Modular assembly of ring-fused and π-extended phenanthroimidazoles via C-H activation and alkyne annulation

Article abstract of DOI:10.1021/jo500401n

π-Extension of 2-aryl-phenanthroimidazoles via rhodium(III)-catalyzed C-H activation and alkyne annulation is developed. This method enables rapid, practical and modular assembly of diverse ring-fused phenanthroimidazoles, including an unusual rearrangement product using aryl-alkyl asymmetric alkyne and a thiophene fused product which could serve as a Fe³⁺ fluorescent probe. The feasibility of the one-pot synthesis and ruthenium(II)-catalyzed versions of this reaction was also verified.

Full text of DOI:10.1021/jo500401n

Article
pubs.acs.org/joc
Modular Assembly of Ring-Fused and π‑Extended
Phenanthroimidazoles via C−H Activation and Alkyne Annulation
Liyao Zheng and Ruimao Hua*
Department of Chemistry, Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Tsinghua
University, Beijing 100084, China
S
* Supporting Information
ABSTRACT: π-Extension of 2-aryl-phenanthroimidazoles via
rhodium(III)-catalyzed C−H activation and alkyne annulation
is developed. This method enables rapid, practical and
modular assembly of diverse ring-fused phenanthroimidazoles,
including an unusual rearrangement product using aryl-alkyl
asymmetric alkyne and a thiophene fused product which could
serve as a Fe3+ fluorescent probe. The feasibility of the one-pot
synthesis and ruthenium(II)-catalyzed versions of this reaction
was also verified.
Scheme 1. Examples of Phenanthroimidazole Derivatives for
Use
INTRODUCTION
■
1H-Phenanthro[9,10-d]imidazole, which is usually called
phenanthroimidazole (PI) for short, is a rigid π-conjugated
heterocyclic skeleton fused by imidazole and phenanthrene.
The PI unit shows excellent electron injection and transport
properties and good thermal stability, making it a suitable
component for organic semiconductors used in organic light-
emitting diodes (OLEDs)1 and solar cells2 (Scheme 1). For
example, some PI−triphenylamine derivatives were employed
in OLEDs as efficient deep-blue emitters,1a and some PI−
carbazole derivatives are applicable bipolar hosts for green and
yellow phosphorescent OLEDs.1b PI chromophore were
developed for dye-sensitized solar cells which exhibited good
efficiencies up to 4.68%.2a PI unit has also been widely used in
syntheses of useful fluorophores,3 such as superradiant laser
dye,3a ratiometric fluorescent probes for cysteine and
homocysteine,3b fluorescent ionic liquid sensor arrays,3c and
green component for RGB-emitting molecular pixel system.3d
In addition, the PI unit has been employed as a component for
host molecules,4 such as a molecular tweezer to host 1,3,5-
trinitrobenzene.4a
Ring-fusion of a conjugated parent molecule is a robust tool
to build a library of π-extended derivatives with tunable π-
electron distribution and π−π stacking.5 The related optical and
electrical properties, such as fluorescence, electron mobility,
and band gap are shifted and diversified after π-extension,
which is crucial for development of new materials. PI
derivatives for use are typically substituted with aryls at the 2-
and/or 1-position via σ-bonds (Scheme 1).1−4 Though a few
ring-fused PI derivatives are known, they are synthesized from
restrictive substrates under harsh conditions,6 while direct π-
extension of the PI parent molecule is still challenging. As
alkyne is an ideal C2 synthon to extend a conjugated system
with high atom economy and substitution degree, we focused
on direct π-extension of the PI parent molecule via alkyne
annulation.
In the past decade, C−H activation has emerged as a robust
and versatile tool for atom-economical assembly of hetero-
cycles,7−10 syntheses, and late-stage diversification of functional
Received: February 19, 2014
Published: April 8, 2014
© 2014 American Chemical Society
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molecules.11 In 2008, Satoh and Miura8 disclosed an
imidazoisoquinoline synthesis via Rh(III)-catalyzed oxidative
coupling of 2-aryl-1H-imidazoles and alkynes. This work
unveiled a direct strategy for alkyne annulation of arene−
azaarene biaryls via C−H/N−H bond cleavage.8−10 However,
only two examples were investigated, and a costly ligand
tetraphenylcyclopentadiene (C5H2Ph4) was needed to activate
the Rh(III) catalyst.
a
Table 1. Optimization of Conditions
Encouraged by Miura’s work8a and our continuous efforts12
on N-annulation via C−H activation, we envisioned that 2-aryl-
PIs should be suitable substrates for alkyne annulation to form
π-extended PIs with a unique phenanthrene/imidazole/
isoquinoline fused heterocyclic system (Scheme 2). It should
b
entry
catalyst
additive
solvent
time (h)
yield (%)
c
d
1
Rh(III)
Rh(III)
Rh(III)
Rh(III)
Rh(III)
Rh(III)
DMF
16
12
12
12
12
12
12
12
24
24
24
24
24
30
61
68
74
d
2
3
4
5
DMF
d
d
dioxane
acetone
Scheme 2. Reaction Design
e
acetone
acetone
acetone
acetone
acetone
DCE
81 (83 )
f
6
80
78
75
35
37
42
40
g
7
Rh(III)
Rh(III)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
Ru(II)
h
8
9
10
11
12
13
i
AgSbF6
DCE
i
KPF6
DCE
j
e
Na2CO3
DCE
56 (58 )
a
Conditions: 1a (0.20 mmol), 2a (0.28 mmol), Cu(OAc)2·H2O (0.44
mmol), [Cp*RhCl2]2 (2.5 mol %) or [Ru(p-cymene)Cl2]2 (5 mol %),
b
c
d
solvent (2.0 mL). Isolated yield of 3aa. 80 °C. 1.0 mL of solvent.
