Secondary phosphine oxides assisted palladium complexes catalyzed catellani reaction for the formation of carbazole derivatives

Article abstract of DOI:10.1016/j.jorganchem.2017.07.018

Several secondary phosphine oxides (SPOs, 2a-2d) as well as 2a-chelated palladium complex 2a_Pd were employed in Catellani type reaction for the synthesis of 1-methyl-9H-carbazole (4) from 2-iodotoluene and N-(2-bromophenyl)acetamide (3). The application

Full text of DOI:10.1016/j.jorganchem.2017.07.018

Accepted Manuscript
Secondary phosphine oxides assisted palladium complexes catalyzed catellani
reaction for the formation of carbazole derivatives
Ya-Chan Chen, Hsueh-Min Chou, I-Hsiang Kao, Yu-Chang Chang, Fung-E. Hong
PII:
S0022-328X(17)30447-3
10.1016/j.jorganchem.2017.07.018
JOM 20032
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 20 May 2017
Revised Date: 7 July 2017
Accepted Date: 12 July 2017
Please cite this article as: Y.-C. Chen, H.-M. Chou, I.-H. Kao, Y.-C. Chang, F.-E. Hong,
Secondary phosphine oxides assisted palladium complexes catalyzed catellani reaction for the
formation of carbazole derivatives, Journal of Organometallic Chemistry (2017), doi: 10.1016/
j.jorganchem.2017.07.018.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Secondary Phosphine Oxides Assisted Palladium Complexes Catalyzed Catellani Reaction
for the Formation of Carbazole Derivatives
Ya-Chan Chen, Hsueh-Min Chou, I-Hsiang Kao, Yu-Chang Chang,
and Fung-E Hong*
Department of Chemistry, National Chung Hsing University,
250 Kuo-Kuang Road, Taichung 40227, Taiwan
E-mail: fehong@dragon.nchu.edu.tw

ACCEPTED MANUSCRIPT
Secondary Phosphine Oxides Assisted Palladium Complexes Catalyzed Catellani
Reaction for the Formation of Carbazole Derivatives
Ya-Chan Chen, Hsueh-Min Chou, I-Hsiang Kao, Yu-Chang Chang,
and Fung-E Hong*
Department of Chemistry, National Chung Hsing University,
250 Kuo-Kuang Road, Taichung 40227, Taiwan
E-mail: fehong@dragon.nchu.edu.tw
* Author to whom correspondence should be addressed.
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Abstract
Several secondary phosphine oxides (SPOs, 2a-2d) as well as 2a-chelated
palladium complex 2a_Pd were employed in Catellani type reaction for the synthesis
of 1-methyl-9H-carbazole (4) from 2-iodotoluene and N-(2-bromophenyl)acetamide
(3). The application of these ligands (2a-2d) and palladium complex (2a_Pd) in this
reaction is beneficial in terms of increasing the yield of the major product, 4. An
elaborated mechanism was proposed to account for the observation of 4 as well as
some side products, 5, 6, 7, and 8, via C-C and C-N bonds formation processes.
Keywords: Carbazole; Secondary phosphine oxide; Catellani reaction; C-H activation;
Palladium; C-N bond formation.
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1. Introduction
The importance of carbazole derivatives is evidenced from the fact that the
skeleton of it could be found in many biologically active molecules, natural products,
therapeutic agents and photoelectrical materials.[1] Because the applications of
carbazole derivatives are so diverse and useful in various aspects, thereby, the
searching for more effective methods for the syntheses of new functional carbazoles
have attracted much attention from synthetic chemists. Indeed, several applicable
methods had been reported for the preparations of carbazoles with various
substituents.[2] For example, the N-substituent carbazole derivative,
9-phenyl-9H-carbazole (1a), was prepared based on the method demonstrated by
Ackermann (Scheme 1).[3] In that reaction, the palladium catalyzed reaction of
diphenylamine and 1,2-dibromobenzene led to the formation of 1a in good yield. Here,
a notable C-H activation process takes place on the diphenylamine during the
preparation of 1a. Needless to say, the N-substituent free carbazoles are much
desirable molecules due to their potential to be subjected to further modification on
the nitrogen site by various functional groups.[4] Unfortunately, our previous attempts
to synthesize N-substituent free carbazole derivatives, 1b and 1c, via aforementioned
Ackermann’s method were resulted in unacceptable low yields.[5] It is believed that
the methyl group in position-2 (R2) or electron-withdrawing group in position-4 (R3)
might hinder the formation of N-substituent free carbazole derivative 1b or 1c.
