CuCl-Catalyzed Ullmann-Type C-N Cross-Coupling Reaction of Carbazoles and 2-Bromopyridine Derivatives

Article abstract of DOI:10.1021/acs.joc.6b02595

A CuCl-catalyzed Ullmann-type C-N cross-coupling reaction of carbazoles and 2-bromopyridine derivatives has been developed for the synthesis of N-heteroarylcarbazole derivatives employing 1-methyl-imidazole and t-BuOLi as ligand and base, respectively, both of which are found to significantly promote the reaction. Low cost and low loading of both catalyst and ligand, together with high reaction yields, render this practical reaction to be suitable for large-scale preparations and could be useful in material science.

Full text of DOI:10.1021/acs.joc.6b02595

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Article
CuCl-Catalyzed Ullmann-Type C-N Cross-Coupling
Reaction of Carbazoles and 2-Bromopyridine Derivatives
Xiangdong Zhao, Yuanbin She, Kun Fang, and Guijie Li
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 22 Dec 2016
Downloaded from http://pubs.acs.org on December 23, 2016
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CuClꢀCatalyzed UllmannꢀType CꢀN CrossꢀCoupling Reaction of Carbazoles and 2ꢀBromopyridine
Derivatives
Xiangdong Zhao, Yuanbin She*, Kun Fang, Guijie Li*
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014,
P. R. China
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Eꢀmail: guijieli@zjut.edu.cn
A CuClꢀcatalyzed Ullmannꢀtype CꢀN crossꢀcoupling reaction of carbazoles and 2ꢀbromopyridine
derivatives has been developed for the synthesis of Nꢀheteroarylcarbazole derivatives employing
1ꢀmethylꢀimidazole and tꢀBuOLi as ligand and base respectively, both of which are found to promote
the reaction significantly. Low costs and low loading of both catalyst and ligand, together with high
reaction yields render this practical reaction to be suitable for largeꢀscale preparation, and could be
useful in material science.
■ INTRODUCTION
Figure 1. Selected phosphorescent emitters and host material with a 9ꢀ(2ꢀpyridinyl)ꢀ9Hꢀcarbazole
moiety.
Nꢀ(Hetero)arylcarbazole compounds and their derivatives are wildly utilized in material science,1
such as energy transfer materials2, host materials1b,3 and charge transporting materials1b,4 in the
organic lightꢀemitting devices (OLEDs) fields due to their high thermal and electrochemical
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stabilities (Figure 1). Moreover, Nꢀ(hetero)arylcarbazole moieties are also wildly incorporated in
recently developed thermally activated delayed fluorescence (TADF) materials5 and tetradentate
platinum and palladium based phosphorescent materials6 to serve as perfect donors and
cyclometalated ligands. Both of the materials demonstrate remarkable electroluminescent properties
and promising applications in lowꢀcost display and solidꢀstate lighting.7
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Scheme 1: Previous Reports for the Synthesis of N-(Hetero)arylcarbazole Derivatives
Generally, Nꢀ(hetero)arylcarbazole derivatives can be synthesized through CarylꢀN bond
formation reactions between corresponding carbazoles and aryl halides, which has been
demonstrated to have a great impact on the fields of material science, medicinal chemistry and
natural product synthesis.8 A series of powerful approaches for the CarylꢀN bond formation have been
developed.9ꢀ14,19ꢀ21 Especially during the past two decades, remarkable progress was achieved in this
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field, for example, the palladiumꢀcatalyzed crossꢀcoupling of amines and aryl halides
(BuchwaldꢀHartwig reaction)9 and the copperꢀcatalyzed Ullmannꢀtype coupling reactions promoted
by bidentate ligands,10ꢀ14 both of which demonstrated mild reaction conditions and broad reaction
scopes. Because of extensive application in both academia and industry,8ꢀ11,15 the development of
new practical methods for the CarylꢀN bond formation still attracted a great deal of attention in recent
years. In 2011, Yum's group disclosed a LiClꢀmediated Nꢀarylation of carbazoles reaction to
synthesize the Nꢀ(hetero)arylcarbazoles,16 meanwhile, a microwaveꢀassisted process was also
developed by the same group.17 However, both required 10 mol% CuI as catalyst with long reaction
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o
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time of two days at high reaction temperature (150 C and 220 C respectively) (Scheme 1a). Later,
Wu and coꢀworkers discovered palladium(II)ꢀcatalyzed process to prepare
a
9ꢀ(2ꢀpyridinyl)ꢀ9Hꢀcarbazoles through a cascade CꢀH bond activation/intramolecular CꢀN bond
formation reactions with a mixture of two products owing to low chemoselectivity (Scheme 1b).18
Moreover, in 2013, Peters and Fu developed versatile protocols for the Ullmann CarylꢀN coupling
reactions between various heteroaryl nucleophiles and aryl halides catalyzed by CuI under ultraviolet
(UV) light irradiation.19 Recently, Kobayashi et al performed the visible lightꢀpromoted
Ullmannꢀtype CarylꢀN crossꢀcoupling of carbazole derivatives and aryl iodides in the presence of CuI
and photocatalyst Ir(ppy)3 (Scheme 1c).20 And it was believed that both of the photo promoted
CarylꢀN crossꢀcoupling reactions involved single electro transfer (SET) processes. In addition, a
NHCꢀnickel(0) catalyzed CarylꢀN crossꢀcoupling of indoles and carbazoles with aromatic chlorides
was also achieved recently by Belderrain and Nicasio (Scheme 1d).22 And also, Nakayama group
developed an efficient palladiumꢀcatalyzed coupling reaction between (hetero)aryl chlorides and
Nꢀcarbazolylmagnesium chloride (Scheme 1e).8d Thus, various approaches had been developed to
form the CarylꢀN bond, however, the reports for the synthesis of Nꢀheteroarylcarbazoles, especially
for the 9ꢀ(2ꢀpyridinyl)ꢀ9Hꢀcarbazole derivatives6cꢀd,18, was still rare. Furthermore, the reaction
conditions had some disadvantages, including high catalyst loading6c,6d,16,17,19, high temperature16,17
,
long reaction time6c,6d, or incompatibility of bromine atom on the product molecules because of the
palladium8d and nickel22 based catalyst, which may result in CꢀBr bond reduction or cleavage. In
order to overcome these drawbacks, it is highly desirable to develop a more practical method for the
preparation of the Nꢀheteroarylcarbazoles. Herein we report an efficient CuClꢀcatalyzed
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Ullmannꢀtype CarylꢀN crossꢀcoupling of carbazoles and 2ꢀbromopyridine derivatives with the
advantages of low catalyst and ligand loading and good functional group tolerance, especially for
2ꢀbromo, 3ꢀbromo, 2,7ꢀdibromo and 3,6ꢀdibromo Nꢀheteroarylcarbazole products, which was critical
for their further functionalization. More importantly, this practical method is suitable for large scale
synthesis of the Nꢀheteroarylcarbazoles, which is important for the preparation of advanced materials
in material science field.
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■ RESULTS AND DISCUSSION
2ꢀBromoꢀ9ꢀ(2ꢀpyridinyl)ꢀ9Hꢀcarbazole 3a and its derivatives were critical intermediates in the
synthesis of tetradentate platinum and palladium based phosphorescent materials.6 And based on our
previous study,6c it was valuable to note that the starting material 1a should be consumed completely
to avoid purification problems because of the low solubility of 1a in common solvents, such as
hexane, ethyl acetate and dichloromethane. We initially adopted 2ꢀbromocarbazole 1a and
2ꢀbromopyridine 2a as model substrates to investigate the optimal reaction conditions. To our
disappointment, only 33% desired product 3a was obtained when the previous reported
CuIꢀcatalyzed Nꢀarylation reaction condition13a was employed using transꢀcyclohexanediamine (L1)
as ligand and K3PO4 as base in dioxane (Table 1, entry 1). Then, the reaction was performed in
toluene utilizing 1ꢀmethylꢀ1Hꢀimidazole (L2) as ligand and K2CO3 as base to form the desired
product 3a in quantitative yield with high chemoselectivity, however, six days was needed to
complete the reaction (Table 1, entry 2). The influences of other bases on the product yields were
then investigated. Both tꢀBuOK and tꢀBuONa afforded disappointed results (Table 1, entries 3 and 4).
