Catellani type N-H activation of indole derivatives and resolution of palladium complexes containing norbornene or dicyclopentadiene moieties

Article abstract of DOI:10.1016/j.tet.2015.06.109

The reactions of indole (1) with iodotoluene in the presence of norbornene or dicyclopentadiene led to the formation of indole derivative (2a). It is through the C-H activation at ortho-position of indole by Catellani-type reactions. Besides, several palladium complexes (4a, 4b, 5a, 5b, 6a, and 6b), containing either single or double norbornene or dicyclopentadiene fragments via insertion into the Pd-C(aryl) bond of the formerly formed palladium-containing intermediate, were obtained and characterized by spectroscopic means as well as by X-ray diffraction methods. The ratios of 2a to 5a could be altered by employing different palladium sources. Triple insertion of norbornene or dicyclopentadiene into the Pd-C(aryl) bond was not observed.

Full text of DOI:10.1016/j.tet.2015.06.109

Accepted Manuscript
Catellani Type N-H Activation of Indole Derivatives and Resolution of Palladium
Complexes Containing Norbornene or Dicyclopentadiene Moieties
Ya-Qian Chen, Fung-E. Hong
PII:
S0040-4020(15)01006-6
10.1016/j.tet.2015.06.109
TET 26945
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 May 2015
Revised Date: 25 June 2015
Accepted Date: 29 June 2015
Please cite this article as: Chen Y-Q, Hong F-E, Catellani Type N-H Activation of Indole Derivatives and
Resolution of Palladium Complexes Containing Norbornene or Dicyclopentadiene Moieties, Tetrahedron
(2015), doi: 10.1016/j.tet.2015.06.109.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
For table of contents use only
Catellani Type N-H Activation of Indole Derivatives and Resolution of Palladium
Complexes Containing Norbornene or Dicyclopentadiene Moieties
Ya-Qian Chen and Fung-E Hong*
Department of Chemistry, National Chung Hsing University,
2
50 Kuo-Kuang Road, Taichung 40227, Taiwan
E-mail: fehong@dragon.nchu.edu.tw
Several palladium complexes incorporated either single or double norbornene or
dicyclopentadiene fragments via insertion processes were obtained from
Catellani-type reactions.
-1-

ACCEPTED MANUSCRIPT
For table of contents use only
Catellani Type N-H Activation of Indole Derivatives and Resolution of Palladium
Complexes Containing Norbornene or Dicyclopentadiene Moieties
Ya-Qian Chen and Fung-E Hong*
Department of Chemistry, National Chung Hsing University,
2
50 Kuo-Kuang Road, Taichung 40227, Taiwan
E-mail: fehong@dragon.nchu.edu.tw
Several palladium complexes incorporated either single or double norbornene or
dicyclopentadiene fragments via insertion processes were obtained from
Catellani-type reactions.
-1-

ACCEPTED MANUSCRIPT
Catellani Type N-H Activation of Indole Derivatives and Resolution of Palladium
Complexes Containing Norbornene or Dicyclopentadiene Moieties
Ya-Qian Chen and Fung-E Hong*
Department of Chemistry, National Chung Hsing University,
2
50 Kuo-Kuang Road, Taichung 40227, Taiwan
E-mail: fehong@dragon.nchu.edu.tw
*
Author to whom correspondence should be addressed.
-2-

ACCEPTED MANUSCRIPT
Abstract
The reactions of indole (1) with iodotoluene in the presence of norbornene or
dicyclopentadiene led to the formation of indole derivative (2a). It is through the C-H
activation at ortho-position of indole by Catellani-type reactions. Besides, several
palladium complexes (4a, 4b, 5a, 5b, 6a and 6b), containing either single or double
norbornene or dicyclopentadiene fragments via insertion into the Pd-C(aryl) bond of
the formerly formed palladium-containing intermediate, were obtained and
characterized by spectroscopic means as well as by X-ray diffraction methods. The
ratios of 2a to 5a could be altered by employing different palladium sources. Triple
insertion of norbornene or dicyclopentadiene into the Pd-C(aryl) bond was not
observed.
Keywords: Catellani Reaction, C-H activation, Norbornene, Dicyclopentadiene,
Indole, Palladium.
-3-

ACCEPTED MANUSCRIPT
1
.
Introduction
The far-reaching applications of transition metal complexes catalyzed
cross-coupling reactions in various fields characterize one of the great achievements
[
1]
of the modern synthetic chemistry. Diverse methodologies of cross-coupling
reactions were developed for the formation of C-C or C-Heteroatom bonds from
[
2]
corresponding aryl-, alkyl- or heteroatom-containing reactants. In spite of the great
success of these methods, their scopes are limited by merely combining two
substances at a time. Further efforts are required for joining the third party into the
cross-coupled organic compounds. It shall be advantages if a one-pot reaction could
be carried out properly by joining all the necessary components into a targeted
compound at the designated positions.
Catellani Reaction, developed from mid-1980s, stands out above the rest of
[
3]
contemporary multiple-component reactions. The reaction skillfully enhances the
C-H activation process of aryl halide at its ortho-position, and the reaction is
accomplished through replacing the ortho-position hydrogen by a alkyl- or aryl group.
In this remarkable reaction, the employment of norbornene is an indispensable factor.
The process that to activate inert C-H bond of organic molecules, called “C-H
[3a, 4]
activation”, has always been a challenge to synthetic chemists.
Yet, through the
process of the Catellani reaction, the C-H activation of the ortho-position hydrogen of
aryl halide (mostly aryl iodide) can be readily achieved. The addition of norbornene
firstly allows the reaction undergoes C-H activation of the ortho-position hydrogen
and later followed by termination reactions, such as Heck- and Suzuki-type reactions.
Catellani indeed developed the corresponding Heck- and Suzuki-type reactions
besides others that could act as termination reactions after the process of C-H
[
5]
activation (Scheme 1).
-4-