Scheme 1. Preparations of carbazole derivatives via Ackermann’s method
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Although Catellani reaction can be regarded as a shrewd extension of
conventional cross-coupling reactions in one sense,[6] it can also be regarded as one of
the most intriguing reactions for ortho- C-H activation of arylhalide.[7] In fact,
Catellani also explored a method for the preparation of carbazoles and proposed a
mechanism to account for its reaction pathway.[8] In the Catellani’s early work, the R1
has to be tosyl- or sulfonyl-group to ensure the catalytic reaction achieving its
reasonable performance. No ligand was participated in this particular reaction. In
addition, the ratio of the stoichiometric amount of palladium catalyst employed here
against the substance in this Catellani reaction is fairly high.[9] Lautens was the one
firstly tried to apply ligands to burst the rate of the Catellani reaction and to enhance
the yield of the major product.[10] As demonstrated, phosphine ligands in some
occasions indeed exhibited improved performance on the Catellani type reactions.
Nevertheless, the effect of phosphine ligand in Catellani type reactions is not always
as affirmative as that in the cross-coupling reactions. In addition, the success of
Catellani reaction is in debt to the co-catalyst norbornene, which plays a unique role
in Catellani reaction.[11] Without the presence of norbornene, the process of C-H
activation in Catellani type reaction will not be executable.[6]
Phosphines (tri-alkyl and tri-aryl substituted) are one of the most important
categories of ligands employed in transition metal complexes catalyzed reactions due
to their flexible shapes and functions.[12] Nevertheless, most phosphines are
malodorous and also sensitive to air/moisture, those characteristics cause these types
of compounds unpleasant and difficult to handle in normal laboratory operation.[13] To
overcome these obstacles, a trend has been emerged in the last few decades by using
air/moisture much stable secondary phosphine oxides (SPOs) as the acting ligands
rather than the conventional tri-substituted phosphines.[14] Nevertheless, caution
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should be taken for using SPOs as ligands since they might undergo undesirable
reductive elimination with aryl (or alkyl) group in the transition metal complex
intermediate(s) during catalytic cycle and forming ineffective tri-substituted
phosphine oxides.[15]
In the generally accepted mechanism of Catellani reaction, the valence of active
palladium species are believed to be circulated among three different valences, i.e.
Pd(0), Pd(II) and Pd(IV). Especially, high-valence Pd(IV) species are proposed as the
potentially active intermediates for C-H activation processes. That is presumably the
reason why the application of trialky- or triarylphosphine in Catellani reaction is
relatively unfavorable due to its much readily reducing capacity towards high-valence
palladium species. In contrast with phosphines, the reducing potential of secondary
phosphine oxides (SPOs) is relatively milder. Thereby the secondary phosphine oxide
has the potential to act as authentic phosphine ligand after converting to its tautomeric
form (phosphinous acid) and at the same time without too strong reducing capacity to
interfere the formation of high valence Pd(IV) species.
To the best of our knowledge, there have only rather limited examples for using
secondary phosphine oxides as ligands in palladium complexes catalyzed Catellani
reactions been reported.[16] Therefore, we are interested in exploring the catalytic
potential of several selected SPOs as alternative phosphine ligands in Catellani
reaction in the processes of preparing N-substituent free carbazole derivatives.
2. Results and Discussion
2.2 Preparation of Carbazoles by SPO-assisted palladium complexes-catalyzed
Catellani type reactions
Palladium complexes catalyzed Catellani type reactions of 2-iodotoluene and
N-(2-bromophenyl)acetamide (3) have been carried out by employing selected SPOs
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(2a, 2b, 2c & 2d) as ligands as well as using preformed palladium complex 2a_Pd as
pre-catalyst (Diagram 1). Two frequently used conventional tri-substituted phosphine
ligands such as PPh3 and dppe were employed as well in the reactions for the purpose
of comparison.