However, it was encouraging to find that tꢀBuOLi exhibited extremely high efficiency, the reaction
could be accomplished in four hours in excellent yield with good chemoselectivity (Table 1, entry 5).
Decreasing the amount of tꢀBuOLi or replacing the ligand L2 with L1 or Lꢀproline (L3) prolonged
the reaction time without affecting yields and chemoselectivities (Table 1, entries 6ꢀ9). Next, control
experiments were examined, and no reaction was observed in the absence of CuI, revealing that it
was not a nucleophilic substitution reaction path (Table 1, entries 10ꢀ12). As expected, reducing
reaction temperature also prolonged the reaction time (Table 1, entry 13). Surprisingly, both CuBr
and CuCl demonstrated catalytic activation and chemoselectivities comparable with CuI (Table 1,
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entries 6, 14,15). Last, it was worth pointing out that this reaction could also be performed under air
without significantly decreasing the yield and chemoselectivity (Table 1, entry 18). In consideration
of the relative low cost of catalyst and ligand, the CuCl/L2 catalytic system was employed for the
next reaction scope investigation.
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Table 1. Optimization Study on the Ullmann-Type Caryl-N Cross-Coupling Reactiona
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With the optimized condition in hand, we next examined the substrate scope of
2ꢀbromocarbazole 1a with a range of 2ꢀbromopyridine derivatives (Table 2). To our delight, all the
target product 2ꢀbromoꢀ9ꢀ(2ꢀpyridinyl)ꢀ9Hꢀcarbazole derivatives 3aꢀ3l could be obtained with
excellent chemoselectivities and purities higher than 97%. The 2ꢀbromopyridine derivatives bearing
electronꢀdonating group at the either 3, 4 or 5ꢀposition underwent crossꢀcoupling efficiently,
affording the corresponding products 3bꢀ3d in excellent yields of 91ꢀ95% with the ratios of 3/4 not
less than 98:2. Incorporating electronꢀwithdrawing group, like 5ꢀbromo or 4ꢀflouro, at the the
pyridinyl ring also generated CarylꢀN crossꢀcoupling products 3e and 3f in good to excellent yields,
and no 2,5ꢀdi(2ꢀbromoꢀ9Hꢀcarbazolꢀ9ꢀyl)pyridine was observed attributed to different reaction
activities of the two bromo in 2e. In addition, all the 2ꢀbromopyrimidine 2g, 2ꢀbromopyrazine 2h and
2ꢀbromoquinoline 2i were suitable for this condition and reacted smoothly with 1a. However,
product 3j was obtained in only 24% even the reaction time was prolonged to five days with 2 mol%
CuCl/4 mol% L2 loading, due to the low activity of 1ꢀchloroisoquinoline. This result indicated that
the reaction activities of the aryl halides played a important role in this reaction, and high yield could
be achieved if 1ꢀbromoisoquinoline was employed. Interesting, 2ꢀthiazolyl and 2ꢀbenzothiazolyl
could be also incorporated successfully to the product (3k, 3l) employing corresponding bromide
substrates 2k and 2l. Importantly, because of the 3ꢀbromo at the carbazolyl ring, these functional
products could be further transformed easily and provided various tetradentate ligands for the
platinum and palladium base phosphorescent materials with tunable photophysical properties.6
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Table 2. Substrate Scope of 2-Bromopyridine/2-Bromothiazole Derivatives a
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Table 3. Substrate Scope of Carbazole Derivatives and other N
-Heterocyclesa
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Next, we investigated the scope of the carbazole substrates (Table 3). Gratifyingly, it was found
that carbazole 1b could react with various heteroaryl bromides smoothly under the optimized
reaction conditions, leading to the corresponding products incorporated with 2ꢀpyridinyl (3m, 3n),
2ꢀbenothiazolyl (3o) and 1ꢀmethylꢀbenzo[d]imidazolꢀ2ꢀyl (3p) groups in 50ꢀ93% yields in 8ꢀ26
hours. As expected, carbazole bearing bromo at 3ꢀposition or dibromo at 2,7ꢀpositions or
3,6ꢀpositions were all compatible under the reaction conditions to generate products 3qꢀ3s in 83ꢀ95%
yields. It is interesting to note that no further functionalized products like 4 were observed.
Satisfactorily, carbazole substrates containing electronꢀdonating group, such as phenyl and
3,6ꢀdiꢀtertꢀbutyl, also successfully coupled with 2ꢀbromopyridine to give the products 3t and 3u in
99% and 96% yields respectively. However, when 1,3,6ꢀtriꢀtertꢀ9Hꢀbutylcarbazole was introduced as
the reactant, product 3v was obtained in relative low yield (59%), mainly owing to the large steric
effect of the tertꢀbutyl group at the 1ꢀposition of the carbazolyl ring. In addition, we also examined
the indole and phenoxazine, both were converted into the desired products 3w and 3y in 97% and 40%
yields respectively. Furthermore, this CuClꢀcatalyzed Ullmannꢀtype CarylꢀN crossꢀcoupling reaction
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was successfully employed for the preparation of 9,9'ꢀ(2,6ꢀpyridinediyl)bisꢀ9Hꢀcarbazole 3x
(26mCPy) in 92% yield, which is wildly used as host material in OLED field.1c,3a
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To further demonstrate the synthetic practicality of this protocol, gramꢀscale experiments were
carried out under the optimized condition (Scheme 2). To our delight, coupling products 3a, 3m and
3x (26mCPy) could be prepared on large scales in 87ꢀ95% yields. More importantly, the product
purifications were achieved through filtration and recrystallization without column chromatograph
for 3a and 3x, making this protocol more suitable for largeꢀscale preparations. Furthermore, no 4a
was observed in the product 3a after recrystallization.
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Scheme 2: Gram-Scale Experiments and Application for the Synthesis of 26mCPy
To gain insight into the reaction mechanism, control experiments were subsequently performed.
2,2,6,6ꢀTetramethylꢀ1ꢀpiperidinyloxy (TEMPO) as a radical scavenger was added to the reaction
mixture of 1a and 2a under the optimized condition, the reaction was suppressed to a great extent
and the desired product 3a was obtained only in 7% yield (Scheme 3I). It was also found that 3 equiv
of TEMPO could hamper the reaction between 1b and 2a nearly completely (Scheme 3II). Moreover,
electron paramagnetic resonance (EPR) experiment was also performed using
5,5ꢀdimethyꢀ1ꢀpyrrolineꢀNꢀoxide (DMPO) as radical probe. As shown in Figure 1, two kinds of
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radical signals were detected after a reaction mixture of 1a, 2a, CuCl, L2 and tBuOLi in toluene was
heated for 1 hour at 130oC in the presence of DMPO. These results indicated that the reactions were
involvement of radicalꢀmediated pathways.
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Scheme 3: Control Experiments
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Figure 1. EPR measurement of 1a (1.0 equiv), 2a (1.1 equiv), CuCl (1 mol%), L2 (2 mol%) and tBuOLi (1.5 equiv)
in toluene in the presence of DMPO (2.2 equiv).
