CuCl-Catalyzed Hydroxylation of N-Heteroarylcarbazole Bromide: Approach for the Preparation of N-Heteroarylcarbazolyl Phenols and Its Application in the Synthesis of Phosphorescent Emitters

Article abstract of DOI:10.1021/acs.joc.7b01568

An efficient and practical CuCl-catalyzed hydroxylation of N-heteroarylcarbazole bromide for the preparation of N-heteroarylcarbazolyl phenols with a broad functional group scope and yield up to 98% was developed. It was found that both the ligand and base played critical roles in the functional group transformation and that different products could be generated by changing the base for some substrates. t-BuONa was demonstrated to be a better base for the catalytic system to avoid the formation of the ether byproduct. In addition, this approach was suitable for large-scale preparation and was successfully applied in the gram-scale synthesis of phosphorescent emitters PtNON and PdNON, demonstrating its practicability in organic synthesis methodology and materials science. Furthermore, the X-ray crystal diffraction, DFT calculations, and photophysical properties were also investigated for the metal complexes.

Full text of DOI:10.1021/acs.joc.7b01568

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Article
CuCl-Catalyzed Hydroxylation of N-Heteroarylcarbazole Bromide:
Approach for the Preparation of N-Heteroarylcarbazolyl Phenols
and Its Application in the Synthesis of Phosphorescent Emitters
Guijie Li, Xiangdong Zhao, Kun Fang, Jian Li, and Yuanbin She
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01568 • Publication Date (Web): 01 Aug 2017
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CuClꢀCatalyzed Hydroxylation of NꢀHeteroarylcarbazole Bromide: Approach for the Preparation of
NꢀHeteroarylcarbazolyl Phenols and Its Application in the Synthesis of Phosphorescent Emitters
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Guijie Li,† Xiangdong Zhao,† Kun Fang,† Jian Li,‡ Yuanbin She*†
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†State Key Laboratory Breeding Base of Green ChemistryꢀSynthesis Technology, College of
Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R.
China.
‡Department of Materials Science and Engineering, Arizona State University, Tempe, AZ 85284,
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USA
Eꢀmail: guijieli@zjut.edu.cn; sheyb@zjut.edu.cn
An efficient and practical CuClꢀcatalyzed hydroxylation of Nꢀheteroarylcarbazole bromide for the
preparation of Nꢀheteroarylcarbazolyl phenols with broad functional group scope and yield up to
98% was developed. It was found that both the ligand and base played critical roles in the functional
group transformation, and different products could be generated by changing the base for some
substrates. tꢀBuONa was demonstrated to be a better base for the catalytic system to avoid the
formation of the ether byproduct. In addition, this approach was suitable for largeꢀscale preparation
and was successfully applied in gramꢀscale synthesis of phosphorescent emitters PtNON and
PdNON, demonstrating its practicability in organic synthesis methodology and material science.
Furthermore, Xꢀray crystal diffraction, DFT calculation and photophysical properties were also
investigated for the metal complexes.
■ INTRODUCTION
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Hydroxyl carbazoles are very important synthetic intermediates and structural
constituents for numerous pharmaceuticals, materials and natural products.1ꢀ7 Moreover,
Nꢀheteroarylcarbazolyl phenols and their derivatives are wildly utilized in the organic
lightꢀemitting diodes (OLEDs) fields, especially, in the synthesis of phosphorescent
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t
etradentate platinum(II) complexes (Figure 1) 8ꢀ13, which have attracted significant attention
from both academia and industry owing to their promising commercial application for energy
efficient fullꢀcolour displays and solidꢀstate lighting.14ꢀ17 However, many challenges still
remain in the development of such phosphorescent emitters to meet commercial requirements.
One of which is the efficient and economical largeꢀscale synthesis of the complexes to
promote their further development in OLED technology.
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Pt
O
Pt
O
Pt
O
Pt
O
PtNON
PtON7-tBu
PtON7-dtb
PtON1-tBu
stable blue emitter
pure blue emitter
pure blue emitter
deep blue emitter
Chem. Mater., 2016, 28, 3276
Adv. Opt. Mater., 2015, 3, 390
Adv. Mater., 2014, 26, 7116
Adv. Mater., 2014, 26, 7116
N
N
N
N
N
N
N
N
N
N
N
N
N
Pt
N
N
Pt
Pt
Pt
O
O
O
O
PtON6-tBu
PtON11Me
red emitter
Org. Electron., 2014, 15, 1862
PtON1
blue emitter
Angew. Chem., Int. Ed.,
2013, 52, 6753
PtON7
deep blue emitter
pure blue emitter
Angew. Chem., Int. Ed.,
2013, 52, 6753
Adv. Mater., 2014, 26, 7116
Figure 1. Selected tetradentate platinumꢀbased phosphorescent emitters containing
2ꢀoxyꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazole skeleton
Generally, hydroxyl group can be introduced into molecules through nucleophilic
substitution of activated aryl halides18, borylation/oxidation19ꢀ21 or directly hydroxylation of
aryl halide. The first two routes usually suffer from substrate limitation or complicated
operation process.22 Thanks to excellent work of Buchwald23,24, Beller25,26, You27, Ma28ꢀ30 and
other groups29,30, remarkable progress has been made for the Pdꢀ and Cuꢀcatalyzed
hydroxylation of aryl halide.31ꢀ32 However, the synthetic application of the Pdꢀcatalyzed
hydroxylation of aryl halide was limited, particularly for largeꢀscale preparation due to the
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high cost of Pd catalysts and phosphine ligands. Consequently, the development of the
Cuꢀcatalyzed hydroxylation attracted plenty of attention, and it had been demonstrated that a
variety of bidentate ligands could successfully promote the transformation in recent
years.27ꢀ30,34ꢀ46 Especially, Ma and coꢀworkers recently developed a CuIꢀmediated
hydroxylation of (hetero)aryl halides under mild conditions promoted by a bisꢀoxalamide
ligand and realized direct hydroxylation of aryl chlorides.28 In addition, 2ꢀhydroxylcarbazoles
could be prepared through intermolecular ringꢀclosure via nitrene intermediate47,
Pd(II)ꢀcatalyzed CꢀH bond activation48, or Pummerer reaction of sulfinyl compounds49.
However, to the best of our knowledge, the Cuꢀcatalyzed hydroxylation of
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Nꢀheteroarylcarbazole bromide to synthesis
Nꢀheteroarylcarbazolyl phenols is not reported.
■ RESULTS AND DISCUSSION
N
ꢀheteroarylcarbazolyl phenols are critical intermediates and wildly used for the
synthesis of the
ꢀ(pyridinꢀ2ꢀyl)carbazole based phosphorescent emitters,8ꢀ13 like PtNON9,50
PtON7ꢀdtb12, all of which demonstrated inspiring device performances. So far, mainly two
synthetic routes were employed to make the ꢀheteroarylcarbazolyl phenols (See Figure S2).
N
,
N
One route is to utilize 2ꢀnitroiodobenzene and 4ꢀmethoxyphenylboronic acid as starting
materials through Pd(PPh3)4ꢀcatalyzed CꢀC bond coupling, P(OEt)3ꢀpromoted cyclization
o
reaction at 165 C, Pd2(dba)3ꢀinduced CꢀN bond crossꢀcoupling, and demethylation reaction
o
in the presence of excess pyridine hydrochloride at 200 C.11 The other is via hydroxyl
protection of expensive 2ꢀhydroxylcarbazole (about $110/5g), Pd2(dba)3ꢀcatalized CꢀN bond
crossꢀcoupling, and removal of protective group. Both of these routes have many
disadvantages, such as the use of expensive Pd catalysts and phosphine ligands, high reaction
temperature, or employing expensive starting material, which limited their application in the
field of material science. Recently, we developed an efficient and economical approach to
synthesize 2ꢀbromoꢀ
Nꢀheteroarylcarbazole derivatives employing inexpensive CuCl,
Nꢀmethylimidazole and 2ꢀbromocarbazole (about $740/1kg) as catalyst, ligand and starting
material
respectively.51
We
envision
that
direct
hydroxylation
of
the
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2ꢀbromoꢀ
Nꢀheteroarylcarbazole derivatives catalyzed by cheap copper salts will benefit to
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their application in organic synthesis and material field.
Table 1. Optimization of the Reaction Conditionsa
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5 mol% catalyst
5 mol% ligand
2.1 equiv base
N
N
N
N
N
N
+
OH
O
Br solvent/H2O (4:1)
temp., time
2
3
1a
2a
entrya
ligande
yieldb/2a yieldb/3
time
catalyst
base
solvent temp.
