Palladium-catalyzed/norbornene-mediated C-H activation/ N-tosylhydrazone insertion reaction: A route to highly functionalized vinylarenes

Article abstract of DOI:10.1002/chem.201402097

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium-catalyzed, norbornene-mediated C-H activation/carbene migratory insertion is described. Extension to a one-pot procedure is also developed. Furthermore, this

Full text of DOI:10.1002/chem.201402097

DOI: 10.1002/chem.201402097
Full Paper
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Palladium Catalysis
Palladium-Catalyzed/Norbornene-Mediated CÀH Activation/
N-Tosylhydrazone Insertion Reaction: A Route to Highly
Functionalized Vinylarenes
Ping-Xin Zhou,[a] Lan Zheng,[a] Jun-Wei Ma,[a] Yu-Ying Ye,[a] Xue-Yuan Liu,[a] Peng-Fei Xu,*[a]
and Yong-Min Liang*[a, b]
Abstract: A straightforward method for the synthesis of
highly functionalized vinylarenes through palladium-cata-
lyzed, norbornene-mediated CÀH activation/carbene migra-
tory insertion is described. Extension to a one-pot procedure
is also developed. Furthermore, this method can also be
used to generate polysubstituted bicyclic molecules. The re-
action proceeds under mild conditions to give the products
in satisfactory yields using readily available starting materi-
als. This is a Catellani–Lautens reaction that incorporates dif-
ferent types of coupling partners. Additionally, this reaction
is the first to demonstrate the possibility of combining Pd-
catalyzed insertion of diazo compounds and Pd-catalyzed
CÀH activation.
Introduction
Multicomponent reactions (MCRs), which can create complex
molecules in a single process from simple building blocks,
have attracted significant attention over the past decades.[1]
Unlike stepwise processes, these reactions preclude the need
for the synthesis of complex or prefunctionalized starting ma-
terials and these reactions are carried out in an efficient, atom
economic way. For many years, palladium-catalyzed MCRs have
been employed as one of the most reliable and powerful
methods for the synthesis of complex organic compounds.[2]
Among them, palladium-catalyzed/norbornene mediated CÀH
activation, which was initially reported by Catellani and further
developed by Lautens and others, have become more attrac-
tive because it is of fundamental importance in organic synthe-
sis and because it offers a range of novel synthetic variations.[3]
The Catellani–Lautens reaction involves direct activation of an
aromatic carbonÀhydrogen bond and ortho-functionalization,
followed by terminal cross-coupling processes for the forma-
tion of a diverse range of highly functionalized aromatic com-
pounds. As shown in Scheme 1, the Catellani–Lautens reaction
Scheme 1. Reaction mechanism of the Catellani–Lautens reaction.
starts with oxidative addition of an aryl halide to Pd0 to give
palladium complex A, followed by carbopalladation of norbor-
nene to form B. Next, CÀH activation of the ortho position of
the aryl halide and subsequent deprotonation delivers pallada-
cycle C. This PdII complex reacts with a second alkyl halide, af-
fording PdIV complex D. Reductive elimination followed by de-
insertion of norbornene through b-carbon elimination provides
PdII species F, which can further undergo palladium-catalyzed
terminal cross-coupling reaction.[4] In classic Catellani–Lautens
reactions the type of coupling partners are often alkene or
alkyne (Scheme 2, Eq. (1)),[5 ]organometallic reagent (Scheme 2,
Eq. (2)),[6] nucleophile reagent (Scheme 2, Eq. (3)),[7] hydrogen
transfer reagent (Scheme 2, Eq. (4)),[8] or heteroaromatics com-
pound (Scheme 2, Eq. (5)).[9] In view of the diverse require-
ments of synthetic organic chemistry, incorporation of different
types of coupling partners in the reaction with terminal aryl-
palladium(II) species F is highly desired.