be note that the 2-aryl-PI substrates are readily available via
facile multicomponent reaction of 9,10-phenanthraquinone,
aryl aldehyde, and ammonium acetate. In addition, this reaction
could also be incorporated with the subsequent alkyne
annulation in one-pot. Thus, a highly π-extended polyheter-
ocyclic library could be rapid assembled from simple building
blocks in a modular fashion.
e
f
g
0.5 mmol scale. Cu(OAc)2 (0.44 mmol) as oxidant. [Cp*Rh-
h
i
(MeCN)3](SbF6)2 (5 mol %) as catalyst. Without N2 protection. 20
mmol %. 2.0 equiv.
j
10) compared to Rh(III)-catalyzed conditions (entry 5).
Adding an additive such as AgSbF6 or KPF6 gave only a
slightly improved yield (entries 11 and 12), while adding 2.0
equiv of Na2CO3 gave 58% yield on a 0.5 mmol scale (entry
13). With our keen interest in C−H activation and alkyne
annulation of in situ ammoniated species,12,13 we embarked on
preparation and π-extension of 2-aryl-PIs in one pot.
Trifluoroethanol (TFE) was found to be an optimal medium
for its high compatibility in both steps.14 Though the yield was
only moderate [56% using cat. Rh(III); 32% using cat. Ru(II)],
this protocol enables assembly of ring-fused PIs from simple
building blocks in a step-economic procedure (Scheme 3).
RESULTS AND DISCUSSION
■
We commenced our study by employing 2-phenyl-PI (1a) and
diphenylacetylene (2a) as substrates, [Cp*RhCl2]2 as catalyst
precursor, and stoichiometric Cu(OAc)2·H2O as oxidant, yet
without the C5H2Ph4 ligand (Table 1). Ring-fused product 3aa
was obtained as expected. The reaction was sluggish at 80 °C
(entry 1), and elevating the temperature to 120 °C gave an
improved yield (entry 2). After an extensive survey of solvents,
reaction in dioxane (entry 3) or acetone (entry 4) gave nearly
full conversion, while using other solvents such as DCE,
toluene, and t-AmOH gave lower conversion. Due to the low
solubility of 1a and Cu(II) salt in acetone, the reaction was
carried out in a dilute solvent and gave an improved yield
(entry 5). A satisfactory yield (83%) was obtained under these
conditions on a 0.5 mmol scale. The yield was not further
improved by either replacing Cu(OAc)2·H2O with anhydrous
Cu(OAc)2 (entry 6) or using a cation form of Rh(III) catalyst
[Cp*Rh(MeCN)3](SbF6)2 (entry 7). Reaction carried out
without nitrogen protection also proceeded smoothly, with a
slightly declined yield (entry 8). However, using catalytic
Cu(II) for aerobic oxidative annulation gave an unsatisfactory
result in either acetone with an air balloon or o-xylene in an
open flask.
Scheme 3. One-Pot Synthesis of 3aa
Under the optimized conditions (Table 1, entry 5, in 0.5
mmol scale; also “standard conditions” for following studies),
we set out to examine the generality of the reaction (Table 2).
With 2a as alkyne substrate, a range of 2-aryl-PI substrates with
different para-substituents were surveyed. Both alkyl- and aryl-
substituted substrates reacted well to afford 3ba (92%) and 3ca
(85%), respectively. Compound 3ba has a much better
solubility in common organic solvents than 3aa, which would
be beneficial for fabrication of solution-processed devices.
We then turned our attention to [Ru(p-cymene)Cl2]2,7e
a
Ru(II) catalyst that has similar structure, similar catalytic
activity in many examples, and much lower price with
[Cp*RhCl2]2. Ru(II) was also found to be active for catalyzing
the reaction, though the conversion was much lower even with
higher catalyst loading and longer reaction time (entries 9 and
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a
reductive elimination to obtain 4ad. For a complete proposed
mechanism for the formation of 3ad and 4ad, see Scheme S1 in
the Supporting Information.
Table 2. General Substituent Scope
As shown in the crystal structure of 4ad (Figure 1), the
phenyl group is almost perpendicular to the PI skeleton. The
entry
1 (R1)
1a (H)
2 (R2)
2a (Ph)
3
yield (%)
1
2
3aa
3ba
3ca
3da
3ea
3fa
83
92
85
42
67
51
90
93
80
64
1b (t-Bu)
1c (Ph)
1d (OMe)
1e (NMe2)
1f (F)
2a
3
2a
4
2a
5
2a
6
2a
7
1g (Cl)
1h (Br)
1a
2a
3ga
3ha
3ab
3ac
8
2a
9
2b (4-MeOC6H4)
2c (4-ClC6H4)
10
1a
a
Reactions were carried out using 1 (0.50 mmol) and 2 (0.70 mmol)
Figure 1. X-ray structural details of 4ad: (a) ORTEP drawing of 4ad
(one of the enantiomers) with 50% probability ellipsoids; (b) dimer of
the two enantiomers in a unit cell; (c) one-dimensional packing of the
two enantiomers along the a direction.
with [Cp*RhCl2]2 (2.5 mol %) and Cu(OAc)2·H2O (1.1 mmol) in 5.0
mL of acetone at 120 °C for 12 h under N2.