Diagram 1. Secondary phosphine oxides 2a, 2b, 2c and 2d as well as 2a chelated
palladium complex 2a_Pd
The preparations and applications of 2a, 2b and 2a_Pd were reported
previously.[17, 16a] Moreover, 2c and 2d were also prepared herein and characterized by
spectroscopic methods. To our delight, the crystal structure of 2c was resolved (Figure
1). The existence of a double bond between P(1)-O(2) in 2c is evidenced by its short
bond length, 1.476(3) Å. The bond length between C(7)-C(8) is 1.326(5) Å, a typical
double bond. The phosphorous atom is obviously sited on a pseudo-tetrahedral
surrounding and attached by a benzofuranyl ring as well as a tert-butyl group.
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Figure 1. ORTEP drawing of 2c
Several factors that potentially affect the efficiency of the reaction, including
temperature, time, concentration, base, transition metal/ligand ratio and solvent etc.,
have been screened in order to achieve its optimized reaction condition. The general
procedure for the reaction under investigation is presented as the follows. Under N2
atmosphere, a 20 mL Schlenk tube was charged with 0.2 mmol 2-iodotoluene, 0.4
mmol N-(2-bromophenyl)acetamide (3), 2.0 mL solvent, 0.8 mmol base, 0.42 mmol
norbornene, 10 mol% palladium salt, and 10~20 mol% ligand. The reaction was
executed at preset temperature (135 °C) for scheduled time. It was then followed by
work-up necessary to yield the product(s). The conversion rates were determined from
the measurements of products’ distinct 1H NMR signals against the standard one;
while, the isolated yields were calculated from the products purified by the technique
of column chromatography. The targeted compound 1-methyl-9H-carbazole, 4, was
observed as the major product along with some side products,
1-((4aS,9aS)-5-methyl-1,2,3,4,4a,9a-hexahydro-9H-1,4-methanocarbazol-9-yl)ethan-1
-one, 5, and
(1S,4R,4aR,12bS)-5,9-dimethyl-1,2,3,4,4a,12b-hexahydro-1,4-methanotriphenylene, 6
(Scheme 2).
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Scheme 2. Syntheses of 4 as well as 5 and 6 via Catellani reaction method
In the preliminary screening, the reactions were carried out with/without ligands
to the formation of 4 (Table 1). As illustrated, the catalytic performances toward the
preparation of 4 in the presence of the newly-made SPOs (2a, 2b, 2c & 2d), 2a_Pd
and dppe are generally much efficient than that without ligand. The performance is
found worst in the presence of PPh3 (entry 7). It is probably due to the fairly reducing
capacity of it towards high-valence palladium species such as Pd(IV), generated
during the reaction as intermediate, and thereby depressed the reaction yield. The
catalytic performance of using 2c as ligand is the best and, hence, was chosen as the
executing ligand for the optimization process thereafter.
Table 1. Catellani reactions of 2-iodotoluene and N-(2-bromophenyl)acetamide
employed various ligands[a]
Entry
Ligand (L)
4, Yield. (%)[b]
1
-
2a
26
39
36
61
44
37
24
36
2
3
2b
4
2c
5
2d
6
2a_Pd
PPh3
dppe
7[c]
8[d]
Conditions: [a] 2-iodotoluene (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), K2CO3 (0.8 mmol), Pd(OAc)2 (10 mol%), DMA (2 mL), 135
oC, 20 hr.; [b] Isolated yield of 4; [c] Pd/L = 1:2; [d] Pd/L = 1:1.
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As demonstrated repeatedly, a properly chosen base is crucial to the
performance of Catellani reaction. In this case, a strong base might cause the
hydrolysis of amide to amine, therefore, several mild bases were screened. As shown
in Table 2, the catalytic performance is better for using K2CO3 or CsF as base. While,
the employment of CsF might be slightly better than K2CO3 in this case; however,
K2CO3 is chosen as the operating base due to its ready availability.
Table 2. Catellani reactions of 2-iodotoluene and N-(2-bromophenyl)acetamide
employed various bases[a]
Entry
Base
4, Yield(%)[b]
1
2
3
4
Na2CO3
K2CO3
Cs2CO3
CsF
35
43
31
47
Conditions: [a] 2-iodotoluene (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), base (0.8 mmol), Pd (OAc)2 (10 mol%), 2c (20 mol%),
DMA (2 mL), 135 oC, 1 hr.; [b] Isolated yield of 4.