[a] Dr. P.-X. Zhou, L. Zheng, J.-W. Ma, Y.-Y. Ye, X.-Y. Liu, Prof. Dr. P.-F. Xu,
Prof. Dr. Y.-M. Liang
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (P.R. China)
Fax: (0086)931-8912582
E-mail: xupf@lzu.edu.cn
liangym@lzu.edu.cn
[b] Prof. Dr. Y.-M. Liang
State Key Laboratory of Solid Lubrication
Lanzhou Institute of Chemical Physics
Chinese Academy of Science, Lanzhou 730000 (P.R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402097.
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In this paper, we report the first example of the use of N-to-
sylhydrazones as a coupling partner in the Catellani–Lautens
reaction. We also demonstrate the possibility of combining Pd-
catalyzed insertion of a diazo compound and Pd-catalyzed CÀ
H activation.
Results and Discussion
At the outset, the three-component reaction of 1-iodo-2-meth-
ylbenzene (1a), 1-chloromethyl-4-methoxybenzene (2a), and
N-tosylhydrazone 3a was catalyzed by Pd(OAc)2 (10 mol%)/
PPh3 (20 mol%)/norbornene (3.0 equiv) in the presence of
tBuOLi as base in dioxane at 908C for 15 h (Table 1, entry 1).[17]
Table 1. Optimization of reaction conditions.[a]
Scheme 2. Terminal cross-coupling.
Recently, diazo compounds have been considered as a new
type of cross-coupling partner in palladium-catalyzed reac-
tions.[10] In 2001, the first example of using stabilized trimethyl-
silyldiazomethane as the coupling partner in palladium-cata-
lyzed reactions was reported by Van Vranken.[11] In 2007, Bar-
luenga was the first to employ tosylhydrazones as a source of
diazo compound in this unique reaction, which greatly ex-
panded its scope.[12] Over the past few years, significant advan-
ces have been made in the application of diazo compounds
and tosylhydrazones as the coupling partner in this new class
of reaction. However, most of these cross-couplings are still
limited to oxidative addition and palladium carbene migratory
insertion, followed by b-hydride elimination (Scheme 3).[10] In-
Entry
Catalyst
Solvent
Base
Yield [%][b]
1
2
3
4
5
6
7
8
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/[HPtBu3]BF4
Pd(OAc)2/TFP
Pd(OAc)2/Xphos
Pd(OAc)2/Phen
Pd(OAc)2/dppb
PdCl2/PPh3
Pd(CH3CN)2Cl2/PPh3
Pd(PPh3)4/PPh3
Pd2(dba)3·CHCl3/PPh3
Pd2(dba)3/PPh3
none
dioxane
dioxane
dioxane
dioxane
dioxane
DCE
tBuOLi
tBuOK
Na2CO3
K2CO3
0
trace
0
trace
63
<10
<10
0
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CH3CN
2-MeTHF
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
9
<10
91[c]
0[c]
10
11
12
13
14
15
16
17
18
19
20
21
<10[c]
0[c]
0[c]
72[c]
74[c]
81[c]
45[c]
<10[c]
<10[c]
0[c]
Scheme 3. Traditional mechanism of Pd carbene migratory insertion.
[a] Reaction conditions: 1a (0.3 mmol, 1.0 equiv), 2a (0.75 mmol,
2.5 equiv), 3a (0.6 mmol, 2.0 equiv), Pd (10 mol%), ligand (20 mol%), nor-
bornene (0.90 mmol, 3.0 equiv), base (1.35 mmol, 4.5 equiv), solvent
(3 mL), 908C, 15 h. [b] Yield of isolated product. [c] H2O (5.0 equiv) was
added as an additive.
corporation of the well-established chemistry of Pd concepts
such as CÀH activation, decarboxylative coupling, cascade re-
actions, oxidative cross-coupling reactions, and transmetalla-
tion, in this unique process would provide more novel transfor-
mations. Indeed, Wang and co-workers reported the first oxida-
tive cross-coupling of boronic acids with a-diazocarbonyl com-
pounds.[13] Recently, the combination of transmetalation with
palladium carbene migratory insertion has also been demon-
strated by the same group.[14] Van Vranken and co-workers de-
veloped a three-component cascade reaction of ethyl diazoa-
cetate, vinyl halide, and secondary amine.[15] We also reported
a very interesting reaction that can be used to merge decar-
boxylation coupling with Pd carbene migratory insertion.[16]
However, to our knowledge, incorporation of CÀH activation in
the palladium-catalyzed insertion of a diazo compound has
not been explored.