Scheme 4: Proposed Mechanistic Pathway
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Based on the above results and previous literature reports,20,21a,21c,23 a plausible catalytic cycle is
depicted in Scheme 4. Initially, ligand L2 coordinated with CuCl to generate CuI complex 5, which
was subsequently attacked by the intermediate 6 at the metal center to give the other CuI complex 7.
Oxidative addition might not be unfavourable because of high energy of CuIII intermediate reported
by Houk, Buchwald and coꢀworkers23d and also its steric hindrance. Then a SET reaction between the
CuI complex 7 and 2 occurred to form a caged radical pairs23d of CuII complex 8 and
2ꢀbromopyridine derivatives radical anion 9. Thereafter, 9 could fragment to generate bromide anion
and the pyridinyl radical, which reacted with 8 rapidly to deliver the corresponding final product 3
and along with the regeneration of the CuI complex 5 or 5'.
■ CONCLUSION
In summary, we have developed a facile and efficient CuClꢀcatalyzed Ullmannꢀtype CꢀN
crossꢀcoupling reaction of carbazoles and 2ꢀbromopyridine derivatives using the
1ꢀmethylꢀ1Hꢀimidazole and tꢀBuOLi as ligand and base respectively. It was found that both the
ligand and base could promote the reaction significantly. This reaction could be employed to
efficiently synthesis various of Nꢀheteroarylcarbazole derivatives in good to excellent yields under
mild conditions. Furthermore, the low costs and low loading of both catalyst and ligand rendered this
crossꢀcoupling reaction suitable for largeꢀscale preparation, and further applications of this approach
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in material science for the synthesis and development of new functional materials are ongoing in our
laboratory.
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■ EXPERIMENTAL SECTION
1
General Information. H NMR spectra were recorded at 500 MHz, and 13C NMR spectra were
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recorded at 126 MHz NMR instruments in CDCl3 solutions and chemical shifts were referenced to
residual signal of TMS or CDCl3. 1H NMR spectra were recorded with residual TMS (δ = 0.00 ppm)
as internal reference; 13C NMR spectra were recorded with CDCl3 (δ = 77.00 ppm) as internal
1
reference. The following abbreviations (or combinations thereof) were used to explain H NMR
ultiplicities: s = singlet, d = doublet, t = triplet, m = multiplet. All the new compounds were analyzed
for HRMS on an ESIꢀQTOF mass spectrometer using electrospray ionization in the positive ion
1
mode. All the ratios of 3:4 were determined by H NMR of the isolated products after
chromatography. EPR spectra were recorded at EPR Spectrometer. All chemicals and reagents were
purchased from commercial sources and used directly without further purification. Toluene was dried
with Na2SO4 over night before being used.
General Experimental Procedure for the Synthesis of Compounds 3a-3y. Carbazole derivatives 1,
heteroaryl bromide 2 (if solid), CuCl and tꢀBuOLi were added to a dry threeꢀnecked flask equipped
with a magnetic stir bar and a condenser. The flask was then evacuated and backfilled with nitrogen,
this evacuation and backfill procedure was repeated twice. Then ligand 1ꢀmethylꢀ1Hꢀimidazole L2,
heteroaryl bromide 2 (if liquid) and solvent toluene were added under nitrogen. The mixture was
o
then stirred under reflux at 130 C until the carbazole derivatives 1 was consumed completely
monitored by TLC. The reaction mixture was allowed to cool to room temperature and quenched
with a solution of Na2SO3, diluted with EtOAc, then filtered through a pad of celite and washed with
EtOAc. The organic layer was then separated, dried over Na2SO4, filtered and the filtrate was
concentrated to remove the solvent and the excess heteroaryl bromide 2 (if liquid) under reduced
pressure, and the residue was purified through column chromatography on silica gel to afforded the
desired product 3. Note: It was better to remove the heteroaryl bromide 2 (if liquid) as much as
possible from the crude product before purification, otherwise, it might result in separation problem
with the desired product in some cases.
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2-Bromo-9-(pyridin-2-yl)-9H-carbazole (3a): Following the general procedure, 2ꢀbromocarbazole 1a
(3.69 g, 15.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (1.57 mL, 16.50 mmol, 1.1 eq)
using CuCl (14.9 mg, 0.15 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (23.8 uL, 0.30 mmol, 0.02 eq)
and tꢀBuOLi (1.80 g, 22.50 mmol, 1.5 eq) in toluene (56.6 mL) for 4.8 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 1:1ꢀ0:1) afforded the title
compound as a white solid 4.70 g in 97% yield with a ratio of 3a:4a = 98:2. 3a: mp. 169.5ꢀ170.4 oC.
1H NMR (500 MHz, CDCl3): δ 7.31ꢀ7.34 (m, 2H), 7.42 (dd, J = 8.0, 1.5 Hz, 1H), 7.44ꢀ7.47 (m, 1H),
7.61 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.93ꢀ7.96 (m, 2H), 8.01 (d, J = 1.5 Hz, 1H), 8.08
(d, J = 7.5 Hz, 1H), 8.73 (dd, J = 5.0, 1.5 Hz, 1H). MS (ESI): calcd for C17H11BrN2 M+ 323.0, found
323.2. The 1H NMR data are in agreement with that previously reported.6c
2-(2-Bromocarbazol-9-yl)-9-(pyridin2-yl)-carbazole (4a) was confirmed by HPLCꢀMS spectra
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analysis. Column: C18 250×4.6mm, H2O/CH3CN=85:15ꢀ5:95,
flow 1.0 mL/min, 254 nm. (See
supporting information for the spectra) MS (ESI): calcd for C29H18BrN3 [M+H]+ 488.1, found 488.2.
1H NMR (500 MHz, CDCl3): δ 7.28ꢀ7.31 (m, 2H), 7.37ꢀ7.42 (m, 4H), 7.46 (dd, J = 8.0, 1.5 Hz, 1H),
7.50ꢀ7.53 (m, 1H), 7.56 (d, J = 1.5 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H),
7.90ꢀ7.94 (m, 1H), 8.00 (d, J = 1.0 Hz, 1H), 8.01 (s, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.0
Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H), 8.68 (ddd, J = 5.0, 2.0, 1.0 Hz, 1H).
2-Bromo-9-(3-methylpyridin-2-yl)-9H-carbazole (3b): Following the general procedure,
2ꢀbromocarbazole 1a (492.2 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromoꢀ3ꢀmethylpyridine 2b
(334.2 uL, 3.00 mmol, 1.5 eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(3.2 uL, 0.04 mmol, 0.02 eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 2.5
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/EtOAc =
40:1ꢀ1:1) afforded the title compound as a white solid 611.9 mg in 91% yield with a ratio of 3b:4b =
98:2. 3b: mp. 182.1ꢀ183.3 oC. 1H NMR (500 MHz, CDCl3): δ 2.08 (s, 3H), 7.08 (d, J = 8.0 Hz, 1H),
7.26 (d, J = 1.5 Hz, 1H), 7.27ꢀ7.31 (m, 1H), 7.38ꢀ7.42 (m, 3H), 7.83 (dd, J = 7.5, 1.0 Hz, 1H), 7.98
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(d, J = 8.0 Hz, 1H), 8.10 (d, J = 7.5 Hz, 1H), 8.58 (dd, J = 5.0, 1.5 Hz, 1H). C NMR (126 MHz,
CDCl3): δ 17.4, 110.3, 113.2, 119.5, 120.4, 120.5, 121.5, 122.5, 122.9, 123.3, 123.9, 126.4, 131.5,
140.3, 140.7, 141.0, 147.9, 149.1. HRMS (ESI): calcd for C18H14BrN2 [M+H]+ 337.0335, found
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2-Bromo-9-(4-methylpyridin-2-yl)-9H-carbazole (3c): Following the general procedure,
2ꢀbromocarbazole 1a (492.2 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromoꢀ4ꢀmethylpyridine 2c
(334.0 uL, 3.00 mmol, 1.5 eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(3.2 uL, 0.04 mmol, 0.02 eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 2.5
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/DCM =
10:1ꢀ1:1) afforded the title compound as a white solid 643.2 mg in 95% yield with a ratio of 3c:4c =
99:1. 3c: mp. 181.4ꢀ183.0 oC. 1H NMR (500 MHz, CDCl3): δ 2.47 ( s, 3H), 7.13 (d, J = 5.0 Hz, 1H),
7.29ꢀ7.32 (m, 1H), 7.39ꢀ7.46 (m, 3H), 7.72 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.97 (d, J =
1.5 Hz, 1H), 8.06 (d, J = 7.5 Hz, 1H), 8.56 (d, J = 5.0 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ 21.2,
111.1, 114.3, 119.7, 119.7, 120.2, 121.1, 121.2, 122.9, 123.1, 123.5, 123.9, 126.5, 139.7, 140.4, 149.4,
150.2, 151.3. HRMS (ESI): calcd for C18H14BrN2 [M+H]+ 337.0335, found 337.0321.
