Synthesis of Multisubstituted 1-Naphthoic Acids via Ru-Catalyzed C-H Activation and Double-Alkyne Annulation under Air

Article abstract of DOI:10.1021/acs.joc.9b00926

An efficient [2 + 2 + 2] benzannulation of phthalic acids/anhydrides with two alkynes was developed for synthesis of multisubstituted 1-naphthoic acids via Ru-catalyzed C-H activation. The reaction preceded well using atmospheric oxygen as the sole oxidant with high atom/step economies. Facilitated by the free carboxyl group, the products can be easily converted to diverse polycyclic molecules.

Full text of DOI:10.1021/acs.joc.9b00926

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Article
Synthesis of Multisubstituted 1-Naphthoic Acids via Ru-
Catalyzed C-H Activation and Double Alkyne Annulation Under Air
Honghao Chen, Lufeng Ouyang, Jidan Liu, Wen-Jing Shi, Guoshu Chen, and Liyao Zheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00926 • Publication Date (Web): 13 Jun 2019
Downloaded from http://pubs.acs.org on June 13, 2019
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Synthesis of Multisubstituted 1-Naphthoic Acids via Ru-Catalyzed
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C−H Activation and Double Alkyne Annulation Under Air
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Honghao Chen,† Lufeng Ouyang,† Jidan Liu, Wen-Jing Shi, Guoshu Chen, and Liyao Zheng*
School of Chemistry and Chemical Engineering, Guangzhou University,
Guangzhou 510006, P.R. China
HO2C
Ar
Ar
Ar
Ar
Ar
R
CO2H
diverse
fused
cat. Ru
+
2
– CO2
products
CO2H
R
under air
H
Ar
+ high regioselectivity + air as the sole oxidant + free CO2H for conversions
Abstract: An efficient [2+2+2] benzannulation of phthalic acids/anhydrides with two alkynes
was developed for synthesis of multisubstituted 1-naphthoic acids via Ru-catalyzed C−H
activation. The reaction preceded well using atmospheric oxygen as the sole oxidant with high
atom/step economies. Facilitated by the free carboxyl group, the products can be easily
converted to diverse polycyclic molecules.
Introduction
Owing to their unique electronic properties and geometries, multisubstituted naphthalenes
have been widely used as key components for fluorophores and semiconductors1, as well as
structural units or precursors of unusual aromatic architectures2. Meanwhile, functionalized
naphthalenes including 1-naphthoic acid are core substructures in some natural products and
bioactive molecules.3 Therefore, modular synthetic methods are highly desirable to access
multisubstituted and functionalized naphthalenes from readily available building blocks.
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The combination of C–H activation and alkyne annulation has been established as a
powerful strategy for construction of heterocycles and carbocycles.4 Since pioneer works of
Miura and Satoh,5 much progress has been made for oxidative [2+2+2] benzannulation,5-7 by
which multisubstituted naphthalenes can be obtained from simple aromatics such as benzoic
acids (Scheme 1a). These reactions are commonly catalyzed by Ir, Rh, or Pd, while Ru
catalysis seems to be favored for other coupling modes (Scheme 1b–e).4c,8,9 In particular,
Ackermann et al.9a developed a synthesis of isocoumarins using O2 as the sole oxidant. Zhao
et al.9c reported a decarboxylative hydroarylation of alkynes, and trace amount of tetraphenyl
naphthalene was detected as a by-product. These works inspired us to quest which reaction
modes would occur by using phthalic acid and alkynes.10 We envisioned that one carboxyl
group in phthalic acid may be activated by the other one, thus selective decarboxylative
coupling would be possible to afford annulated products with a free carboxyl group.11
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Scheme 1. Coupling Modes of Aromatic Acids and Alkynes
previous works
O
R
(b)
(a)
CO2H
R
R
cat. Ru
cat. Ir, Rh, Pd
O
H
O2
[O], – CO2
R
+
R
R
R
R
cat. Ru
(c)
cat. Ru
(d) cat. Ru
– CO2
O
(e)
CO2H
O
R
R
R
R
R
R
CO2H incorporated
in heterocycles
CO2H retained as a
CO2H as a traceless
directing group
functional group
this work
HO2C
R
R
R
+ free carboxyl group
+ high sustainability
+ selective annulation
R
R
CO2H
cat. Ru
+
2
– CO2
CO2H
R
under air
H
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With our continuous interests in C–H functionalization and cyclization,4d,12 we disclosed
herein a Ru(II)-catalyzed decarboxylative [2+2+2] benzannulation for rapid and modular
assembly of multisubstituted 1-naphthoic acids from readily available phthalic acids (Scheme
1). In this reaction, one carboxyl group serves as an auto-cleavable and traceless directing
group for C–H functionalization,13 while the other one is kept in the product as an easily
transformable functional group. Notably, this reaction enables air as the sole oxidant, which
improves the atom economy, sustainability and functional group tolerance.14
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Results and Discussion
We commenced the study by employing phthalic acid (1a) and diphenylacetylene (3a) as the
substrates with [Ru(p-cymene)Cl2]2 as the catalyst precursor (Table 1). When the reaction
was carried out in DMF at 100 °C under air, a 1:2 coupling product 4aa was obtained in 28%
yield with ~60% conversion of 3a (entry 1). After survey of a variety of additives, halide salts
were found to increase the reactivity and selectivity, among which tetrabutylammonium
bromide (TBAB)15 showed to be the most effective (entry 2–5). Other types of additives such
as PPh3, KPF6, NaOAc or HOAc gave lower yields (< 20%). DMAc and NMP gave no
improvement, while DMSO and toluene gave inferior results (entry 6–9). To our delight, a
biomass-derived green solvent γ-valerolactone (GVL)16 was found to be quite suitable for this
reaction (entry 10). The high boiling point and flash point nature of GVL can improve the
convenience and safety for reaction under air. As detected by TLC, significant side products
with smaller Rf were detected by using DMF as solvent, while a little side product with high
polarity was detected by using GVL. With mixed solvent of GVL and DMF as a reaction
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medium, the selectivity of the reaction can be tuned to afford 4aa up to 81% yield (entry
6
7
11–13).