ACCEPTED MANUSCRIPT
R2
R2
+
X
R1
R1
B(OH)2
H
H
+
+ [Pd], base
X
R +
1
+
R3
X: I, Br
R3
R1
R1
Scheme 1. Catellani-type Heck and Suzuki reactions.
The generally accepted mechanism for Catellani reaction is shown below (Figure
[
6]
1
). Initially, an oxidative addition process of aryl halide to Pd(0) takes place (Step 1).
It is followed by the addition (or insertion) of norbornene to Pd-C(Ar) bond (Step 2).
This is the most unique step in Catellani reaction which enables the following C-H
activation process. The C-H activation process arose from the availability of
palladium moiety in the proximity of C-H bond of aryl group (Step 3). Further
oxidative addition process of another aryl halide to Pd(II) takes place again to form
Pd(IV) (Step 4). Comments against the formation of the high valence Pd(IV) have
[
6a,7]
often been raised.
Subsequently, intramolecular reductive elimination process
occurs and followed by extrusion of norbornene (Step 5 & 6). The reduced Pd(II)
species might be reacted further with either alkene or boronic acid and undergoes
Heck or Suzuki reactions, respectively, or proceeds other termination reactions (Step
[
5a,8]
7
).
If examined closely, more fascinating observations can be found in this
[
4i,9]
mechanism that apart it from the conventional cross-coupling reactions.
The most
significant feature of the Catellani reaction is the C-H activation of the initial aryl
halide in its ortho-position.
-5-

ACCEPTED MANUSCRIPT
Figure 1. A generally accepted mechanism for Catellani reaction.
Since the first revelation of Catellani reaction in 1990s, there have many
[
10]
enthralling variations of this type of reactions been reported. In 2012, Bach et al.
firstly reported the C-H activation of indole derivative (1) to the production of
2
-substituted indoles (2) using the methodology of Catellani reaction. Here, the
[11]
presence of norbornene is crucial to the success of this reaction (Scheme 2).
Scheme 2. Preparation of 2-substituted indoles via Catellani-type reaction.
Bach et al. perceived that the palladium compound (3a) is a metastable
-6-

ACCEPTED MANUSCRIPT
compound, which is formed after the insertion of norbornene into the Pd-N(indole)
bond of a palladium containing intermediate, and could not be isolated from the
reaction. In order to affirm the major structural moiety of 3a, they did execute the
process for the preparation of the dppe-coordinated palladium complex (4a). It is
through the reaction of indole (1) with Pd(OAc) in the presence of norbornene and
2
followed by addition of dppe to the presumably resulted product 3a (Scheme 3). They
were able to obtain 4a and later characterize it by spectroscopic means. Unfortunately,
[
11,12]
there is no crystal structure available for 4a from Bach’s work.
Thereby, the real
structural feature of 4a remains an unsolved puzzle.
Scheme 3. The preparation of a dppe-coordinated palladium complex 4a
The major structural motif of dicyclopentadiene can be regarded as a counterpart
of norbornene. However, the extended fragment of dicyclopentadiene, compared to
norbornene, might provide the steric repulsion which is needed for its extrusion from
[
13]
the catalytic cycle, which is a compelling factor for Catellani reaction. Thereby, it
is worthwhile to check the possibility of replacing the role of norbornene in Catellani
reaction by a functionally and structurally related dicyclopentadiene. In addition,
since the authentic conformation of 4a is critical to substantiate the abovementioned
Catellani reaction mechanism, we were interested in resolving the crystal structure of
4
a. Herein, we report the preparations of several palladium complexes which were
formed through the insertion of norbornene and dicyclopentadiene to the Pd-N(indole)
7-
-

ACCEPTED MANUSCRIPT
bond of reaction intermediates and the mechanistic portrayal of their formation
pathways.
2
.
Results and Discussion
2
.1 Preparation of the dppe-coordinated palladium complex 4
The reaction of Bach as shown in Scheme 3 was repeated again under the same
condition, and 4a was obtained in good yield. The identity of 4a was characterized by
various spectroscopic means as well as the X-ray diffraction methods. Its ORTEP
drawing is depicted in Fig. 2(a). As revealed from the crystal structure, it is clear to
see that a norbornene insertion to the previously formed Pd-N bond of a reaction
intermediate indeed took place and resulted in the formation of 4a. The original
C(9)-C(15) bond length of norbornene moiety is elongated to 1.576 Å, an apparent
single bond. The dppe ligand is coordinated to palladium metal in a bi-dentate manner.
The bond lengths of Pd-C(1), Pd-C(15), Pd-P(1), Pd-P(2) are 2.057(7), 2.132(8),
2
.3038(19), 2.313(2) Å, respectively. The bond angles of C(1)-Pd-C(15) and
P(1)-Pd-P(2) are 83.1(3)° and 85.90(7)°, respectively. It indicates that Pd(II) metal
center in 4a is surrounded by a square planar environment.
Palladium complex 4b, the counterpart of 4a, was obtained by way of similar
reaction procedures except that dicyclopentadiene rather than norbornene was
employed (Figure 3). The crystal structure of 4b was determined by X-ray diffraction
methods and is depicted in Fig. 2(b). The formation of 4b implies that the stinky
[
4d]
smelly norbornene can be replaced by a less smelly dicyclopentadiene if necessary.
In principle, there are two possible conformations, exo- & endo-forms, of the
dicyclopentadiene moiety in 4b might be yielded (Fig. 3). Indeed, two sets of
corresponding signals in the ratio of 3:2 for endo/exo-forms were observed for 4b in
8-
-