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2-Bromo-9-(5-methylpyridin-2-yl)-9H-carbazole (3d): Following the general procedure,
2ꢀbromocarbazole 1a (492.2 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromoꢀ5ꢀmethylpyridine 2d
(516.1 mg, 3.00 mmol, 1.5 eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(3.2 uL, 0.04 mmol, 0.02 eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 2.0
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/DCM =
10:1ꢀ1:1) afforded the title compound as a white solid 617.1 mg in 92% yield with a ratio of 3d:4d =
100:0. 3d: mp. 189.1ꢀ190.1oC. 1H NMR (500MHZ, CDCl3): δ 2.44 (s, 3H), 7.30 (t, J = 7.5 Hz, 1H),
7.41 (dd, J = 8.0, 1.5 Hz, 1H, 7.42ꢀ7.45 (m, 1H), 7.47 (d, J = 8.0, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.72
(dd, J = 8.5, 2.5 Hz, 1H), 7.93 (s, 1H), 7.94 (d, J = 6 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.54 (d, J =
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1.5 Hz, 1H). C NMR (126 MHz, CDCl3): δ 18.0, 111.0, 114.2, 118.7, 119.7, 120.2, 121.0, 121.2,
123.0, 123.5, 123.8, 126.5, 131.5, 139.2, 139.8, 140.5, 148.8, 149.9. HRMS (ESI): calcd for
C18H14BrN2 [M+H]+ 337.0335, found 337.0347.
2-Bromo-9-(5-bromopyridin-2-yl)-9H-carbazole (3e): Following the general procedure,
2ꢀbromocarbazole 1a (246.1 mg, 1.00 mmol, 1.0 eq) was coupled with 2,5ꢀdibromopyridine 2e
(355.3 mg, 1.50 mmol, 1.5 eq) using CuCl (1.0 mg, 0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(1.6 uL, 0.02 mmol, 0.02 eq) and tꢀBuOLi (120.1 mg, 1.50 mmol, 1.5 eq) in toluene (3.8 mL) for 5.0
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hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/DCM =
10:1ꢀ1:1) afforded the title compound as a white solid 311.6 mg in 80% yield with a ratio of 3e:4e =
100:0. 3e: mp. 193.1ꢀ194.4 oC. 1H NMR (500 MHz, CDCl3)：δ 7.33 (t, J = 7.5 Hz, 1H), 7.42 (dd, J =
8.5, 1.5 Hz, 1H), 7.46 (d, J = 7.5 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.93 (d,
J = 8.0 Hz, 1H), 7.98 (d, J = 1.5 Hz, 1H), 8.01 (dd, J = 8.5, 2.5 Hz, 1H), 8.05 (d, J = 7.5 Hz, 1H),
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8.75 (d, J = 2.0 Hz, 1H). C NMR (126 MHz, CDCl3)：δ 111.0, 114.4, 117.4, 119.9, 119.9, 120.3,
121.3, 121.6, 123.3, 123.8, 124.4, 126.7, 139.3, 140.0, 141.2, 149.9, 150.7. HRMS (ESI): calcd for
C17H11Br2N2 [M+H]+ 400.9284, found 400.9290.
2-Bromo-9-(5-fluoropyridin-2-yl)-9H-carbazole
(3f):
Following
the
general
procedure,
2ꢀbromocarbazole 1a (246.1 mg, 1.00 mmol, 1.0 eq) was coupled with 2ꢀbromoꢀ4ꢀfluoroꢀpyridine 2f
(155.0 uL, 1.50 mmol, 1.5eq) using CuCl (1.0 mg, 0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(1.6 uL, 0.02 mmol, 0.02 eq) and tꢀBuOLi (120.1 mg, 1.50 mmol, 1.5 eq) in toluene (3.8 mL) for 4.0
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/DCM =
5:1ꢀ1:1) afforded the title compound as a white solid 319.1 mg in 93% yield with a ratio of 3f:4f =
98:2. 3f: mp. 206.7ꢀ207.6 oC. 1H NMR (500 MHz, CDCl3): δ 7.05ꢀ7.08 ( m, 1H), 7.32ꢀ7.36 ( m, 2H),
7.44 (dd, J = 8.0, 1.5 Hz, 1H ), 7.45ꢀ7.48 (m, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H),
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8.05 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 1.5 Hz, 1H), 8.68 (dd, J = 8.5, 4.0 Hz, 1H). C NMR (126
MHZ, CDCl3)：δ 106.3 (d, J = 20.0 Hz), 109.7 (d, J = 17.4 Hz), 111.2, 114.7, 120.0, 120.3, 121.2,
121.8, 123.4, 123.9, 124.6, 126.8, 139.6 (d, J = 98.75 Hz), 151.8 (d, J = 8.8 Hz), 153.5 (d, J = 10.0
Hz), 168.9, 171.0. HRMS (ESI): for C17H11BrFN2 [M+H]+ calcd 341.0084, found 341.0082.
2-Bromo-9-(pyrimidin-2-yl)-9H-carbazole (3g): Following the general procedure, 2ꢀbromocarbazole
1a (492.2 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyrimidine 2g (476.9 mg, 3.00 mmol,
1.5 eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2 uL, 0.04 mmol,
0.02 eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 7.0 hours. Purification
of the crude product by flash chromatography on silica gel (eluent: PE/DCM = 5:1ꢀ1:1) afforded the
title compound as a white solid 621.7 mg in 96% yield with a ratio of 3g:4g = 100:0. 3g: mp.
o
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215.3ꢀ216.9 C. H NMR (500 MHz, CDCl3):δ 7.09 (t, J = 4.5 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H),
7.46 (dd, J = 8.0, 1.5 Hz, 1H), 7.48ꢀ7.52 (m, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 7.5 Hz, 1H),
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8.80 (d, J = 4.5 Hz, 2H), 8.82 (d, J = 8.5 Hz, 1H), 9.06 (d, J = 2.0 Hz, 1H); C NMR (126 MHz,
CDCl3): δ 116.2, 116.5, 119.4, 119.5, 120.1, 120.4, 122.6, 124.7, 125.0, 125.4, 127.0, 139.2, 139.7,
157.8, 158.8. HRMS (ESI): calcd for C16H11BrN3 [M+H]+ 324.0131, found 324.0127.