To our disappointment, none of the desired product 4a was
detected. A similar result was afforded when the base was
changed to tBuOK, Na2CO3, or K2CO3 (Table 1, entries 2–4).
Gratifyingly, the desired product was isolated in 63% yield
when Cs2CO3 was utilized as the base (Table 1, entry 5). With
Cs2CO3 as the optimal base, we went on to evaluate other re-
action parameters, such as solvent, additive, ligand and cata-
lyst. Solvents such as 1,2-dichloroethane (DCE), CH3CN, 2-meth-
yltertrahydrofuran, and toluene were surveyed, but were found
to be ineffective (Table 1, entries 6–9). We further investigated
the effect of the additive. Barluenga and co-workers have
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shown that using water as additive in Pd-catalyzed cross-cou-
pling with N-tosylhydrazone could significant improve the
yield.[18] Indeed, the yield could be further improved to 91% in
the presence of 5.0 equiv. H2O (Table 1, entry 10). To enhance
the solubility of the sulfonylhydrazone salt, 2.0 equiv benzyl
triethylammonium chloride (BTAC) was used as an additive,
but this was found to be ineffective (data not shown). The use
of 1.5 equiv of NEt3 as co-base did not improve the yield (data
not shown). No reaction occurred when [HPtBu3]BF4, Xphos, or
Phen was used as the ligand, and a lower yield was obtained
when the reaction was performed with tri(furan-2-yl)phosphine
(TFP) (Table 1, entries 11–14). Employing dppb as the ligand
gave moderate yields (Table 1, entry 15). For the palladium cat-
alysts, various PdII and Pd0 were investigated, however, they
were less efficient than Pd(OAc)2 (Table 1, entries 16–20). Final-
ly, a control experiment showed that the reaction did not pro-
ceed without palladium catalyst (Table 1, entry 21).
Table 3. Intermolecular benzylation/carbene migratory insertion reaction:
scope of the reaction with benzyl chloride 2.[a]
[a] Reaction conditions: 1a (0.3 mmol, 1.0 equiv),
2
(0.75 mmol,
With the optimized reaction conditions established, the
scope of this reaction was explored with a range of N-tosylhy-
drazones 3; the results are summarized in Table 2. It was found
2.5 equiv), 3a (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%),
norbornene (0.90 mmol, 3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3
(1.35 mmol, 4.5 equiv), dioxane (3 mL), 908C, 15 h under Ar. Yield of iso-
lated product.
Table 2. Intermolecular benzylation/carbene migratory insertion reaction;
scope of the reaction with N-tosylhydrazone 3.[a]
corresponding products were obtained in moderate to good
yields. Both electron-withdrawing and electron-releasing
groups on the aromatic ring were tolerated. The position of
the substituent also did not noticeably affect the cross-cou-
pling.
Finally, we tested the scope of the reaction with respect to
aryl iodides under the standard conditions as shown in Table 2
and Table 3. Both electron-rich and electron-poor aryl iodides
afforded the expected products 4 in moderate to good yields.
Highly sterically hindered 1-iodo-2-isopropylbenzene success-
fully afforded the product 4-27 in 72% yield. 1-Iodonaphtha-
lene was also suitable for the reactions. According to previous
reports, aryl iodides containing a substituent ortho to the CÀH
activation site are less reactive, which may be due to steric hin-
drance during the palladation of the CÀH bond.[9a,d,e] To our
delight, the reaction proceeded efficiently and afforded the
product in good yields (Table 4, 4-31, 4-32, and 4-33).
The success of ortho-substituted aryl iodide in the CÀH acti-
vation/carbene migratory insertion encouraged us to extend
this methodology to prepare dibenzylated products by
a double CÀH activation of two ortho positions of aryl iodide.