ACCEPTED MANUSCRIPT
1
31
H- and P-NMR. Here, the crystal structure of 4b exhibits an endo-form of the
expected product, presumably, a stable one.
-9-

ACCEPTED MANUSCRIPT
Figure 2. ORTEP drawings of 4a (up) and 4b (down).
-10-

ACCEPTED MANUSCRIPT
Figure 3. Two possible conformations of 4b.
2
.2 The effect of ligand on the C-H activation in Catellani-type reaction of indole and
iodotoluene
The reaction as shown in Scheme 4 was carried out either in the presence of
phosphine ligand or without. Three new type of phosphine ligands (IA, IB and IC) as
[14]
well as IB-coordinated palladium complex (IIB) were employed in the reactions.
+
or
I
H +
+
or
I
I
N
Pd
N
Pd
+
+
[Pd]/L
H
H
Ph3P
Ph3P
base, solvent
1
2a
o
5b
5
a
7
0 C, 20 hr
Scheme 4. The formations of compounds 2a, 5a and 5b from Catellani-type reactions
As shown in Table 1, the presence of phosphine ligand in fact retards the
catalytic performances (Entries 3-7 vs. 1-2). It is reasoned by the fact that the
reducing power of phosphine is not favorable for the formation of Pd(IV), a necessary
active palladium species proposed by Catellani, in catalytic cycle. Thereby,
electron-rich phosphine ligand led to poor performance in this type of reaction (Entry
7
). Besides, the catalytic efficiency for the dicyclopentadiene-containing palladium
complexes is less than that of norbornene-containing counterpart (Entry 2 vs. 1). It
11-
-

ACCEPTED MANUSCRIPT
indicates that palladium complexes containing dicyclopentadiene are somewhat stable
than those with norbornene moiety, which is also evidenced from the yields of the
corresponding reactions. It also observed in experiments that the tendency for the
decomposition of norbornene-containing palladium complex is normally greater than
its dicyclopentadiene counterpart. The result also shows that the pre-formed
palladium complex IIB as catalyst precursor is not as good as in situ application of
the combination of free ligand IB with PdCl (MeCN) (Entry 4 vs. 5). It implies that
2
2
IIB is unlikely to be the real active species.
Table 1. The effect of ligand on the C-H activation in Catellani-type reaction for the
2
[a]
formation of 2-(p-tolyl)-1λ -indole (2a)
[
b]
Entry
1
Ligand
-
NMR conv. (%)
54.8
24.9
10.3
16.2
8.3
[
[
[
c]
d]
d]
2
3
4
5
6
7
-
IA
IB
IIB
IC
[
[
e]
e]
4.2
PPh3
7.1
Conditions: [a] indole (1.0 mmol), 4-iodotoluene (2.0 mmol), norbornene (2.1 mmol),
o
K CO (2.0 mmol), PdCl (MeCN) (10 mol%), DMA (5 mL, 0.5 M H O), 70 C, 20 hr;
2
3
2
2
2
1
[
b] Determined by H NMR; [c] Norbornene was replaced by dicyclopentadiene; [d]
Pd / L = 1:1; [e] Pd / L = 1:2.
-12-

ACCEPTED MANUSCRIPT
2
.3 The effect of palladium source on the C-H activation in Catellani-type reaction of
indole and iodotoluene
As revealed in the crystal structures of 4a and 4b, the norbornene and
dicyclopentadiene indeed inserted into the Pd-N(indole) bond of a palladium complex
intermediate, which had been originated from the previous oxidative addition step.
The efficiencies of Calellani reactions are also affected by employing various ligands
as demonstrated above. Here, the reactions of indole with iodotoluene and norbornene
in the presence of mixed catalysts, a mixture of PdCl (MeCN) and Pd(PPh ) , were
2
2
3 4
carried out (Scheme 4). As expected, the C-H activation took place and the coupling
of two substances also proceeded well. Compound 2a was obtained as the organic
product. Interestingly, there is a unique palladium complex 5a besides 2a being
observed. To our delight, suitable crystals of 5a were obtained from the crystal
growing process and its structure was determined by X-ray diffraction methods. As
shown in the ORTEP drawing of 5a (Fig. 4(a)), there are two sets of norbornenyl and
toluenyl moieties being incorporated into the palladium complex. The bond lengths of
C(8)-C(9) and C(8)-C(13) are 1.410(8) and 1.411(8) Å, respectively. In order to
maintain the +2 valence of palladium metal center, the interaction between C(8)-C(9)
bond and metal is better regarding as a dative bond. The bond lengths of Pd(1)-C(1),
Pd(1)-P(1), Pd(1)-I(1) and Pd(1)-C(8) are 2.056(5), 2.2505(15), 2.7246(6) and
2
1
.399(5) Å, respectively. The bond lengths of norbornene moiety are elongated to
.553 and 1.610 Å, respectively, for C(1)-C(7) and C(15)-C(21), apparent single
bonds.
Another interesting result, the formation of 5b, came from the same reaction as
shown in Scheme 4 except that the reactant norbornene was replaced by
dicyclopentadiene. Here, the crystal structure of 5b was determined by X-ray
-13-