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Table 1. Optimization of Conditionsa
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O
Ph
Ph
CO2H
Ph
CO2H
CO2H
Ph
Ph
cat. Ru
or
O
2
+
conditions
Ph
O
H
H
1a
2a
3a
4aa
entry substrate additive
solvent
yield (%)b
28
40
51
48
56
52
51
0
1c
2
3
4
5
6
7
8
-
DMF
DMF
DMF
DMF
DMF
DMAc
NMP
DMSO
PhMe
GVL
GVL/DMF (4:1)
GVL/DMF (9:1)
GVL/DMF (19:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
H2O
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
2a
2a
2a
2a
1a
1a
1a
NaCl
LiBr
TMABd
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
CuBr2
AgOAc
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
9
38
70
73
81
77
55
76
0
10
11
12
13
14e
15f
16
17
18c
19g
20
21
22h
23i
24c, j
0
77
80
0
59
62
73
64
GVL/H2O (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
GVL/DMF (9:1)
a Conditions: 1a or 2a (0.30 mmol), 3a (0.40 mmol), [Ru(p-cymene)Cl2]2
(0.01 mmol), additive (0.04 mmol), solvent (1.0 mL), 100 °C, 12 h, under air.
b Isolated yield of 4aa based on 3a. c 20 h. d TMAB: tetramethylammonium
bromide. e 6 mol% RuCl3·xH2O (37% Ru) was used. f O2 balloon was used. g
H2O (20 μL) was added. h 80 °C, 24 h. i 120 °C, 8 h. j 1a (0.20 mmol) and 3a
(0.44 mmol) were used, the yield was based on 1a.
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The reaction can also catalyzed by RuCl3, yet an increased catalyst loading was needed for
full conversion (entry 14). No desired product was detected by using [Cp*IrCl2]2 (Cp* =
pentamethylcyclopentadienyl), [Cp*RhCl2]2, [Cp*Rh(OAc)2]2, PdCl2 or Pd(OAc)2, though
these catalysts have been widely used in reported naphthalene synthesis.5,6 Reaction under O2
could not further improve the yield, while the formation of 4aa was completely inhibited by
Cu(II) or Ag(I) salts (entry 15–17). Phthalic anhydride (2a) is an upstream industrial
chemicals of 1a and can also be obtained from renewable source.17 The reaction using 2a
gave comparable yield in 20 h and can be accelerated by addition of 20 μL water, but using
water as a sole solvent or cosolvent gave inferior results (entry 18–21). The reaction was
sluggish at 80 °C, while side reactions were increased at 120 °C, affording 4aa in lower yield
(entry 22–23). Using excess of alkyne 3a gave slower conversion and lower yield (entry 24).
With the optimized conditions in hand, a series of substituted phthalic acids 1 or
anhydrides 2 were employed to couple with alkynes 3 to synthesize multisubstituted
1-naphthoic acids 4 (Scheme 2). Typically, comparable yields can be obtained by using the
corresponding phthalic acids or anhydrides, while their commercial availability and prices
were differed by the substituents. Various 4-substituted substrates successfully reacted with 3a
to afford products (73–90% yields) with alkyl or alkoxy groups (4ba–4da), halides (4ea, 4fa),
as well as strong electron-withdrawing groups such as CF3 (4ga) and NO2 (4ha). Trimellitic
acid also reacted well to afford 1,3-naphthalic diacid 4ia in 76% yield, while the
corresponding anhydride gave an inferior result. Dihalogenated products 4ja and 4ka could
be obtained from corresponding 4,5-disubstituted phthalic anhydrides. 2,3-Naphthalic diacid
was also reactive and a multisubstituted 9-phenanthroic acid 4la was obtained.
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Scheme 2. Scope for Synthesis of 1-Naphthoic Acidsa
5
6
7
8
Ar CO2H
Ar
R
CO2H
CO2H
Ar
Ar
cat. Ru, TBAB
+
2
GVL/DMF (9:1)
100 °C, 12 or 20 h
under air
9
R'
R
Ar
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H
Ar R'
1 (or anhydrides 2)
3
4 (R' = H or R)
Ph CO2H
Ph
Ph CO2H
Ph CO2H
Ph
Ph
Ph
Ph
Ph
Me
tBu
Ph
Ph
Ph
4aa, 81%, 80%b,c
4ba, 84%, 82%b,c
4ca, 77%b,c
Ph CO2H
Ph
Ph CO2H
Ph CO2H
Ph
Ph
Ph
Ph
Ph
OMe
Cl
Br
Ph
Ph
Ph
4da [X-ray], 85%
4ea, 83%, 85%b
4fa, 84%, 90%b
Ph CO2H
Ph CO2H
Ph CO2H
Ph
Ph
Ph
Ph
Ph
Ph
CF3
NO2
CO2H
Ph
Ph
4ha, 73%d
Ph
4ga, 86%
4ia, 76%
Ph CO2H
Ph CO2H
Ph CO2H
Ph
Ph
Ph
Ph
Ph
Ph
F
Cl
Ph
F
Ph Cl
4ka, 41%b,c,d
Ph
4la, 64%d
4ja, 78%b
Ar CO2H R = Me, 4ab, 78%
OMe, 4ac, 72%
R
R = Me,
4ai, 72%d
Ar
Ar
Ar =
Ar =
F, 4ad, 75%
R = Cl,
4aj, 56%d
Cl, 4ae, 71%
R
Ar
Br, 4af, 80%
CF3, 4ag, 76%
OCF3, 4ah, 69%d
S
R
Ar =
4ak, 42%
a
Conditions: 1 (0.30 mmol), 3 (0.40 mmol), [Ru(p-cymene)Cl2]2 (0.01 mmol),
TBAB (0.04 mmol), GVL/DMF (9:1, 1.0 mL), 100 °C, 12 h, under air. b Anhydride
2 was used. c 20 μL H2O was added. d 20 h.
