chloride
506
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
(0.134 g, 1 mmol) was added. The reaction mixture was heated under
boiling conditions for 24 h to afford the imine product of N-
(diphenylmethylene)-4-methylaniline. Subsequently, diethyl acetyle-
nedicarboxylate (0.17 g, 1 mmol), AgNTf2 (0.02 g, 0.05 mmol), HOTf
(0.015 g, 0.1 mmol), and chromatography-purified imine were added
to a Schlenk flask. The reaction mixture was heated at 80 °C for 8 h
and the resulting solvent-free residue was purified by silica gel
chromatography (dichloromethane/petroleum ether = 1/1, v/v) to
afford the product, see eq 4.
charged with AgNTf2 (0.02 g, 0.05 mmol) and HOTf (0.0075 g,
0.05 mmol) and 5 mL of toluene. The mixture was stirred at 80 °C for
24 h, then cooled down to room temperature, diluted with 10 mL of
dichloromethane and washed with 10 mL of H2O. The aqueous layer
was extracted twice with dichloromethane (10 mL) and the combined
organic phase was dried over anhydrous Na2SO4. After evaporation of
the solvent, the residue was purified by silica gel chromatography
(dichloromethane/petroleum ether = 1/1, v/v) to afford the product,
see eq 9.
Procedure for Investigating the Reactivity of an Alkyne
toward an ortho-Methylated N-Arylimine. 2,6-Dimethyl-N-(4-
methylbenzylidene)aniline (0.223 g, 1 mmol), AgNTf2 (0.02 g, 0.05
mmol), HOTf (0.0075 g, 0.05 mmol), and 1-phenyl-1-propyne (0.128
g, 1.1 mmol) were added to a Schlenk flask containing 5 mL of
toluene. The mixture was stirred at 80 °C for 8 h, then cooled down to
room temperature. No product was observed, see eq 5.
2,6-Dimethyl-N-(4-methylbenzylidene)aniline (0.223 g, 1 mmol),
AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g, 0.05 mmol), and
phenylacetylene (0.112 g, 1.1 mmol) were added to a Schlenk flask
containing 5 mL of toluene. The mixture was stirred at 80 °C for 8 h,
then cooled down to room temperature, diluted with 10 mL of
dichloromethane and washed with 10 mL of H2O. The aqueous layer
was extracted twice with dichloromethane (10 mL) and the combined
organic phase was dried over anhydrous Na2SO4. After evaporation of
the solvent, the residue was purified by silica gel chromatography
(dichloromethane/petroleum ether = 1/1, v/v) to afford the product,
see eq 5.
(E)-2-(prop-1-enyl)aniline (0.133 g, 1 mmol) and p-tolualdehyde
(0.12 g, 1 mmol) were added to a Schlenk flask. After stirring for
10 min, the Schlenk flask was further charged with AgNTf2 (0.02 g,
0.05 mmol) and HOTf (0.0075 g, 0.05 mmol) and 5 mL of toluene.
The mixture was stirred at 80 °C for 24 h, then cooled down to room
temperature, diluted with 10 mL of dichloromethane and washed with
10 mL of H2O. The aqueous layer was extracted twice with dichloro-
methane (10 mL) and the combined organic phase was dried over
anhydrous Na2SO4. After evaporation of the solvent, the residue was
purified by silica gel chromatography (dichloromethane/petroleum
ether = 1/1, v/v) to afford the product, see eq 9.
Procedure for Kinetic Isotope Effect Experiments. AgNTf2
(0.02 g, 0.05 mmol), HOTf (0.0075 g, 0.05 mmol), 1-phenyl-1-
propyne (0.058 g, 0.5 mmol) or 2-pentyne (0.034 g, 0.5 mmol), and
4-methyl-N-(4-methylbenzylidene)aniline (0.105 g, 0.5 mmol), 4-
methyl-N-(4-methylbenzylidene)-aniline-d2 (0.106 g, 0.5 mmol) were
added to a Schlenk flask containing 5 mL of toluene. The tube was
capped and stirred at 80 °C for 24 h, then cooled down to room
temperature, diluted with 10 mL of dichloromethane and washed with
10 mL of H2O. The aqueous layer was extracted twice with dichloro-
methane (10 mL) and the combined organic phase was dried over
anhydrous Na2SO4. After evaporation of the solvent, the residue was
purified by silica gel chromatography (dichloromethane/petroleum
ether = 1/1, v/v) to afford the product. The resulting residue was
analyzed by 1H NMR. In the case of 1-phenyl-1-propyne, the
quantitative NMR integration of the H signal area at the eighth
position of the quinoline derivative (with the Me group at the third
position of the quinoline as the internal reference) equals 0.91 for
reaction with pure 4-methyl-N-(4-methylbenzylidene)aniline. The area
is decreased to 0.48 when the reaction is carried out in the presence of
both 4-methyl-N-(4-methylbenzylidene)aniline and 4-methyl-N-(4-
methylbenzylidene)aniline-d2. Therefore KIE = kH/kD = 0.48/(0.91−
0.48) = 1.12. In the case of 2-pentyne, the quantitative NMR
integration of the H signal area at the eighth and second (two o-H on
the p-tolyl group) positions of the quinoline derivative (with one of
the Me groups as the internal reference) equals 2.71 for reaction with
pure 4-methyl-N-(4-methylbenzylidene)aniline. The area is decreased
to 2.37 when the reaction is carried out in the presence of both 4-
methyl-N-(4-methylbenzylidene)aniline and 4-methyl-N-(4-
methylbenzylidene)aniline-d2. Therefore KIE = kH/kD = (2.37−2)/
(2.71−2.37) = 1.10. The experiments were repeated three times, see
eq S2, Supporting Information.
Procedure for 13C Labeling for the Investigation of Reaction
Mechanism Involving an Aliphatic Internal Alkyne. 4-Methyl-
N-(4-methylbenzylidene)aniline (0.209 g, 1 mmol), AgNTf2 (0.02 g,
0.05 mmol), HOTf (0.0075 g, 0.05 mmol), and 2-octyne-13C (0.122 g,
1.1 mmol) were added to a Schlenk flask containing 5 mL of toluene.