Several palladium sources were screened here for this Catellani reaction (Table
3). The performance of using Pd(OAc)2 as palladium complex is among the best. Due
to its availability and price, Pd(OAc)2 was chosen as the executing agent of the
palladium source.
Table 3. Catellani reactions of 2-iodotoluene and N-(2-bromophenyl)acetamide
employed palladium sources[a]
Entry
Palladium sources
Pd(OAc)2
4, Yield[b]
1
2
3
4
43
47
25
25
PdI2
PdCl2(MeCN)2
Pd(COD)Cl2
Conditions: [a] 2-iodotoluene (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), K2CO3 (0.8 mmol), Pd source (10 mol%), 2c (20 mol%),
DMA (2 mL), 135 oC, 1 hr.; [b] Isolated yield of 4.
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It was proven formerly that polar solvents rather than non-polar solvents are
better media for this type of reactions.[18] Here, several polar solvents were employed
in this Catellani type reaction (Table 4). The catalytic performance of the reaction in
DMA and DMSO are among the best. Due to its much gentle requirement in
experimental operation, DMA is chosen as the solvent. Furthermore, the performance
dropped notably by mixing DMA with water.[19]
Table 4. Catellani reactions of 2-iodotoluene and N-(2-bromophenyl)acetamide
employed palladium sources[a]
Entry
Solvent
DMA
4, Yield(%) [b]
1
2
3
43
36
49
DMF
DMSO
Conditions: [a] 2-iodotoluene (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), K2CO3 (0.8 mmol), Pd(OAc)2 (10 mol%), 2c (11 mol%),
solvent (2 mL), 135 oC, 1 hr.; [b] Isolated yield of 4.
The following table shows the results of reactions under varying executing times.
It shows that the reaction almost reaches its maximum performance at 8 hours (Table
5, entry 4). Only slight change was observed for further prolonging the reaction hours.
Table 5. Catellani reactions of 2-iodotoluene and N-(2-bromophenyl)acetamide under
various reaction hours[a]
Entry
Time ( hr )
4, Yield(%) [b]
1
2
3
4
5
1
2
38
38
45
62
61
4
8
20
Conditions: [a] 2-iodotoluene (0.2mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), K2CO3 (0.8 mmol), Pd(OAc)2 (10 mol%), 2c (20 mol%),
DMA (2 mL), 135 oC. [b] Isolated yield of 4.
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The reactions employing the combination of Pd(OAc)2 with 2a (or 2c) as
catalytic precursor for various substituted iodotoluenes and
N-(2-bromophenyl)acetamide were also carried out at 135 oC for varying reaction
hours (Table 6). As shown, the catalytic performance was acceptable only for
2-iodotoluene (Entry 1). It is poor for using either heterocyclic iodide (Entries 4 & 5)
or -F, -CN and -COOMe substituted iodobenzene (Entries 6, 7 & 8).
Table 6. Catellani reactions of various halide and N-(2-bromophenyl)acetamide[a]
Entry
Aryl halide
Product
Time (hr)
4, Yield (%) [b]
1
8
62
2
8
37
3[c]
4[c]
5[c]
48
20
20
9.5
[d]
-
[d]
-
[d]
6[c]
7[c]
8[c]
20
20
20
-
[d]
-
[d]
-
Conditions: [a] halide (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
norbornene (0.42 mmol), K2CO3 (0.8 mmol), Pd(OAc)2 (10 mol%), 2c (20 mol%),
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DMA (2 mL), 135oC. [b] Isolated yield of 4. [c] 2a (20 mol%) was employed. [d] Not
detected.
In Catellani type reaction, norbornene is regarded as one of the most
indispensable ingredients. It was speculated how a slight variation of its structure
might affect the reaction performance. Thereby, norbornene as well as its structurally
related co-catalysts, dicyclopentadiene and norbornadiene, were employed in the
same catalytic reactions for comparison (Diagram 2). It was found that the
employment of norbornene is the best among all these three co-catalysts. The worst
performance was observed for using norbornadiene as the co-catalyst. It could be due
to the presence of two active double bonds in either norbornadiene or
dicyclopentadiene that caused undesirable side reactions thus diminished the yield of
the major product, 4.