Substrates bearing an electron-donating group such as OMe
and NMe2, as well as fluorinated substrate, afforded 3da−fa in
lower yield. Gratifyingly, substrates with Cl and Br reacted quite
well to afford the corresponding halogenated products (3ga,
90%; 3ha, 93%), which would greatly facilitate further
derivatization of the fused PI products via functional group
transformations or cross-coupling reactions. The reaction
proceeded smoothly with diarylalkynes with OMe or Cl as
para-substituents to afford 3ab and 3ac, respectively.
Interestingly, when asymmetric alkyne 2d was employed, two
types of products (3ad and 4ad) were obtained, with the
phenyl at different positions (Scheme 4). The rearrangement
product 4ad has a chiral center adjacent to a nitrogen atom and
an exocyclic double bond. A possible pathway8a to form the
rearrangement product 4ad may be triggered by β-elimination
of rhodacycle intermediate M1 to form M2, followed by
intramolecular allene insertion15 to form M3 and then
two enantiomers of 4ad formed a dimer in the unit cell and
packed alternately along the a direction. The one-dimensional
molecular packing was also observed in crystal structures of 3aa
and 3ad (see the Supporting Information), indicating π−π
stacking of the PI skeleton.
As replacing benzene to polycyclic arene or heterocyclic
arene is a widely used strategy to regulate properties of
fluorophores and organic semiconductors, we became inter-
ested in extending this method to PI substrates with other 2-
aryls. Naphthalene-fused products (3ia and 3ja) and thiophene-
fused products (3ka and 3la) were obtained as expected from
the corresponding 2-aryl PIs 1i−l (Table 3). The regioselective
formation of 3ja was confirmed with X-ray analysis, and one-
dimensional molecular packing was also observed in its crystal
structure. Though the yields were not high, these products
greatly enriched the diversity of the fused PI library. In
particular, we envisioned that 3ka could be a candidate for a
fluorescent ligand for metal ions.
Scheme 4. Formation of the Rearrangement Products
To illustrate the utility of our product, we employed 3ka as a
fluorescent probe for Fe3+ detection.16 As shown in Figure 2a,
the fluorescence intensity of acetone solution of 3ka showed
4.6 times enhancement and slightly blue shift after Fe3+ adding.
In addition, the fluorescence change could be detected under a
UV lamp by naked eye. Almost no change were observed in the
fluorescence emission spectra of 3ka solution by adding other
metal ions, such as Li+, Ag+, Zn2+, Cu2+, Ni2+, and Co2+, while
only Cr3+ gave some interference (Figure 2b).16 In control
experiments, adding Fe3+ into solution of 3aa or 3ia showed no
change in the fluorescence emission spectrum, while adding
Fe3+ into solution of 2-(2-thienyl)-PI 1k weakened the
fluorescence slightly. We surmised that N in imidazole and S
in thiophene in 3ka could serve as a bidentate ligand for Fe3+,17
while the fused ring could enhance the structural rigidity and
change the π-electron distribution.
In summary, we have developed a modular approach for
rapid access ring-fused phenanthroimidazoles via Rh(III)-
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Table 3. Scope of Diverse Fused Products
catalyzed C−H activation and alkyne annulation. This method
enables direct π-extension of 2-arylphenanthroimidazoles,
which is a class of widely used and readily available parent
molecules. One-pot synthesis and Ru(II)-catalyzed C−H
activation for the reaction were also explored. One-dimensional
molecular packing was observed in the crystal structures of
fused product 3 and the unusual rearrangement product 4ad.
The thiophene-fused product 3ka showed a selective
fluorescent response for Fe3+, which gave an illustration for
materials development using molecules with novel skeletons
that assembled by newly developed synthetic tools such as C−
H activation.
Figure 2. Selective Fe3+ detection using 3ka: (a) fluorescence emission
spectra (λex = 356 nm) of 3ka acetone solvent with different
concentration of Fe3+ (10−70 μM). (b) Fluorescence emission spectra
(λex = 356 nm) of 3ka acetone solvent (50 μM) with different metal
ions (50 μM). Insert: photo of 3ka acetone solvent without (c-1) or
with (c-2) Fe3+ under a UV lamp (λex = 365 nm).
ized Mo Kα radiation at 294 1 K. Raw intensities were corrected for
Lorentz and polarization effects. The structures were refined on F2 by
full-matrix least-squares methods.
Fluorescence Analysis. Fluorescence emission spectra were
measured under excitation at 356 nm. Test solutions containing 50
μM 3ka and 10x μM Fe3+ (x = 1, 2, 3, 4, 5, 6, 7) were prepared by
adding 100x μL FeCl3·6H2O acetone solution (0.4 mM) and (2000−
100x) μL acetone to 2 mL of 3ka acetone solution (0.1 mM). Test
solutions containing other metal ions (Li+, Ag+, Zn2+, Cu2+, Ni2+, Co2+,
and Cr3+) were prepared by using their chlorides (for Li+, Zn2+, and
Co2+) or nitrates (for Ag+, Ni2+, and Cr3+) instead of FeCl3·6H2O.