The mixture was stirred at 80 °C for 24 h, then cooled down to room
temperature, diluted with 10 mL of dichloromethane and washed with
10 mL of H2O. The aqueous layer was extracted twice with
dichloromethane (10 mL) and the combined organic phase was
dried over anhydrous Na2SO4. After evaporation of the solvent, the
residue was purified by silica gel chromatography (dichloromethane/
petroleum ether = 1/1, v/v) to afford the product, see eq 6.
Procedure for Deuterium Labeling for the Investigation of
Reaction Mechanism Involving an Aliphatic Internal Alkyne. 4-
Methyl-N-(4-methylbenzylidene)aniline-d2 (0.211 g, 1 mmol), AgNTf2
(0.02 g, 0.05 mmol), HOTf (0.0075 g, 0.05 mmol), and 2-pentyne
(0.075 g, 1.1 mmol) or 2-octyne (0.121 g, 1.1 mmol) were added to a
Schlenk flask containing 5 mL of toluene. The mixture was stirred at
80 °C for 24 h, then cooled down to room temperature, diluted with
10 mL of dichloromethane and washed with 10 mL of H2O. The
aqueous layer was extracted twice with dichloromethane (10 mL) and
the combined organic phase was dried over anhydrous Na2SO4. After
evaporation of the solvent, the residue was purified by silica gel
chromatography (dichloromethane/petroleum ether = 1/1, v/v) to
afford the product, see eq 7.
Procedure for Competition Experiments Involving a
Terminal Alkyne. AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g,
0.05 mmol), phenylacetylene (0.051 g, 0.5 mmol), and 4-fluoro-N-(4-
methylbenzylidene)aniline (0.105 g, 0.5 mmol), 4-methoxy-N-(4-
methylbenzylidene)aniline (0.113 g, 0.5 mmol) were added to a
Schlenk flask containing 5 mL of toluene. The reaction mixture was
stirred at 80 °C for 6 h, then cooled down to room temperature,
diluted with 10 mL of dichloromethane and washed with 10 mL of
H2O. The aqueous layer was extracted twice with dichloromethane
(10 mL) and the combined organic phase was dried over anhydrous
Na2SO4. After evaporation of the solvent, the residue was purified by
silica gel chromatography (dichloromethane/petroleum ether = 3/2, v/v),
see eq 10.
AgNTf2 (0.02 g, 0.05 mmol), HOTf (0.0075 g, 0.05 mmol), phenyl-
acetylene (0.051 g, 0.5 mmol), and 3-fluoro-N-(4-methyl-
benzylidene)aniline (0.105 g, 0.5 mmol), 3-methoxy-N-(4-methyl-
benzyl idene)aniline (0.113 g, 0.5 mmol) were added to a Schlenk
flask containing 5 mL of toluene. The reaction mixture was stirred at
80 °C for 6 h, then cooled down to room temperature, diluted with
Procedure for Investigation of Reaction Mechanism Involv-
ing an Aliphatic Internal Alkyne through the Addition of a
Deuterated Species. 4-Methyl-N-(4-methylbenzylidene)aniline
(0.209 g, 1 mmol), AgNTf2 (0.02 g, 0.05 mmol), CF3COOD
(0.0058 g, 0.05 mmol) or HOTf (0.075 g, 0.05 mmol)/D2O (0.5 mL,
25 mmol), and 2-pentyne (0.075 g, 1.1 mmol) were added to a
Schlenk flask containing 5 mL of toluene. The mixture was stirred at
80 °C for 24 h, then cooled down to room temperature, diluted with
10 mL of dichloromethane and washed with 10 mL of H2O. The
aqueous layer was extracted twice with dichloromethane (10 mL) and
the combined organic phase was dried over anhydrous Na2SO4. After
evaporation of the solvent, the residue was purified by silica gel
chromatography (dichloromethane/petroleum ether =1/1, v/v) to
afford the product, see eq 8.
Procedure for Investigation of the C−C Bond Cleavage
Mechanism Involving an Aliphatic Internal Alkyne through an
Intramolecular Cyclization Reaction. 2-Isopropenylaniline (0.133 g,
1 mmol) and p-tolualdehyde (0.12 g, 1 mmol) were added to a
Schlenk flask. After stirring for 10 min, the Schlenk flask was further
507
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
10 mL of dichloromethane and washed with 10 mL of H2O. The
aqueous layer was extracted twice with dichloromethane (10 mL) and
the combined organic phase was dried over anhydrous Na2SO4. After
evaporation of the solvent, the residue was purified by silica gel
chromatography (dichloromethane/petroleum ether = 3/2, v/v), see
eq 11.
128.7, 128.5, 128.3, 125.3, 124.3, 123.5, 102.7, 62.3, 61.8, 55.6, 14.0,
13.5; HRMS (EI) Calcd. for C22H21NO5: [M+], 379.1420. Found: m/z
379.1422.
Ethyl 2-p-Tolyl-6-methylquinoline-3-carboxylate (4j). 1H NMR
(500 MHz, CDCl3) δ ppm: 8.52 (s, 1H), 8.35 (s, 1H), 8.12 (q, 3H),
7.61 (d, J = 8.0 Hz, 1H), 7.36 (q, 2H), 4.54−4.59 (q, 2H), 2.60 (s,
3H), 2.46 (s, 3H), 1.51−1.54 (t, 3H); 13C NMR (500 MHz, CDCl3) δ
ppm: 166.7, 155.8, 147.9, 139.6, 137.7, 136.2, 135.3, 132.0, 129.9,
129.6, 127.2, 124.2, 123.9, 119.9, 61.8, 22.1, 21.3, 14.4; HRMS (EI)
Calcd. for C20H19NO2: [M+], 305.1416. Found: m/z 305.1420.