1
2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
CuI
L1
LiOH.H2O DMSO 100 oC 24 h
LiOH.H2O DMSO 100 oC 24 h
NRc
NR
NR
L2
LiOH.H2O DMSO 100 oC
3
24 h
L3
L4
L5
LiOH.H2O DMSO 100 oC
LiOH.H2O DMSO 100 oC
LiOH.H2O DMSO 100 oC
NR
NR
NR
4
24 h
24 h
24 h
24 h
5
6
L6
LiOH.H2O DMSO 100 oC
LiOH.H2O DMSO 100 oC 24 h
7
L7
NR
NR
NR
8
L8
LiOH.H2O DMSO 100 oC
9
24 h
L9
LiOH.H2O DMSO 100 oC
LiOH.H2O DMSO 100 oC
LiOH.H2O DMSO 100 oC
NR
NR
NR
10
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12
13
14
15
16
L10
L11
L12
L13
L14
L14
L14
L14
L14
L14
L14
24 h
24 h
24 h
24 h
12 h
24 h
24 h
48 h
24 h
24 h
24 h
24 h
24 h
LiOH.H2O DMSO 100 oC
NR
DMSO 100 oC
DMSO 100 oC
DMSO 100 oC
LiOH.H2O
LiOH.H2O
LiOH.H2O
LiOH.H2O
LiOH.H2O
LiOH.H2O
LiOH.H2O
trace
trace
trace
trace
trace
trace
79%
80%
80%
66%
40%
100 oC
100 oC
100 oC
17d
18
Cu(OAc)2
DMSO
DMSO
DMF
.
CuSO4 5H2O
19
20
CuCl
CuCl
CuCl
CuCl
43%
trace
o
Dioxane
DMSO
DMSO
100 C
110 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
21
22
L14 NaOH
L14 KOH
88%
83%
30%
trace
trace
K3PO4
K2CO3
Cs2CO3
23
24
25
26
CuCl
L14
L14
L14
DMSO
DMSO
DMSO
DMSO
DMSO
24 h
24 h
24 h
24 h
24 h
24 h
8%
6%
8%
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
25%
65%
88%
95%
92%
78%
88%
L14 t-BuOLi
L14 t-BuONa
27
28
29
30
t-BuOK
DMSO 110 oC
DMSO 110 oC 24 h
DMSO 110 oC 24 h
L14
L14 MeONa
L14 EtONa
trace
aAll reactions wre conducted on a scale of 0.5ꢀ1.0 mmol unless otherwise
noted. bIsolated yields after chromatography. c NR = no reaction. dReaction
was conducted on a scale of 5.0 mmol. e
NH2
N
COOH
COOH
N
N
R
N
H
L6
N
N
N
N
N
COOH
O
NH2
L7
L8
R = H, L3
R = Me, L4
L1
L2
L5
O
O
HO
O
O
OH
H
N
Ph
HO
R
R
N
O
OR
R = H, L9
OH
H
R = Me, L11
R = t-Bu, L12
Ph
O
N
L13
H
L14
R = Na, L10
2
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Based on this idea, our initial investigations focused on the substrate of
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2ꢀbromoꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazole 1a and catalyst CuCl in a mixture of DMSO and H2O,
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where 1a could be prepared in largeꢀscale without purification through column
chromatography according our previous reported method.51 No reaction was observed
employing L1, (±)ꢀtransꢀcyclohexaneꢀ1,2ꢀdiamine L2, amino acid L3 and L4 as ligands
(Table 1, entries 1ꢀ4), all of which could effectively promote CꢀN bond crossꢀcoupling51ꢀ55. It
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, L ,
has been well demonstrated that picolinic acid L530 ꢀproline L643, 2,2'ꢀbipyridine L7
1,10ꢀphenanthroline L827,30 ꢀisoascorbic acid L941 and its salt L1034,41, 1,3ꢀdione L1146 and
,
D
L1246 could serve as ligands to promote hydroxylation of aryl halide, to our disappointment,
all of them did not work for this transformation (Table 1, entries 5ꢀ12), which was owing to
the strong coordination ability or the pyridiyl group of the substrate 1a to lead to deactivation
of
2ꢀhydroxylꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ9
byproduct Bis[2ꢀ( ꢀ(2ꢀpyridinyl)carbazolyl)] ether
LiOH·H2O employing 'ꢀbis(4ꢀhydroxyꢀ2,6ꢀdimethylphenyl)ꢀoxalamide L14 as ligand,
catalysts.
It
was
encouraging
ꢀcarbazole 2a could be obtained in 79% yield with trace of
in the presence of 2.1 equiv of
to
find
that
desired
product
H
N
3
N,N
which was developed by Ma's group28 (Table 1, entry 14). Then, the effects of various copper
salts, bases and solvents on the reaction were also investigated. Both CuBr and CuI displayed
efficient catalytic activities similar with that of CuCl, while Cu(OAc)2 and CuSO4·5H2O gave
lower yields (Table 1, entries 15ꢀ18). 2a could be obtained in moderate yield if the reaction
was carried out in DMF/H2O, however, nearly no product was obtained using dioxane/H2O as
solvent, due to the poor solubility of 1a and ligand L14 in dioxane/H2O (Table 1, entries 19,
20). Importantly, we found that base also played critical roles in the transformation. Thus,
strong bases KOH and MeONa showed similar efficiency with LiOH·H2O, however,
inexpensive NaOH was superior to LiOH·H2O (Table 1, entries 21, 22 and 29). Notably,
exclusive product 2a could be obtained with high yields of 88ꢀ95% employing
ꢀBuONa or ꢀBuOK as base (Table 1, entries 26ꢀ28, 30). This is probably due to their
stronger ability for the deprotonation of the ligand and the ꢀBuOH in suit to inhibit the
coupling of resultant 2a with 1a. However, weak bases would induce lower yields with
significant byproduct (Table 1, entries 23ꢀ25).
tꢀBuOLi,
t
t
t
3
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Table 2. Substrate Scope of CuCl-Catalyzed Hydroxylation
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5
6
7
8
R1
R1
5 mol% CuCl
5 mol% L14
N
N
2.1 equiv basea
N
N
OH
DMSO/H2O
temp., time
yieldb
Br
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1a - 1l
2a - 2l
N
N
N
N
N
N
N
N
OH
OH
OH
OH
2a
2b
2c
2d
condition A: 12 h, 79%
condition B: 24 h, 88%
condition C: 24 h, 95% condition C: 24 h, 98%
condition A: 24 h, 89%
condition B: 24 h, 91%
condition A: 24 h, 94%
condition B: 24 h, 78%
condition C: 24 h, 88%
condition A: 24 h, 83%
condition B: 24 h, 86%
condition C: 24 h, 90%
N
N
N
N
N
N
N
N
N
N
OH
OH
OH
OH
2g
2e
2f
2h
condition A: 24 h, 75%
condition A: 48 h, 44%
condition A: 24 h, 74%
condition A: 24 h, 88%
condition B: 24 h, 38%c condition B: 24 h, 73%
condition B: 24 h, 26%d condition B: 24 h, 57%
condition C: 24 h, 0%e
F3C
condition C: 24 h, 98%
condition C: 24 h, 95%
condition C: 24 h, 91%
N
S
N
N
N
N
N
OH
OH
2j
OH
2k
2i
condition A: 36 h, 81%f
condition B: 36 h, 57%
condition C: 24 h, 91%
condition A: 24 h, 86%
condition B: 24 h, 97%
condition C: 24 h, 92%
condition A: 24 h, 75%
condition B: 24 h, 91%
condition C: 24 h, 91%
aCondition A: LiOH.H2O as base at 100 oC; condition B: NaOH as base at 110 oC; condition C: tꢀBuONa as base
at 110 oC. bIsolated yield. c20% 1e was recycled. d74% 2ꢀbromocarbazole was obtained. e99% 2ꢀbromocarbazole
was obtained. fAt 110 oC.
Having the optimized conditions in hand, we next turned our attention to examine the
substrate scope of the
and the bisꢀoxalamide ligand L14 were used with three different bases, LiOH·H2O, NaOH,
and ꢀBuONa (Table 2). To our delight, electronꢀdonating group ꢀMe could be well tolerated,
whether it was on 3ꢀ, 4ꢀ or 5ꢀposition of pyridyl ring, and desired products 2b 2d could be
achieved in high yields of 78ꢀ98%. For the substrate of
Nꢀheteroarylcarbazole bromide derivatives. The cheaper CuCl catalyst
t
ꢀ
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2ꢀbromoꢀ9ꢀ(quinolinꢀ2ꢀyl)ꢀ9
H
ꢀcarbazole 1e, only 44% and 38% yields were obtained using
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8
LiOH·H2O and NaOH as base respectively, however,
to undergo smoothly to give 2e with 98% yield. Similar result was also observed for substrate
containing 1ꢀisoquinolinyl group 1f, and ꢀBuONa was proved to be a better base to give 2f in
95% yield. For pyrimidineꢀbased substrate 1g, to our surprise, strong base ꢀBuONa would
tꢀBuONa enabled the hydroxylation
9
t
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t
induce it to decompose completely, which involved nucleophilic substitution on 1ꢀposition of
pyrimidine, and 2ꢀbromocarbazole was separated in quantitative yield. However, desired
product 2g could be obtained in 75% employing LiOH·H2O as base. Gratifyingly,
incorporating other heteroaryl group, such as 2ꢀpyrazinyl or 2ꢀthiazolyl, into substrates also
generated desired product 2h and 2i in excellent yields except adopting NaOH as base for 1h
.