Diagram 2
Table 8. The effect of norbornene structurally related co-catalysts on the yield of 4[a]
Entry
Co-catalyst
Yield[d] (%)
1
2
3
Norbornene
46
2
Norbornadiene[b]
Dicyclopentadiene[c]
35
[a] Conditions: 2-iodotoluene (0.2 mmol), N-(2-bromophenyl)acetamide (0.4 mmol),
co-catalyst (0.42 mmol), K2CO3 (0.8 mmol), Pd(OAc)2 (10 mol%), DMA (2 mL), 135
oC, 20 hr; [b] Norbornadiene (0.42 mmol); [c] Dicyclopentadiene (0.42 mmol); [d]
Isolated yield of 1-methyl-9H-carbazole by chromatotron.
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2.3 Mechanism for Carbazole formation by Catellani reaction methods
As noticed, there are several side products (5, 6, 7 and 8) besides the targeted
major product, 4, were observed in the previous reaction (Scheme 2).[20] The
quantities of these side products could be altered by varying the ratio of the starting
materials. The mechanism for the formations of carbazole 4 and side products is
proposed as shown in Diagram 3. It is presumed that there are two major catalytic
cycles, Cycle A and Cycle B, being executed in this proposed mechanism. The
process for the formations of 4 and side product 7 is believed through several
consecutive steps as shown in the outer cycle of Cycle A. Besides, the process for the
formations of side products 6 and 8 is presumed via the inner cycle of Cycle A. It is
through Cycle B that another side product 5 is obtained. This complicate mechanism
is consisted of commonly observed steps in Catellani type reactions such as oxidative
addition, norbornene insertion, reductive elimination, norbornene extrusion.
Meanwhile, the rule of Ortho Effect in Catellani type reaction is also held here.[21]
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Diagram 3. Proposed mechanism for the formations of the targeted major product, 4,
as well as side products, 5, 6, 7 and 8.
It was also found that the quantity of the side product, 5, could be manipulated by
the amount of 3 employed in the presetting of the reaction. As shown in the following
table, the formation of 5 is restrained while only slightly more than one equivalent of
3 is applied (Table 9, entry 2). The results indicate that Cycle A is the major reaction
pathway which leads to the production of 4. The rate for the consumption of 3 in
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Cycle A is in much faster rate than that of Cycle B. Thereby, the side product 5 could
be obtained only after the complete formation of 4 and in the meanwhile excess 3 is
present.
Table 9. The effect of the amount of N-(2-bromophenyl)acetamide on the products
distribution[a]
NMR conv. (%)[b]
Entry
Molar equiv. of 3
4
5
1
2
2.0
1.1
41.1
43.9
16.1
trace
Conditions: [a] 2-iodotoluene 0.2 mmol, K2CO3 0.8 mmol, Pd(OAc)2 (10 mol %), 2a
(11 mol%), DMA (2 mL), 135 oC, 20 hr.; [b] Isolated yield of 4 or 5.
2.5 Summary
N-substituent free carbazole derivatives could be obtained via SPO assisted
palladium catalyzed Catellani type reaction starting from 2-iodoaryl (or
2-iodo-heterocyclic compounds) and N-(2-bromophenyl)acetamide. During the
reaction, C-H activation and C-N bond formation processes are implemented. A more
extended mechanism is proposed to account for the formations of several side
products (5, 6, 7 and 8) besides the targeted carbazole, 4.
3. Experimental Section
3.1. General
All reactions were carried out under a nitrogen atmosphere using standard
Schlenk techniques or in a nitrogen flushed glove box. Freshly distilled solvents were
used. All processes of separations of the products were performed by Centrifugal Thin
Layer Chromatography (CTLC, Chromatotron, Harrison model 8924) or column
chromatography. Routine 1H NMR spectra were recorded on a Varian-400
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spectrometer at 399.756 MHz. The chemical shifts are reported in ppm relative to
internal standards TMS (δ = 0.0 ppm). 31P and 13C NMR spectra were recorded at
161.835 and 100.529 MHz, respectively. The chemical shifts for the former and the
latter are reported in ppm relative to internal standards H3PO4 (δ = 0.0 ppm) and
CHCl3 (δ = 77 ppm), respectively. Mass spectra were recorded on JOEL JMS-SX/SX
102A GC/MS/MS spectrometer. Electrospray ionization-high resolution mass spectra
(ESI-HRMS) were recorded on a Finnigan/Thermo Quest Mat 95 XL mass
spectrometer.