Ethyl 2-p-Tolyl-6-methoxyquinoline-3-carboxylate (4k). 1H
NMR (500 MHz, CDCl3) δ ppm: 8.30 (d, J = 7.5 Hz, 1H), 8.10 (s,
1H), 7.47 (d, J = 8.0 Hz, 3H), 7.38 (d, J = 7.5 Hz, 2H), 7.28 (s, 1H),
4.56 (q, 2H), 3.84 (s, 3H), 2.50 (s, 3H), 1.49−1.52 (t, 3H); 13C NMR
(500 MHz, CDCl3) δ ppm: 165.7, 159.5, 148.2, 145.4, 144.3, 138.6,
135.0, 132.7, 129.5, 129.33, 129.26, 122.8, 121.8, 103.4, 62.1, 55.6,
21.3, 14.4; HRMS (EI) Calcd. for C20H19NO3: [M+], 321.1365.
Found: m/z 321.1368.
Compound Characterization Data. 2,4-Diphenyl-3-methyl-
quinoline (4a).7a 1H NMR (500 MHz, CDCl3) δ ppm: 8.26 (d, J =
8.5 Hz, 1H), 7.66−7.71 (m, 3H), 7.51−7.60 (m, 5H), 7.42−7.50 (m,
3H), 7.36 (t, 2H), 2.21 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm:
160.9, 147.9, 146.3, 141.5, 137.8, 129.41, 129.35, 129.0, 128.7, 128.6,
128.3, 128.1, 127.9, 127.1, 126.8, 126.3, 126.0, 18.6; HRMS (EI)
Calcd. for C22H17N: [M+], 295.1361. Found: m/z 295.1360.
1
2-p-Tolyl-3,6-dimethyl-4-phenylquinoline (4b). H NMR (500 MHz,
CDCl3) δ ppm: 8.12 (d, J = 8.5 Hz, 1H), 7.51−7.56 (m, 6H), 7.33−
7.35 (m, 4H), 7.18 (s, 1H), 2.46 (s, 3H), 2.43 (s, 3H), 2.18 (s, 3H);
13C NMR (500 MHz, CDCl3) δ ppm: 160.0, 147.1, 145.0, 138.8,
138.0, 137.7, 136.0, 130.7, 129.4, 129.2, 128.97, 128.95, 128.7, 127.7,
127.0, 126.7, 124.7, 21.8, 21.3, 18.7; HRMS (EI) Calcd. for C24H21N:
[M+], 323.1674. Found: m/z 323.1675.
Ethyl 2-p-Tolyl-6-nitroquinoline-3-carboxylate (4l). 1H NMR
(500 MHz, CDCl3) δ ppm: 9.7 (d, J = 2.5 Hz, 1H), 8.50 (s, 1H),
8.45 (d, J = 2.5 Hz, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.12 (d, J = 8.5 Hz,
2H), 7.36 (q, 2H), 4.60 (q, 2H), 2.47 (s, 3H), 1.55−1.58 (t, 3H); 13C
NMR (500 MHz, CDCl3) δ ppm: 165.3, 159.8, 151.1, 146.0, 141.4,
137.1, 134.8, 131.6, 129.8, 127.6, 123.2, 122.9, 122.8, 121.7, 62.5, 21.4,
14.3; HRMS (EI) Calcd. for C19H16N2O4: [M+], 336.1110. Found:
m/z 336.1114.
2-(4-Methoxyphenyl)-3,6-dimethyl-4-phenylquinoline (4c). 1H
NMR (500 MHz, CDCl3) δ ppm: 8.10 (d, J = 8.5 Hz, 1H), 7.56−
7.62 (m, 4H), 7.50−7.53 (m, 2H), 7.33 (d, J = 7.0 Hz, 2H), 7.16 (s,
1H), 7.05 (d, J = 8.5 Hz, 2H), 3.89 (s, 3H), 2.43 (s, 3H), 2.19 (s, 3H);
13C NMR (500 MHz, CDCl3) δ ppm: 159.6, 159.5, 147.1, 145.0,
138.1, 135.9, 134.2, 130.7, 130.4, 129.4, 129.1, 128.7, 127.7, 126.9,
126.8, 124.7, 113.4, 55.4, 21.80, 18.8; HRMS (EI) Calcd. for
C24H21NO: [M+], 339.1623. Found: m/z 339.1622.
2,4-Diphenylquinoline (4m).7a,11c,13 1H NMR (500 MHz, CDCl3)
δ ppm: 8.43 (d, J = 8.0 Hz, 1H), 8.34 (d, J = 8.0 Hz, 2H), 8.00 (d, J =
8.5 Hz, 1H), 7.92 (s, 1H), 7.80 (t, 1H), 7.51−7.64 (m, 9H); 13C NMR
(500 MHz, CDCl3) δ ppm: 156.9, 149.2, 149.1, 139.8, 138.6, 130.4,
129.7, 129.6, 129.5, 129.0, 128.7, 128.5, 127.8, 126.5, 125.9, 125.8,
119.4; HRMS (EI) Calcd. for C21H15N: [M+], 281.1204. Found: m/z
281.1207.
2-p-Tolyl-3-methyl-4-phenyl-6-methoxyquinoline (4d). 1H NMR
(500 MHz, CDCl3) δ ppm: 8.10 (d, J = 9.0 Hz, 1H), 7.49−7.59 (m,
5H), 7.31−7.35 (m, 5H), 6.66 (d, J = 2.5 Hz, 1H), 3.72 (s, 3H), 2.45
(s, 3H), 2.17 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 158.5,
157.5, 146.5, 142.5, 138.7, 138.1, 137.6, 130.9, 129.3, 129.0, 128.9,
128.7, 127.9, 127.8, 127.0, 120.6, 104.2 55.3, 21.3, 18.7; HRMS (EI)
Calcd. for C24H21NO: [M+], 339.1623. Found: m/z 339.1622.
2-p-Tolyl-3-methyl-4-phenyl-6-fluoroquinoline (4e). 1H NMR
(500 MHz, CDCl3) δ ppm: 8.17−8.19 (q, 1H), 7.57−7.60 (t, 2H),
7.51−7.53 (m, 3H), 7.41−7.45 (m, 1H), 7.28−7.35 (q, 4H), 7.02 (q,
1H), 2.47 (s, 3H), 2.20 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm:
167.2, 148.5, 141.7, 139.9, 139.1, 132.9, 129.6, 129.5, 129.0, 128.3,
127.9, 127.8, 127.6, 126.2, 123.0, 120.1, 100.0, 21.3, 18.1; HRMS (EI)
Calcd. for C23H18NF: [M+], 327.1423. Found: m/z 327.1424.