Furthermore, substrate bearing a bromide on 3ꢀposition of carbazole ring or a strong
electronꢀwithdrawing group ꢀCF3 on 4ꢀposition of pyridyl ring could also be hydroxylated
efficiently to give 2j or 2k in high yields within expectations. Importantly, these obtained
Nꢀheteroarylcarbazolꢀ2ꢀol derivatives can be as key intermediates for synthesis of platinumꢀ
and palladiumꢀbased phosphorescent materials, and provide various modified tetradentate
ligands, which enable the materials to have tunable photophysical properties.8ꢀ13,15,17
Given the above encouraging results, substrates with two halides were also explored.
We were pleased to see that this CuClꢀbased catalytic system also worked well for various
N
ꢀheteroarylcarbazole derivatives bearing two halides on heteroaryl or carbazolyl rings
(Scheme 1). For example, 2ꢀbromoꢀ9ꢀ(4ꢀfluoropyridinꢀ2ꢀyl)ꢀ9 ꢀcarbazole 1l could be
selectively hydroxylated from fluorine to form 2l remaining bromide unchanged with
LiOH·H2O or ꢀBuONa as base in 27% and 55% yields respectively (eqs 1,2). Similar
H
t
chemoselectivity was also observed for the chlorine substrate 1m and 72% of 2l was obtained
using NaOH as base. It is worth mentioning that 2l could be also separated in 50% yield
without CuCl and L14, indicating that this reaction was involvement of nucleophilic
substitution mechanism, owing to high activity of the chlorine on the 4ꢀposition of the pyridyl
ring (eq 3). Interestingly, the remaining bromide of 2l could be further hydroxylated to give
4a in 69% in the presence of 4.2 equiv
t
ꢀBuONa (eq 3). These reactions demonstrated that the
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halides on the substrates could be hydroxylated separately through reaction condition control,
making the functional group transformations to be more useful in organic synthesis.
Furthermore, both bromides could be hydroxylated for 1n in the presence of 10 mol% CuCl,
9
10 mol% L14 and 4.2 equiv tꢀBuONa to give 63% of 4b (eq 5). Interestingly, symmetric
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substrate 1o could be also selectively hydroxylated through controlling the strength of the
base to afford 2ꢀhydroxyl product 2m with LiOH·H2O and 2,7ꢀdihydroxyl product 4c was not
observed even reaction time was prolonged to 48 h (eq 6). However, 4c could be formed
using
2,7ꢀdibromoꢀ9ꢀ(pyrimidinꢀ2ꢀyl)ꢀ9
base to form 62% of 2,7ꢀdihydroxyl product 4d (eq 9), whose chemoselectivity was much
different with 1o These results revealed that the reaction was influenced significantly by the nature
t
ꢀBuONa as base in 81% yield (eq 8). It is worth pointing out that the conversion of
H
ꢀcarbazole 1p could undergo smoothly with LiOH·H2O as
.
of the substrates, and the choice of base was also critical to the successful transformation.
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Scheme 1. CuCl-Catalyzed Selective Hydroxylation
5
F
HO
6
7
8
5 mol% CuCl
5 mol% L14
2.1 equiv base
N
N
N
N
Br
Br
9
DMSO/H2O
temp., time, yield
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2l
1l
Condition A: LiOH.H2O, 100 oC, 24 h; 2l, 27%
Condition C: t-BuONa, 110 oC, 24 h; 2l, 55%
(1)
(2)
Cl
HO
5 mol% CuCl
5 mol% L14
5 mol% CuCl
N
N
5 mol% L14
4.2 equiv t-BuONa
2.1 equiv NaOH
N
N
2l
(3)
Br
OH
DMSO/H2O
110 oC, 24 h, 72%
(50%, withou CuCl and L14)
DMSO/H2O
110 oC, 24 h
69%
4a
1m
10 mol% CuCl
10 mol% L14
4.2 equiv t-BuONa
(4)
1m
4a, 35%
+
2l, 48%
DMSO/H2O
110 oC, 24 h
Br
OH
10 mol% CuCl
10 mol% L14
4.2 equiv t-BuONa
N
N
N
N
(5)
Br
OH
DMSO/H2O
110 oC, 24 h
63%
1n
4b
10 mol% CuCl
10 mol% L14
4.2 equiv LiOH.H2O
N
N
N
N
(6)
OH
Br
DMSO/H2O
100 oC, 48 h
49%
Br
Br
1o
2m
10 mol% CuCl
10 mol% L14
4.2 equiv base
N
N
1o
HO
OH
DMSO/H2O
Temp., time
yield
4c
Condition B, NaOH, 110 oC, 24 h; 4c, 24%
Condition C, t-BuONa, 110 oC, 24 h; 4c, 81%
(7)
(8)
10 mol% CuCl
10 mol% L14
4.2 equiv LiOH.H2O
N
N
N
N
N
N
(9)
HO
OH
DMSO/H2O
100 oC, 24 h
62%
Br
Br
1p
4d
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To further demonstrate the practical utility of this protocol, gramꢀscale experiment was carried out
under the optimized conditions to give 2a in good to excellent yields (Scheme 2, eq 1), which was
greatly superior to the previously reported route50 (see Figure S2). Moreover, PtNON, a highly
stable and efficient platinumꢀbased phosphorescent emitter with sky blue emission9, was effectively
prepared via metallization with K2PtCl4 in gramꢀscale (3.75 g, eq 2) with a total yield of 64% for
four steps from inexpensive 2ꢀbromocarbazole (see Figure S2). which could provide a practical
method for the synthesis of PtNON and benefit its application in OLED field. More importantly, a
new palladiumꢀbased phosphorescent emitter PdNON was also synthesized concisely in gramꢀscale
(5.00 g, eq 3), indicating the CuClꢀcatalyzed hydroxylation reaction would be useful in material
science.
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Scheme 2. Large-Scale Synthesis and Its Application
15 mmol scale
1.2 equiv 1a
10 mol% CuI
20 mol% L5
30 mmol scale
5 mol% CuCl
5 mol% L14
2.1 equiv base
N
N
2.0 equiv K3PO4
N
N
(1)
(2)
(3)
1a
2a
DMSO
95-105 oC, 3 d
85%
DMSO/H2O, 48 h
9.70 g
condition A: 2a, 6.04 g, 79%
condition C: 2a, 7.27 g, 93%
O
3, 6.44 g
5.8 mmol scale
1.1 equiv K2PtCl4
10 mol% n-Bu4NBr
N
N
N
N
Pt
O
3
AcOH, rt, 12 h, then
105-115 oC, 3.5 d
93%
PtNON (x-ray), 3.75 g
10 mmol scale
N
N
1.1 equiv Pd(OAc)2
N
N
10 mol% n-Bu4NBr
Pd
O
3
AcOH, reflux, 3 d
82%
PdNON (x-ray), 5.00 g
The molecular structures of both PtNON and PdNON were confirmed through
singleꢀcrystal Xꢀray diffraction analysis (Figures 2). And B3LYP density functional theory (DFT)
calculations were also performed using the Titan software package56 (wave function, Inc.) at the
LACVP**56,57, level to gain insightful understanding of the nature of transitions of the complexes. A
similar theoretical approach had been utilized to investigate the optimized molecular geometry,
ground and excited states properties for Pt(II) complexes.56,57 And the bond lengths and angles from
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DFT calculations matched well with these of the Xꢀray data (Table 3). It should be noted that the
change of the central metal ion did not affect their bond lengths and angles significantly except the
bond angle of PtNON (163.99o) was larger than that of PdNON (160.6o). Importantly, both
complexes exhibited significant distortion from planarity on the carbazole section of the ligand, to
accommodate square planar coordination to the metal, which can be prove by the bond angles of
N1ꢀPt1(Pd1)ꢀC1 and C1ꢀPt1(Pd1)ꢀN4. These nonplanar structures of molecules could prevent the
formation of excimers, which would benefit to their applications as blue phosphorescent emitters in
display and lighting fields. In addition, the HOMO and LUMO orbitals for PtNON and PdNON
were also shown in Figure 3. Their HOMO consisted of a mixture of localized carbazolylꢀπ and Ptꢀd
orbitals, while their LUMO predominantly occupied on the pyridylꢀπ orbitals with very little metal
orbital character. These indicated that the transitions could be assigned as a mixed state involving
metal to ligand charge transfer (MLCT) and ligand centered charge transfer (LC).
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Figure 2. Xꢀray molecular structures of PtNON and PdNON. Ellipsoids are shown at the 50%
probability level.
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Table 3: Selected bond lengths and angles for PtNON and PdNON based on the DFT calculation
and Xꢀray crystallographic analysis.
8
9
PtNON
PdNON
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calculation Xꢀray calculation Xꢀray
Pt1(Pd1)ꢀN1
Pt1(Pd1)ꢀC1
2.19 Å
1.99 Å
1.99 Å
2.19 Å
87.08 o
94.61 o
88.26 o
93.83 o
163.65 o
166.68 o
2.121 Å
1.974 Å
1.984 Å
2.115 Å
90.50 o
91.8 o
90.29 o
90.10 o
163.20 o
163.99 o
2.20 Å
1.99 Å
1.99 Å
2.19 Å
87.35 o
92.51 o
89.92 o
94.50 o
163.57 o
164.84 o
2.120 Å
1.976 Å
1.973 Å
2.127 Å
89.7 o
90.5 o
91.4 o
93.6 o
164.4 o
160.6 o
Pt1(Pd1)ꢀC2
Pt1(Pd1)ꢀN4
N1ꢀPt1(Pd1)ꢀC1
C1ꢀPt1(Pd1)ꢀC2
C2ꢀPt1(Pd1)ꢀN4
N1ꢀPt1(Pd1)ꢀN4
N1ꢀPt1(Pd1)ꢀC1
C1ꢀPt1(Pd1)ꢀN4
Figure 3. Calculated orbital density for the HOMO (down) and LUMO (up) of PtNON and PdNON
at their optimized S0 geometries.