General Procedure for Synthesis of 3. To a 25 mL tube
equipped with a magnetic stirrer were added sequentially 2-aryl-1H-
phenanthro[9,10-d]imidazole 1 (0.5 mmol), 1,2-diarylacetylene 2 (0.7
mmol), [Cp*RhCl2]2 (7.7 mg, 0.0125 mmol, 2.5 mmol %), and
Cu(OAc)2·H2O (220.0 mg, 1.1 mmol). The tube was evacuated and
backfilled with nitrogen for three cycles. Acetone (5.0 mL) was added
under nitrogen, and the tube was sealed. The tube was immersed in an
oil bath (120 °C) and stirred for 12 h. After removal of the solvent
under reduced pressure, purification was performed by flash column
chromatography on silica gel with petroleum ether/acetone (typically
gradient mixture ratio from 100:0 to 80:20) as eluant to afford 3.
5,6-Diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]isoquinoline
(3aa): pale yellow solid (194.5 mg, 83%); mp 264−266 °C; 1H NMR
(300 MHz, CDCl3) δ 9.11−9.04 (2H, m), 8.66−8.58 (2H, m), 7.80−
7.65 (3H, m), 7.53−7.48 (1H, m), 7.38−6.94 (13H, m), 6.83−6.78
(1H, m); 13C NMR (75 MHz, CDCl3) δ 148.0, 140.7, 137.1, 135.6,
135.0, 131.8, 130.0, 129.8, 129.1, 128.4, 128.3, 128.2, 128.1, 128.0,
127.4, 127.3, 126.64, 126.56, 126.2, 124.7, 124.6, 124.1, 123.8, 123.7,
EXPERIMENTAL SECTION
■
General Methods. All organic compounds and metal salts were
analytically pure and used directly after purchased. All solvents were
used without any particular precautions to extrude moisture. 2-Aryl-
1H-phenanthro[9,10-d]imidazoles 1 were prepared following a
literature procedure.18 1,2-Bis(4-methoxyphenyl)ethyne 2b and 1,2-
bis(4-chlorophenyl)ethyne 2c were prepared by a reported proce-
dure19 with our improvement.12a [Cp*RhCl2]2 was prepared from
RhCl3·xH2O following a literature procedure.20 All products are new
compounds, which were characterized by H and 13C NMR, HRMS,
1
and melting point. Nuclear magnetic resonance (NMR) spectra were
1
recorded using CDCl3 as solvent at 298 K. H NMR (300 MHz)
chemical shifts (δ) were referenced to internal standard TMS (for 1H,
δ = 0.00). 13C NMR (75 MHz) chemical shifts were referenced to
internal solvent CDCl3 (for 13C, δ = 77.16). In some 13C NMR
spectra, the number of distinguishable peaks is less than expected due
to overlap. HRMS spectra were obtained on a high-resolution
magnetic sector mass spectrometer with electron spray ionization
(ESI) source. The melting points were uncorrected.
X-ray Analysis. Single crystals of 3aa, 3ja, 3ad, and 4ad·MeOH
were obtained by slow evaporation of their solution by using a good
solvent (acetone or CH2Cl2) and a poor solvent (MeOH or hexane) as
cosolvent systems. The single-crystal X-ray diffraction data were
collected on a diffractometer equipped with graphite-monochromat-
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123.5, 123.3, 123.0; HRMS (ESI) calcd for C35H23N2 [M + H]+
471.1856, found 471.1854.
3-tert-Butyl-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ba): off-white solid (242.7 mg, 92%); mp 260−262 °C;
1H NMR (300 MHz, CDCl3) δ 9.07−8.99 (2H, m), 8.61−8.54 (2H,
5,6-Bis(4-methoxyphenyl)phenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ab): pale yellow solid (212.4 mg, 80%); mp 258−259
1
°C; H NMR (300 MHz, CDCl3) δ 9.07−9.03 (2H, m), 8.63−8.55
(2H, m), 7.77−7.61 (3H, m), 7.49−7.22 (3H, m), 7.04−6.96 (3H, m),
6.90−6.80 (5H, m), 6.48−6.45 (2H, m), 3.80 (3H, s), 3.61 (3H, s);
13C NMR (75 MHz, CDCl3) δ 159.4, 158.7, 148.0, 140.7, 135.1, 132.7,
132.2, 131.2, 129.7, 129.2, 129.0, 128.2, 128.1, 127.7, 127.4, 127.2,
126.5, 126.4, 125.4, 124.60, 124.55, 124.5, 123.7, 123.5, 123.2, 123.0,
113.8, 113.4, 55.3; HRMS (ESI) calcd for C37H27N2O2 [M + H]+
531.2067, found 531.2065.
m), 7.77−7.60 (3H, m), 7.36−7.15 (7H, m), 7.03−6.89 (6H, m),
6.79−6.74 (1H, m), 1.28 (9H, s); 13C NMR (75 MHz, CDCl3) δ
152.2, 148.0, 140.7, 137.1, 135.7, 134.7, 131.7, 131.5, 129.9, 129.7,
128.1, 128.0, 127.9, 127.4, 127.3, 127.1, 126.44, 126.39, 126.1, 124.4,
123.9, 123.7, 123.5, 123.4, 123.2, 122.9, 122.5, 121.4, 35.2, 31.3;
HRMS (ESI) calcd for C39H31N2 [M + H]+ 527.2482, found 527.2480.