ACCEPTED MANUSCRIPT
diffraction methods and its ORTEP drawing is depicted in Fig. 4(b). The major
structure features of 5b, an obvious counterpart of 5a, are the same as that of 5a
except that the location of norbornene was replaced by a dicyclopentadiene. Crystal
data reveal the bond lengths of I-Pd, Pd-C(1), Pd-P and Pd-C(11) are 2.7300(7),
2
.069(3), 2.2386(9) and 2.407(3) Å, respectively. Besides, the bond lengths of
C(11)-C(12) and C(11)-C(16) are 1.402(5) and 1.412(5) Å. It is longer than the
commonly observed C-C bond length of benzene ring, which is within the range of
1
.38-1.39 Å. Again, it is better regarding the bonding between C(11)-C(12) and
2
C(11)-C(16) toward Pd(II) as a η -coordination mode. This interesting discovery
indicates that the role played by norbornene can be readily replaced by
dicyclopentadiene in closely related reactions.
-14-

ACCEPTED MANUSCRIPT
Figure 4. ORTEP drawings of 5a (up) & 5b (down).
-15-

ACCEPTED MANUSCRIPT
Since there are two dicyclopentadiene moieties in 5b, thereby, in principle there
are four possible conformations of the two dicyclopentadienes arranged in exo-exo,
1
exo-endo, endo-exo & endo-endo manners shall be observed. Indeed, the HNMR
spectrum of the products exhibit complicated signals pattern for 5b. Here, the crystal
structure of 5b shows an endo-endo form, presumably the most stable form, of the
targeted products (Fig. 5).
Figure 5. Four possible conformations of 5b.
We also observed that the application of different palladium sources might
greatly affect the outcome of the products. For example, while PdCl (MeCN) was
2
2
used as the solo palladium source, 54.8 % of 2a was observed without observing any
trace amount of 5a (Table 2, Entry 1) By contrast, while only Pd(PPh ) was applied,
3
4
6
4 % of 5a was obtained. It was found later that the combination of equal molar
equivalent of PdCl (MeCN) and Pd(PPh ) as catalyst precursor is beneficial for the
2
2
3 4
formation of 5a, the formation of 5a is greater than 92 % and less than 1 % of 2a was
obtained (Table 2, Entry 6). The reasoning is as the follows. Although a pure Pd(0)
species such as Pd(PPh ) is good for oxidative addition process, yet, a large amount
3
4
of coordinated PPh ligand in Pd(PPh ) is not desirable for the formation of a
3
3 4
-16-

ACCEPTED MANUSCRIPT
unsaturated and thereby an active Pd(0)(PPh ) (n ≤ 2) species in reaction via
3
n
[
4g]
releasing of excess coordinated ligand to solution. But, the addition of a Pd(II)
species, such as Pd(II)Cl (MeCN) , could take up the released excess PPh ligand and
2
2
3
converts its oxidation state to Pd(0). This synergistic effect for the combination of
equal molar equivalent of Pd(II)Cl (MeCN) and Pd(0)(PPh ) will generate
2
2
3 4
[
3e,5a,15]
Pd(0)(PPh ) (n ≤ 2) as catalytic active species.
In the generally accepted
3
n
mechanism of Catellani reaction, a Pd(0) ↔ Pd(II) ↔ Pd(IV) catalytic cycle is
[
16]
proposed. Thereby, the balance between proper oxidation states of the active
palladium species is crucial to the catalytic performance of the reaction. The fact that
the increasing of the ratio of Pd(0) (Pd(PPh ) ) is not beneficial to the reaction is
3
4
comprehensible since that too many released PPh from Pd(PPh ) will make the
3
3 4
formation of Pd(IV) difficult, thereby, is not favorable to the reaction.
Table 2. The effect of palladium sources on the N-H activation in Catellani-type
[
a]
reaction
[
b]
NMR conv.(%)
Entry
Pd(PPh3)4
PdCl (MeCN)
2
2
2
a
5a
1
2
3
4
5
6
0
1
2
3
4
5
10
9
54.8
9.8
3.0
2.0
2.3
<1
0.0
-
-
-
-
8
7
6
[
c]
5
92
Conditions: [a] indole (1.0 mmol), 4-iodotoluene (2.0 mmol), norbornene (2.1 mmol),
K CO (2.0 mmol), Pd source (maximum 10 mol%), DMA (5 mL, 0.5 M H O), 70 °C,
2
3
2
1
2
0 hr; [b] Determined by H NMR; [c] Isolated yield.
-17-

ACCEPTED MANUSCRIPT
2
.4 The effect of the amount of norbornene on the formation of norbornene insertion
product(s)
Presumably, palladium complex(es) from “single norbornene insertion” process
shall be obtained while the reaction is proceeded with only one molar equivalent of
norbornene in the previous reaction. The reaction was carried out with slightly excess
of iodotoluene to norbornene and in the absence of base. As expected, the formations
of “single norbornene insertion” products (6a, 6b and 6c) were obtained (Figure 6).
The crystal structures of 6a & 6b were resolved by X-ray diffraction methods and
their ORTEP drawings are depicted in Fig. 7.
I
I
I
Pd
Pd
Pd
OMe
Ph3P
Ph3P
Ph3P
6a
6b
Figure 6.
6c
Crystal data of 6a reveal the bond lengths of I-Pd, Pd-C(1), Pd-P, Pd-C(8) and
Pd-C(9) are 2.7306(5), 2.073(4), 2.2611(11), 2.421(4) and 2.612(4) Å. Similar to the
previous cases, the bond length of C(8)-C(9) is 1.400(6) Å which is slightly longer
2
2
3
3
than the C(sp )-C(sp ) bond, yet, shorter than the C(sp )-C(sp ) bond. The bonding
mode of C(8)-C(9) towards palladium metal is also regarded as a π-bonding. The
major structural motif of 6b is similar to that of 6a.
-18-