The photophysical property of PdNON was also investigated and compared with that of
PtNON9 (Figure 4). PdNON exhibits a structured emission spectrum similar with that of
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PtNON at 77K, but has a higher triplet state energy with dominant emission peak at 436 nm
(438 nm for PtNON). However, PdNON has a Gaussian type emission spectrum peaking at
492 nm and a significant blueꢀshift of 16 nm comparing with that of PtNON peaking at 508
nm. This will provide an important approach to tune triplet energies and emission colours of
phosphorescent complexes through central metal ion control, which is critical for the
development of blue phosphorescent emitters.
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Figure 4. Photoluminescence spectra of PdNON and PtNON at 77K in 2ꢀMeꢀTHF and at
room temperature in CH2Cl2.
■ CONCLUSION
In conclusion, we have realized an efficient and practical CuClꢀcatalyzed hydroxylation of
Nꢀheteroarylcarbazole bromides in up to 98% yield. It was found that both ligand and base were
critical to this functional group transformation. tꢀBuONa was demonstrated to be a better base for the
catalytic system to avoid the formation of the ether byproduct. Moreover, dihalide substrates could
be hydroxylated separately or simultaneously through reaction condition control. Furthermore, this
practical method was suitable for largeꢀscale preparation, and was successfully applied in the
gramꢀscale synthesis of phosphorescent emitters PtNON and PdNON, demonstrating its
practicability in material science. Furthermore, the molecular structures of the metal complexes were
confirmed by the Xꢀray crystal diffraction analysis, DFT calculation and photophysical properties
were also investigated.
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■ EXPERIMENTAL SECTION
1
General Information. H NMR spectra were recorded at 400 or 500 MHz, and 13C NMR spectra
were recorded at 100 or 126 MHz NMR instruments in CDCl3 or DMSOꢀd6 solutions and chemical
shifts were referenced to tetramethylsilane (TMS) or residual protiated solvent. If CDCl3 was used as
solvent, 1H NMR spectra were recorded with TMS (δ = 0.00 ppm) as internal reference; 13C NMR
spectra were recorded with CDCl3 (δ = 77.00 ppm) as internal reference. If DMSOꢀd6 was used as
solvent, 1H NMR spectra were recorded with TMS (δ = 0.00 ppm) or residual H2O (δ = 3.33 ppm) as
internal reference; 13C NMR spectra were recorded with DMSOꢀd6 (δ = 39.52 ppm) as internal
reference. All of the new compounds were analyzed for HRMS on an ESIꢀQTOF mass spectrometer
using electrospray ionization in positive ion mode. Steady state emission experiments were
performed on a Horiba Jobin Yvon FluoroLogꢀ3 spectrometer. The following abbreviations (or
combinations thereof) were used to explain 1H NMR ultiplicities: s = singlet, d = doublet, t = triplet,
q = quartet, p = quintet, m = multiplet, br = broad. Mass spectra were recorded on Voyager DEꢀSTR
MALDIꢀTOF mass spectrometer from Applied Biosystems. The Microanalysis Laboratory at
Shanghai Institute of Organic Chemistry performed the elemental analysis. B3LYP density functional
theory (DFT) calculations were performed using the Titan software package56 (wave function, Inc.)
at the LACVP**56,57 level for DFT calculations.
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General Experimental Procedure for Hydroxylation of 2-Bromo-9-(pyridin-2-yl)-9H-carbazole
and Its Analogues. 2ꢀBromoꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazole or its analogues, CuCl, ligand and base
were added to a dry Schlenk tube equipped with a magnetic stir bar. The tube was then evacuated and
backfilled with nitrogen, this evacuation and backfill procedure was repeated twice. Then DMSO
and H2O were added into the tube under nitrogen atmosphere. The tube was placed in oil bath (100
or 110 0C) and stirred for 12ꢀ48 h until the starting material was consumed completely monitoring by
TLC. Then the mixture was cooled down, diluted with ethyl acetate. The organic layer was then
separated, and aqueous layer was extracted with ethyl acetate three times. The combined organic
layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The
residue was purified through column chromatography on silica gel using petroleum ether/ethyl
acetate as eluent to afford the desired product (Unless other notes, Condition A: LiOH.H2O as base at
100 oC; Condition B: NaOH as base at 110 oC; Condition C: tꢀBuONa as base at 110 oC).
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9ꢀ(Pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2a):
5
6
7
8
Condition A: Following the general procedure, the reaction of 1a (323.2 mg, 1.00 mmol, 1.0 eq),
CuCl (5.0 mg, 0.05 mmol, 0.05 eq), ligand L14 (16.4 mg, 0.05 mmol, 0.05 eq) and LiOH.H2O (88.1
o
9
mg, 2.1 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 12 hours afforded 2a (eluent:
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petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 206.9 mg in 79% yield.
Condition B: Following the general procedure, the reaction of 1a (161.1 mg, 0.5 mmol, 1.0 eq), CuCl
(2.5 mg, 0.03 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.05 eq) and NaOH (42.0 mg, 1.1
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2a (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 114.5 mg in 88% yield.
Condition C: Following the general procedure, the reaction of 1a (161.1 mg, 0.5 mmol, 1.0 eq), CuCl
(2.5 mg, 0.03 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.05 eq) and tꢀBuONa (100.9 mg, 1.1
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2a (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 123.5 mg in 95% yield.
o
1
mp: 191.1ꢀ192.4 C. H NMR (500 MHz, DMSOꢀd6): δ 6.79 (dd, J = 8.5, 2.0 Hz, 1H), 7.18 (d, J =
2.0 Hz, 1H), 7.23ꢀ7.26 (m, 1H ), 7.32 (td, J = 8.5, 1.0 Hz, 1H), 7.47 (ddd, J = 7.5, 5.0, 1.0 Hz, 1H),
7.69 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 8.5 Hz, 1H), 8.06 (d, J = 7.5 Hz, 1H),
8.11 (td, J = 8.0, 2.0 Hz, 1H), 8.72 (ddd, J = 5.0, 2.0, 0.5 Hz, 1H), 9.61 (s, 1H). 13C NMR (126 MHz,
DMSOꢀd6): δ 97.1, 110.3, 110.8, 115.9, 119.0, 119.1, 120.78, 121.1, 121.8, 124.0, 124.5, 138.8,
139.3, 140.5, 149.5, 150.9, 157.0. HRMS (ESI): calcd for C17H13N2O [M + H]+ 261.1022, found
261.1028.
9ꢀ(3ꢀMethypyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2b):
Condition A: Following the general procedure, the reaction of 1b (337.2 mg, 1.00 mmol, 1.0 eq),
CuCl (5.0 mg, 0.05 mmol, 0.05 eq), ligand L14 (16.4 mg, 0.05 mmol, 0.05 eq) and LiOH.H2O (88.1
o
mg, 2.1 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2b (eluent:
petroleum ether/ethyl acetate = 10:1ꢀ3:1) as a brown solid 245.2 mg in 89% yield.
Condition B: Following the general procedure, the reaction of 1b (84.3 mg, 0.25 mmol, 1.0 eq),
CuCl (1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.01 mmol, 0.05 eq) and NaOH (21.0 mg,
o
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2b (eluent:
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petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 65.2 mg in 91% yield.
5
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7
8
Condition C: Following the general procedure, the reaction of 1b (212.9 mg, 0.63 mmol, 1.0 eq),
CuCl (3.1 mg, 0.03 mmol, 0.05 eq), ligand L14 (10.3 mg, 0.03 mmol, 0.05 eq) and tꢀBuONa (127.1
mg, 1.32 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2b (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 168.9 mg in 98% yield.
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o
1
mp: 242.8ꢀ244.4 C. H NMR (500 MHz, DMSOꢀd6): δ 2.01 (s, 3H), 6.38 (d, J = 2.0 Hz, 1H), 6.74
(dd, J = 8.5, 2.5 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 7.21 (td, J = 7.5, 1.0 Hz, 1H), 7.27 (td, J = 7.0, 1.0
Hz, 1H), 7.57 (dd, J = 8.0, 5.0 Hz, 1H), 8.00 (d, J = 8.5 Hz, 1H), 8.04ꢀ8.07 (m, 2H), 8.57 (dd, J = 4.5,
1.0 Hz, 1H), 9.50 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 16.9, 95.8, 109.6, 109.8, 115.1, 119.4,
112.0, 121.4, 123.2, 124.2, 124.4, 131.0, 139.6, 141.0, 141.4, 147.8, 148.8, 157.0. HRMS (ESI):
calcd for C18H15N2O [M + H]+ 275.1179, found 275.1191.