3,5,6-Triphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]isoquinoline
(3ca): pale yellow solid (232.8 mg, 85%); mp 277−279 °C; 1H NMR
(300 MHz, CDCl3) δ 9.09−9.03 (2H, m), 8.60−8.54 (2H, m), 7.88−
7.84 (1H, m), 7.75−7.70 (1H, m), 7.64−7.49 (4H, m), 7.40−7.10
(9H, m), 7.05−6.87 (6H, m), 6.78−6.73 (1H, m); 13C NMR (75
MHz, CDCl3) δ 147.8, 141.6, 140.9, 140.7, 136.9, 135.5, 135.2, 132.0,
131.7, 130.0, 129.7, 129.0, 128.31, 128.26, 128.2, 127.9, 127.7, 127.42,
127.35, 127.2, 127.1, 126.6, 126.1, 125.2, 124.6, 124.5, 124.1, 123.72,
123.69, 123.4, 123.2, 122.9, 122.6; HRMS (ESI) calcd for C41H27N2
[M + H]+ 547.2169, found 547.2167.
5,6-Bis(4-chlorophenyl)phenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ac): pale yellow solid (173.4 mg, 64%); mp 292−293
1
°C; H NMR (300 MHz, CDCl3) δ 9.04−8.99 (2H, m), 8.63−8.56
(2H, m), 7.78−7.64 (3H, m), 7.47−7.44 (1H, m), 7.33−7.23 (4H, m),
7.05−6.83 (8H, m); 13C NMR (75 MHz, CDCl3) δ 147.7, 140.8,
135.2, 134.6, 133.8, 133.7, 133.0, 131.1, 129.8, 129.2, 128.8, 128.43,
128.35, 128.3, 127.4, 127.2, 126.8, 126.2, 125.1, 124.7, 124.6 124.1,
124.0, 123.72, 123.65, 123.4, 123.3, 123.0; HRMS (ESI) calcd for
C35H21Cl2N2 [M + H]+ 539.1076, found 539.1075.
7,8-Diphenylbenzo[h]phenanthro[9′,10′:4,5]imidazo[2,1-a]-
1
isoquinoline (3ia): yellow solid (104.5 mg, 40%); mp >300 °C; H
NMR (300 MHz, CDCl3) δ 11.33 (1H, d, J = 8.6 Hz), 9.22 (1H, d, J =
7.6 Hz), 8.67−8.58 (2H, m), 8.03−7.68 (6H, m), 7.45−6.80 (14H,
m); 13C NMR (75 MHz, CDCl3) δ 148.1, 141.2, 137.7, 135.7, 135.6,
133.0, 132.05, 131.3, 130.1, 130.0, 129.9, 129.8, 129.6, 128.4, 128.33,
128.28, 128.1, 127.9, 127.51, 127.47, 127.3, 127.0, 126.8, 126.7, 124.6,
124.2, 124.1, 123.8, 123.4, 123.3, 123.1, 122.2, 118.8; HRMS (ESI)
calcd for C39H25N2 [M + H]+ 521.2012, found 521.2011.
10,11-Diphenylbenzo[g]phenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ja): yellow solid (138.7 mg, 53%); mp 288−290 °C;
1H NMR (300 MHz, CDCl3) δ 9.54 (1H, s), 9.07−9.04 (1H, m),
3-Methoxy-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3da): pale yellow solid (104.6 mg, 42%); mp 228−229
1
°C; H NMR (300 MHz, CDCl3) δ 9.05−8.99 (2H, m), 8.67−8.59
(2H, m), 7.80−7.65 (2H, m), 7.33−7.24 (5H, m), 7.18−7.15 (2H, m),
7.10−6.94 (6H, m), 6.83−6.75 (2H, m), 3.73 (3H, s); 13C NMR (75
MHz, CDCl3) δ 160.4, 148.3, 140.7, 137.1, 135.7, 135.6, 133.5, 131.7,
130.0, 129.7, 128.4, 127.99, 127.95, 127.43, 127.38, 127.2, 126.6,
126.5, 125.8, 124.6, 123.9, 123.7, 123.54, 123.49, 123.4, 123.3, 123.0,
117.8, 117.0, 108.7, 55.4; HRMS (ESI) calcd for C36H25N2O [M +
H]+ 501.1961, found 501.1961.
8.64−8.56 (2H, m), 8.16 (1H, d, J = 8.1 Hz), 7.78−7.63 (4H, m),
7.57−7.44 (2H, m), 7.37−7.19 (6H, m), 7.08−6.91 (6H, m), 6.84−
6.79 (1H, m); 13C NMR (75 MHz, CDCl3) δ 148.3, 140.2, 137.2,
135.5, 134.5, 133.4, 132.6, 131.8, 130.1, 129.8, 129.6, 128.6, 128.4,
128.3, 127.9, 127.5, 127.3, 126.8, 126.5, 126.2, 126.0, 124.6, 124.2,
123.94, 123.88, 123.6, 123.4, 123.3, 123.0, 122.1; HRMS (ESI) calcd
for C39H25N2 [M + H]+ 521.2012, found 521.2011.