3.2. Synthesis and characterization of 2c-2d
A 50 mL round-bottomed flask was firstly vacuumed and refilled with N2. Then, it
was charged with 6 mmol benzofuran (708 mg) and 20 mL THF. The flask was kept at
-78 °C while 11.0 mmol n-BuLi (2.5 M in hexane, 4 mL) was slowly added into it.
The mixed solution was stirred for 1 hour. At the same time, a 20 mL Schlenk tube
containing 50 mL tBuPCl (954 mg) and 10 mL THF was ready. The solution in the
round-bottomed flask was slowly transferred to the Schlenk tube using cannula
technique. The mixed solution was allowed to warm up to 25°C and stirred for 6
hours before 10 mL of K2CO3(aq) (3M) was added to it for hydrolysis. The solution
was concentrated and followed by column chromatography. A pale-yellow solid 2c
(1.13 g, 5.09 mmol, 84.8%) was obtained after all solvent was removed by vacuum.
Similar procedures for the preparation of 2d were carried out. The pale-yellow solid
2d was obtained in 84.7% yield (1.21 g, 5.08 mmol).
‡ Spectroscopic data for 2c:
1H NMR (CDCl3, 400 MHz): δ 7.20 (d, JP-H = 472.1 Hz, 1H), 7.67 (d, J = 7.6 Hz, 1H),
13
7.53 (m, 2H), 7.41 (t, J = 7.6 Hz, 1H), 7.30 (m, 1H), 1.26 (d, J = 18.0 Hz, 9H); C
NMR (CDCl3, 100 MHz): δ 157.3 (d, J = 7.6 Hz), 147.8 (d, J = 111.1 Hz, P-Ar),
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126.7, 126.2 (d, J = 8.4 Hz), 123.54, 122.2, 119.0, 111.8, 32.0 (d, JP-C = 73.6 Hz,
t
31
P-C-Me3), 23.1 (s, Bu); P NMR (CDCl3, 162 MHz): δ 31.31 (d, JP-H = 492.1 Hz);
HRMS (EI): calcd. for C12H15O2P (m/z M+): 222.0810, found: 222.0805. Anal. Calcd.
for C12H15O2P: C, 64.86 %; H, 6.80 %. Found: C, 64.88 %; H, 6.94 %.
‡ Spectroscopic data for 2d:
1H NMR (CDCl3, 400 MHz): δ 7.87 (m, 3H), 7.25 (d, JP-H = 466.1 Hz, 1H), 7.42 (m,
2H), 1.23 (d, J = 17.6 Hz, 9H); 13C NMR (CDCl3, 100 MHz): δ 142.9 (d, J = 4.5 Hz),
138.8 (d, J = 13.4 Hz), 133.2 (d, J = 8.3 Hz), 129.9, 129.0, 126.3, 124.8 (d, J = 12.1
Hz), 122.3, 32.2 (d, JP-C = 80.4 Hz), 23.2 (d, J = 2.7 Hz, tBu); 31P NMR (CDCl3, 162
MHz): δ 38.10 (d, JP-H = 492.9 Hz); HRMS (EI): calcd. for C12H15OPS (m/z M+):
238.0581, found: 238.0583; Anal. calcd. for C12H15OPS: C, 60.49 %; H, 6.34 %.
Found: C, 61.45 %; H, 6.92 %.
3.3. General procedure for Catellani reactions
A nitrogen filled 20 mL brown Schlenk tube charged with a magnetic stirrer was
placed with N-(2-bromophenyl)acetamide (0.4 mmol, 0.086 g), Pd(OAc)2 (0.02 mmol,
5.0 mg), 2c (0.022 mmol, 8.14 mg), K2CO3 (0.8 mmol, 0.111 g) and norbornene (0.42
mmol, 0.040 g). This was processed in fume hood and then the tube was capped with
tight seal. The air in the tube was pumped out and then backup with nitrogen. Repeat
the process for three times. Subsequently, 2-iodotoluene (0.2 mmol, 0.0254 mL) and
DMA (2.0 mL) were added under nitrogen. The solution was then heated in oil bath
for 20 hours at 135 °C. After that, it was cooled down to room temperature and the
resulted products were extracted with water and ether. The extracted solution was
filtrated by flash column and concentrated. Further purification was carried out by
Centrifugal Thin Layer Chromatography. Finally, the conversion rates of the
particular products were analyzed by their distinct chemical shifts in 1H NMR.