2-p-Tolyl-3-methyl-4-phenyl-6-nitroquinoline (4f). 1H NMR (500
MHz, CDCl3) δ ppm: 8.42 (q, 1H), 8.37 (d, J = 2.0, 1H), 8.28 (d, J =
9.0, 1H), 7.61 − 7.64 (t, 2H), 7.59−7.60 (t, 3H), 7.34−7.37 (m, 4H),
2.47 (s, 3H), 2.25 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm:
164.4, 149.7, 148.4, 145.4, 138.8, 137.8, 136.2, 131.2, 129.2, 129.12,
129.08, 128.8, 128.7, 128.0, 126.1, 123.0, 122.0, 21.3, 18.9; HRMS
(EI) Calcd. for C23H18N2O2: [M+], 354.1368. Found: m/z 354.1366.
2,4-Diphenyl-6-methylquinoline (4n).7a,11c,13 1H NMR (500 MHz,
CDCl3) δ ppm: 8.85 (d, J = 9.0 Hz, 1H), 8.15 (t, 2H), 7.97 (d, J = 3.5
Hz, 2H), 7.88 (s, 1H), 7.62−7.73 (m, 8H), 2.61 (s, 3H); 13C NMR
(500 MHz, DMSO-d6) δ ppm: 155.7, 153.4, 140.0, 139.4, 136.2, 136.1,
132.9, 132.7, 130.5, 130.2, 129.8, 129.6, 129.5, 125.9, 125.5, 123.1,
121.8, 21.8; HRMS (EI) Calcd. for C22H17N: [M+], 295.1361. Found:
m/z 295.1357.
2-p-Tolyl-4-phenyl-6-methylquinoline (4o). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.30 (d, J = 9.0 Hz, 1H), 8.23 (s, 1H), 8.18 (d, J = 7.5
Hz, 2H), 7.93 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.67−7.72 (m, 5H),
7.51 (d, J = 8.0 Hz, 2H), 2.52 (s, 3H), 2.46 (s, 3H); 13C NMR (500
MHz, CDCl3) δ ppm: 158.5, 153.0, 144.6, 140.7, 137.7, 137.1, 135.2,
130.8, 129.40, 129.36, 129.0, 127.2, 126.0, 125.8, 121.8, 121.529,
120.9, 21.9, 21.5; HRMS (EI) Calcd. for C23H19N: [M+], 309.1517.
Found: m/z 309.1521.
2,4-Di-p-tolyl-6-methylquinoline (4p). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.61 (d, J = 14.5 Hz, 1H), 8.00 (d, J = 13.5 Hz,
2H), 7.89 (d, J = 12.0 Hz, 2H), 7.70 (d, J = 14.5 Hz, 1H), 7.53 (d, J =
13.5 Hz, 2H), 7.45 (d, J = 13.0 Hz, 2H), 7.32 (d, J = 13.0 Hz, 2H),
2.54 (s, 3H), 2.47 (s, 3H), 2.27 (s, 3H); 13C NMR (500 MHz, CDCl3)
δ ppm: 158.5, 152.6, 144.4, 141.4, 140.5, 137.5, 136.9, 132.2, 130.6,
130.1, 129.5, 128.9, 127.1, 126.0, 125.8, 121.2, 120.6, 21.8, 21.39,
21.36; HRMS (EI) Calcd. for C24H21N: [M+], 323.1674. Found: m/z
323.1679.
1
2-p-Tolyl-3,4-diphenyl-6-methylquinoline (4g). H NMR (500 MHz,
CDCl3) δ ppm: 8.18 (d, J = 8.5 Hz, 1H), 7.58 (d, J = 10.0 Hz, 1H),
7.29−7.34 (m, 6H), 7.14−7.16 (m, 2H), 7.03−7.04 (m, 5H), 6.91−
6.93 (m, 2H), 2.45 (s, 3H), 2.31 (s, 3H); 13C NMR (500 MHz,
CDCl3) δ ppm: 158.0, 147.0, 146.0, 138.7, 138.3, 137.2, 136.3, 132.9,
131.6, 131.4, 130.4, 129.9, 129.4, 128.4, 127.7, 127.3, 127.1, 126.5,
126.2, 125.3, 113.8, 21.9, 21.2; HRMS (EI) Calcd. for C29H23N: [M+],
385.1830. Found: m/z 385.1827.
2-(4-Methoxyphenyl)-4-p-tolyl-6-methylquinoline (4q).14 1H
NMR (500 MHz, CDCl3) δ ppm: 8.38 (d, J = 9.0 Hz, 1H), 8.00
(d, J = 4.5 Hz, 2H), 7.73 (d, J = 6.0 Hz, 2H), 7.66 (d, J = 9.0 Hz, 1H),
7.45 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 6.89 (d, J = 9.0 Hz,
2H), 3.67 (s, 3H), 2.45 (s, 3H), 2.43 (s, 3H); 13C NMR (500 MHz,
CDCl3) δ ppm: 163.3, 156.4, 152.5, 140.7, 139.3, 138.9, 135.8, 132.8,
130.5, 129.9, 129.5, 125.6, 125.4, 123.4, 122.3, 119.9, 115.2, 55.5, 21.7,
21.3; HRMS (EI) Calcd. for C24H21NO: [M+], 339.1623. Found: m/z
339.1620.
1
Diethyl 2-Phenyl-6-methylquinoline-3,4-dicarboxylate (4h). H NMR
(500 MHz, CDCl3) δ ppm: 8.12 (d, J = 9.0 Hz, 1H), 7.85 (s, 1H), 7.67
(t, 3H), 7.44−7.50 (m, 3H), 4.53−4.57 (q, 2H), 4.13−4.17 (q, 2H),
2.59 (s, 3H), 1.44−1.46 (t, 3H), 1.02−1.05 (t, 3H); 13C NMR (500
MHz, CDCl3) δ ppm: 167.6, 166.3, 155.9, 146.9, 140.2, 138.6, 138.4,
133.7, 129.7, 128.8, 128.5, 128.4, 124.5, 124.0, 122.2, 62.4, 61.8, 21.9,
14.0, 13.5; HRMS (EI) Calcd. for C22H21NO4: [M+], 363.1471.