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Notably, the C–H site with less steric hindrance was more favorable for this reaction to
afford 1-naphthoic acids with different substituents at 3-position with high regioselectivity
(>25:1). Clear J3 coupling of two hydrogen atoms on the naphthalene ring was observed in 1H
NMR spectrum of 4ca, 4ea and 4fa. Furthermore, the structure of 4da was unambiguously
identified by single crystal X-ray analysis (Figure S1a), which confirmed the regioselectivity.
Symmetric diaryl alkynes with either electron-donating or -withdrawing groups as
para-substituents reacted smoothly with phthalic acid to afford 4ab–4ah in 69–80% yields.
Diaryl alkynes with two methyl or chloride meta-substituents were also reactive for this
reaction to afford 4ai and 4aj, respectively. Diaryl alkynes with ortho-substituents gave low
conversion probably due to steric hindrance, while unsymmetrical diaryl alkynes gave messy
results probably due to poor regioselectivity in both alkyne insertion steps.18 When dialkyl
alkynes such as 3-hexyne and 4-octyne were used, small amounts of side products were
detected in TLC, but no expected products were obtained. When an aryl–alkyl unsymmetrical
alkyne 3l was used, one of the isomers 4al can be isolated (Scheme 3a) and its structure was
confirmed by X-ray analysis (Figure S2a).
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Heterocyclic substrates were next explored to extend the scope of this reaction. Compound
4ak with four thiophene rings could be obtained from bis(3-thienyl)ethyne in acceptable yield
(Scheme 2), but only trace amount of product was obtained by using bis(2-thienyl)ethyne.
When thiophene-3,4-dicarboxylic acid (1m) was used, [2+2+2] benzannulation did not occur.
A 1:1 coupling product 5ma with a fused heterocyclic skeleton was obtained in 82% yield
(Scheme 3b), but this type of product was not detected using phthalic acids.
Pyridine-containing substrates including 1n were also tested, but no product was detected.
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Scheme 3. Extension and Utilization of the Reaction
(a) reaction using unsymmetrical alkyne
6
Ph CO2H
7
8
9
Ph
Me
Ph
CO2H
mixture
of other
isomers
cat. Ru
+
2
+
10
11
12
13
14
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standard
conditons
CO2H
Me
H
Me
(<15%)
1a
3l
4al [X-ray], 21%
(b) reaction using heterocyclic diacids
O
CO2H
HO2C
CO2H
HO2C
O
cat. Ru
N
Ph
CO2H
H
Ph
Ph
1n
S
S
Ph
1m
3a
5ma, 82%
no reaction
(c) gram scale reaction & access to fluorophores
O
Ph CO2H
1a or 2f
(4 mmol)
+
Ph
Ph
Ph
cat. Ru
SOCl2
Ph
R
R
3a (6 mmol)
Ph
Ph
R = H, 4aa, 1.12 g, 78%
Br, 4fa, 1.35 g, 81%
R = H, 6aa, 92%
Br, 6fa, 85%
(d) one-pot double C–H functionalizations
O
O
Ph
Ph
Ph
Ph
one-pot
CO2Et
cat. Ru
CO2Et
[ 4aa ]
1a
Ph
Ph
3a
7aa, 56%
To demonstrate the practical use of this method, scale-up reactions were carried out to
afford 4aa and 4fa in gram scale (Scheme 3c). The free carboxyl group in the products can
serve as a handle for further transformations. Compound 4aa can undergo intramolecular
Friede-Crafts acylation to afford a multiaryl benzanthrone 6aa (Scheme 3c), which is reported
as a fluorophore synthesized from highly preactivated substrates.19 Brominated benzanthrone
6fa can also be obtained, which can be used for cross-coupling reactions to synthesize
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complex benzanthrone fluorophores. The carboxyl group can be also employed as a directing
group for further C−H functionalization. After the first step was finished, acrylate was added
to the reaction tube for the second annulation in one-pot, and product 7aa with a fused
skeleton was obtained as expected (Scheme 3d).