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2-Bromo-9-(pyrazin-2-yl)-9H-carbazole (3h): Following the general procedure, 2ꢀbromocarbazole 1a
(246.1 mg, 1.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyrazine 2h (135.7 uL, 1.50 mmol, 1.5 eq)
using CuCl (1.0 mg, 0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (1.6 uL, 0.02 mmol, 0.02 eq)
and tꢀBuOLi (120.1 mg, 1.50 mmol, 1.5 eq) in toluene (3.8 mL) for 7.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 5:1ꢀ1:1) afforded the title
compound as a white solid 300.6 mg in 93% yield with a ratio of 3h:4h = 98:2. 3h: mp. 207.9ꢀ208.9
oC. 1H NMR (500 MHz, CDCl3): δ 7.35 ( t, J = 7.0 Hz, 1H), 7.43ꢀ7.49 (m, 2H), 7.80 (d, J = 8.0 Hz,
1H), 7.92 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 5.0 Hz, 1H), 8.06 (s, 1H), 8.56 (d, J = 2.5 Hz, 1H), 8.67
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(dd, J = 2.0, 1.5 Hz, 1H), 9.01 (d, J = 1.5 Hz, 1H). C NMR (126 MHz, CDCl3): δ 110.9, 114.4,
120.1, 120.4, 121.3, 122.1, 123.6, 124.1, 124.9, 126.9, 139.0, 139.8, 140.5, 141.5, 143.5, 148.3.
HRMS (ESI): calcd for C16H11BrN3 [M+H]+ 324.0131, found 324.0143.
2-Bromo-9-(quinolin-2-yl)-9H-carbazole (3i): Following the general procedure, 2ꢀbromocarbazole 1a
(246.1 mg, 1.00 mmol, 1.0 eq) was coupled with 2ꢀbromoquinoline 2i (312.1 mg, 1.50 mmol, 1.5 eq)
using CuCl (1.0 mg, 0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (1.6 uL, 0.02 mmol, 0.02 eq)
and tꢀBuOLi (120.1 mg, 1.50 mmol, 1.5 eq) in toluene (3.8 mL) for 3.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 5:1ꢀ3:1) afforded the title
compound as a white solid 351.6 mg in 94% yield with a ratio of 3i:4i = 97:3. 3i: mp. 199.6ꢀ200.3 oC.
1H NMR (500 MHz, CDCl3): δ 7.34 (t, J = 7.5 Hz, 1H), 7.42ꢀ7.48 (m, 2H), 7.60 (td, J = 7.5, 1.0 Hz,
1H), 7.74 (d, J = 9.0 Hz, 1H), 7.78ꢀ7.81 (m, 1H), 7.91 (t, J = 8.5 Hz, 2H), 7.96 (d, J = 8.0 Hz, 1H),
8.08 (d, J = 7.5 Hz, 1H) , 8.17 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 1.5 Hz, 1H), 8.35 (d, J = 8.5 Hz, 1H).
13C NMR (126 MHz, CDCl3): δ 111.5, 114.8, 117.5, 119.9, 120.3, 121.3, 121.6, 123.4, 123.9, 124.3,
126.6, 126.6, 126.7, 127.6, 128.8, 130.5, 139.0, 139.6, 140.3, 147.7, 150.3. HRMS (ESI): calcd for
C21H14BrN2 [M+H]+ 373.0335, found 373.0342.
2-Bromo-9-(isoquinolin-2-y)-9H-carbazole (3j): Following the general procedure, 2ꢀbromocarbazole
1a (626.2 mg, 2.54 mmol, 1.0 eq) was coupled with 1ꢀchloroisoquinoline 2j (624.2 mg, 3.82 mmol,
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1.5 eq) using CuCl (5.0 mg, 0.05 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (8.2 uL, 0.10 mmol,
0.04 eq) and tꢀBuOLi (305.0 mg, 3.82 mmol, 1.5 eq) in toluene (9.7 mL) for 5.0 days. Purification of
the crude product by flash chromatography on silica gel (eluent: PE/DCM = 10:1ꢀ1:1) afforded the
title compound as a white solid 228.6 mg in 24% yield with a ratio of 3j:4j = 99:1. 3j: mp. 70.3ꢀ71.4
oC. 1H NMR (500 MHz, CDCl3): δ 7.09 (d, J = 8.0 Hz, 1H), 7.30ꢀ7.38 (m, 3H), 7.42 (dd, J =8.5, 1.5
Hz, 1H), 7.50ꢀ7.53 (m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.77ꢀ7.80 (m, 1H), 7.86 (d, J = 5.5 Hz, 1H),
8.02 (d, J =8.5 Hz, 2H), 8.14 (d, J =8.0 Hz, 1H), 8.64 (d, J =5.5 Hz, 1H). 13C NMR (126 MHz,
CDCl3)：δ 111.1, 114.0, 119.6, 120.3, 120.9, 121.5, 121.6, 122.9, 123.3, 123.7, 125.0, 125.5, 126.4,
127.3, 128.3, 131.2, 138.7, 141.4, 142.0, 142.3, 149.6. HRMS (ESI): calcd for C21H14BrN2 [M+H]+
373.0335, found 373.0319.
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2-Bromo-9-(thiazol-2-yl)-9H-carbazole (3k): Following the general procedure, 2ꢀbromocarbazole 1a
(492.2 mg, 2.0 mmol, 1.0 eq) was coupled with 2ꢀbromothiazole 2k (270.4 uL, 3.00 mmol, 1.5 eq)
using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2 uL, 0.04 mmol, 0.02 eq)
and tꢀBuOLi (240.2 mg, 3.0 mmol, 1.5 eq) in toluene (7.8 mL) for 11.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 3:1ꢀ1:1) afforded the title
compound as a white solid 613.2 mg in 93% yield with a ratio of 3k:4k = 100:0. 3k: mp.
189.5ꢀ190.5 oC. 1H NMR (500 MHz, CDCl3)：δ 7.27 (d, J = 4 Hz, 1H), 7.35ꢀ7.38 (m, 1H), 7.47 (dd, J
= 8.0, 1.5 Hz, 1H), 7.52 (td, J = 7.5, 1.0 Hz, 1H), 7.79 (d, J = 3.5 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H),
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8.03 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.5 Hz, 1H), 8.46 (d, J = 1.5 Hz, 1H). C NMR (126 MHz,
CDCl3): δ 112.1, 115.1, 115.9, 120.2, 120.4, 121.1, 122.5, 123.5, 124.1, 125.4, 127.2, 139.3, 140.0,
140.1, 158.5. HRMS (ESI): calcd for C15H10BrN2S [M+H]+ 328.9743, found 328.9753.
2-Bromo-9-(benzothiazol-2-yl)-9H-carbazole
(3l):
Following
the
general
procedure,
2ꢀbromocarbazole 1a (123.1 mg, 0.50 mmol, 1.0 eq) was coupled with 2ꢀbromobenzothiazole 2l
(160.6 mg, 0.75 mmol, 1.5 eq) using CuCl (0.5 mg, 0.005 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole
L2 (0.8 uL, 0.01 mmol, 0.02 eq) and tꢀBuOLi (60.0 mg, 0.75 mmol, 1.5 eq) in toluene (4.0 mL) for 2
days. Purification of the crude product by flash chromatography on silica gel (eluent: PE/EtOAc =
20:1) afforded the title compound as a white solid 149.1 mg in 79% yield with a ratio of 3l:4l = 97:3.
3l: mp. 209.1ꢀ209.9 oC. 1H NMR (500 MHz, CDCl3)：δ 7.39ꢀ7.44 (m, 2H), 7.52 (dd, J = 8.0, 1.5 Hz,
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1H), 7.54ꢀ7.58 (m, 2H), 7.90 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 7.5 Hz, 1H),
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CDCl3): δ 112.9, 116.7, 120.2, 120.6, 121.1, 121.2, 122.5, 123.0, 124.0, 124.6, 124.9, 125.9, 126.7,
127.3, 132.1, 139.1, 140.0, 150.1, 157.2. HRMS (ESI): calcd for C19H12BrN2S [M+H]+ 378.9899,
found 378.9918.