Found: m/z 363.1476.
1
Diethyl 2-Phenyl-6-methoxyquinoline-3,4-dicarboxylate (4i). H NMR
(500 MHz, CDCl3) δ ppm: 8.11 (d, J = 9.0 Hz, 1H), 7.65 (q, 2H),
7.45−7.50 (m, 5H), 4.51−4.56 (q, 2H), 4.13−4.18 (q, 2H), 3.97 (s,
3H), 1.43−1.46 (t, 3H), 1.02−1.05 (t, 3H); 13C NMR (500 MHz,
CDCl3) δ ppm: 167.8, 166.3, 159.1, 154.2, 144.7, 140.1, 137.2, 131.5,
2-(4-Methoxyphenyl)-4-phenyl-6-methylquinoline (4r). 1H NMR
(500 MHz, CDCl3) δ ppm: 8.20 (d, J = 8.5 Hz, 2H), 7.91 (t, 2H), 7.81
(s, 1H), 7.68 (d, J = 3.5 Hz, 3H), 7.61−7.62 (m, 2H), 7.18−7.21
(t, 3H), 3.95 (s, 3H), 2.58 (s, 3H); 13C NMR (500 MHz, DMSO-d6) δ
508
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
ppm: 163.4, 155.8, 152.8, 139.7, 138.7, 136.14, 136.06, 131.7, 130.5,
130.2, 129.5, 128.6, 125.6, 124.3, 122.4, 121.4, 115.4, 56.2, 21.8; HRMS
(EI) Calcd. for C23H19NO: [M+], 325.1467. Found: m/z 325.1468.
2,4-Di-p-tolyl-6-methoxyquinoline (4s). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.17 (t, 3H), 7.77 (s, 1H), 7.71 (s, 1H), 7.58 (d,
J = 10.5 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.00 Hz, 2H),
7.08 (d, J = 8.5 Hz, 2H), 3.91 (s, 3H), 2.53 (s, 3H), 2.50 (s, 3H); 13C
NMR (500 MHz, CDCl3) δ ppm: 160.7, 155.7, 148.4, 147.4, 138.2,
135.83, 135.77, 132.4, 131.7, 129.6, 129.5, 129.3, 128.8, 125.6, 124.5,
119.0, 114.2, 55.4, 21.8, 21.3; HRMS (EI) Calcd. for C24H21NO:
[M+], 339.1623. Found: m/z 339.1617.
103.9, 21.3, 18.2; HRMS (MALDI/DHB) Calcd. for C23H19NF: [M +
H]+, 328.1496. Found: m/z 328.1487.
2-p-Tolyl-3-methyl-4-phenyl-7-methoxyquinoline. 1H NMR
(500 MHz, CDCl3) δ ppm: 8.22 (d, J = 8.0 Hz, 1H), 8.14 (d, J =
8.0 Hz, 2H), 7.55−7.64 (m, 5H), 7.45 (d, J = 8.0 Hz, 1H), 7.37 (d, J =
8.0 Hz, 2H), 7.25 (d, J = 2.0 Hz, 1H), 3.82 (s, 3H), 2.48 (s, 3H), 2.26
(s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 161.2, 157.3, 150.7,
148.9, 139.3, 138.7, 137.1, 129.54, 129.52, 128.6, 128.3, 127.5, 126.7,
119.2, 117.3, 115.5, 108.1, 55.6, 21.3, 18.4; HRMS (MALDI/DHB)
Calcd. for C24H22NO: [M + H]+, 340.1696. Found: m/z 340.1697.
Diethyl-2-(2-(diphenylmethyleneamino)-5-methylphenyl)-
maleate. 1H NMR (500 MHz, CDCl3) δ ppm: 7.33−7.35 (m, 3H),
7.25−7.28 (m, 1H), 7.15−7.18 (t, 2H), 6.98−7.04 (m, 4H), 6.75−6.76
(d, J = 8.5 Hz, 2H), 6.61−6.63 (d, J = 8.0 Hz, 2H), 4.34−4.39 (q, 2H),
3.92−3.96 (q, 2H), 2.28 (s, 3H), 1.34−1.36 (t, 3H), 0.92−0.95 (t,
3H); 13C NMR (500 MHz, CDCl3) δ ppm: 165.4, 164.6, 152.8, 137.7,
137.4, 137.0, 136.0, 130.3, 129.6, 129.1, 128.7, 128.2, 128.1, 125.0,
92.5, 59.8, 59.6, 20.9, 14.4, 14.2; HRMS (EI) Calcd. for C28H27NO4:
[M+], 441.1940. Found: m/z 441.1941.
2,4-Diphenyl-6-methoxyquinoline (4t). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.20 (t, 3H), 7.81 (t, 1H), 7.53−7.56 (m, 3H),
7.57−7.62 (m, 4H), 7.42−7.49 (m, 2H), 7.22 (d, J = 3.0 Hz, 1H), 3.83
(s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 157.9, 154.5, 147.8,
145.1, 139.8, 138.9, 131.8, 129.5, 129.1, 128.9, 128.8, 128.4, 127.4,
126.8, 121.9, 119.6, 103.8, 55.4; HRMS (EI) Calcd. for C22H17NO:
[M+], 311.1310. Found: m/z 311.1308.
2-(4-Methoxyphenyl)-4-p-tolyl-6-methoxyquinoline (4u). 1H NMR
(500 MHz, CDCl3) δ ppm: 8.16 (d, J = 8.5 Hz, 3H), 7.76 (s, 1H), 7.51
(d, J = 8.0 Hz, 2H), 7.38−7.42 (m, 3H), 7.25 (d, J = 2.5 Hz, 1H),
7.06−7.07 (d, J = 8.50 Hz, 2H), 3.89 (s, 3H), 3.82 (s, 3H), 2.51 (s,
3H); 13C NMR (500 MHz, CDCl3) δ ppm: 160.6, 157.5, 154.3, 147.8,
144.9, 138.2, 135.9, 132.4, 131.4, 129.4, 129.3, 128.6, 126.5, 121.6,
119.2, 114.2, 103.9, 55.43, 55.35, 21.3; HRMS (EI) Calcd. for
C24H21NO2: [M+], 355.1572. Found: m/z 355.1571.