9ꢀ(4ꢀMethypyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2c):
Condition A: Following the general procedure, the reaction of 1c (337.2 mg, 1.00 mmol, 1.0 eq),
CuCl (5.0 mg, 0.05 mmol, 0.05 eq), ligand L14 (16.4 mg, 0.05 mmol, 0.05 eq) and LiOH.H2O (88.1
o
mg, 2.1 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2c (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 258.4 mg in 94% yield.
Condition B: Following the general procedure, the reaction of 1c (84.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.01 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2c (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 53.8 mg in 78% yield.
Condition C: Following the general procedure, the reaction of 1c (210.0 mg, 0.62 mmol, 1.0 eq),
CuCl (3.1 mg, 0.03 mmol, 0.05 eq), ligand L14 (10.2 mg, 0.03 mmol, 0.05 eq) and tꢀBuONa (124.9
mg, 1.30 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2c (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 150.1 mg in 88% yield.
mp: 178.4ꢀ179.2 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 2.48 (s, 3H), 6.78 (dd, J = 8.5, 2.0 Hz, 1H),
7.16 (d, J = 2.0 Hz, 1H), 7.23ꢀ7.26 (m, 1H), 7.30ꢀ7.33 (m, 2H), 7.57 (s, 1H), 7.68 (d, J = 8.5 Hz, 1H),
7.99 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 7.5 Hz, 1H), 8.57 (d, J = 5.0 Hz, 1H), 9.59 (s, 1H). 13C NMR
(100 MHz, DMSOꢀd6): δ 20.7, 97.2, 110.3, 110.9, 115.8, 119.2, 119.5, 120.7, 121.1, 122.9, 124.0,
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124.5, 138.9, 140.6, 149.1, 150.5, 151.0, 157.0. HRMS (ESI): calcd for C18H15N2O [M + H]+
275.1179, found 275.1190.
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9ꢀ(5ꢀMethypyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2d):
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Condition A: Following the general procedure, the reaction of 1d (337.2 mg, 1.00 mmol, 1.0 eq),
CuCl (5.0 mg, 0.05 mmol, 0.05 eq), ligand L14 (16.4 mg, 0.05 mmol, 0.05 eq) and LiOH.H2O (88.1
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60
o
mg, 2.1 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2d (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 226.6 mg in 83% yield.
Condition B: Following the general procedure, the reaction of 1d (55.7 mg, 0.17 mmol, 1.0 eq),
CuCl (0.8 mg, 0.01 mmol, 0.05 eq), ligand L14 (2.6 mg, 0.01 mmol, 0.05 eq) and NaOH (13.9 mg,
o
0.35 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2d (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 39.0 mg in 86% yield.
Condition C: Following the general procedure, the reaction of 1d (183.2 mg, 0.54 mmol, 1.0 eq),
CuCl (2.7 mg, 0.03 mmol, 0.05 eq), ligand L14 (8.9 mg, 0.03 mmol, 0.05 eq) and tꢀBuONa (109.0
mg, 1.13 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2d (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 133.9 mg in 90% yield.
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mp: 201.3ꢀ202.6 oC. H NMR (500 MHz, DMSOꢀd6): δ 2.43 (s, 3H), 6.77 (dd, J = 8.0, 2.0 Hz, 1H),
7.10 (d, J = 2.0 Hz, 1H), 7.22ꢀ7.25 (m, 1H), 7.29ꢀ7.32 (m, 1H), 7.62ꢀ7.64 (m, 2H), 7.93 (ddd, J = 8.5,
2.5, 0.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 8.04ꢀ8.06 (m, 1H), 8.55 (dd, J = 2.0, 1.0 Hz, 1H), 9.59 (s,
1H). 13C NMR (100 MHz, DMSOꢀd6): δ 17.5, 97.0, 110.2, 110.7, 115.8, 118.6, 119.2, 120.6, 121.1,
123.9, 124.5, 131.3, 139.0, 139.6, 140.7, 148.6, 149.5, 157.0. HRMS (ESI): calcd for C18H15N2O [M
+ H]+ 275.1179, found 275.1180.
9ꢀ (Quinolinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2e):
Condition A: Following the general procedure, the reaction of 1e (93.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and LiOH.H2O (22.0 mg,
o
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 48 hours afforded 2e (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 33.8 mg in 44% yield.
Condition B: Following the general procedure, the reaction of 1e (93.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
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mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2e (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 29.4 mg in 38% yield and 1e was recycled 18.5 mg in
20% yield.
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Condition C: Following the general procedure, the reaction of 1e (93.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and tꢀBuONa (50.5 mg,
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60
o
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2e (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 76.4 mg in 98% yield.
mp: 217.3ꢀ 218.7 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 6.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.28ꢀ7.31 (m,
1H), 7.37 (td, J = 8.0, 1.0 Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 7.67ꢀ7.70 (m, 1H), 7.86ꢀ7.89 (m, 1H),
7.90 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 8.09 (t, J = 8.5 Hz, 2H),
8.12ꢀ8.13 (m, 1H), 8.66 (d, J = 8.5 Hz, 1H), 9.67 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 97.7,
110.7, 111.3, 116.2, 117.7, 119.3, 121.2, 121.3, 124.4, 124.7, 126.3, 126.5, 128.1(2C), 130.6,138.8,
139.5, 140.5, 147.0, 150.4, 157.2. HRMS (ESI): calcd for C21H15N2O [M + H]+ 311.1179, found
311.1170.
9ꢀ (Isoquinolinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2f):
Condition A: Following the general procedure, the reaction of 1f (186.6 mg, 0.50 mmol, 1.0 eq),
CuCl (2.5 mg, 0.025 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.025 mmol, 0.05 eq) and LiOH.H2O (44.1
o
mg, 1.05 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2f (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 114.5 mg in 74% yield.
Condition B: Following the general procedure, the reaction of 1f (93.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2f (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 56.3 mg in 73% yield.
Condition C: Following the general procedure, the reaction of 1f (186.6 mg, 0.50 mmol, 1.0 eq),
CuCl (2.5 mg, 0.025 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.025 mmol, 0.05 eq) and tꢀBuONa (100.9
o
mg, 1.05 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2f (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 147.9 mg in 95% yield.
mp: 247.5ꢀ248.2 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.37 (d, J = 2.0 Hz, 1H), 6.78 (dd, J = 8.5,
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2.0 Hz, 1H), 6.96ꢀ6.98 (m, 1H), 7.21ꢀ7.26 (m, 2H), 7.48 (d, J = 7.5 Hz, 1H), 7.62ꢀ7.66 (m, 1H),
7.88ꢀ7.92 (m, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.12ꢀ8.13 (m, 2H), 8.23 (d, J = 8.0 Hz, 1H), 8.66 (d, J =
5.5 Hz, 1H), 9.49 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 96.4, 110.1, 110.4, 115.5, 119.4, 120.4,
121.5, 121.8, 123.6, 124.4, 124.4, 124.8, 127.6, 128.7, 131.4, 138.3, 140.8, 142.2, 142.4, 149.3,
157.0. HRMS (ESI): calcd for C21H15N2O [M + H]+ 311.1179, found 311.1186.
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9ꢀ (Pyrimidinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2g):
Condition A: Following the general procedure, the reaction of 1g (54.3 mg, 0.17 mmol, 1.0 eq), CuCl
(0.8 mg, 0.008 mmol, 0.05 eq), ligand L14 (2.8 mg, 0.008 mmol, 0.05 eq) and LiOH.H2O (15.0 mg,
o
0.36 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2g (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 33.2 mg in 75% yield.
Condition B: Following the general procedure, the reaction of 1g (81.0 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
o
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours using petroleum ether/ethyl
acetate = 5:1ꢀ3:1 as eluent afforded 2ꢀbromocarbazole 46.6 mg in 74% yield and 2g as a brown solid
17.1 mg in 26% yield.
Condition C: Following the general procedure, the reaction of 1g (81.0 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and tꢀBuONa (50.5 mg,
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded
2ꢀbromocarbazole (eluent: petroleum ether/ethyl acetate = 5:1ꢀ3:1) 61.7 mg in 99% yield.
2g: mp: 157.1ꢀ158.8 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 6.85 (dd, J = 8.0, 2.0 Hz, 1H), 7.32 (td, J
= 7.5, 1.0 Hz, 1H), 7.37ꢀ7.40 (m, 1H), 7.41 (t, J = 4.5, 1H), 7.98 (d, J = 8.5 Hz, 1H), 8.05 (dd, J =
7.5, 0.5 Hz, 1H), 8.25 (d, J = 2.0 Hz, 1H), 8.72 (d, J = 8.0 Hz, 1H), 8.99 (d, J = 4.5 Hz, 2H), 9.69 (s,
1H). 13C NMR (100 MHz, DMSOꢀd6): δ 102.5, 111.3, 115.9, 116.9, 117.2, 118.7, 120.5, 122.3,
124.9, 125.5, 138.3, 139.9, 157.2, 158.3, 158.6 (2C). HRMS (ESI): calcd for C16H12N3O [M + H]+
1
262.0975, found 262.0977. 2-Bromocarbazole: H NMR (500 MHz, DMSOꢀd6): δ 7.17ꢀ7.20 (m,
1H), 7.29 (dd, J = 8.5, 2.0 Hz, 1H), 7.40ꢀ7.43 (m, 1H), 7.51 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 2.0 Hz,
1H), 8.07 (d, J = 8.5 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 11.40 (s, 1H). The structure was confirmed
by comparison of 1H NMR spectrum with that of purchased sample.