N,N-Dimethyl-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinolin-3-amine (3ea): yellow solid (172.8 mg, 67%); mp 275−
277 °C. 1H NMR (300 MHz, CDCl3) δ 9.05 (1H, d, J = 7.9 Hz), 8.89
(1H, d, J = 8.9 Hz), 8.63−8.55 (2H, m), 7.77−7.60 (2H, m), 7.27−
6.74 (14H, m), 6.37−6.36 (1H, m), 2.83 (6H, s); 13C NMR (75 MHz,
CDCl3) δ 150.8, 149.0, 140.7, 137.6, 136.0, 135.0, 133.5, 131.7, 130.0,
129.6, 128.13, 128.08, 127.8, 127.6, 127.4, 127.1, 127.0, 126.2, 126.0,
125.9, 124.4, 123.7, 123.6, 123.2, 123.12, 123.06, 122.9, 114.5, 113.9,
106.8, 40.2; HRMS (ESI) calcd for C37H28N3 [M + H]+ 514.2278,
found 514.2274.
4,5-Diphenylphenanthro[9′,10′:4,5]imidazo[1,2-a]thieno[2,3-c]-
1
pyridine (3ka): yellow solid (161.6 mg, 68%); mp 299−301 °C; H
NMR (300 MHz, CDCl3) δ 9.04−9.01 (1H, m), 8.67−8.60 (2H, m),
7.79−7.67 (2H, m), 7.53 (1H, d, J = 5.2 Hz), 7.33−6.99 (13H, m),
6.83−6.78 (1H, m); 13C NMR (75 MHz, CDCl3) δ 145.5, 141.6,
139.3, 137.7, 135.0, 134.8, 131.0, 130.0, 128.5, 128.3, 128.21, 128.15,
128.0, 127.4, 127.24, 127.21, 126.9, 125.5, 124.6, 124.1, 124.04,
123.97, 123.7, 123.3, 123.0, 122.8; HRMS (ESI) calcd for C33H21N2S
[M + H]+ 477.1420, found 477.1417.
3-Fluoro-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3fa): off-white solid (125.1 mg, 51%); mp 283−285 °C;
1H NMR (300 MHz, CDCl3) δ 9.05−8.97 (2H, m), 8.62−8.55 (2H,
m), 7.76−7.62 (2H, m), 7.39−7.22 (5H, m), 7.10−6.89 (10H, m); 13
C
1
NMR (75 MHz, CDCl3) δ 163.1 (d, JCF = 248.5 Hz), 147.5, 140.7,
3
136.6, 136.1, 135.3, 133.6 (d, JCF = 9.1 Hz), 131.6, 130.7, 129.9,
4,5-Diphenylphenanthro[9′,10′:4,5]imidazo[1,2-a]thieno[3,2-c]-
pyridine (3la): pale yellow solid (116.4 mg, 49%); mp 255−257 °C;
1H NMR (300 MHz, CDCl3) δ 9.02−9.00 (1H, m), 8.67−8.60 (2H,
129.8, 128.6, 128.5, 128.2, 128.0, 127.6, 127.34, 127.25, 126.7, 125.3
(d, 4JCF = 3.3 Hz), 124.6, 124.0, 123.74, 123.67, 123.5, 123.34, 123.26,
2
2
123.0, 120.2, 116.7 (d, JCF = 23.8 Hz), 111.7 (d, JCF = 23.5 Hz);
HRMS (ESI) calcd for C35H22FN2 [M + H]+ 489.1762, found
489.1760.
m), 8.26 (1H, d, J = 5.4 Hz), 7.79−7.66 (2H, m), 7.56 (1H, d, J = 5.4
Hz), 7.34−7.11 (7H, m), 7.05−6.98 (5H, m), 6.83−6.78 (1H, m); 13
C
NMR (75 MHz, CDCl3) δ 146.4, 141.8, 141.2, 137.9, 134.8, 133.7,
130.4, 130.1, 129.9, 128.6, 128.2, 128.1, 128.0, 127.5, 127.4, 127.3,
126.8, 124.5, 124.0, 123.8, 123.7, 123.6, 123.5, 123.3, 123.2, 123.0,
122.6; HRMS (ESI) calcd for C33H21N2S [M + H]+ 477.1420, found
477.1419.
3-Chloro-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ga): pale yellow solid (228.1 mg, 90%); mp 285−287
1
°C; H NMR (300 MHz, CDCl3) δ 9.00−8.96 (2H, m), 8.64−8.57
(2H, m), 7.78−7.58 (3H, m), 7.34−7.24 (5H, m), 7.13−7.05 (3H, m),
7.02−6.92 (5H, m), 6.82−6.76 (1H, m); 13C NMR (75 MHz, CDCl3)
δ 147.3, 140.8, 136.3, 136.1, 135.2, 135.1, 132.8, 131.6, 129.9, 129.8,
128.6, 128.5, 128.3, 128.0, 127.7, 127.3, 127.2, 126.8, 126.3, 125.8,
125.0, 124.6, 124.1, 123.9, 123.7, 123.3, 123.0, 121.9; HRMS (ESI)
calcd for C35H22ClN2 [M + H]+ 505.1466, found 505.1466.