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Several control experiments were conducted to unveil the mechanism of this [2+2+2]
benzannulation. Only trace of 4aa was detected under strictly deoxygenized conditions with
either 1a or 2a as the substrate, while 4aa could be obtained in moderate to good yield when
the reaction tube was sealed or using diluted air (Table S3). These results illustrated the
aerobic nature of the reaction and suggested that the catalyst turnover can be accomplished
with a rather low concentration of oxygen. Benzoic acid, isophthalic acid and terephthalic
acid, as well as benzoic acids with ortho-Me, OMe, Cl, Br, or NO2 all showed low reactivity
with 3a under standard conditions. Similar [2+2+2] annulation can proceed by using
2-acetylbenzoic acid (8a) to afford 9aa in 32% yield (Scheme 4a), which indicated that one
carboxyl group may promote the decarboxylation of the other one. Either with or without 3a,
no H/D scrambling was observed by using 1a with 50 μL D2O or using deuterium labeling
substrate 1a-d4, indicating that the cleavage of the C−H bond is irreversible. A primary kinetic
isotope effect (KIE) was observed by independent reactions using 1a or 1a-d4 as the substrate
(kH/kD ≈ 3.8) (Scheme 4b, see the Supporting Information for details). The KIE was also
observed via parallel reactions or intermolecular competition, which product ratio
n(4aa)/n(4aa-d3) determined by HRMS analysis was 4.1 and 3.7, respectively. These results
indicated that the cleavage of the C−H bond should be crucial for shaping the reaction
kinetics.20
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Scheme 4. Experiments for Preliminary Mechanism Studies
6
(a) reactions of related substrates
7
8
9
O
R
O
Ph
Ph
standard
conditions
Ph
Ph
CO2H
CO2H
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R = H, Me, OMe,
Cl, Br, NO2
Ph
Ph
H
3a
8a
9aa, 32%
< 20% conversion
(b) kinetic isotope effect
Ph CO2H
H/D
H/D
Ph
standard
conditions
Ph
Ph
H/D
H/D
CO2H
CO2H
+
H/D
Ph
Ph H/D
H/D
1a or 1a-d4
1a or 1a-d4
kinetic measurement
parallel reactions
kH/kD 3.8
n(4aa)/n(4aa-d3) = 4.1
1a 1a-d
intermolecular competition n(4aa)/n(4aa-d3) = 3.7
+
4
Based on these observations and related literatures,5a,8,9,21 a catalytic cycle of this reaction is
proposed (Scheme 5). Initially, de-dimerization of [Ru(p-cymene)Cl2]2 with TBAB and
solvents forms active catalyst species, which undergoes ligand exchange and C−H bond
cleavage to afford Int-A. Subsequent insertion of alkyne 3a furnishes Int-B, which undergoes
decarboxylation to afford Int-C1 with weak coordination8c of the remained carboxyl group to
Ru. The second alkyne insertion generates Int-D1, which undergoes reductive elimination to
give the product 4aa. Anionic complexes Int-C2 and Int-D2 with H+ or tetrabutylammonium
as the counterion may also be possible,22 and Int-E with an alternative fashion for the second
alkyne insertion cannot be ruled out. Finally, Ru(0) species can be oxidized to the active Ru(II)
catalyst with air as oxidant. Phthalic anhydride 2a can be hydrolyzed to 1a by added water or
trace of water in the solvent to enter the catalytic cycle, and the water formed by annulation
could be recycled for the hydrolysis. Though the reaction is aerobic, an alternative reaction
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pathway triggered by Ru-catalyzed decarbonylation of anhydride23 cannot be completely
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ruled out (Scheme S1).
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Scheme 5. Proposed Reaction Mechanism
2a
1a
H2O
2HX
1
2
O2 + 2HX
[RuLX2]
CO2H
O
L = p-cymene
X = Cl, Br, RCO2
[RuL]
O
4aa
Ru
Int-A
L
3a
HO
O
L
Ph
Ru
O
HO2C
Ph
Ph
O
Ru
L
Ph
Int-D1
HO
O
Ph
Int-B
L
Ph
Ru
Ph
3a
CO2
Ph
Int-C1
–
–
O
O
L
O
O
Ph
Ph
HO2C
L
Ph
Ph
Ph
Ru
Ru
Ru
Ph
L
Ph
Ph
Int-E
Ph
Int-D2
Ph
Int-C2
In summary, we have developed a convenient method for synthesis of multisubstituted
1-naphthoic acids via Ru-catalyzed C−H activation and double alkyne annulations of phthalic
acids/anhydrides. The reaction proceeds with high regioselectivity in moderate to good yields.
The use of air as the sole oxidant improves the sustainability and practicability of this
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synthetic method, while the free carboxyl group in the products enables further C−H
functionalization and annulation to afford diverse polycyclic molecules. Future works are still
in progress on extension the Ru catalytic systems for other aerobic annulations.
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Experimental Section
General Methods. Unless otherwise noted, all organic compounds, inorganic salts and
solvent were analytically pure and used directly after purchased. All new products were
characterized by 1H, 13C{1H} NMR, and HRMS. Nuclear magnetic resonance (NMR) spectra
1
were recorded at 298 K. H NMR (500 MHz) chemical shifts (δ) were referenced to internal
standard TMS (δ = 0.00 ppm), and 13C{1H} NMR (126 MHz) chemical shifts were referenced
to internal solvent CDCl3 (δ = 77.16 ppm) or DMSO-d6 (δ = 39.52 ppm). HRMS data were
obtained on a high resolution magnetic sector mass spectrometer with electron spray
ionization (ESI) source. The melting points were uncorrected and those below 300 °C were
recorded.24 Alkyne 3k was prepared via Sonogashira reaction following the literature.25
Typical Procedure for Alkyne Annulation. To a 10 mL tube with a branch pipe, a
magnetic stirrer, [Ru(p-cymene)Cl2]2 (6.1 mg, 0.01 mmol), phthalic acid 1a (49.8 mg, 0.3
mmol), diphenylacetylene 3a (71.3 mg, 0.4 mmol), TBAB (12.9 mg, 0.04 mmol), 900 μL
GVL and 100 μL DMF were added sequentially. The top of the tube was sealed and the
branch pipe was open to air. The tube was put in a metallic heating mould (or immersed in an
oil bath) at 100 °C and stirred for 12 h. The reaction mixture was then cool down, diluted with
EtOAc and washed with water. After purification by flash column chromatography on silica
gel with petroleum ether/EtOAc (gradient mixture ratio from 1:0 to 4:1) as eluant, 4aa (77.5
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mg, 81%) was obtained as a pale yellow solid. When phthalic anhydride 2a (44.4 mg, 0.3
mmol) was used in place of 1a, 20 μL water was added with the solvent, and 4aa (76.2 mg,
80%) was obtained.
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Following this procedure, other products 4 in Scheme 2 were synthesized from
corresponding diacids 1 or anhydrides 2 (0.3 mmol) and alkynes 3 (0.4 mmol), of which the
yields were based on alkynes, i.e., 0.2 mmol expected products. Similarly, product 4al was
obtained by reaction of 1a (0.6 mmol) and 3l (0.8 mmol) for 20 h. Product 5ma was obtained
by reaction of 1m (0.3 mmol) and 3a (0.4 mmol) for 16 h, and the yield was based on 1m.