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9ꢀ (Pyrazinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2h):
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Condition A: Following the general procedure, the reaction of 1h (54.3 mg, 0.17 mmol, 1.0 eq),
CuCl (0.8 mg, 0.008 mmol, 0.05 eq), ligand L14 (2.8 mg, 0.008 mmol, 0.05 eq) and LiOH.H2O (15.0
mg, 0.36 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 oC for 24 hours afforded 2h (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 39.2 mg in 88% yield.
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Condition B: Following the general procedure, the reaction of 1h (81.0 mg, 0.25 mmol, 1.0 eq),
CuCl (1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg,
o
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2h (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 37.7 mg in 57% yield.
Condition C: Following the general procedure, the reaction of 1h (81.0 mg, 0.25 mmol, 1.0 eq),
CuCl (1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and tꢀBuONa (50.5
mg, 0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2h (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 59.6 mg in 91% yield.
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mp: 204.9ꢀ206.1 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.23 (d, J =
2.0 Hz, 1H), 7.29 (td, J = 7.5, 1.0 Hz, 1H), 7.33ꢀ7.37 (m, 1H), 7.77 (d, J = 8.0 Hz, 1H), 8.02 (d, J =
8.5 Hz, 1H), 8.07ꢀ8.09 (m, 1H), 8.71 (d, J = 3.0 Hz, 1H), 8.81 (dd, J = 2.5, 1.5 Hz, 1H), 9.12 (d, J =
1.0 Hz, 1H), 9.70 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 97.2, 110.9, 111.0, 116.2, 119.3, 121.3,
121.6, 124.5, 124.8, 138.5, 140.3, 140.7, 142.0, 143.8, 147.8, 157.3. HRMS (ESI): calcd for
C16H12N3O [M + H]+ 262.0975, found 262.0981.
9ꢀ (Thiazolꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol (2i):
Condition A: Following the general procedure, the reaction of 1i (164.6 mg, 0.50 mmol, 1.0 eq),
CuCl (2.5 mg, 0.025 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.025 mmol, 0.05 eq) and LiOH.H2O (44.1
o
mg, 1.05 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2i (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 113.9 mg in 86% yield.
Condition B: Following the general procedure, the reaction of 1i (82.3 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.013 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2i (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 64.7 mg in 97% yield.
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Condition C: Following the general procedure, the reaction of 1i (164.6 mg, 0.50 mmol, 1.0 eq),
CuCl (2.5 mg, 0.025 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.025 mmol, 0.05 eq) and tꢀBuONa (100.9
o
mg, 1.05 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2i (eluent:
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petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 122.8 mg in 92% yield.
mp: 152.6ꢀ 154.5 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 6.86 (dd, J = 8.5, 2.0 Hz, 1H), 7.35 (td, J =
7.5, 1.0 Hz, 1H), 7.42ꢀ7.45 (m, 1H), 7.66 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 3.5 Hz, 1H), 7.88 (d, J =
3.5 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 8.08ꢀ8.10 (m, 1H), 8.15 (d, J = 8.0 Hz, 1H), 9.87 (s, 1H). 13C
NMR (100 MHz, DMSOꢀd6): δ 99.6, 111.5, 112.0, 116.2, 116.3, 119.4, 121.4, 122.3, 124.7, 125.3,
138.4, 139.7, 140.1, 157.7, 158.3. HRMS (ESI): calcd for C15H11N2OS [M + H]+ 267.0587, found
267.0575.
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9ꢀ(Pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ3ꢀol (2j):
Condition A: Following the general procedure, the reaction of 1j (61.9 mg, 0.19 mmol, 1.0 eq), CuCl
(1.0 mg, 0.010 mmol, 0.05 eq), ligand L14 (3.1 mg, 0.010 mmol, 0.05 eq) and LiOH.H2O (16.7 mg,
o
0.40 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2j (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 37.1 mg in 75% yield.
Condition B: Following the general procedure, the reaction of 1j (80.8 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg, 0.53
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2j (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 59.0 mg in 91% yield.
Condition C: Following the general procedure, the reaction of 1j (80.8 mg, 0.25 mmol, 1.0 eq), CuCl
(1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.01 mmol, 0.05 eq) and tꢀBuONa (50.5 mg, 0.53
mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2j (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ3:1) as a brown solid 59.1 mg in 91% yield.
mp: 163.9ꢀ164.8 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 6.95 (dd, J = 9.0, 2.5 Hz, 1H), 7.25ꢀ7.29 (m,
1H), 7.40ꢀ7.44 (m, 2H), 7.53 (d, J = 2.5 Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H),
7.82 (d, J = 8.5 Hz, 1H), 8.06ꢀ8.09 (m, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.70 (ddd, J = 5.0, 2.0, 0.5 Hz,
1H), 9.26 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 105.1, 111.3, 112.1, 115.3, 118.4, 120.3, 120.4,
121.3, 123.5, 124.5, 126.2, 132.7, 139.2 (2 C), 149.3, 151.1, 152.2. HRMS (ESI): calcd for
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C17H13N2O [M + H]+ 261.1022, found 261.1033.
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9ꢀ(4ꢀTrifluoromethylpyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ3ꢀol (2k):
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Condition A: Following the general procedure, the reaction of 1k (106.0 mg, 0.27 mmol, 1.0 eq),
CuCl (1.4 mg, 0.014mmol, 0.05 eq), ligand L14 (4.5 mg, 0.014 mmol, 0.05 eq) and LiOH.H2O (23.8
mg, 0.57 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 oC for 36 hours afforded 2k (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 72.1 mg in 81% yield.
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Condition B: Following the general procedure, the reaction of 1k (99.5 mg, 0.25 mmol, 1.0 eq),
CuCl (1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg,
o
0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 36 hours afforded 2k (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 47.2 mg in 57% yield.
Condition C: Following the general procedure, the reaction of 1k (96.0 mg, 0.245 mmol, 1.0 eq),
CuCl (1.2 mg, 0.012 mmol, 0.05 eq), ligand L14 (4.0 mg, 0.012 mmol, 0.05 eq) and tꢀBuONa (73.0
mg, 0.22 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 oC for 24 hours afforded 2k (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 73.0 mg in 91% yield.
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mp: 155.1ꢀ156.7 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.83 (dd, J = 8.0, 2.0 Hz, 1H), 7.22 (d, J =
2.0 Hz, 1H), 7.28 (t, J = 2.5 Hz, 1H), 7.35 (t, J = 3.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.83 (d, J =
5.0 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 6.5 Hz, 2H), 9.00 (d, J = 5.0 Hz, 1H), 9.71 (s, 1H).
13C NMR (126 MHz, DMSOꢀd6): δ 97.2, 110.9, 110.9, 114.4 (d, J= 3.8 Hz, 1C), 116.2, 117.0 (q, J=
3.2 Hz, 1C), 119.2, 121.2, 121.6, 122.6 (q, J= 274.1 Hz, 1C), 124.4, 124.7, 138.5, 139.4 (q, J= 31.2
Hz, 1C), 140.2, 151.3, 152.0, 157.2. HRMS (ESI): calcd for C18H12F3N2O [M + H]+ 329.0896, found
329.0906.
2ꢀBromo ꢀ9ꢀ(4ꢀhydroxypyridinꢀ2ꢀyl)ꢀ 9Hꢀcarbazole (2l) (Scheme 1, eqs 1ꢀ3):
Condition A: Following the general procedure, the reaction of 1l (343.2 mg, 1.0 mmol, 1.0 eq), CuCl
(5.0 mg, 0.05 mmol, 0.05 eq), ligand L14 (16.4 mg, 0.05 mmol, 0.05 eq) and LiOH.H2O (88.1 mg,
o
2.10 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 24 hours afforded 2l (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a white solid 93.0 mg in 27% yield.
Condition C: Following the general procedure, the reaction of 1l (168.4 mg, 0.49 mmol, 1.0 eq),
CuCl (2.4 mg, 0.03 mmol, 0.05 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.05 eq) and tꢀBuONa (98.9 mg,
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1.03 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2l (eluent:
5
6
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 74.3 mg in 55% yield.
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Condition B: Following the general procedure, the reaction of 1m(89.4 mg, 0.25 mmol, 1.0 eq),
CuCl (1.3 mg, 0.01 mmol, 0.05 eq), ligand L14 (4.1 mg, 0.013 mmol, 0.05 eq) and NaOH (21.0 mg,
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0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 2l (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 52.9 mg in 72% yield.