Indeed, dibenzylated products were obtained in moderate
yields when aryl iodide was subjected to slightly modified
standard reaction conditions. The reactions with meta- and
para-substituted benzyl chloride all worked efficiently (Table 5,
4-35, 4-36, 4-37, 4-38, 4-39, and 4-40). For the aryl iodide,
electronic effects of the substituent had a notable effect on
the yield. Better results were obtained when the aryl iodide
was substituted with an electron-rich group (Table 5, 4-41 and
4-42). A diminished yield was observed when the ring was
substituted with an electron-poor group (Table 5, 4-45). The
structure of 4-38 was confirmed by X-ray crystallographic anal-
ysis.[19]
[a] Reaction conditions: 1a (0.3 mmol, 1.0 equiv),
2
(0.75 mmol,
2.5 equiv), 3 (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%),
norbornene (0.90 mmol, 3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3
(1.35 mmol, 4.5 equiv), dioxane (3 mL), 908C, 15 h under Ar. Yield of iso-
lated product.
that N-tosylhydrazones with electron-donating or electron-
withdrawing groups on the aromatic ring worked smoothly to
afford the desired product 4 in moderate to good yields. Nota-
bly, the NO2 group was compatible with the reaction (Table 2,
4-12). Additionally, ortho-substituted substrates also proceeded
efficiently (Table 2, 4-13, 4-14, and 4-15). It is worth noting
that chloro- and bromo-substituents were tolerated under the
Pd-catalyzed conditions, which allows further metal-catalyzed
coupling reactions (Table 2, 4-5, 4-6, 4-10, and 4-11).
Next, a series of substituted benzyl chlorides were subjected
to the optimized reaction conditions (Table 3). In all cases, the
Alkyl iodide was employed as the alkylating agent to further
demonstrate the generality of this reaction. Various alkyl io-
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dides with substituents on the side chain reacted
smoothly to afford the corresponding products in
moderate to good yields. Chloride and oxygen atoms
were tolerated, which could further undergo a variety
of transformations (Table 6, 4-47 and 4-49). Introduc-
tion of a CF3 group was also accomplished, affording
product 4-52 in 72% yield.
Table 4. Intermolecular benzylation/carbene migratory insertion reaction: scope of
the reaction with aryl iodide 1.[a]
As summarized in Table 7, the three-component di-
alkylation/carbene migratory insertion cross-coupling
could proceed smoothly with a wide range of alkyl
iodide and para-substituted iodobenzene derivatives
to give the products in moderate yields under the
standard conditions.
We further extended the method to prepare poly-
substituted bicyclic molecules. This coupling is more
challenging because after intramolecular alkylation,
the palladium species of substrate 1s–v can react
with itself instead of 2k or 5 f. To our delight, when
an excess of 2k or 5 f was used, the desired product
was isolated in moderate to good yields (Scheme 4).
These results are consistent with a previous report.[5f]
Taking into account that N-tosylhydrazone 3a is
readily formed by condensation of acetophenone
with 4-methylbenzenesulfonohydrazide, we em-
ployed a one-pot reaction for the synthesis of prod-
uct 4-1 and 4-51. To our delight, when the reaction
was performed directly from carbonyl compounds
without the isolation of tosylhydrazone, a comparable
yield was obtained to those observed for the two-
step process (Scheme 5).
[a] Reaction conditions:
1 (0.3 mmol, 1.0 equiv), 2a (0.75 mmol, 2.5 equiv), 3a
(0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%), norbornene (0.90 mmol,
3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3 (1.35 mmol, 4.5 equiv), dioxane (3 mL),
908C, 15 h under Ar. Yield of isolated product.
A plausible mechanism of ortho CÀH activation/
carbene migratory insertion reaction is proposed in
Scheme 6. Initial oxidative addition of Pd0 to aryl
iodide affords intermediate A, which undergoes car-
bopalladium of norbornene to give intermediate B.