Procedure for Synthesis of 3ad and 4ad. To a 25 mL tube
equipped with a magnetic stirrer were added sequentially 2-phenyl-1H-
phenanthro[9,10-d]imidazole 1a (147.2 mg, 0.5 mmol), [Cp*RhCl2]2
(7.7 mg, 0.0125 mmol, 2.5 mmol %), and Cu(OAc)2·H2O (220.0 mg,
1.1 mmol). The tube was evacuated and backfilled with nitrogen for
three cycles. 1-Phenyl-1-propyne 2d (92.9 mg, 0.8 mmol) was
dissolved in acetone (5.0 mL) and added under nitrogen. The tube
was sealed, immersed in an oil bath (120 °C), and stirred for 12 h.
After removal of the solvent under reduced pressure, purification was
performed by flash column chromatography on silica gel with
petroleum ether/acetone (gradient mixture ratio from 100:0 to
80:20) as eluant to afford 3ad (49.8 mg, 24%) and 4ad (79.2 mg,
39%).
3-Bromo-5,6-diphenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ha): pale yellow solid (256.5 mg, 93%); mp >300 °C;
1H NMR (300 MHz, CDCl3) δ 9.01−8.91 (2H, m), 8.66−8.57 (2H,
m), 7.79−7.66 (3H, m), 7.49−7.48 (1H, m), 7.36−6.94 (12H, m),
6.83−6.78 (1H, m); 13C NMR (75 MHz, CDCl3) δ 147.4, 140.9,
136.3, 136.2, 135.2, 133.1, 131.7, 131.2, 129.94, 129.87, 128.9, 128.7,
128.5, 128.3, 128.1, 127.7, 127.4, 127.2, 126.8, 126.4, 125.0, 124.7,
124.2, 124.0, 123.8, 123.7, 123.6, 123.3, 123.0, 122.3; HRMS (ESI)
calcd for C35H22BrN2 [M + H]+ 549.0961, found 549.0958.
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Article
6-Methyl-5-phenylphenanthro[9′,10′:4,5]imidazo[2,1-a]-
isoquinoline (3ad): pale yellow solid (49.8 mg, 24%); mp 228−230
Tan, W. Org. Lett. 2008, 10, 5577. (c) Zhu, W.; Li, W.; Yang, H.; Jiang,
Y.; Wang, C.; Chen, Y.; Li, G. Chem.−Eur. J. 2013, 19, 11603.
(d) Kwon, J. E.; Park, S.; Park, S. Y. J. Am. Chem. Soc. 2013, 135,
11239.
1
°C; H NMR (300 MHz, CDCl3) δ 8.99−8.95 (2H, m), 8.64−8.61
(2H, m), 7.94−7.92 (1H, m), 7.76−7.20 (12H, m), 2.51 (3H, s); 13C
NMR (75 MHz, CDCl3) δ 147.8, 141.3, 137.7, 131.84, 131.76, 131.2,
129.7, 129.0, 128.9, 128.5, 128.1, 127.4, 127.2, 126.6, 126.4, 125.6,
125.4, 124.6, 124.42, 124.35, 124.3, 124.2, 123.6, 123.2, 123.0, 22.9;
HRMS (ESI) calcd for C30H21N2 [M + H]+ 409.1699, found 409.1699.
5-Methylene-6-phenyl-5,6-dihydrophenanthro[9′,10′:4,5]-
imidazo[2,1-a]isoquinoline (4ad): pale yellow solid (79.2 mg, 39%);
(4) (a) Krebs, F. C.; Jørgensen, M. J. Org. Chem. 2001, 66, 6169.
(b) Botana, E.; Nattinen, K.; Prados, P.; Rissanen, K.; de Mendoza, J.
̈
Org. Lett. 2004, 6, 1091.
(5) For a review, see: (a) Wu, W.; Liu, Y.; Zhu, D. Chem. Soc. Rev.
2010, 39, 1489. For recent examples, see: (b) Gao, X.; Di, C.; Hu, Y.;
Yang, X.; Fan, H.; Zhang, F.; Liu, Y.; Li, H.; Zhu, D. J. Am. Chem. Soc.
2010, 132, 3697. (c) Yue, W.; Gao, J.; Li, Y.; Jiang, W.; Di Motta, S.;
Negri, F.; Wang, Z. J. Am. Chem. Soc. 2011, 133, 18054. (d) Fukutomi,
Y.; Nakano, M.; Hu, J.-Y.; Osaka, I.; Takimiya, K. J. Am. Chem. Soc.
2013, 135, 11445. (e) Fukazawa, A.; Kishi, D.; Tanaka, Y.; Seki, S.;
Yamaguchi, S. Angew. Chem., Int. Ed. 2013, 52, 12091.
1
mp 209−211 °C; H NMR (300 MHz, CDCl3) δ 8.89 (1H, dd, J =
8.0, 1.2 Hz), 8.74−8.70 (1H, m), 8.64 (1H, d, J = 8.3 Hz), 8.51−8.49
(1H, m), 8.06−8.03 (1H, m), 7.76−7.70 (1H, m), 7.64−7.04 (11H,
m), 6.93 (1H, s), 5.71 (1H, s), 5.70 (1H, s); 13C NMR (75 MHz,
CDCl3) δ 146.6, 141.9, 138.9, 138.6, 130.6, 129.8, 129.6, 129.2, 129.0,
128.3, 128.1, 127.5, 127.4, 126.8, 126.2, 125.7, 125.4, 125.12, 125.08,
124.9, 124.3, 123.2, 122.9, 122.8, 120.9, 115.6, 64.6; HRMS (ESI)
calcd for C30H21N2 [M + H]+ 409.1699, found 409.1697.