Condition B (without CuCl and L14): Following the general procedure, the reaction of 1m (89.4 mg,
0.25 mmol, 1.0 eq) and NaOH (21.0 mg, 0.53 mmol, 2.1 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110
oC for 24 hours afforded 2l (eluent: petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 42.7 mg
in 50% yield.
mp: 125.7ꢀ126.1 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.90 (dd, J = 5.5, 2.0 Hz, 1H), 7.10 (d, J =
1
2.0 Hz, 1H), 7.33ꢀ7.36 (m, 1H), 7.48 (dd, J = 8.0, 2.0 Hz, 1H), 7.49ꢀ7.52 (m, 1H), 7.77 (d, J = 8.0
Hz, 1H), 7.98 (d, J = 1.5 Hz, 1H), 8.21 (d, J = 7.5 Hz, 1H), 8.27 (d, J = 2.5 Hz, 1H), 8.44 (d, J = 5.5
Hz, 1H), 11.89 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 106.1, 110.6, 111.4, 114.2, 118.9, 120.6,
121.2, 122.1, 122.5, 122.7, 123.5, 126.8, 139.0, 139.8, 150.5, 151.6, 166.2. HRMS (ESI): calcd for
C17H12BrN2O [M + H]+ 339.0128, found 339.0138.
9ꢀ(4ꢀHydroxypyridinꢀ2ꢀyl)ꢀ 9Hꢀ carbazolꢀ2ꢀol (4a) (Scheme 1, eqs 3, 4):
Condition C: Following the general procedure, the reaction of 2l (48.7 mg, 0.14 mmol, 1.0 eq), CuCl
(0.7 mg, 0.007 mmol, 0.05 eq), ligand L14 (2.3 mg, 0.007 mmol, 0.05 eq) and tꢀBuONa (56.5 mg,
o
0.59 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 110 C for 24 hours afforded 4a (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a white solid 26.7 mg in 69% yield.
Condition C: Following the general procedure, the reaction of 1m (89.4 mg, 0.25 mmol, 1.0 eq),
CuCl (2.5 mg, 0.025 mmol, 0.10 eq), ligand L14 (8.2 mg, 0.025 mmol, 0.10 eq) and tꢀBuONa (100.9
o
mg, 1.05 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/1.0 mL) at 110 C for 24 hours afforded 2l (eluent:
petroleum ether/ethyl acetate = 3:1ꢀ1:1) as a white solid: 40.4 mg in 48% yield and 4a (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 23.9 mg in 35% yield.
mp: 298.3ꢀ299.7 oC. 1H NMR (500 MHz, DMSOꢀd6): δ 6.77 (dd, J = 8.5, 2.0 Hz, 1H), 6.86 (dd, J =
6.0, 2.0 Hz, 1H), 7.03 (d, J = 2.0 Hz, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.21ꢀ7.24 (m, 1H), 7.31 (td, J =
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7.5, 1.5 Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.97 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 7.5 Hz, 1H), 8.40 (d,
13
J = 6.0 Hz, 1H), 9.58 (s, 1H), 11.08 (s, 1H). C NMR (100 MHz, DMSOꢀd6): δ 97.3, 105.8, 110.1,
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8
9
110.2, 111.0, 115.8, 119.0, 120.6, 121.0, 123.9, 124.4, 138.9, 140.6, 150.3, 152.3, 156.9, 166.0.
HRMS (ESI): calcd for C17H13N2O2 [M + H]+ 277.0972, found 277.0973.
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9ꢀ(5ꢀHydroxypyridinꢀ2ꢀyl)ꢀ 9Hꢀ carbazolꢀ2ꢀol (4b) (Scheme 1, eq 5):
Condition C: Following the general procedure, the reaction of 1n (100.5 mg, 0.25 mmol, 1.0 eq),
CuCl (2.5 mg, 0.03 mmol, 0.10 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.10 eq) and tꢀBuONa (100.9
mg, 1.05 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/1.0 mL) at 110 oC for 24 hours afforded 4b (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a white solid 43.8 mg in 63% yield.
1
mp: 257.0ꢀ258.3 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.75 (dd, J = 8.0, 2.0 Hz, 1H), 6.95 (d, J =
2.0 Hz, 1H), 7.19ꢀ7.22 (m, 1H), 7.29 (td, J = 7.0, 1.0 Hz, 1H), 7.47ꢀ7.49 (m, 2H), 7.53 (d, J = 8.5 Hz,
1H), 7.96 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 7.5 Hz, 1H), 8.24ꢀ8.25 (m, 1H), 9.54 (s, 1H), 10.26 (s,
1H) . 13C NMR (100 MHz, DMSOꢀd6): δ 96.4, 109.8, 110.2, 115.4, 119.1, 120.1, 120.5, 121.0, 123.4,
124.3, 125.2, 137.0, 139.4, 141.2, 142.2, 152.6, 156.9. HRMS (ESI): calcd for C17H13N2O2 [M + H]+
277.0972, found 277.0983.
7ꢀ Bromo ꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ 9Hꢀ carbazolꢀ2ꢀol (2m) (Scheme 1, eq 6):
Condition A: Following the general procedure, the reaction of 1o (61.3 mg, 0.15 mmol, 1.0 eq), CuCl
(1.5 mg, 0.015 mmol, 0.10 eq), ligand L14 (4.9 mg, 0.015 mmol, 0.10 eq) and LiOH.H2O (26.4 mg,
o
0.63 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/0.5 mL) at 100 C for 48 hours afforded 2m (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ3:1) as a white solid 24.5 mg in 49% yield.
1
mp: 196.0ꢀ196.7 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.82 (dd, J = 8.5, 2.0 Hz, 1H), 7.12 (d, J =
2.0 Hz, 1H), 6.82 (dd, J = 8.5, 2.0 Hz, 1H), 7.41 (dd, J = 8.0, 2.0 Hz, 1H), 7.51 (ddd, J = 7.5, 5.0,
1.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 1.5 Hz, 1H), 8.04 (dd, J = 8.0, 2.5 Hz, 1H), 8.14
(td, J = 8.0, 2.0 Hz, 1H), 8.74ꢀ8.76 (m, 1H), 9.74 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6): δ 97.0,
110.9, 113.6, 115.2, 117.0, 119.2, 120.9, 121.6, 122.3, 123.3, 123.6, 139.7, 139.7, 140.8, 149.7, 150.4,
157.6. HRMS (ESI): calcd for C17H12BrN2O [M + H]+ 339.0128, found 339.0128.
9ꢀ(Pyridinꢀ2ꢀyl)ꢀ 9Hꢀ carbazolꢀ2,7ꢀdiol (4c) (Scheme 1, eqs 7, 8):
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Condition B: Following the general procedure, the reaction of 1o (80.4 mg, 0.20 mmol, 1.0 eq), CuCl
(2.0 mg, 0.02 mmol, 0.10 eq), ligand L14 (6.5 mg, 0.02 mmol, 0.10 eq) and NaOH (33.6 mg, 0.84
mmol, 4.2 eq) in DMSO/H2O (2.0 mL/1.0 mL) at 110 oC for 24 hours afforded 4c (eluent: petroleum
ether/ethyl acetate = 5:1ꢀ1:1) as a white solid 16.5 mg in 24% yield.
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Condition C: Following the general procedure, the reaction of 1o (100.5 mg, 0.25 mmol, 1.0 eq),
CuCl (2.5 mg, 0.03 mmol, 0.10 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.10 eq) and tꢀBuONa (100.9
mg, 1.05 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/1.0 mL) at 110 oC for 24 hours afforded 4c (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a brown solid 55.8 mg in 81% yield.
1
mp: 266.1ꢀ267.6 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.71 (dd, J = 8.5, 2.0 Hz, 2H), 7.09 (d, J =
2.0 Hz, 2H), 7.45 (ddd, J = 7.5, 5.0, 1.0 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H),
8.10 (td, J = 8.0, 2.0 Hz, 1H), 8.72 (ddd, J = 5.0, 2.0, 0.5 Hz, 1H), 9.37 (s, 2H) . 13C NMR (100 MHz,
DMSOꢀd6): δ 97.2, 109.9, 116.5, 118.9, 119.8, 121.8, 139.3, 140.3, 149.5, 151.1, 155.6. HRMS (ESI):
calcd for C17H13N2O2 [M + H]+ 277.0972, found 277.0961.
9ꢀ (pyrimidinꢀ2ꢀyl)ꢀ9Hꢀ carbazolꢀ2,7ꢀdiol (4d) (Scheme 1, eq 9):
Condition A: Following the general procedure, the reaction of 1p (100.8 mg, 0.25 mmol, 1.0 eq),
CuCl (2.5 mg, 0.03 mmol, 0.10 eq), ligand L14 (8.2 mg, 0.03 mmol, 0.10 eq) and LiOH.H2O (44.1
o
mg, 1.05 mmol, 4.2 eq) in DMSO/H2O (2.0 mL/1.0mL) at 100 C for 24 hours afforded 4d (eluent:
petroleum ether/ethyl acetate = 5:1ꢀ1:1) as a white solid 42.8 mg in 62% yield.
1
mp: 267.3ꢀ268.9 oC. H NMR (500 MHz, DMSOꢀd6): δ 6.77 (dd, J = 8.5, 2.0 Hz, 2H), 7.38 (t, J =
5.0 Hz, 1H), 7.78 (d, J = 8.5 Hz, 2H), 8.19 (d, J = 2.0 Hz, 2H), 8.97 (d, J = 5.0 Hz, 2H), 9.46 (s, 2H).
13C NMR (126 MHz, DMSOꢀd6): δ 102.8, 110.9, 116.7, 117.8, 119.0, 139.6, 115.7, 158.3, 158.4.