Product 9aa was obtained by reaction of 8a (0.45 mmol) and 3a (0.6mmol) for 24 h. Large
scale synthesis of 4aa and 4fa were conducted in a 50 mL round-bottom flask using 6 mmol
3a and 4 mmol 1a or 2f with other chemicals scale-up proportionally based on 3a.
5,6,7,8-Tetraphenyl-1-naphthoic acid (4aa). Pale yellow solid (77.5 mg, 81%, from diacid;
76.2 mg, 80%, from anhydride; 1.121 g, 78%, large scale): mp 282–284 °C; 1H NMR (500
MHz, CDCl3) δ 7.74 (dd, J = 8.6, 1.3 Hz, 1H), 7.66 (dd, J = 7.0, 1.3 Hz, 1H), 7.39 (dd, J = 8.5,
7.0 Hz, 1H), 7.25–7.22 (m, 2H), 7.21–7.16 (m, 3H), 7.09–7.04 (m, 5H), 6.86–6.80 (m, 6H),
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6.78–6.76 (m, 2H), 6.73–6.71 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 174.4, 141.3,
140.35, 140.32, 140.27, 140.1, 139.4, 139.0, 137.3, 133.5, 132.4, 131.5, 131.4, 131.3, 131.1,
130.8, 129.0, 128.3, 127.8, 127.2, 126.8, 126.74, 126.69, 126.5, 125.6, 125.5, 124.5; HRMS
(ESI) calcd for C35H24O2 [M – H]– 475.1704, found 475.1712.
3-Methyl-5,6,7,8-tetraphenyl-1-naphthoic acid (4ba). Pale yellow solid (82.2 mg, 84%,
from diacid; 80.1 mg, 82%, from anhydride): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ
7.49 (s, 2H), 7.23–7.22 (m, 2H), 7.19–7.15 (m, 3H), 7.07–7.01 (m, 5H), 6.85–6.80 (m, 6H),
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6.76–6.74 (m, 2H), 6.72–6.70 (m, 2H), 2.42 (s, 3H); C{1H} NMR (126 MHz, CDCl3) δ =
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175.0, 140.49, 140.47, 140.4, 140.3, 140.1, 139.6, 138.4, 137.1, 134.3, 133.7, 132.4, 131.5,
131.45, 131.43, 131.1, 130.4, 129.6, 127.7, 127.4, 127.1, 126.7, 126.6, 126.5, 125.5, 125.4,
21.6; HRMS (ESI) calcd for C36H26O2 [M – H]– 489.1860, found 489.1869.
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3-(tert-Butyl)-5,6,7,8-tetraphenyl-1-naphthoic acid (4ca). Pale yellow solid (81.8 mg, 77%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 2.0 Hz, 1H), 7.68 (d, J = 2.0 Hz, 1H),
7.25–7.22 (m, 2H), 7.19–7.17 (m, 3H), 7.10–7.02 (m, 5H), 6.86–6.80 (m, 6H), 6.77–6.76 (m,
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2H), 6.73–6.71 (m, 2H), 1.28 (s, 9H); C{1H} NMR (126 MHz, DMSO-d6) δ 170.2, 146.7,
140.12, 140.05, 139.9, 139.4, 139.2, 139.1, 138.2, 136.9, 134.0, 132.5, 132.0, 130.9, 130.8,
130.7, 127.5, 126.6, 126.5, 126.4, 126.34, 126.30, 126.0, 125.4, 125.2, 123.6, 34.3, 30.5;
HRMS (ESI) calcd for C39H32O2 [M – H]– 531.2330, found 531.2337.
3-Methoxy-5,6,7,8-tetraphenyl-1-naphthoic acid (4da). Pale yellow solid (86.2 mg, 85%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 2.7 Hz, 1H), 7.25–7.22 (m, 2H),
7.18–7.16 (m, 3H), 7.08–7.02 (m, 6H), 6.86–6.81 (m, 6H), 6.77–6.75 (m, 2H), 6.72–6.70 (m,
13
2H), 3.70 (s, 3H); C{1H} NMR (126 MHz, CDCl3) δ 173.5, 156.0, 140.6, 140.43, 140.37,
139.7, 139.0, 137.9, 137.3, 135.1, 133.1, 132.4, 131.5, 131.3, 131.1, 127.9, 127.1, 126.8,
126.70, 126.65, 126.58, 125.5, 125.4, 124.5, 120.6, 109.1, 55.5; HRMS (ESI) calcd for
C36H26O3 [M – H]– 505.1809, found 505.1820.
3-Chloro-5,6,7,8-tetraphenyl-1-naphthoic acid (4ea). Pale yellow solid (85.1 mg, 83%,
from diacid; 86.6 mg, 85%, from anhydride): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ
7.70 (d, J = 2.2 Hz, 1H), 7.58 (d, J = 2.2 Hz, 1H), 7.25–7.19 (m, 3H), 7.16–7.14 (m, 2H),
7.07–7.03 (m, 5H), 6.87–6.81 (m, 6H), 6.76–6.73 (m, 2H), 6.73–6.71 (m, 2H); 13C{1H} NMR
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(126 MHz, CDCl3) δ 173.6, 141.6, 141.2, 139.9, 139.85, 139.81, 138.7, 138.4, 137.4, 134.5,
133.3, 132.3, 131.3, 131.2, 130.9, 130.5, 129.1, 128.7, 128.0, 127.5, 127.3, 127.1, 126.81,
126.79, 126.76, 125.8, 125.7; HRMS (ESI) calcd for C35H23ClO2 [M – H]– 509.1314, found
509.1319.