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9-(pyridin-2-yl)-9H-carbazole (3m): Following the general procedure, carbazole 1b (334.4 mg, 2.00
mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (286.1 uL, 3.00 mmol, 1.5 eq) using CuCl (2.0
mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2uL, 0.04 mmol, 0.02 eq) and tꢀBuOLi
(240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 8.0 hours. Purification of the crude product by
flash chromatography on silica gel (eluent: PE/DCM = 5:1ꢀ1:1) afforded the title compound as a
o
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white solid 455.0 mg in 93% yield. mp. 159.7ꢀ160.6 C. H NMR (500 MHz, CDCl3): δ 7.27 (ddd,
J= 8.5, 5.0, 1.0 Hz, 1H ), 7.29ꢀ7.32 (m, 2H), 7.43 (td, J= 8.5, 1.5 Hz, 2H), 7.61 (d, J = 8.0 Hz, 1H),
7.83 (d, J = 8.0 Hz, 2H), 7.88 (td, J=8.0, 2.0 Hz, 1H), 8.11 (d, J = 7.5 Hz, 2H), 8.71 (dd, J= 5.0, 1.0
Hz, 1H). The 1H NMR data are consistent with that previously reported.8d
9-(4-methylpyridin-2-yl)-9H-carbazole (3n): Following the general procedure, carbazole 1b (334.4
mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromoꢀ4ꢀmethylyridine 2d (245.0 uL, 2.20 mmol, 1.1 eq)
using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2uL, 0.04 mmol, 0.02 eq)
and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 11.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 3:1ꢀ1:1) afforded the title
1
compound as a light yellow sticky liquid 489.4 mg in 95% yield. H NMR (500 MHz, CDCl3): δ
2.44 ( s, 3H), 7.09 (d, J = 5.0 Hz, 1H), 7.30 (t, J = 7.5 Hz , 2H), 7.41ꢀ7.44 (m, 3H), 7.80 (d, J = 8.0
Hz, 2H), 8.10 (d, J = 8.0 Hz, 2H), 8.55 (d, J = 5.0 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ 21.1,
1
111.1, 119.7, 120.1, 120.7, 122.4, 124.2, 126.1, 139.6, 149.2, 149.9, 151.8. The H NMR data are
consistent with that previously reported.24
9-(benzo[d]thiazol-2-yl)-9H-carbazole (3o): Following the general procedure, carbazole 1b (41.8 mg,
0.25 mmol, 1.0 eq) was coupled with 2ꢀbromopbenzo[d]thiazole 2l (80.3 mg, 0.38 mmol, 1.5 eq)
using CuCl (0.3 mg, 0.003 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (0.4 uL, 0.005 mmol, 0.02 eq)
and tꢀBuOLi (30.0 mg, 0.38 mmol, 1.5 eq) in toluene (2.0 mL) for 26.0 hours. Purification of the
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crude product by flash chromatography on silica gel (eluent: PE/DCM = 10:1) afforded the title
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compound as a light yellow sticky liquid 58.6 mg in 78% yield. mp. 138.3ꢀ139.1 C. H NMR (500
MHz, CDCl3)：δ 7.38ꢀ7.42 (m, 3H), 7.52ꢀ7.57 (m, 3H), 7.89 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.5 Hz,
1H), 8.09 (d, J = 8.0 Hz, 2H), 8.49 (d, J = 8.5 Hz, 2H); 13C NMR (126 MHZ, CDCl3)：δ 113.3, 120.1,
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121.1, 122.3, 122.7, 124.6, 125.3, 126.6, 127.0, 132.1, 139.3, 150.3, 157.8. The C NMR data are
consistent with that previously reported.25
9-(1-methylbenzo[d]imidazol-2-yl)-9H-carbazole (3p): Following the general procedure, carbazole 1b
(83.6 mg, 0.5 mmol, 1.0 eq) was coupled with 2ꢀbromopbenzo[d]imidazole 2m (158.3 mg, 0.75
mmol, 1.5 eq) using CuCl (0.3 mg, 0.025 mmol, 0.05eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (4.0 uL, 0.05
mmol, 0.10 eq) and tꢀBuOLi (120.1 mg, 1.50 mmol, 3.0eq) in toluene (2.0 mL) for 24.0 hours.
Purification of the crude product by flash chromatography on silica gel (eluent: PE/EtOAc = 10:1)
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afforded the title compound as a white solid 74.3 mg in 50% yield. mp. 195.2ꢀ160.6 C. H NMR
(500 MHz, CDCl3): δ 3.52 (s, 3H), 7.30ꢀ7.34 (m, 4H), 7.37ꢀ7.44 (m, 5H) 7.87ꢀ7.90 (m, 1H), 8.10 (d,
J = 8.0 Hz, 2H). 13C NMR (126 MHz, CDCl3): δ 30.6, 109.7, 110.7, 120.2, 120.5, 121.4, 122.9,
123.3, 124.0, 126.6, 135.2, 140.4, 141.6, 144.6. HRMS (ESI): calcd for C20H16N3 [M+H]+ 298.1339,
found 298.1337.
3-Bromo-9-(pyridin-2-yl)-9H-carbazole (3q): Following the general procedure, 3ꢀbromoꢀ9Hꢀcarbazole
1c (492.2 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (286.1 uL, 3.00 mmol, 1.5
eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2 uL, 0.04 mmol, 0.02
eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 3.5 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 3:1ꢀ0:1) afforded the title
compound as a white solid 613.7 mg in 95% yield. mp. 191.9ꢀ192.2 oC. 1H NMR (500 MHz, CDCl3):
δ 7.29ꢀ7.33 (m, 2H), 7.45 (t, J = 8.0 Hz, 1H), 7.50 (dd, J = 8.5, 2.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H),
7.72 (d, J = 9.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.91 (td, J = 8.0, 1.5 Hz, 1H), 8.05 (d, J = 8.0 Hz,
1H), 8.21 (d, J = 2.0 Hz, 1H), 8.71 (dd, J = 4.5, 1.5 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ 111.2,
112.8, 113.7, 118.9, 120.4, 121.2, 121.5, 122.9, 123.2, 126.0, 126.9, 128.8, 138.2, 138.6, 139.8,
149.7, 151.4. HRMS (ESI): calcd for C17H12BrN2 [M+H]+ 323.0178, found 323.0178.
2,7-Dibromo-9-(pyridin-2-yl)-9H-carbazole
(3r):
Following
the
general
procedure,
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2,7ꢀdibromoꢀ9Hꢀcarbazole 1d (325.0 mg, 1.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a
(143.0 uL, 1.50 mmol, 1.5 eq) using CuCl (1.0 mg, 0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(1.6 uL, 0.02 mmol, 0.02 eq) and tꢀBuOLi (120.1 mg, 1.50 mmol, 1.5 eq) in toluene (3.8 mL) for 4.5
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/EtOAc =
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o
10:1ꢀ1:1) afforded the title compound as a white solid 332.9 mg in 83% yield. mp. 208.0ꢀ209.3 C.
1H NMR (500 MHz, CDCl3): δ 7.36 (dd, J = 7.0, 5.0 Hz, 1H), 7.42 (dd, J = 8.0, 1.0 Hz, 2H), 7.57 (d,
J = 8.0 Hz, 1H), 7.90 (d, J = 8.5 Hz, 2H), 7.93 (d, J = 0.5 Hz, 2H), 7.97 (td, J = 8.0, 1.5 Hz, 1H),
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8.74 (d, J = 4.0 Hz, 1H). C NMR (126 MHz, CDCl3): δ 114.4, 119.0, 120.2, 121.3, 122.1, 122.5,
124.5, 138.9, 140.4, 150.0, 150.7. The H NMR and 13C NMR data are consistent with that
1
previously reported.24
3,6-Dibromo-9-(pyridin-2-yl)-9H-carbazole
(3s):
Following
the
general
procedure,
3,6ꢀdibromoꢀ9Hꢀcarbazole 1e (650.0 mg, 2.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a
(286.1 uL, 3.00 mmol, 1.5 eq) using CuCl (2.0 mg, 0.02 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2
(3.2 uL, 0.04 mmol, 0.02 eq) and tꢀBuOLi (240.2 mg, 3.00 mmol, 1.5 eq) in toluene (7.6 mL) for 9.0
hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/EtOAc =
o
20:1ꢀ5:1) afforded the title compound as a white solid 738.0 mg in 92% yield. mp. 256.8ꢀ257.8 C.