(Z)-2,6-Dimethyl-N-(3-phenyl-1-p-tolylprop-2-ynylidene)-
aniline. 1H NMR (500 MHz, CDCl3) δ ppm: 7.79 (m, 1H), 7.53 (m,
2H), 7.18 (d, J = 8.0 Hz, 2H), 7.10 (t, 4H), 6.94−6.99 (m, 2H), 6.60−
6.63 (d, J = 16.5 Hz, 1H), 2.34 (s, 3H), 2.13 (s, 6H); 13C NMR (500
MHz, CDCl3) δ ppm: 167.2, 148.5, 141.7, 139.9, 132.9, 129.6, 129.0,
128.3, 127.9, 127.6, 126.2, 123.0, 120.1, 21.3, 18.1; HRMS (EI) Calcd.
for C24H21N: [M+], 323.1674. Found: m/z 323.1671.
2-p-Tolyl-4-phenyl-6-fluoroquinoline (4v). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.24 (q, 1H), 8.11 (d, J = 8.5 Hz, 2H), 7.85 (s, 1H),
7.50−7.61 (m, 7H), 7.36 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H); 13C NMR
(500 MHz, CDCl3) δ ppm: 161.5, 159.5, 156.3, 148.6, 145.9, 139.5,
138.1, 136.6, 132.5, 129.6, 129.4, 128.8, 128.6, 127.4, 119.7, 119.4,
108.9, 21.3; HRMS (EI) Calcd. for C22H16NF: [M+], 313.1267.
Found: m/z 313.1271.
2-p-Tolyl-4-methylquinoline. 1H NMR (500 MHz, CDCl3) δ
ppm: 8.78 (d, J = 9.0 Hz, 1H), 8.19 (t, 1H), 8.02−8.07 (m, 3H), 7.97
(s, 1H), 7.86 (t, 1H), 7.42 (d, J = 8.0 Hz, 2H), 3.03 (s, 3H), 2.42 (s,
3H); 13C NMR (500 MHz, DMSO-d6) δ ppm: 156.7, 153.4, 143.4,
138.4, 134.0, 130.1, 129.2, 128.9, 128.8, 126.8, 125.6, 122.1, 121.7,
21.2, 19.5; HRMS (EI) Calcd. for C17H15N: [M+], 233.1204. Found:
m/z 233.1207.
2-p-Tolyl-4-phenyl-6-nitroquinoline (4w). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.87 (d, J = 2.0 Hz, 1H), 8.51 (d, J = 11.0 Hz, 1H),
8.38 (d, J = 8.5 Hz, 1H), 8.19 (d, J = 8.0 Hz, 2H), 7.99 (s, 1H), 7.59−
7.65 (m, 5H), 7.39(d, J = 8.0 Hz, 2H), 2.48 (s, 3H); 13C NMR (500
MHz, CDCl3) δ ppm: 159.9, 151.1, 145.2, 140.9, 137.0, 135.7, 131.6,
129.8, 129.5, 129.3, 129.1, 127.7, 124.7, 123.0, 122.9, 120.5, 21.5;
HRMS (EI) Calcd. for C22H16N2O2: [M+], 340.1212. Found: m/z
340.1217.
2-p-Tolyl-3-methylquinoline. 1H NMR (500 MHz, CDCl3) δ
ppm: 8.16 (d, J = 8.5 Hz, 1H), 8.02 (s, 1H), 7.79 (d, J = 8.0 Hz, 1H),
7.68 (t, 1H), 7.53 (d, J = 8.0 Hz, 3H), 7.33 (d, J = 7.5 Hz, 2H), 2.50 (s,
3H), 2.46 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 160.6, 146.7,
138.1, 138.0, 136.7, 129.4, 129.3, 129.0, 128.8, 128.7, 127.6, 126.7,
126.3, 21.4, 20.7; HRMS (EI) Calcd. for C17H15N: [M+], 233.1204.
Found: m/z 233.1201.
2-p-Tolyl-4-propyl-6-methylquinoline (4x). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.02−8.07 (t, 3H), 7.75 (s, 1H), 7.64 (s, 1H), 7.50
−7.52 (d, J = 10.5 Hz, 1H), 7.31 (d, J = 10.0 Hz, 2H), 3.03−3.07 (t,
2H), 2.55 (s, 3H), 2.42 (s, 3H), 1.81−1.86 (m, 2H), 1.05−1.08 (q,
3H); 13C NMR (500 MHz, CDCl3) δ ppm: 156.1, 148.1, 147.0, 139.0,
137.2, 135.5, 131.3, 129.5, 128.2, 127.4, 126.5, 122.4, 118.6, 34.5, 23.3,
22.0, 21.3, 14.2; HRMS (EI) Calcd. for C20H21N: [M+], 275.1674.
Found: m/z 275.1677.
2-p-Tolyl-4-phenyl-6-methoxyquinoline. 1H NMR (500 MHz,
CDCl3) δ ppm: 8.28 (d, J = 8.5 Hz, 1H), 8.21 (d, J = 8.5 Hz, 2H),
7.95 (d, J = 8.0 Hz, 1H), 7.81 (s, 1H), 7.74 (q, 1H), 7.46−7.50 (m,
3H), 7.38 (d, J = 7.50 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 3.90 (s, 3H),
2.51 (s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 157.0, 146.0,
144.9, 137.7, 136.2, 135.3, 130.5, 130.4, 129.3, 128.8, 128.4, 127.3,
126.7, 126.3, 126.1, 125.1, 124.3, 54.3, 20.8; HRMS (EI) Calcd. for
C23H19NO: [M+], 325.1467. Found: m/z 325.1468.