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3-Bromo-5,6,7,8-tetraphenyl-1-naphthoic acid (4fa). Pale yellow solid (93.2 mg, 84%,
from diacid; 100.1 mg, 90%, from anhydride; 1.354 g, 81%, large scale): mp >300 °C; 1H
NMR (500 MHz, CDCl3) δ 7.87 (d, J = 2.1 Hz, 1H), 7.70 (d, J = 2.1 Hz, 1H), 7.26–7.19 (m,
3H), 7.15–7.14 (m, 2H), 7.07–7.03 (m, 5H), 6.86–6.80 (m, 6H), 6.76–6.72 (m, 2H), 6.71–6.68
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(m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 173.6, 141.7, 141.2, 139.9, 139.82, 139.81,
138.6, 138.3, 137.5, 134.8, 133.3, 132.4, 132.3, 131.3, 131.2 (overlapped), 130.9, 128.0,
127.7, 127.3, 127.1, 126.81, 126.79, 126.76, 125.8, 125.7, 118.5; HRMS (ESI) calcd for
C35H23BrO2 [M – H]– 553.0809, found 553.0821.
5,6,7,8-Tetraphenyl-3-(trifluoromethyl)-1-naphthoic acid (4ga). Pale yellow solid (93.3 mg,
86%): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 8.04 (m, 1H), 7.80 (d, J = 1.7 Hz, 1H),
7.28–7.21 (m, 3H), 7.17–7.15 (m, 2H), 7.08–7.04 (m, 5H), 6.88–6.83 (m, 6H), 6.76–6.74 (m,
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2H), 6.72–6.70 (m, 2H); 19F NMR (471 MHz, CDCl3) δ -62.5; C{1H} NMR (126 MHz,
CDCl3) δ 174.0, 143.6, 141.6, 140.2, 139.7, 139.63, 139.61, 138.3, 137.6, 132.9, 132.8, 132.4,
131.3, 131.1, 130.9, 130.3, 128.1 (q, J = 4.5 Hz), 128.0, 127.4, 126.91 (overlapped), 126.86,
126.5 (q, J = 33.1 Hz), 125.94, 125.90, 125.0, 123.9 (q, J = 272.2 Hz), 123.7 (q, J = 2.8 Hz);
HRMS (ESI) calcd for C36H23F3O2 [M – H]– 543.1577, found 543.1588.
3-Nitro-5,6,7,8-tetraphenyl-1-naphthoic acid (4ha). Yellow solid (76.4 mg, 73%):
mp >300 °C; 1H NMR (500 MHz, DMSO-d6) δ 12.75 (brs, 1H), 8.40 (d, J = 1.7 Hz, 1H), 8.19
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(d, J = 1.7 Hz, 1H), 7.33–7.28 (m, 5H), 7.15–7.12 (m, 1H), 7.09–7.06 (m, 2H), 7.04–7.02 (m,
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7
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2H), 6.90–6.86 (m, 8H), 6.80–6.79 (m, 2H); C{1H} NMR (126 MHz, DMSO-d6) δ 168.2,
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9
144.6, 143.6, 141.5, 140.5, 139.12, 139.11, 138.3, 137.9, 137.6, 136.3, 131.9, 130.9, 130.6,
130.4 (overlapped), 127.9, 127.5, 127.0, 126.8, 126.6, 126.5, 125.9, 125.8, 124.4, 120.1;
HRMS (ESI) calcd for C35H23NO4 [M – H]– 520.1554, found 520.1566.
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5,6,7,8-Tetraphenylnaphthalene-1,3-dicarboxylic acid (4ia). Pale yellow solid (104.0 mg,
76%): mp >300 °C; 1H NMR (500 MHz, DMSO-d6) δ 12.77 (brs, 2H), 8.24 (s, 1H), 7.99 (s,
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1H), 7.29–7.24 (m, 5H), 7.10–7.03 (m, 5H), 6.88–6.79 (m, 10H); C{1H} NMR (126 MHz,
DMSO-d6) δ 169.5, 166.6, 142.9, 140.4, 139.73, 139.68, 138.9, 138.5, 137.5, 134.8, 132.3,
132.1, 131.0, 130.71, 130.67, 130.0, 127.8, 127.2, 127.0, 126.8, 126.7, 126.6, 125.8, 125.7;
HRMS (ESI) calcd for C36H24O4 [M – H]– 519.1602, found 519.1613.
3,4-Difluoro-5,6,7,8-tetraphenyl-1-naphthoic acid (4ja). Pale yellow solid (119.8 mg, 78%):
mp >300 °C; 1H NMR (500 MHz, DMSO-d6) δ 12.49 (s, 1H), 7.74 (s, 1H), 7.19–7.10 (m,
10H), 6.82–6.74 (m, 10H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.0, 145.9 (dd, J =
245.9, 13.5 Hz), 145.8 (dd, J = 258.4, 12.8 Hz), 142.1, 141.1, 140.3 (d, J = 4.0 Hz), 139.4,
139.0, 138.6, 137.7, 134.3 (d, J = 4.9 Hz), 132.2, 131.7 (dd, J = 5.3, 5.3 Hz), 130.64, 130.60,
129.72 (d, J = 3.1 Hz), 126.9, 126.82, 126.79, 126.7, 126.5, 126.4, 126.3, 125.6, 125.5, 123.5
(d, J = 4.5 Hz), 118.3 (d, J = 21.8 Hz); 19F NMR (471 MHz, DMSO-d6) δ -132.13 (d, J = 18.9
Hz), -140.86 (d, J = 19.1 Hz); HRMS (ESI) calcd for C35H22F2O2 [M – H]– 511.1515, found
511.1519.
3,4-Dichloro-5,6,7,8-tetraphenyl-1-naphthoic acid (4ka). Pale yellow solid (44.4 mg, 41%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.70 (s, 1H), 7.10–7.07 (m, 3H), 7.05–6.98 (m,
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7H), 6.84–6.80 (m, 6H), 6.64–6.61 (m, 4H); 13C{1H} NMR (126 MHz, CDCl3) δ 172.5, 143.4,
141.7, 141.0, 139.62, 139.59, 139.5, 138.0, 137.6, 133.1, 132.9, 132.0, 131.9, 131.5, 131.4,
131.1, 131.0, 130.2, 128.9, 127.3, 127.2, 127.0, 126.8, 126.7, 126.6, 125.8, 125.7; HRMS
(ESI) calcd for C35H22Cl2O2 [M – H]– 543.0924, found 543.0935.