ACCEPTED MANUSCRIPT
Figure 7. ORTEP drawings of 6a (up) & 6b (down)
-19-

ACCEPTED MANUSCRIPT
Similar to the case of 5b, there are two possible conformations, exo- &
endo-forms, of the dicyclopentadiene in 6b shall be existed (Fig. 8). It is also
1
31
substantiated by the observation from H- and P-NMR experiments. There are two
sets of signals in the ratio of 3:2 (endo:exo) were observed for 6b. An endo-form of
the product, 6b, revealed in its crystal structure also supports this assumption.
Figure 8. Two possible conformations of 6b.
The attempt for the preparation of palladium complex from “triple norbornene
insertion” was pursued. Unfortunately, there was not such palladium complex being
resulted from the reaction. Presumably, the third insertion of norbornene (or
dicyclopentadiene) to the Pd-C(norbornene) bond of 5a (or 5b) is not accessible
[
6a,17]
probably due to ortho-effect.
2
.5 A proposed mechanism for the formations of compounds 5a, 6a and 7
A mechanism is proposed to accommodate for the formations of the
corresponding compounds (Scheme 5). As revealed, the formation of 6a is readily
accessed by oxidation addition of the first aryl halide and followed by the insertion of
norbornene. The formation of 5a is presumably through the oxidation addition of the
second arylhalide and followed by the insertion of another norbornene. A Pd(IV)
species is presumably formed as intermediate. While the amount of norbornene is
-20-

ACCEPTED MANUSCRIPT
lacking, organic compound 7 is formed through a sequential C-H activation and
reductive elimination processes from a Pd(IV) species.
I
PPh3
Pd0Ln
PdII
I
Insertion
Oxidative Addition
Pd
PPh3
I
Ph3P
6a
I
PPh3
ꢀ
HI
(
IV)
I
Pd
Ph3P
Pd
Oxidative Addition
Ph3P
PPh3
I
PPh3
Pd
PPh3
Pd
I
Ph3P
Insertion
PPh3
CꢀH activation
ꢀ
PPh3
ꢀ
HPdI(PPh3)2
Reductive Elimination
I
Pd
Ph3P
7
5a
Scheme 5. Proposed mechanism for the formations of 5a and 6a. It is also held true
for the formations of 5b and 6b while using dicyclopentadiene rather than
norbornene.
2
.6 Summary
Several palladium complexes (4a, 4b, 5a, 5b, 6a, 6b) containing norbornene or
21-
-

ACCEPTED MANUSCRIPT
dicyclopentadiene moieties in their frameworks were prepared and characterized. As
revealed from the crystal structures of these palladium complexes, the previous
assumption that norbornene (or dicyclopentadiene) could insert to the Pd-C(benzenyl)
or Pd-N(indole) bond is validated.
3
.
Experimental Section
.1. General
All reactions were carried out under a nitrogen atmosphere using standard
3
Schlenk techniques or in a nitrogen-flushed glove box. Freshly distilled solvents were
used. All processes of separations of the products were performed by column
chromatography. GC-MS analysis was performed on an Agilent 5890 gas
chromatograph (Restek Rtx-5MS fused silica capillary column: 30m, 0.25mm, 0.5µm)
®
1
with an Agilent 5972 mass selective detector. Routine H NMR spectra were
recorded on a Varian-400 spectrometer at 400.00 MHz. The chemical shifts are
3
1
13
reported in ppm relative to internal standards TMS (δ = 0.0). P and C NMR spectra
were recorded at 162.1 and 100.7 MHz, respectively. The chemical shifts for the
former and the latter are reported in ppm relative to internal standards H PO (δ=0.0)
3
4
and CHCl (δ=77), respectively. Mass spectra were recorded on JOEL JMS-SX/SX
3
1
02A GC/MS/MS spectrometer.
3
.2.1 Synthesis and characterization of 4a & 4b
Into a 20 mL brown Schlenk tube was placed indole (0.206 mmol, 0.0242 g),
Pd(OAc) (0.204 mmol, 0.0459 g), norbornene (0.794mmol, 0.0748 g) and K CO
3
2
2
(
0.873 mmol, 0.121 g). Under N , 8 mL DMA (containing 0.5 M H O) was added and
2
2
o
o
the mixture was stirred at 70 C for 3 hours before it was cooled down to 25 C.
-22-