1H NMR (500 MHz, CDCl3): δ 7.35 (dd, J = 7.0, 5.0 Hz, 1H), 7.53 (dd, J = 8.5, 1.5 Hz, 2H), 7.57 (d,
J = 8.0 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.95 (td, J = 7.5, 1.5 Hz, 1H), 8.17 (d, J = 1.5 Hz, 2H),
13
8.72 (d, J = 3.5 Hz, 1H). C NMR (126 MHz, CDCl3): δ 112.9, 114.1, 118.9, 121.8, 123.1, 124.9,
129.6, 138.7, 138.5, 149.8, 151.1. The H NMR and 13C NMR data are consistent with that
1
previously reported.24
3-Phenyl-9-(pyridin-2-yl)-9H-carbazole (3t): Following the general procedure, 3ꢀphenylꢀ9Hꢀcarbazole
1f (60.8 mg, 0.25 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (35.8 uL, 0.375 mmol, 1.5 eq)
using CuCl (0.5 mg, 0.005 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (0.8 uL, 0.01 mmol, 0.04 eq)
and tꢀBuOLi (40.0 mg, 0.50 mmol, 2.0 eq) in toluene (1.0 mL) for 3.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 5:1ꢀ1:1) afforded the title
compound as a white solid 79.0 mg in 99% yield. mp. 178.9ꢀ179.6 oC. 1H NMR (500 MHz, CDCl3):
δ 7.27ꢀ7.35 (m, 3H), 7.42ꢀ7.45 (m, 3H), 7.55 (dd, J = 8.5, 1.5 Hz, 1H), 7.63ꢀ7.67 (m, 3H), 7.82 (d, J
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= 8.5 Hz, 1H), 7.89 (td, J = 8.0, 2.0 Hz, 1H), 8.02 (d, J = 1.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.14
13
(d, J = 8.0 Hz, 1H), 8.72 (dd, J = 4.5, 1.5 Hz, 1H). C NMR (126 MHz, CDCl3): δ 109.7, 111.1,
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119.2, 120.2, 120.4, 120.6, 121.0, 121.3, 123.5, 124.0, 126.2, 127.0, 127.6, 128.7, 138.5, 139.7,
140.0, 140.1, 142.0, 149.7, 151.7. HRMS (ESI): calcd for C23H17N2 [M+H]+ 321.1386, found
321.1378.
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3,6-Di-tert-butyl-9-(pyridin-2-yl)-9H-carbazole
(3u):
Following
the
general
procedure,
3,6ꢀdiꢀtertꢀbutylꢀ9Hꢀcarbazole 1g (89.1 mg, 0.25 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine
2a (47.7 uL, 0.50 mmol, 2.0 eq) using CuCl (0.5 mg, 0.005 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole
L2 (0.8 uL, 0.01 mmol, 0.04 eq) and tꢀBuOLi (40.0 mg, 0.50 mmol, 2.0 eq) in toluene (1.0 mL) for
29.0 hours. Purification of the crude product by flash chromatography on silica gel (eluent: PE/DCM
o
= 10:1ꢀ1:1) afforded the title compound as a white solid 85.4 mg in 96% yield. mp. 217.0ꢀ217.9 C.
1H NMR (500 MHz, CDCl3): δ 1.46 (s, 18H), 7.21ꢀ7.23 (m, 1H), 7.49 (dd, J = 8.5, 2.0 Hz, 2H), 7.62
(d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.87 (td, J = 8.0, 2.0 Hz, 1H), 8.11 (d, J = 2.0 Hz, 2H),
8.68 (dd, J = 5.0, 1.5 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ 31.9, 34.7, 110.7, 116.1, 118.3, 120.5,
123.9, 124.4, 137.9, 138.2, 143.8, 149.5, 152.2. HRMS (ESI): calcd for C25H29N2 [M+H]+ 357.2325,
found 357.2326.
1,3,6-Tri-tert-butyl-9-(pyridin-2-yl)-9H-carbazole (3v): Following the general procedure,
1,3,6ꢀtriꢀtertꢀbutylꢀ9Hꢀcarbazole 1h (167.8 mg, 0.50 mmol, 1.0 eq) was coupled with
2ꢀbromopyridine 2a (95.4 uL, 1.00 mmol, 2.0 eq) using CuCl (2.5 mg, 0.025 mmol, 0.05 eq),
1ꢀmethylꢀ1Hꢀimidazole L2 (4.0 uL, 0.05 mmol, 0.1 eq) and tꢀBuOLi (80.1 mg, 1.00 mmol, 2.0 eq) in
toluene (2.0 mL) for 29.0 hours. Purification of the crude product by flash chromatography on silica
gel (eluent: PE/DCM = 10:1ꢀ1:1) afforded the title compound as a white solid 121.5 mg in 59%. The
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recovery of 1,3,6ꢀtriꢀtertꢀbutylꢀ9Hꢀcarbazole was 42.5 mg in 25% yield. 3v: mp. 211.4ꢀ212.7 C. H
NMR (500 MHz, CDCl3): δ 1.18 (s, 9H), δ 1.41 (s, 9H), δ 1.46 (s, 9H), 7.13 (d, J = 8.0 Hz, 1H),
7.24ꢀ7.27 (m, 2H), 7.34 (dd, J = 8.5, 2.0 Hz, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.72 (td, J = 8.0, 2.0 Hz,
1H), 7.92 (d, J = 2.0 Hz, 1H), 7.99 (d, J = 1.5 Hz, 1H), 8.62 (dd, J = 5.0, 1.5 Hz, 1H). 13C NMR (126
MHz, CDCl3): δ 31.6, 31.9, 31.9, 34.6, 34.8, 35.4, 112.1, 114.0, 115.6, 122.2, 122.3, 123.8, 124.5,
125.7, 129.0, 137.0, 138.0, 139.7, 143.9, 144.4, 144.6, 149.2, 158.2. HRMS (ESI): calcd for
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C29H37N2 [M+H]+ 413.2951, found 413.2935.