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5,6,7,8-Tetraphenylphenanthrene-9-carboxylic acid (4la). Pale brown solid (67.6 mg, 64%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.97 (s, 1H), 7.85–7.84 (m, 1H), 7.51 (d, J = 8.7
Hz, 1H), 7.44–7.41 (m, 1H), 7.17–7.15 (m, 3H), 7.11–7.08 (m, 3H), 7.05–7.02 (m, 5H),
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6.86–6.82 (m, 6H), 6.70–6.67 (m, 4H); C{1H} NMR (126 MHz, CDCl3) δ 174.2, 143.0,
141.5, 140.5, 140.4, 140.3, 140.2, 138.4, 137.9, 133.3, 132.1, 131.6, 131.5, 131.4, 130.88,
130.86, 130.25, 129.1, 128.9, 128.5, 128.1, 127.1, 127.0, 126.74, 126.68, 126.65, 126.63,
126.56, 125.5, 125.4; HRMS (ESI) calcd for C39H26O2 [M – H]– 525.1860, found 525.1868.
5,6,7,8-Tetra-p-tolyl-1-naphthoic acid (4ab). Pale yellow solid (83.2 mg, 78%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.70 (dd, J = 8.6, 1.2 Hz, 1H), 7.62 (dd, J = 7.0,
1.2 Hz, 1H), 7.32 (dd, J = 8.5, 7.0 Hz, 1H), 7.03–7.01 (m, 4H), 6.92–6.90 (m, 2H), 6.84–6.83
(m, 2H), 6.65–6.61 (m, 6H), 6.58–6.57 (m, 2H), 2.30 (s, 3H), 2.15 (s, 3H), 2.093 (s, 3H),
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2.086 (s, 3H); C{1H} NMR (126 MHz, CDCl3) δ 175.2, 141.4, 140.3, 138.8, 137.7, 137.5,
137.4, 137.2, 136.7, 136.02, 136.00, 134.60, 134.56, 133.8, 132.2, 131.5, 131.3, 131.1, 130.9,
130.8, 129.4, 128.4, 128.0, 127.8, 127.41, 127.36, 124.0, 21.45, 21.37, 21.2 (overlapped);
HRMS (ESI) calcd for C39H32O2 [M – H]– 531.2330, found 531.2341.
5,6,7,8-Tetrakis(4-methoxyphenyl)-1-naphthoic acid (4ac). Pale yellow solid (86.3 mg,
72%): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.73 (dd, J = 8.6, 1.1 Hz, 1H), 7.68 (dd, J
= 7.0, 1.1 Hz, 1H), 7.37 (dd, J = 8.6, 7.0 Hz, 1H), 7.06–7.04 (m, 2H), 6.97–6.96 (m, 2H),
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6.79–6.78 (m, 2H), 6.65–6.64 (m, 2H), 6.62–6.59 (m, 4H), 6.43–6.41 (m, 4H), 3.79 (s, 3H),
3.63–3.62 (m, 9H); 13C{1H} NMR (126 MHz, CDCl3) δ 174.8, 158.3, 158.2, 157.14, 157.12,
141.4, 140.3, 138.8, 137.0, 133.8, 133.5, 133.2, 133.1, 133.0, 132.5, 132.3, 132.14, 132.08,
131.5, 130.6, 129.4, 128.1, 124.3, 113.3, 112.7, 112.4, 55.3, 55.14, 55.08, 55.05; HRMS (ESI)
calcd for C39H32O6 [M – H]– 595.2126, found 595.2139.
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5,6,7,8-Tetrakis(4-fluorophenyl)-1-naphthoic acid (4ad). Pale yellow solid (109.6 mg, 75%):
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mp 296–298 °C; H NMR (500 MHz, CDCl3) δ 7.72–7.71 (m, 2H), 7.48–7.45 (m, 1H),
7.12–7.09 (m, 2H), 7.074–7.01 (m, 2H), 6.98–6.95 (m, 2H), 6.80–6.76 (m, 2H), 6.70–6.58 (m,
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8H); F NMR (471 MHz, DMSO-d6) δ -115.3, -115.6, -116.4, -116.5; C{1H} NMR (126
MHz, DMSO-d6) δ 170.2, 161.0 (d, J = 244.0 Hz), 160.9 (d, J = 243.5 Hz), 160.1 (d, J =
243.0 Hz), 160.0 (d, J = 243.1 Hz), 139.9, 138.6, 137.7, 136.6, 136.2 (d, J = 2.5 Hz,
overlapped), 135.4 (d, J = 2.9 Hz), 135.0 (d, J = 3.1 Hz), 134.1, 133.9 (d, J = 8.1 Hz), 132.73
(d, J = 8.2 Hz), 132.65 (d, J = 8.2 Hz), 132.6, 132.5 (d, J = 8.1 Hz), 128.4, 127.9, 127.8, 125.5,
114.7 (d, J = 21.3 Hz), 113.7 (d, J = 21.2 Hz), 113.6 (d, J = 21.2 Hz), 113.5 (d, J = 21.1 Hz);
HRMS (ESI) calcd for C35H20F4O2 [M – H]– 547.1327, found 547.1339.