ACCEPTED MANUSCRIPT
Another Schlenk tube was placed dppe (0.303 mmol, 0.121 g) and 2 mL DMA
o
(
containing 0.5 M H O). It was stirred at 25 C till dppe was complete dissolved in
2
DMA, then the solution was transferred to the first Schlenk tube. The mixed solution
o
was stirred at 25 C for the next 17 hours. The solution was washed with H O and
2
ether. The organic layer was extracted twice with ether. It was then purified by
column chromatography using ether as eluent. The solvent was removed under
reduced pressure; the residue was further purified by fractional crystallization process
[
12]
by CH Cl and hexanes. The yield is 4a is 76 % (0.108 g, 0.152 mmol). Similar
2
2
processes were taken for the preparation of 4b except that dicyclopentadiene (0.794
mmol, 0.105 g) was used. The fractional crystallization process was carried out by
CH Cl and octane. The yield is 4b is 14 % (0.0212 g, 0.0282 mmol).
2
2
3
.2.2 Synthesis and characterization of 5a & 5b
Into a 20 mL brown Schlenk tube was placed Pd(PPh ) (0.05 mmol, 0.0578 g),
3
4
PdCl (MeCN) (0.05 mmol, 0.0130 g), norbornene (2.1 mmol, 0.2g) and K CO (2.0
2
2
2
3
mmol, 0.277 g). Then, 4-iodotoluene (2.0 mmol, 0.26 mL) as well as 8 mL DMA
containing 0.5 M H O) were transferred to the tube by syringe under N . The mixture
(
2
2
o
was stirred at 70 C for 20 hr. The solution was washed with H O and ether. The
2
organic layer was extracted twice with ether. It was then purified by Centrifugal Thin
Layer Chromatography (CTLC) using CH Cl as eluent. The solvent was removed
2
2
under reduced pressure. The yield is 5a is 98 % (0.0848 g, 0.0980 mmol). The residue
was subjected to crystallization process by CH Cl and hexanes and yellow crystals
2
2
were resulted. Similar processes were taken for the preparation of 5b except that
dicyclopentadiene (2.0 mmol, 0.264 g) was used. The yield is 5b is 98 % (0.0922 g,
0
.0980 mmol). Yellow crystals were resulted in crystallization process by CH Cl and
2 2
-23-

ACCEPTED MANUSCRIPT
heptane.
3
.2.3 Synthesis and characterization of 6a & 6b
Into a 50 mL round-bottomed flask with side arm was placed Pd(PPh ) (1.0
3
4
mmol, 1.156 g) and 20 mL THF. Then, 4-iodotoluene (10.0 mmol, 1.3 mL) was
transferred to the tube by syringe under N . The flask was wrapped with aluminum
2
o
foil. It was stirred at 25 C for 10 minutes then norbornene (7.00 mmol, 0.660 g) was
o
added. The mixture was stirred at 60 C for 8 hours. The organic layer was extracted
twice with ether. It was then purified by Centrifugal Thin Layer Chromatography
(
CTLC) using a mixed solvent (Hexane/CH Cl = 2:1) as eluent. The solvent was
2 2
removed under reduced pressure. The yield is 6a is 40 % (0.270 g, 0.0397 mmol). The
o
residue was subjected to crystallization process by CH Cl and ether at 4 C and
2
2
yellow crystals were resulted. Similar processes were taken for the preparation of 6b
except that dicyclopentadiene (3.50 mmol, 0.463 g) was used. The yield of 6b is 74 %
(0.266 g, 0.370 mmol). Yellow crystals were resulted in crystallization process by
o
CH Cl and ether at 4 C. Repeat the same processes except that 2-iodoanisole (5.0
2
2
mmol, 0.65 mL) was the reactant rather than 4-iodotoluene. The yield of a yellow 6c
is 27 % (0.0926 g, 0.133 mmol).
‡
Selected spectroscopic data for 4b
(Mixture of isomers)
1
H NMR (CDCl , δ/ppm): 7.82-7.92 (m, 3 H), 7.76-7.81 (m, 2 H), 7.62-7.73 (m, 4 H),
3
7.40-7.50 (m, 10 H), 7.34-7.38 (m, 2 H), 7.28 (t, 1 H, J = 3.2 Hz), 7.22 (d, 1 H, J =
8.4 Hz), 6.91 (t, 1 H, J = 7.6 Hz), 6.84 (t, 1 H, J = 7.2 Hz), 5.75-5.76 (m, 1 H),
5.69-5.71(m, 1H), 5.48-5.51 (m, 1 H), 4.36-4.41 (m, 1 H), 3.21-3.26 (m, 1H), 3.01 (s,
-24-

ACCEPTED MANUSCRIPT
1
H), 2.85-2.86 (m, 1H), 2.63-2.67 (m, 1H), 2.18-2.52 (m, 3H), 2.06-2.07 (d, 1 H, J =
.6 Hz), 1.99 (s, 1H), 1.71-1.78 (m, 1H), 1.43 (d, 1H, J = 17.2 Hz), 1.15-1.19 (m, 1H).
3
3
1
P NMR (CDCl , δ/ppm): 42.6 (d, JP-P = 12.9 Hz), 36.0 (d, JP-P = 13.8 Hz), 35.5 (d,
3
1
3
JP-P = 13.8 Hz); C NMR (CDCl , δ/ppm): 170.6(dd, J = 118.2, 14.1 Hz), 135.3,
3
1
34.2(t, J = 12.6 Hz), 133.6-133.9(m, 1C), 133.2(d, J = 12.2 Hz), 132.0, 131.2,
30.1-130.4 (m, 1C), 128.9 (d, J = 9.1 Hz), 128.8(d, J = 9.6 Hz), 128.7(d, J = 11.5
1
Hz), 118.7, 117.4, 116.7, 109.7, 107.9(dd, J = 8.4, 7.2 Hz),64.3(t, J = 5.4 Hz), 53.8(d,
J = 96.5 Hz), 52.3, 48.8, 48.2(d, J = 5.3 Hz), 46.6, 45.2, 43.8(dd, J = 14.1, 4.2 Hz),
+
4
0.0, 32.2, 29.1(dd, J = 24.8, 18.7 Hz), 26.9(dd, J = 23.3, 17.2 Hz); HRMS (ESI ) m/z
+
+
(
M-H ): calcd. for C H N P Pd [M ]: 751.1749; found: 752.1855.
44 41 1 2 1
‡
Selected spectroscopic data for 5a
1
H NMR (CDCl , δ/ppm): 7.65-7.71 (m, 6H), 7.45-7.35 (m, 9H), 7.28 (d, J = 8.0 Hz,
3
1
H), 7.14 (s, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.64-6.72 (q, 4H), 3.86 (d, J = 9.2 Hz, 1H),
3
.48 (d, J = 6.8 Hz, 2H), 3.12 (d, J = 2.8 Hz, 1H), 2.68 (d, J = 10.4 Hz, 1H), 2.49 (d, J
=
2.6 Hz, 1H), 2.44 (d, J = 10 Hz, 1H), 2.27 (s, 3H, Me), 2.13 (s, 3H, Me), 2.06 (d, J =
3
2
1
2
4
2
.6 Hz, 1H), 1.59-1.76 (m, 4H), 1.40-1.51 (m, 2H), 1.29-1.39 (m, 3H), 1.01-1.19 (m,
1
3
H), 0.52-0.55 (m, 1H); C NMR (CDCl , δ/ppm): 144.1 (d, J = 1.9 Hz), 138.8,
3
36.9, 135.0 (d, J = 11.9 Hz), 134.5, 132.0, 131.9 (d, J = 7.2 Hz), 131.5, 130.4 (d, J =
.7 Hz), 128.9, 128.0, 127.9 (d, J = 5.7 Hz), 98.4, 98.2, 54.3, 52.7 (d, J = 2.2 Hz), 50.9,
2.9 (d, J = 3.0 Hz), 42.6, 42.4, 42.0, 39.1, 37.8, 31.8, 30.4, 30.2 (d, J = 10.8 Hz), 29.6,
3
1
+
8.8, 22.0 (1C, Me), 20.7 (1C, Me); P NMR (CDCl , δ/ppm): 40.5; MS (ESI ): m/z
3
+
+
(
%) = 865 [M ], 738 (100) [(M – I) ], 644 (9); Anal. calcd. for C H I P Pd : C,
46 48 1 1 1
6
3.86; H, 5.59. Found: C, 63.77; H, 5.70.
-25-