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Similar procedures were performed as well for using different ligands such as PPh3
and dppe.
‡ Spectroscopic data for 9-phenyl-9H-carbazole 1a
1H NMR (CDCl3, 400 MHz): δ 8.13 (d, J = 7.6 Hz, 2H), 7.56 (m, 4H), 7.44 (m, 1H),
7.39 (d, J = 3.6 Hz, 4H), 7.27 (m, 2H); 13C NMR (CDCl3, 100 MHz): δ 140.8, 137.6,
129.8, 127.4, 127.1, 125.9, 124.1, 123.3, 120.3, 119.9, 109.7; HRMS (EI): calcd. for
C18H13N (m/z M+): 243.1048, found: 243.1044; Anal. calcd. for C18H13N: N, 5.76 %;
C, 88.86 %; H, 5.39 %. Found: N, 5.78 %; C, 88.60 %; H, 5.60 %.
‡ Spectroscopic data for 1-methyl-9H-carbazole 4
1H NMR (CDCl3, 400 MHz): δ 8.05 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 7.6 Hz, 2H),
7.40 (q, J = 8.0 Hz, 2H), 7.22 (m, 2H), 7.15 (t, J = 7.4 Hz, 1H), 2.51 (s, 3H); 13C
NMR (CDCl3, 150 MHz): δ 139.3 (C), 138.8 (C), 126.4 (CH), 125.6 (CH), 123.8 (C),
122.8 (C), 120.4 (CH), 119.7 (C), 119.5 (CH), 119.4 (CH), 117.9 (CH), 110.7 (CH),
16.9 (CH3).; HRMS (EI): calcd. for C13H11N (m/z M+): 181.0891, found: 181.0887;
Anal. calcd. for C13H11N: N, 7.73 %; C, 86.15 %; H, 6.12 %. Found: N, 6.75 %; C,
84.32 %; H, 6.79 %.
‡ Spectroscopic data for 1-(trifluoromethyl)-9H-carbazole
1H NMR (CDCl3, 400 MHz): δ 8.48 (s, 1H), 8.24 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 6.8
Hz, 1H), 7.66 (d, J = 6.0 Hz, 1H), 7.50 (m, 2H), 7.30 (m, 2H); 13C NMR (CDCl3, 150
MHz): δ 139.5 (C), 135.3 (C), 126.9 (CH), 125.0 (C), 125.0 (q, J = 271.4 Hz, C) ,
123.9 (CH), 122.8 (d, J = 4.1 Hz, C), 122.3 (C), 120.4 (CH), 120.3 (CH), 118.8 (CH),
112.6 (q, J = 32.7 Hz, CH), 111.0 (CH); HRMS (EI): calcd. for C13H8F3N (m/z M+):
235.0609, found: 235.0616; Anal. Calcd. for C13H8F3N: N, 5.96 %; C, 66.38 %; H,
3.43 %. Found: N, 5.59 %; C, 65.13 %; H, 4.11 %.
‡ Spectroscopic data for methoxy-6-methyl-9H-carbazole (Glycozolicine)
1H NMR (400 MHz, CDCl3, δ/ppm): 8.16 (br, s, NH), 7.85 (s, 1H), 7.64 (d, 1H, J =
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8.0 Hz), 7.35 (d, 1H, J = 8.0 Hz), 7.23 ( d, 1H, J = 8.0 Hz), 7.14 (t, 1H, J = 8.0 Hz),
6.88 (d, 1H, J = 7.6 Hz), 4.01(s, 3H, OMe), 2.52 (s, 3H, Me); 13C NMR (CDCl3, 150
MHz): δ 145.6 (C), 137.4 (C), 130.1 (C), 128.6 (C), 127.0 (CH), 124.1 (C), 123.8 (C),
120.4 (CH), 119.5 (CH), 112.8 (CH), 110.6 (CH), 105.7 (CH), 55.5 (OCH3), 21.4
(CH3); HR-MS (EI): calcd. for C14H13NO (m/z M+): 211.0997, found: 211.0996; Anal.
calcd. for C14H13NO: N, 6.63 %; C, 79.59 %; H, 6.20 %. Found: N, 5.20 %; C, 78.76
%; H, 7.13 %.