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1-(pyridin-2-yl)-1H-indole (3w): Following the general procedure, indole 1i (117.2 mg, 1.00 mmol,
1.0 eq) was coupled with 2ꢀbromopyridine 2a (143.0 uL, 1.50 mmol, 1.5 eq) using CuCl (1.0 mg,
0.01 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (1.6 uL, 0.02 mmol, 0.02eq) and tꢀBuOLi (120.1
mg, 1.50mmol, 1.5 eq) in toluene (4.0 mL) for 4.0 hours. Purification of the crude product by flash
chromatography on silica gel (eluent: PE/DCM = 10:1ꢀ3:1) afforded the title compound as a yellow
liquid 188.4 mg in 97% yield. 1H NMR (500 MHz, CDCl3): δ 6.71 (d, J = 3.5 Hz, 1H), 7.16 (dd, J =
7.0, 5.0 Hz, 1H), 7.20 (dd, J = 7.5 Hz, 1H), 7.28ꢀ7.31 (m, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.66 (d, J =
8.0 Hz, 1H), 7.72 (d, J = 3.5 Hz, 1H), 7.80ꢀ7.83 (m, 1H), 8.20 (d, J = 8.5 Hz, 1H), 8.57 (dd, J = 5.5,
1.5 Hz, 1H). The 1H NMR data are consistent with that previously reported.22
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9,9'-(2,6-Pyridinediyl)bis-9H-carbazole (3x, 26-mCPy): Following the general procedure, carbazole 1b
(735.7 mg, 4.4 mmol, 2.2 eq) was coupled with 2,6ꢀdibromopyridine 2n (473.8 mg, 2.00 mmol, 1.0
eq) using CuCl (4.0 mg, 0.04 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (6.4 uL, 0.08 mmol, 0.04
eq) and tꢀBuOLi (480.3 mg, 6.0 mmol, 3.0 eq) in toluene (8.0 mL) for 3.0 hours. Purification of the
crude product by flash chromatography on silica gel (eluent: PE/DCM = 1:1) afforded the title
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compound as a yellow liquid 751.3 mg in 92% yield. mp. 243.1ꢀ245.3 C. H NMR (500 MHz,
CDCl3): δ 7.31ꢀ7.34 (m, 4H), 7.39ꢀ7.42 (m, 4H), 7.60 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 8.0 Hz, 4H),
8.08 (t, J = 8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz, 4H). 13C NMR (126 MHz, CDCl3): δ 111.9, 114.9, 120.1,
1
121.2, 124.5, 126.3, 139.5, 140.3, 151.5. The H NMR data are consistent with that previously
reported.3a
10-(Pyridin-2-yl)-10H-phenoxazine (3y): Following the general procedure, phenoxazine 1j (183.2 mg,
1.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (190.7 uL, 2.00 mmol, 2.0 eq) using CuCl
(2.0 mg, 0.02 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (3.2 uL, 0.04 mmol, 0.04 eq) and tꢀBuOLi
(160.1 mg, 2.00 mmol, 2.0 eq) in toluene (3.8 mL) for 24.0 hours. Purification of the crude product
by flash chromatography on silica gel (eluent: PE/DCM = 10:1ꢀ1:1) afforded the title compound as a
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white solid 104.1 mg in 40% yield. mp. 179.3ꢀ180.4 C. H NMR (500 MHz, CDCl3): 6.42 (dd, J =
7.5, 1.5 Hz, 2H), 6.69ꢀ6.72 (m, 2H), 6.75ꢀ6.80 (m, 4H), 7.28 (ddd, J = 7.5, 5.0, 1.0 Hz, 1H), 7.36 (d,
13
J = 8.0 Hz, 1H), 7.84 (td, J = 7.5, 2.0 Hz, 1H), 8.68 (dd, J = 5.0, 1.5 Hz, 1H). C NMR (126 MHz,
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CDCl3): δ 115.9, 116.0, 122.0, 122.1, 122.8, 123.2, 132.8, 139.5, 145.7, 150.4, 153.9. HRMS (ESI):
calcd for C17H13N2O [M+H]+ 261.1022, found 261.1015.
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Procedure for the Gram-Scale Synthesis of 3a. Following the general procedure, 2ꢀbromocarbazole
1a (14.77 g, 60.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (8.58 mL, 90.00 mmol, 1.5
eq) using CuCl (60.0 mg, 0.60 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (95.1 uL, 1.20 mmol,
0.02 eq) and tꢀBuOLi (7.20 g, 90.00 mmol, 1.5 eq) in toluene (240 mL) for 5.0 hours. The reaction
mixture was allowed to cool to room temperature, quenched with a solution of Na2SO3 (100 mL),
then filtered through a pad of celite and washed with EtOAc three times. The organic layer was then
separated and the aqueous layer was extracted with EtOAc three times (100 mL×3). The combined
organic layer was washed with water (50 mL), dried over Na2SO4, filtered and the filtrate was
concentrated in vacuo. The residue was dissolved in DCM (100 mL) and silica gel (4.0 g) was added,
the mixture was stirred under reflux for 3.0 hours to removed the little colored impurities. The
reaction mixture was allowed to cool to room temperature and filtered, washed with DCM. The
filtrated was concentrated under reduced pressure to remove the solvent and the excess
2ꢀbromopyridine. The residue was recrystallized in PE/DCM (40 mL/5 mL) to afford the desired
product as a white solid 16.77 g in 87% yield. The 1H NMR shown that the product did not contain
4a. The mother liquor was concentrated and the residue was purified through column
chromatography on silica gel using PE/DCM = 3:1ꢀ1:1 as eluent to afford product as a white solid
1.07g in 5% yield. And the total yield was 92%.
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Procedure for the Gram-Scale Synthesis of 3m. Following the general procedure, carbazole 1b
(10.03 g, 60.00 mmol, 1.0 eq) was coupled with 2ꢀbromopyridine 2a (8.58 mL, 90.00 mmol, 1.5 eq)
using CuCl (60.0 mg, 0.60 mmol, 0.01 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (95.1 uL, 1.20 mmol, 0.02 eq)
and tꢀBuOLi (7.21 g, 90.00 mmol, 1.5 eq) in toluene (240 mL) for 9.0 hours. Cooled down to room
temperature, quenched with a solution of Na2SO3 (100 mL), then filtered through a pad of celite and
washed with EtOAc three times. The organic layer was then separated and the aqueous layer was
extracted with EtOAc three times (100 mL×3). The combined organic layer was washed with water
(50 mL) and then dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue
was dissolved in DCM (100 mL) and silica gel (4.0 g) was added, the mixture was stirred under
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reflux for 3.0 hours to removed the little colored impurities. The reaction mixture was allowed to
cool to room temperature and filtered, washed with DCM. The filtrated was concentrated under
reduced pressure to remove the solvent and the excess 2ꢀbromopyridine. The residue was
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recrystallized in PE/EtOAc (90 mL/10 mL) to afford the desired product as a white solid 8.61 g in 59%
yield. The mother liquor was concentrated and the residue was purified through column
chromatography on silica gel using PE/DCM = 5:1ꢀ1:1 as eluent to afford product as a white solid
5.48 g in 37% yield. And the total yield was 96%.
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Procedure for the Gram-Scale Synthesis of 3x (26-mCPy). Following the general procedure,
carbazole 1b (22.07 g, 132.00 mmol, 2.2 eq) was coupled with 2,6ꢀdibromopyridine 2n (14.21 g,
60.00 mmol, 1.0 eq) using CuCl (120.0 mg, 1.20 mmol, 0.02 eq), 1ꢀmethylꢀ1Hꢀimidazole L2 (190.2
uL, 2.40 mmol, 0.04 eq) and tꢀBuOLi (14.41 g, 180.00 mmol, 3.0 eq) in toluene (240 mL) for 10.0
hours and the product precititated. The reaction mixture was allowed to cool to room temperature
and diluted with CHCl3, then filtered through a pad of silica gel to remove the salt, washed with
CHCl3 several times to collect all the product. The filtrated was concentrated under reduced pressure
o
to remove the solvent. The residue was stirred in MeOH/toluene (100 mL/34 mL) at 75 C for 2
hours, then cooled to room temperature slowly and was kept stirring over night. Filtered and washed
with nꢀhexane to afford the desired product as a white solid 23.15 g in 94% yield.
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publication website.
13
1H NMR and C NMR for all the compounds, HPLCꢀMS spectra for 3a and its impurity, and the
EPR Experiment.
■ AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: guijieli@zjut.edu.cn
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGEMENTS
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The authors thank the Scientific Research Fund from Zhejiang University of Technology (Grant No.
G5817101102), National Natural Science Foundation of China (Grant Nos. 21276006, 21476270 and
21602198) and " Qianjiang Talents Plan" (Grant No. QJD1602017) for financial support.
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