ACCEPTED MANUSCRIPT
‡
Selected spectroscopic data for 5b
(Mixture of isomers)
1
H NMR (CDCl , δ/ppm): 7.61-7.67 (m, 6H), 7.49 (t, J = 8.0 Hz, 1H), 7.35-7.45 (m,
3
9
H), 7.12-7.19 (m, 2H), 6.71 (t, J = 8.4 Hz, 2H), 6.59 (d, J = 8.0 Hz, 2H), 5.76-5.79
m, 1H), 5.64-5.70 (m, 1H), 5.58-5.9 (m, 1H), 4.87-4.94 (m, 1H), 4.07-4.13 (m, 1H),
.26 (t, 2H, J = 8.8 Hz), 3.21 (m, 1H), 3.02-3.07 (q, 1H), 2.88-2.97 (m, 1H), 2.66-2.75
m, 1H), 2.52 (d, 2H, J = 10.8 Hz), 2.35-2.47 (m, 2H), 2.32 (s, 3H, Me), 2.7 (s, 1H),
(
3
(
2
.17-2.21 (m, 2H), 2.14 (s, 3H, Me), 2.05 (d, 1H, J = 4.0 Hz), 1.99 (d, 1H, J = 2.8 Hz),
1
3
1
.78 (t, 1H, J = 13.2 Hz), 1.62 (t, 2H, J = 8.8 Hz), 1.32 (d, 1 H, J = 18.0 Hz); C
NMR (CDCl , δ/ppm): 144.9 (d, J = 1.5 Hz), 139.5, 137.2, 135.1 (d, J = 11.5 Hz),
3
1
34.6, 132.7, 132.3 (d, J = 10.0 Hz), 131.5, 130.4, 129.1, 128.3, 128.1 (d, J
3.0 Hz), 98.8, 98.6, 54.9, 53.3, 49.3, 48.8, 48.2, 46.4, 45.1, 44.7, 44.5, 44.2, 42.6,
2.1, 41.5, 40.1, 39.2(d, J = 15.6 Hz), 33.8, 32.7, 32.3, 32.2, 31.5, 22.2 (1C, Me), 20.8
=
4
3
1
+
+
(
1C, Me); P NMR (CDCl , δ/ppm): 40.3; MS (ESI ): m/z (%) = 941 [M ], 813 (100)
3
+
[
(M – I) ]; Anal. calcd. for C H I P Pd : C, 66.35; H, 5.57. Found: C, 65.79; H,
5
2
52 1
1
1
5
.83.
‡
Selected spectroscopic data for 6a
1
H NMR (CDCl , δ/ppm): 7.86 (d, J = 7.6 Hz, 2H), 7.68-7.73 (m, 6H), 7.36-7.44 (m,
3
11H), 3.26 (d, J = 7.6 Hz, 1H), 2.69 (d, J = 10.0 Hz, 1H), 2.51 (d, J = 3.6 Hz, 1H),
2
.49 (s, 3H, Me), 1.72 (s, 1H), 1.45 (d, J = 4.0 Hz, 1H), 1.30 (d, J = 8.4 Hz, 1H),
1
3
0
.93-1.0 (m, 2H), 0.83-0.9 (m, 1H), 0.38-0.40 (m, 1H); C NMR (CDCl , δ/ppm):
3
1
43.1, 135.0 (d, J = 11.9 Hz), 132.0, 131.9, 131.4, 130.4 (d, J = 2.6 Hz), 128.1 (d, J =
11.1 Hz), 124.6, 53.9 (d, J = 3.1 Hz), 43.6 (d, J = 4.2 Hz), 42.3 (d, J = 15.6 Hz), 40.6,
3
1
3
7.7, 30.2, 27.8, 21.7 (1C, Me); P NMR (CDCl , δ/ppm): 38.9; HRMS (APCI) m/z
3
-26-