Insertion of PdII to the CÀH bond followed by depro-
tonation generates intermediate C. Subsequently, re-
action of alkyl or benzyl halides with this PdII species
leads to octahedral PdIV intermediate D. Then reduc-
tive elimination takes place to form the PdII complex
E. With steric stain of the two ortho substituents, ex-
trusion of norbornene through b-carbon elimination
occurs and the aryl palladium F is obtained, from
which palladium carbene G is afforded by decompo-
sition of diazo compound 3’ (generated in situ from
N-tosylhydrazone 3), followed by migratory insertion
of the aryl group, and b-H elimination affords the
product and regenerates the catalyst with the aid of
base. Notably, for the PdII complex E, when R=H,
a subsequent ortho CÀH activation will occur to
afford difunctionalized aryl palladium F.
Table 5. Intermolecular dibenzylation/carbene migratory insertion reaction: scope of
the reaction with aryl iodide 1 and benzyl chloride 2.[a]
Conclusion
[a] Reaction conditions:
1 (0.3 mmol, 1.0 equiv), 2 (0.90 mmol, 3.0 equiv), 3a
(0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%), norbornene (0.90 mmol,
3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3 (1.65 mmol, 5.5 equiv), dioxane (3 mL),
908C, 15 h under Ar. Yield of isolated product.
We have reported a Catellani–Lautens reaction with
diazo compounds as a nucleophilic coupling partner
in the termination steps for the synthesis of highly
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Table 6. Intermolecular alkylation/carbene migratory insertion reaction:
scope of the reaction with alkyl iodides 5.[a]
Scheme 4. Palladium-catalyzed sequential intramolecular alkylation/intermo-
lecular alkylation/carbene migratory insertion reaction. Reaction conditions:
1 (0.3 mmol, 1.0 equiv), 2k or 5 f (1.35 mmol, 4.5 equiv), 3a (0.6 mmol,
2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%), norbornene (0.90 mmol,
3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3 (1.65 mmol, 5.5 equiv), dioxane
[a] Reaction conditions: 1a (0.3 mmol, 1.0 equiv),
5
(0.75 mmol,
2.5 equiv), 3a (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%),
norbornene (0.90 mmol, 3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3
(1.35 mmol, 4.5 equiv), dioxane (3 mL), 908C, 15 h under Ar. Yield of iso-
lated product.
1
(3 mL), 908C, 15 h, under Ar. [a] The yield was determined by H NMR spec-
troscopic analysis.
Table 7. Intermolecular dialkylation/carbene migratory insertion reaction:
scope of the reaction with aryl iodides 1 and alkyl iodides 5.[a]
Scheme 5. One-pot synthesis of 4-1 and 4-51.
functionalized vinylarenes 4. A one-pot procedure was also de-
veloped. This unique transformation, which involves a norbor-
nene-mediated Pd-catalyzed CÀH activation/carbene migratory
insertion, was also the first example of incorporation of CÀH
activation in the Pd-catalyzed insertion of diazo compounds.
The reaction has several potential advantages: 1) Two or three
CÀC bonds are formed in this process. 2) The reaction pro-
ceeds in moderate to good yield. 3) A wide range of functional
groups could be compatible. 4) The starting materials are read-
ily accessible. 5) Highly functionalized vinylarenes 4 are gener-
ated that are difficult to achieve by traditional methods.
[a] Reaction conditions: 1 (0.3 mmol, 1.0 equiv), 5 (0.90 mmol, 3.0 equiv),
3a (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol%), PPh3 (20 mol%), norbor-
nene (0.90 mmol, 3.0 equiv), H2O (1.5 mmol, 5.0 equiv), Cs2CO3
(1.65 mmol, 5.5 equiv), dioxane (3 mL), 908C, 15 h under Ar. Yield of iso-
lated product.
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Scheme 6. Proposed mechanism of ortho CÀH activation/carbene migratory
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insertion reaction.
Experimental Section
Preparation of 4
General procedure: A dried Schlenk tube under an argon atmos-
phere was charged with aryl iodide 1, alkyl halides 2 or 5, N-tosyl-
hydrazone 3, Pd(OAc)2, PPh3, norbornene, H2O, Cs2CO3, and diox-
ane (3 mL). The mixture was stirred at RT for 15 min and then
stirred at 908C for 15 h. The resulting mixture was cooled to RT
and filtered through Celite with EtOAc as eluent. The solvents were
evaporated under reduced pressure and the residue was purified
by flash chromatography on silica gel to afford pure 4.