‡ Spectroscopic data for
1-((1R,4S)-1,2,3,4,4a,9a-hexahydro-9H-1,4-methanocarbazol-9-yl)ethan-1-one, 5
1H NMR (400 MHz, CDCl3, δ/ppm): 8.18 (d, 1H, J = 8.0 Hz), 7.16-7.18 (m, 1H),
7.11-7.14 (q, 1H), 7.01 (td, 1H, J = 7.6, 0.8 Hz), 4.12 (d, 1H, J = 8.0 Hz), 3.39 (d, 1H,
J = 8.0 Hz), 2.52 (d, 1H, J = 4.0 Hz), 2.36 (s, 1H), 2.29 (s, 3H, Me), 1.57-1.68 (m, 2H),
1.37-1.46 (m, 1H), 1.29-1.33 (m, 2H), 1.14 (d, 1H, J = 10.8 Hz); 13C NMR (CDCl3,
150 MHz): δ 169.1 (C), 144.6 (C), 133.6 (C), 127.5 (CH), 124.0 (CH), 123.7 (CH),
116.5 (CH), 67.9 (CH), 50.6 (CH), 43.1 (CH), 42.7 (CH), 32.0 (CH2), 27.9 (CH2),
25.7(CH2), 23.7 (CH3); HRMS (EI): calcd. for C15H17NO (m/z M+): 227.1310, found:
227.1316; Anal. Calcd. for C15H17NO: N, 6.16 %; C, 79.26 %; H, 7.54 %. Found: N,
5.94 %; C, 79.25 %; H, 7.74 %.
‡ Spectroscopic data for
(1R,4S,12bR)-5,9-dimethyl-1,2,3,4,4a,12b-hexahydro-1,4-methanotriphenylene, 6
1H NMR (400 MHz, CDCl3, δ/ppm): 7.85(d, 1H, J = 7.2 Hz), 7.74(d, 1H, J = 8.0 Hz),
7.17-7.22(m, 2H), 7.14(t, 1H, J = 8.0 Hz), 7.09(d, 1H, J = 8.0 Hz), 3.29(d, 1H, J = 10.0
Hz), 3.11(d, 1H, J = 9.2 Hz), 2.40(s, 1H), 2.34(s, 3H, Me), 2.20(s, 1H), 1.76 (br, s, 1H),
1.64(s, 3H, Me), 1.38(d, 1H, J = 9.6 Hz), 1.25(s, 2H), 1.04(d, 1H, J = 8.0 Hz), 0.88(br,
s, 1H); 13C NMR (CDCl3, 150 MHz): δ 137.5, 136.9, 136.1, 132.2, 131.2, 130.1,
129.5, 127.5, 126.1, 126.0, 122.3, 120.3, 48.6, 47.5, 46.5, 43.2, 33.5, 31.0, 29.3, 20.1;
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HR-MS (EI) Calcd. for C21H22 [M+]: 274.1722. Found: 274.1729; Anal. Calcd. for
C21H22: C, 91.92 %; H, 8.08 %. Found: C, 91.37 %; H, 7.95 %.
3.8. X-ray crystallographic studies
Suitable crystal of 2c was 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 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 for all non-H atoms,
and fixed isotropic parameters were used for H atoms.
4. Supplementary Material Available
Crystallographic data for the structural analysis have been deposited in the
Cambridge Crystallographic Data Center, CCDC no. 1546486 for 2c.
Acknowledgments
We thank the Ministry of Science and Technology of the ROC (Grant MOST
105-2113-M-005-009) for financial support.
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Highlights
ò The present work described the palladium-catalyzed Catellani reaction for the formations of
carbazoles utilizing several secondary phosphine oxides as acting ligands.
ò Several side products besides the targeted carbazoles were identified from this reaction
which indicates the reaction is much complicated than our previous thought that it shall be.
ò A more extensive mechanism is proposed to account for the formations of carbazole (4) as
well as other side products.