2-p-Tolyl-6-methylquinoline (4y). 1H NMR (500 MHz, CDCl3) δ
ppm: 8.14 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 8.5 Hz, 3H), 7.84 (d, J =
8.5 Hz, 1H), 7.58 (q, 2H), 7.35 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H), 2.46
(s, 3H); 13C NMR (500 MHz, CDCl3) δ ppm: 156.5, 147.6, 146.8,
143.8, 139.2, 136.0, 131.9, 129.5, 129.3, 128.8, 127.3, 126.3, 118.8,
21.6, 21.3; HRMS (EI) Calcd. for C17H15N: [M+], 233.1204. Found:
m/z 233.1199.
2-p-Tolyl-4-phenyl-7-fluoroquinoline. 1H NMR (500 MHz,
CDCl3) δ ppm: 8.17 (d, J = 9.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 2H),
7.79 (s, 1H), 7.53−7.61 (m, 5H), 7.41 (d, J = 9.0 Hz, 1H), 7.35 (d, J =
8.0 Hz, 2H), 7.21 (d, J = 2.0 Hz, 1H) 2.46 (s, 3H); 13C NMR (500
MHz, CDCl3) δ ppm: 157.7, 154.7, 147.7, 144.9, 139.0, 138.9, 137.0,
131.5, 129.5, 129.4, 128.7, 128.3, 127.2, 126.6, 121.7, 119.5, 103.8,
21.3; HRMS (MALDI/DHB) Calcd. for C22H17NF: [M + H]+,
314.1340. Found: m/z 314.1333.
2-p-Tolyl-3-propyl-6-methylquinoline (4z). 1H NMR (500 MHz,
CDCl3) δ ppm: 8.10 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 2H), 7.66
(q, 2H), 7.55 (s, 1H), 7.33 (d, J = 8.0 Hz, 2H), 3.12−3.16 (t, 2H),
2.81−2.84 (m, 2H), 2.55 (s, 3H), 2.45 (s, 3H), 2.15−2.21 (q, 3H);
13C NMR (500 MHz, CDCl3) δ ppm: 160.0, 156.7, 141.7, 135.7,
131.4, 129.5, 128.53, 128.45, 127.4, 126.3, 126.0, 122.3, 118.6, 35.7,
24.6, 21.9, 21.3, 13.1; HRMS (EI) Calcd. for C20H21N: [M+],
275.1674. Found: m/z 275.1675.
2-p-Tolyl-4-phenyl-7-methoxyquinoline. 1H NMR (500 MHz,
CDCl3) δ ppm: 8.09 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 9.5 Hz, 1H),
7.67 (s, 1H), 7.50−7.58 (m, 6H), 7.33 (d, J = 8.0 Hz, 2H), 7.12 (d, J =
8.0 Hz, 1H), 4.00 (s, 3H), 2.44 (s, 3H); 13C NMR (500 MHz, CDCl3)
δ ppm: 160.7, 157.3, 150.7, 148.9, 139.3, 138.7, 137.0, 129.6, 129.5,
128.6, 128.3, 127.4, 126.8, 120.8, 119.3, 117.3, 107.9, 55.6, 21.4;
HRMS (MALDI/DHB) Calcd. for C23H20NO: [M + H]+, 326.1539.
Found: m/z 326.1541.
1
2-p-Tolyl-3-methyl-4-phenyl-7-fluoroquinoline. H NMR (500 MHz,
CDCl3) δ ppm: 8.16 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 9.0 Hz, 2H),
7.53−7.61 (m, 5H), 7.41 (d, J = 9.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H),
7.21 (d, J = 8.0 Hz, 1H), 2.46 (s, 3H), 2.22 (s, 3H); 13C NMR
(500 MHz, CDCl3) δ ppm: 157.8, 154.6, 147.7, 145.0, 139.0, 138.9,
137.0, 131.6, 129.6, 129.4, 128.7, 127.6, 127.2, 126.6, 121.7, 119.5,
509
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510

The Journal of Organic Chemistry
Article
(6) Lu, P.; Boorman, T. C.; Slawin, A. M. Z.; Larrosa, I. J. Am. Chem.
Soc. 2010, 132, 5580−5581.
ASSOCIATED CONTENT
* Supporting Information
Compound characterization data and mechanistic studies. This
material is available free of charge via the Internet at http://
pubs.acs.org.
■
S
(7) (a) Xiao, F.; Chen, Y.; Liu, Y.; Wang, J. Tetrahedron 2008, 64,
2755−2761. (b) Damavandi, J. S.; Zolfigol, M. A.; Karami, B. Synth.
Commun. 2001, 31, 3183−3187.
(8) (a) Nakao, Y.; Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am.
Chem. Soc. 2010, 132, 13666−13668. (b) Nakao, Y.; Idei, H.; Kanyiva,
K. S.; Hiyama, T. J. Am. Chem. Soc. 2009, 131, 15996−15997.
(c) Nakao, Y.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130,
2448−2449.
(9) (a) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610−618.
(b) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38,
870−883. (c) Wang, J.-H.; Chiang, C.-M. J. Am. Chem. Soc. 2000, 122,
11521−11522. (d) Whitesides, G. M.; Bergbreiter, D. E.; Kendall, P. E.
J. Am. Chem. Soc. 1974, 96, 2806−2813.
AUTHOR INFORMATION
Corresponding Author
*jinz@nju.edu.cn
■
ACKNOWLEDGMENTS
■
J.Z. gratefully acknowledges support from the National Natural
Science Foundation of China (20974044, 90923006) and the
National Basic Research Program of China (2011CB935801).
(10) (a) Campeau, L.-C.; Rousseaux, S.; Fagnou, K. J. Am. Chem. Soc.
2005, 127, 18020−18021. (b) Ye, M.; Gao, G.-L.; Edmunds, A. J. F.;
Worthington, P. A.; Morris, J. A.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133,
19090−19093. (c) O’Ferrall, R. A. M. J. Chem. Soc. B 1970, 785−790.
(11) (a) Kuninobu, Y.; Inoue, Y.; Takai, K. Chem. Lett. 2007, 36,
1422−1423. (b) Huang, H.; Jiang, H.; Chen, K.; Liu, H. J. Org. Chem.
2009, 74, 5476−5480. (c) Zhao, Y.-L.; Zhang, W.; Wang, S.; Liu, Q.