One-pot procedure for the preparation of 4-1 and 4-51: Aceto-
phenone (0.66 mmol, 2.2 equiv) and 4-methylbenzenesulfonohy-
drazide (0.60 mmol, 2.0 equiv) were suspended in dioxane (1 mL)
in a 10 mL Schlenk tube and the mixture was heated at 708C for
3 h. After cooling to RT, aryl iodide 1a (0.30 mmol, 1.0 equiv), alkyl
halide 2a or 5 f (0.75 mmol, 2.5 equiv), Pd(OAc)2 (10 mol%), PPh3
(20 mol%), norbornene (0.90 mmol, 3.0 equiv), H2O (0.9 mmol,
3.0 equiv), Cs2CO3 (1.35 mmol, 4.5 equiv), and dioxane (2 mL) were
added. The Schlenk tube was fitted with an Ar balloon, the mixture
was stirred at RT for 15 min, and then stirred at 908C for 15 h. The
resulting mixture was cooled to RT and filtered through Celite with
EtOAc as eluent. The solvents were evaporated under reduced
pressure and the residue was purified by flash chromatography on
silica gel to afford pure 4-1 or 4-51.
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Acknowledgements
We thank the National Science Foundation (NSF 21072080 and
21272101) and the National Basic Research Program of China
(973 Program) 2010CB833203 and the “111” program of MOE
and PCSIRT: IRT1138 for supporting this study.
Keywords: CÀH activation
·
CÀC coupling
·
diazo
compounds · palladium · synthetic methods
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ria, Org. Lett. 2010, 12, 5692; g) M. Blanchot, D. A. Candito, F. Larnaud,
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[17] From the mechanism, norborene could theoretically be used in catalytic
quantities. However, the reaction requires a large excess to favor nor-
bornene insertion and CÀH activation as the early step in the process
instead of the palladium-catalyzed cross-coupling of the diazo com-
pound with aryl iodide reaction. 10% of Pd(OAc)2 was employed may
be to match each step of the reaction. For selected references on Catel-
lani–Lautens reaction and the use of excess norborene and 10%
Pd(OAc)2, see refs. [5d–5f, 5h, 5i, 5k, 5r, 5t, 6c, 6d, 7b, 7c, 7e, 7g, 8b, 8d,
9a–f].
[18] At this stage, the reason for the significantly improved yield with water
is unknown, see: a) J. Barluenga, L. Florentino, F. Aznar, C. Valdꢂs, Org.
Lett. 2011, 13, 510; b) J. Barluenga, M. Escribano, F. Aznar, C. Valdꢂs,
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[19] The molecular structure of 4-38 was determined on the basis of X-ray
crystallographic studies. CCDC-981521 contains the supplementary crys-
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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[12] J. Barluenga, P. Moriel, C. Valdꢂs, F. Aznar, Angew. Chem. 2007, 119,
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Received: February 10, 2014
[13] C. Peng, Y. Wang, J. Wang, J. Am. Chem. Soc. 2008, 130, 1566.
Published online on && &&, 0000
Chem. Eur. J. 2014, 20, 1 – 8
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FULL PAPER
&
Palladium Catalysis
P.-X. Zhou, L. Zheng, J.-W. Ma, Y.-Y. Ye,
X.-Y. Liu, P.-F. Xu,* Y.-M. Liang*
&& – &&
Palladium-Catalyzed/Norbornene-
Mediated CÀH Activation/N-
Tosylhydrazone Insertion Reaction: A
Route to Highly Functionalized
Vinylarenes
Activate and move! A novel method
for the synthesis of highly functional-
ized vinylarenes through palladium-cat-
alyzed, norbornene-mediated CÀH acti-
vation/carbene migratory insertion is
developed under mild reaction condi-
tions with readily available starting ma-
terials (see scheme). This is a Catellani–
Lautens reaction with diazo compound
as a nucleophilic coupling partner. This
unique transformation is also the first
example of incorporation of CÀH activa-
tion in the Pd-catalyzed insertion of
a diazo compound.
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Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
8
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!