HRMS (ESI): calcd for C16H12N3O2 [M + H]+ 278.0924, found 278.0916.
Large-scale Synthesis and Its application:
Synthesis of 9ꢀ(pyridinꢀ2ꢀyl)ꢀ9Hꢀcarbazolꢀ2ꢀol 2a (Scheme 2, eq 1): Condition A: Following
the general procedure, the reaction of 1a (9.70 g, 30.00 mmol, 1.0 eq), CuCl (148.5 mg, 1.50 mmol,
0.05 eq), ligand L14 (493.0 mg, 1.50 mmol, 0.05 eq) and LiOH.H2O (2.64 g, 63.0 mmol, 2.1 eq) in
o
DMSO/H2O (37.5 mL/9.5 mL) at 100 C for 48 hours. Then the mixture was cooled to room
temperature, then H2O (100 mL) and EtOAc (100 mL) were added, filtered through a pad of celite,
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and washed with EtOAc three times. The organic layer was then separated, and the aqueous layer
was extracted with EtOAc (100 mL × 5). The combined organic layer was washed with water (50 mL)
and then dried over Na2SO4, filtered, and the filtrate was concentrated in vacuum. The residue was
recrystallized in PE/EtOAc (20 mL/20 mL) to afford the desired product 2a as a white solid 5.61 g.
The mother liquor was concentrated, and the residue was purified through column chromatography
on silica gel using PE/DCM = 5:1−3:1 as eluent to afford 3 246.6 mg in 3% yield and the product 2a
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1
as a white solid 425.5 mg. The total yield of 2a was 79%. The structure of 3 was confirmed by H
NMR.
Condition C: Following the general procedure, the reaction of 1a (9.70 g, 30.00 mmol, 1.0 eq), CuCl
(148.5 mg, 1.50 mmol, 0.05 eq), ligand L14 (493.0 mg, 1.50 mmol, 0.05 eq) and tꢀBuONa (6.05 g,
o
63.0 mmol, 2.1 eq) in DMSO/H2O (37.5 mL/9.5 mL) at 110 C for 48 hours. Then the mixture was
cooled to room temperature, and H2O (100 mL) and EtOAc (100 mL) were added, 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 (100 mL × 5). The combined organic layer was washed
with water (50 mL) and then dried over Na2SO4 and filtered, and the filtrate was concentrated in
vacuum. The residue was recrystallized in PE/EtOAc (10 mL/10 mL) to afford the desired product as
a white solid 5.77 g. The mother liquor was concentrated, and the residue was purified through
column chromatography on silica gel using PE/DCM = 5:1−3:1 as eluent to afford the product as a
white solid 1.5 g. The total yield was 93%. The structure of 2a was confirmed by 1H NMR.
Synthesis of 2ꢀ(9ꢀ(pyridinꢀ2ꢀyl)ꢀ9
H
ꢀcarbazolꢀ2ꢀyloxy)ꢀ9ꢀ(pyridinꢀ2ꢀyl)ꢀ9
H
ꢀcarbazole
3
(Scheme 2, eq 1): To a dry threeꢀnecked flask equipped with a magnetic stir bar, added 2a (3.90 g,
15.00 mmol, 1.0 eq), 1a (5.82 g, 18.00 mmol, 1.2 eq), CuI (0.29 g, 1.50 mmol, 0.1 eq), picolinic acid
L5 (0.37 g, 3.00 mmol, 0.2 eq), K3PO4 (6.37 g, 30.00 mmol, 2.0 eq). The flask was then evacuated
and backfilled with nitrogen, this evacuation and backfill procedure was repeated twice. Then DMSO
(60 mL) was added under nitrogen and the mixture was stirred at 95ꢀ105oC for 3 days. The mixture
was then cooled down to ambient temperature and diluted with ethyl acetate, filtered and washed
with a plenty of ethyl acetate. The filtrate was then washed with water for three time and then dried
over sodium sulfate. Filtered and the solvent was removed under reduced pressure, the residue was
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purified through column chromatography on silica gel using petroleum ether/ethyl acetate (10:1ꢀ3:1)
1
as eluent to obtain the desired product as a brown solid 6.44 g in 85% yield. H NMR (400 MHz,
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8
9
DMSOꢀd6): δ 7.06 (dd, J = 8.4, 2.4 Hz, 2H), 7.33 (t, J = 7.2 Hz, 2H), 7.41ꢀ7.45 (m, 4H), 7.51 (d, J =
2.4 Hz, 2H), 7.76 (d, J = 8.0 Hz, 4H), 8.06 (td, J = 7.6, 2.0 Hz, 2H), 8.20 (d, J = 7.6 Hz, 2H), 8.24 (d,
J = 8.4 Hz, 2H), 8.64 (dd, J = 5.6, 2.4 Hz, 2H). The spectroscopic data is in agreement with that
previously reported.9
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Synthesis of PtNON: Ligand 3 (2.92 g, 5.81 mmol, 1.00 eq), K2PtCl4 (2.65 g, 6.39 mmol, 1.10 eq),
nBu4NBr (0.19 g, 0.58 mmol, 0.10 eq) 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 AcOH (350 mL) was added under
nitrogen. The mixture was stirred at room temperature for 12 hours , then at 105ꢀ115 oC for 3.5 days.
The mixture was then cooled down to ambient temperature and the solvent was evaporated under
reduced pressure, the residue was purified through column chromatography on silica gel using
petroleum ether/dichloromethane (1:1) as eluent to obtain the desired product as a yellow solid 3.75
1
g in 93% yield. H NMR (400 MHz, DMSOꢀd6): δ 7.20 (d, J = 10.0 Hz, 2H), 7.31 (td, J = 7.0, 3.5
Hz, 2H), 7.42 (t, J = 9.0 Hz, 2H), 7.48ꢀ7.52 (m, 2H), 7.93 (d, J = 10.0 Hz, 2H), 8.08 (d, J = 10.0 Hz,
2H), 8.17ꢀ8.20 (m, 6H), 9.03 (d, J = 7.0 Hz, 2H). 13C NMR (100 MHz, DMSOꢀd6): δ 93.9, 111.7,
114.2, 115.2, 115.9, 116.4, 119.6, 120.3, 122.7, 124.2, 127.7, 137.4, 139.7, 142.2, 147.7, 151.3, 152.0.
The spectroscopic data is in agreement with that previously reported.9
Synthesis of PdNON: Ligand 3 (5.03 g, 10.00 mmol, 1.00 eq), Pd(OAc)2 (2.47 g, 11.00 mmol, 1.10
n
eq), Bu4NBr (0.32 g, 1.00 mmol, 0.10 eq) 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 AcOH (500 mL) was added under
nitrogen and the mixture was refluxed for 3 days. The mixture was then cooled down to ambient
temperature and the solvent was evaporated under reduced pressure, the residue was purified through
column chromatography on silica gel using petroleum ether/dichloromethane (2:1ꢀ3:2ꢀ1:1) as eluent
to obtain the desired product as a yellow solid 5.00 g in 82% yield. 1H NMR (400 MHz, DMSOꢀd6):
δ 7.21 (d, J = 8.4 Hz, 2H), 7.33ꢀ7.37 (m, 2H), 7.40 (td, J = 7.6 Hz, 2H), 7.46ꢀ7.51 (m, 2H ), 7.80 (d,
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J = 8.0 Hz, 2H), 8.06 (d, J = 8.0 Hz, 2H), 8.14 (d, J = 3.6 Hz, 4H), 8.19 (d, J = 7.2 Hz, 2H), 8.90 (d,
J = 5.6 Hz, 2H). 13C NMR (100 MHz, DMSOꢀd6): δ 107.8, 111.7, 114.0, 116.1, 116.3, 117.0, 119.6,
120.2, 122.5, 124.3, 127.6, 137.5, 140.4, 142.9, 148.5, 150.9, 151.0. HRMS (MALDIꢀFT_DHB): for
C34H21N4O102Pd [M+H]+: calcd 603.0766, found 603.0763.
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■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
Comparison of synthetic route for critical intermediate 2a and PtNON (Figure S2); Synthesis of
ligands L13 and L14; Synthesis of starting materials of 1m, 1k and 1p; Our previous synthetic route
for 2a; NMR and HRMS spectra; IR and UV spectra for 2aꢀ2j, 2l, 2m, 4a and 4c. Crystallographic
data (PDF). Compounds PtNON and PdNON (CIF).
■ AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: guijieli@zjut.edu.cn; jian.li.1@asu.edu; sheyb@zjut.edu.cn.
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGEMENTS
We thank the National Natural Science Foundation of China (21602198 and 21476270) and
"Qianjiang Talents Plan" (QJD1602017) for financial support. We also thank Dr. Tyler Fleetham's
helpful discussion from University of Southern California and Min Li form Zhejiang Jiuzhou
Pharmaceutical Company Ltd. for NMR spectra measurements.
■ REFERENCES
(1) Ito, C.; Thoyama, Y.; Omura, M.; Kajiura, I.; Furukawa, H. Chem. Pharm. Bull. 1993, 41, 2096.
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