ACCEPTED MANUSCRIPT
+
+
(
M+H ): calcd. for C H I P Pd [M ]：680.0321; found: 681.0470; Anal. calcd. for
3
2
32 1
1
1
C H I P Pd : C, 56.45; H, 4.74. Found: C, 56.45; H, 5.09.
32
32 1
1
1
‡
Selected spectroscopic data for 6b
(Mixture of isomers)
1
H NMR (CDCl , δ/ppm): 7.89 (s, 2H), 7.67-7.71 (m, 6H), 7.35-7.40 (m, 11H),
3
5
.39-5.41 (m, 2H), 4.47 (d, J = 3.6 Hz, 1H), 3.28 (d, J = 7.2 Hz, 1H), 2.98 (d, J = 10.0
Hz, 1H), 2.53 (d, J = 4.4 Hz, 1H), 2.48 (s, 3H, Me), 2.10 (m, 1H), 1.86 (s, 1H), 1.79 (s,
1
3
1
H), 1.60 (d, J = 7.6 Hz, 1H), 1.25 (s, 1H), 0.82-0.77 (m, 1H); C NMR (CDCl ,
3
δ/ppm): 143.1, 143.0, 134.9 (d, J = 11.9 Hz), 132.0, 131.9, 131.7, 131.5, 131.4, 131.0,
1
30.3 (d, J = 2.2 Hz), 128.0 (d, J = 10.7 Hz), 128.0 (d, J = 11.1 Hz), 65.7, 55.3 (d, J =
0.0 Hz), 52.1, 49.4 (d, J = 3.0 Hz), 48.0 (d, J = 4.2 Hz), 46.3(d, J = 24.0 Hz), 46.3 (d,
1
3
1
J = 22.5 Hz), 44.5, 40.8, 40.7, 37.4, 37.3, 31.8, 30.9, 21.6(1C, Me), 15.2; P NMR
+
+
+
(
CDCl , δ/ppm): 38.9; MS (ESI ): m/z (%) = 719 [M ], 591 (100) [(M – I) ]; Anal.
3
calcd. for C H I P Pd : C, 58.47; H, 4.77. Found: C, 57.97; H, 4.95.
3
5
34 1
1
1
‡
Selected spectroscopic data for 6c
1
H NMR (CDCl , δ/ppm): 7.65-7.71(m, 6H), 7.60 (d, J = 7.6 Hz, 1H), 7.55(t, J = 8.0
3
Hz, 1H), 7.21(d, J = 1.6 Hz, 1H), 7.40-7.41(m, 2H), 7.38-7.39(m, 2H), 7.37(t, J = 2.0
Hz, 3H), 7.35 (t, J = 1.6 Hz, 1H), 7.18(t, J = 7.2 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H),
4
1
1
1
.06(s, 3H, OMe), 3.56-3.59(m, 1H), 2.72(d, J = 10.0 Hz, 1H), 2.37(d, J = 3.6 Hz,
H), 1.64 (t, 1H), 1.42(d, J = 2.8 Hz, 1H), 1.33-1.37 (m, 1H), 1.25-1.29 (m, 1H),
13
.00-1.06 (m, 1H), 0.83-0.90 (m, 1H), 0.47-0.49 (m, 1H); C NMR (CDCl , δ/ppm):
3
62.7, 134.8 (d, J = 11.9 Hz), 133.2, 132.6, 131.8, 131.3, 130.3 (d, J = 2.7 Hz), 127.8
(d, J = 11.1 Hz), 122.6, 111.5, 55.8 (1C, OMe), 50.1, 42.8 (d, J = 2.7 Hz), 42.0 (d, J =
-27-

ACCEPTED MANUSCRIPT
31
1
4.5 Hz), 41.6, 38.8, 29.6 (d, J = 11.0 Hz), 28.5; P NMR (CDCl , δ/ppm): 41.5;
3
+
+
HRMS (APCI) m/z (M+H ): calcd. for C H I O P Pd [M ]: 696.0270; found:
3
2
32 1
1
1
1
6
97.0353; Anal. calcd. for C H I O P Pd : C, 55.15; H, 4.63. Found: C, 54.60; H,
32 32 1 1 1 1
4
.60.
3
.4. X-ray crystallographic studies
Suitable crystals of 4a, 4b, 5a, 5b, 6a and 6b were sealed in thin-walled glass
capillaries under nitrogen atmosphere and mounted on a Bruker AXS SMART 1000
diffractometer. Intensity data were collected in 1350 frames with increasing ω (width
of 0.3° per frame). The absorption correction was based on the symmetry equivalent
reflections using SADABS program. The space group determination was based on a
check of the Laue symmetry and systematic absences, and was confirmed using the
structure solution. The structure was solved by direct methods using a SHELXTL
2
4
package. All non-H atoms were located from successive Fourier maps and hydrogen
atoms were refined using a riding model. Anisotropic thermal parameters were used
2
5
for all non-H atoms, and fixed isotropic parameters were used for H atoms.
Crystallographic data for compounds 4a, 4b, 5a, 5b, 6a and 6b are available from
Supporting Information.
4
.
Supplementary Material Available
Crystallographic data for the structural analysis have been deposited with the
Cambridge Crystallographic Data Center, CCDC no. 1401664, 1401665, 1401666,
401667, 1401668, and 1401669 for 4a, 4b, 5a, 5b, 6a and 6b, respectively.
1
-28-