J. Org. Chem. 2007, 72, 4985−4988. (d) Kikuchi, S.; Iwai, M.;
Fukuzawa, S. Synlett 2007, 2639−2642. (e) Cao, K.; Zhang, F.-M.; Tu,
Y.-Q.; Zhuo, X.-T.; Fan, C.-A. Chem.Eur. J. 2009, 15, 6332−6334.
REFERENCES
■
(1) (a) Caballero, A.; Despagnet-Ayoub, E.; Díaz-Requejo, M. M.;
Díaz-Rodríguez, A.; Gonzal
Ojo, W.-S.; Asensio, G.; Etienne, M.; Per
́
ez-Nunez, M. E.; Mello, R.; Munoz, B. K.;
́
̃
̃
́
ez, P. J. Science 2011, 332,
835−838. (b) Naodovic, M.; Yamamoto, H. Chem. Rev. 2008, 108,
́
3132−3148. (c) Alvarez-Corral, M.; Munoz-Dorado, M.; Rodríguez-
̃
García., I. Chem. Rev. 2008, 108, 3174−3198. (d) Weibel, J.-M.; Blanc,
A.; Pale, P. Chem. Rev. 2008, 108, 3149−3173. (e) Yamamoto, Y.
Chem. Rev. 2008, 108, 3199−3222. (f) Yoshida, S.; Fukui, K.; Kikuchi,
S.; Yamada, T. J. Am. Chem. Soc. 2010, 132, 4072−4073. (g) Oh,
C. H.; Karmakar, S.; Park, H.-S.; Ahn, Y.-C.; Kim, J. W. J. Am. Chem.
Soc. 2010, 132, 1792−1793. (h) Tang, P.; Furuya, T.; Ritter, T. J. Am.
Chem. Soc. 2010, 132, 12150−12154. (i) Su, S.; Porco, J. A. Jr. J. Am.
Chem. Soc. 2007, 129, 7744−7745. (j) Thompson, J. L.; Davies, H. M.
(f) Kulkarni, A.; Torok, B. Green Chem. 2010, 12, 875−878. (g) Xie,
̈
̈
H.; Zhu, J.; Chen, Z.; Li, S.; Wu, Y. Synlett 2010, 17, 2659−2663.
(h) Li, X.; Mao, Z.; Wang, Y.; Chen, W.; Lin, X. Tetrahedron 2011, 67,
3858−3862. (i) Guchhait, S. K.; Jadeja, K.; Madaan, C. Tetrahedron
Lett. 2009, 50, 6861−6865. (j) Yadav, J. S.; Reddy, B. V. S.; Rao, R. S.;
Naveenkumar, V.; Nagaiah, K. Synthesis 2003, 1610−1614. (k) Zhang,
Y.; Li, P.; Wang, L. J. Heterocycl. Chem. 2011, 48, 153−157.
L. J. Am. Chem. Soc. 2007, 129, 6090−6091. (k) Llaveria, J.; Beltran
A.; Díaz-Requejo, M. M.; Matheu, M. I.; Castillon, S.; Perez, P. J.
́
,
(12) (a) Foropoulous, J.; Desmarteau, D. Inorg. Chem. 1984, 23,
3720−3723. (b) Vij, A.; Zheng, Y. Y.; Kirchmeier, R.-L.; Shreeve, J. M.
Inorg. Chem. 1994, 33, 3281−3288. (c) Sweis, R. F.; Schramm, M. P.;
Kozmin, S, A. J. Am. Chem. Soc. 2004, 126, 7442−7443.
́
́
Angew. Chem., Int. Ed. 2010, 49, 7092−7095. (l) Murakami, K.;
Hirano, K.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2008, 47,
5833−5835. (m) Li, Z.; Capretto, D. A.; Rahaman, R.; He, C. Angew.
Chem., Int. Ed. 2007, 46, 5184−5186. (n) Sun, J.; Kozmin, S. A. Angew.
Chem., Int. Ed. 2006, 45, 4991−4993.
(2) (a) Choi, J.; Wang, D. Y.; Kundu, S.; Choliy, Y.; Emge, T. J.;
Krogh-Jespersen, K.; Goldman, A. S. Science 2011, 332, 1545−1548.
(b) Wang, D.-H.; Engle, K. M.; Shi, B.-F.; Yu, J.-Q. Science 2010, 327,
315−319. (c) Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593−
1597. (d) Bergman, R. G. Nature 2007, 446, 391−393. (e) Labinger,
J. A.; Bercaw, J. E. Nature 2002, 417, 507−514. (f) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655.
(g) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890−931. (h) Sanford, M. S.;
Lyons, T. W. Chem. Rev. 2010, 110, 1147−1169.
(13) (a) Martínez, R.; Ramon
1599−1605. (b) Martínez, R.; Ramon
2008, 73, 9778−9780.
́
, D. J.; Yus, M. Eur. J. Org. Chem. 2007,
́
, D. J.; Yus, M. J. Org. Chem.
(14) Majumdar, K. C.; Nandi, R. K.; Ganai, S.; Taher, A. Synlett 2011,
116−120.
(3) Dupont, J.; Consorti, C. S.; Spencer, J. Chem. Rev. 2005, 105,
2527−2571.
(4) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y.
Science 2000, 287, 1992−1995.
(5) (a) Ackermann, L. Chem. Rev. 2011, 111, 1315−1345.
(b) Pintori, D. G.; Greaney, M. F. J. Am. Chem. Soc. 2011, 133,
1209−1211. (c) Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.;
LeBris, A. P.; DeBoef, B. J. Am. Chem. Soc. 2010, 132, 14676−14681.
(d) Rousseaux, S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 10692−10705. (e) Lafrance, M.; Rowley, C. N.;
Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754−8756.
(f) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496−
16497. (g) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am.
Chem. Soc. 2005, 127, 13754−13755. (h) García-Cuadrado, D.;
Mendoza, P. M.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am.
Chem. Soc. 2007, 129, 6880−6886. (i) García-Cuadrado, D.; Braga,
A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128,
1066−1067. (j) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew.
Chem., Int. Ed. 2009, 48, 9792−9826. (k) Arockiam, P. B.;
Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed.
2010, 49, 6629−6632.
510
dx.doi.org/10.1021/jo202087j | J. Org. Chem. 2012, 77, 501−510