(6) (a) Quante, H.; Geerts, Y.; Mullen, K. Chem. Mater. 1997, 9, 495.
̈
́
(b) Mamada, M.; Bolιvar, C. P.; Anzenbacher, P., Jr. Org. Lett. 2011,
13, 4882 Fused PI products were obtained from phenanthrene-9,10-
diamine and naphthalene dicarboxylic anhydride at 220 °C or higher
temperature..
One-Pot Procedure for Synthesis of 3aa. To a 25 mL tube
equipped with a magnetic stirrer were added 9,10-phenanthraquinone
(104.1 mg, 0.5 mmol), NH4OAc (115.6 mg, 1.5 mmol), benzaldehyde
(53.0 mg, 0.5 mmol), and TFE (5.0 mL). The tube was sealed,
immersed in an oil bath (120 °C), and stirred for 2 h. After the tube
was cooled, 1,2-diphenylacetylene (124.8 mg, 0.7 mmol),
[Cp*RhCl2]2 (7.7 mg, 0.0125 mmol, 2.5 mmol %), Cu(OAc)2·H2O
(240.0 mg, 1.2 mmol), and an additional 1.0 mL of TFE were added to
the reaction mixture. The tube was sealed again, immersed back to the
oil bath (120 °C), and stirred for 16 h. Chromatography purification
was performed to afford 3aa (131.1 mg, 56%). Replacing [Cp*RhCl2]2
with [Ru(p-cymene)Cl2]2 (15.3 mg, 0.025 mmol, 5 mol %) also
afforded 3aa (74.8 mg, 32%).
(7) For recent reviews on heterocycle syntheses via C−H activation,
see: (a) Satoh, T.; Miura, M. Chem.−Eur. J. 2010, 16, 11212. (b) Song,
G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (c) Patureau, F.
W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31.
(d) Colby, D. A.; Tsai, A. S.; Bergman, R. G.; Ellman, J. A. Acc. Chem.
Res. 2012, 45, 814. (e) Zhu, C.; Wang, R.; Falck, J. R. Chem.Asian J.
2012, 7, 1502. (f) Ackermann, L. Acc. Chem. Res. 2014, 47, 281.
(8) (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem.,
Int. Ed. 2008, 47, 4019. For related examples on synthesis of
imidazole-fused heterocycles via C−H activation, see: (b) Huang, J.-R.;
Dong, L.; Han, B.; Peng, C.; Chen, Y.-C. Chem.−Eur. J. 2012, 18,
8896. (c) Reddy, V. P.; Iwasaki, T.; Kambe, N. Org. Biomol. Chem.
2013, 11, 2249. (d) Peng, J.; Shang, G.; Chen, C.; Miao, Z.; L, B. J.
Org. Chem. 2013, 78, 1242.
(9) For other examples using this strategy, see: (a) Morimoto, K.;
Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 2068. (b) Li, X.;
Zhao, M. J. Org. Chem. 2011, 76, 8530. (c) Ackermann, L.; Wang, L.;
Lygin, A. V. Chem. Sci. 2012, 3, 177. (d) Li, B.; Feng, H.; Wang, N.;
Ma, J.; Song, H.; Xu, S.; Wang, B. Chem.−Eur. J. 2012, 18, 12873.
(e) Ma, W.; Graczyk, K.; Ackermann, L. Org. Lett. 2012, 14, 6318.
(10) For another leading work on Rh(III)-catalyzed alkyne
annulation via C−H/N−H bond cleavage, see: (a) Stuart, D. R.;
Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474.
See also: (b) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 18326.
ASSOCIATED CONTENT
■
S
* Supporting Information
Proposed mechanism, copies of 1H and 13C NMR spectra of all
products, and X-ray structural details (including CIF) of 3aa,
3ja, 3ad, and 4ad·MeOH. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ruimao@mail.tsinghua.edu.cn.
■
Notes
The authors declare no competing financial interest.
(11) For a review, see: (a) Wencel-Delord, J.; Glorius, F. Nat. Chem.
2013, 5, 369. For examples of syntheses of functional molecules via
Rh(III)-catalyzed C−H activation, see: (b) He, T.; Too, P. C.; Chen,
R.; Chiba, S.; Sun, H. Chem.−Asian J. 2012, 7, 2090. (c) Dong, J.;
Long, D.; Song, F.; Wu, N.; Guo, Q.; Lan, J.; You, J. Angew. Chem., Int.
Ed. 2013, 52, 580. (d) Luo, C.-Z.; Gandeepan, P.; Jayakumar, J.;
Parthasarathy, K.; Chang, Y.-W.; Cheng, C.-H. Chem.Eur. J. 2013,
19, 14181. (e) Lian, Y.; Bergman, R. G.; Lavis, L. D.; Ellman, J. A. J.
Am. Chem. Soc. 2013, 135, 7122.
ACKNOWLEDGMENTS
■
This project was supported by the National Natural Science
Foundation of China (21032004, 21273125) and the
Specialized Research Fund for the Doctoral Program of Higher
Education (20110002110051). We thank Prof. Ruji Wang from
Tsinghua University for his meticulous X-ray analysis.
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