5,6,7,8-Tetrakis(4-chlorophenyl)-1-naphthoic acid (4ae). Pale yellow solid (87.5 mg, 71%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.84 (dd, J = 7.0, 1.1 Hz, 1H), 7.68 (dd, J = 8.6,
1.1 Hz, 1H), 7.46 (dd, J = 8.6, 7.0 Hz, 1H), 7.26–7.25 (m, 2H), 7.07–7.05 (m, 4H), 6.98–6.96
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(m, 2H), 6.91–6.88 (m, 4H), 6.67–6.61 (m, 4H); C{1H} NMR (126 MHz, CDCl3) δ 175.3,
139.8, 138.6, 138.5, 138.4, 138.12, 138.07, 137.3, 136.6, 133.5, 133.39, 133.36, 133.2, 132.5,
132.4, 132.3, 132.2, 132.1, 131.1, 130.6, 129.6, 128.9, 128.4, 127.7, 127.6, 127.5, 125.4;
HRMS (ESI) calcd for C35H20Cl4O2 [M – H]– 611.0145, found 611.0156.
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5,6,7,8-Tetrakis(4-bromophenyl)-1-naphthoic acid (4af). Pale yellow solid (126.7 mg, 80%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 6.8 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H),
7.47–7.40 (m, 3H), 7.22–7.20 (m, 2H), 7.07–6.99 (m, 6H), 6.91–6.89 (m, 2H), 6.61–6.54 (m,
4H); 13C{1H} NMR (126 MHz, CDCl3) δ 175.3, 139.6, 138.9, 138.51, 138.46, 138.410,
138.406, 137.7, 136.5, 133.8, 133.3, 132.8, 132.7, 132.4, 131.4, 131.0, 130.7, 130.6, 130.54,
130.48, 129.9, 128.9, 125.4, 121.6, 121.5, 120.6, 120.5; HRMS (ESI) calcd for
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C35H2079Br2 Br2O2 [M – H]– 790.8083, found 790.8101.
5,6,7,8-Tetrakis(4-(trifluoromethyl)phenyl)-1-naphthoic acid (4ag). Pale yellow solid
(113.3 mg, 76%): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 6.7 Hz, 1H), 7.67
(d, J = 8.3 Hz, 1H), 7.56–7.50 (m, 3H), 7.33–7.30 (m, 4H), 7.18–7.14 (m, 6H), 6.88–6.80 (m,
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4H); F NMR (471 MHz, CDCl3) δ -62.4, -62.7, -62.86, -62.89; C{1H} NMR (126 MHz,
CDCl3) δ 175.3, 143.5, 143.0, 142.9, 142.2, 139.4, 138.6, 138.2, 136.7, 133.3, 132.4, 131.5,
131.4, 131.2, 130.9, 130.8, 130.3, 129.9 (q, J = 32.9 Hz), 129.3 (q, J = 32.4 Hz), 128.87 (q, J
= 32.6 Hz), 128.85, 128.82 (q, J = 32.6 Hz), 126.0, 125.2 (m), 124.4–124.3 (m, overlapped),
124.2 (q, J = 3.8 Hz), 124.1 (q, J = 272.3 Hz, overlapped), 123.90 (q, J = 272.0 Hz), 123.88
(q, J = 272.1 Hz); HRMS (ESI) calcd for C39H20F12O2 [M – H]– 747.1199, found 747.1200.
5,6,7,8-Tetrakis(4-(trifluoromethoxy)phenyl)-1-naphthoic acid (4ah). Pale yellow solid
(112.0 mg, 69%): mp 250–252 °C; 1H NMR (500 MHz, CDCl3) δ 7.77–7.76 (m, 2H), 7.50 (t,
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J = 7.6 Hz, 1H), 7.19–7.06 (m, 6H), 6.93–6.92 (m, 2H), 6.78–6.68 (m, 8H); F NMR (471
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MHz, CDCl3) δ -58.0, -58.1, -58.4, -58.5; C{1H} NMR (126 MHz, CDCl3) δ 175.6, 148.5,
148.3, 147.6, 139.9, 138.7, 138.6, 138.5, 138.4, 138.3, 137.4, 136.6, 133.6, 133.4, 132.6,
132.4, 132.2, 131.1, 130.7, 129.6, 128.8, 125.6, 120.63, 120.60 (q, J = 257.4 Hz), 120.5 (q, J
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= 257.3 Hz), 120.4 (q, J = 257.0 Hz, overlapped), 119.9 (overlapped), 119.8; HRMS (ESI)
calcd for C39H20F12O6 [M – H]– 811.0996, found 811.0990.
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5,6,7,8-Tetrakis(3,5-dimethylphenyl)-1-naphthoic acid (4ai). Pale yellow solid (85.1 mg,
72%): mp 299–301 °C; 1H NMR (500 MHz, CDCl3) δ 7.75 (dd, J = 8.5, 1.1 Hz, 1H), 7.58 (dd,
J = 7.0, 1.1 Hz, 1H), 7.38 (dd, J = 8.5, 7.0 Hz, 1H), 6.79–6.78 (m, 3H), 6.68 (s, 2H), 6.64 (s,
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1H), 6.42–6.37 (m, 6H), 2.21 (s, 6H), 2.08 (s, 6H), 1.97 (s, 6H), 1.95 (s, 6H); C{1H} NMR
(126 MHz, CDCl3) δ 175.2, 141.6, 140.4, 140.18, 140.14, 140.0, 139.5, 138.7, 136.9, 136.7,
136.2, 135.25, 135.21, 133.4, 131.9, 130.7, 130.3, 129.4, 129.3, 129.2, 128.7, 128.0, 127.7,
127.3, 126.7, 126.6, 124.0, 21.34, 21.27, 21.1 (overlapped); HRMS (ESI) calcd for C43H40O2
[M – H]– 587.2956, found 587.2961.
5,6,7,8-Tetrakis(3,5-dichlorophenyl)-1-naphthoic acid (4aj). Pale yellow solid (84.0 mg,
56%): mp 287–290 °C; 1H NMR (500 MHz, CDCl3) δ 7.88 (dd, J = 7.0, 1.1 Hz, 1H), 7.71 (dd,
J = 8.5, 1.1 Hz, 1H), 7.61 (dd, J = 8.5, 7.1 Hz, 1H), 7.33 (t, J = 1.8 Hz, 1H), 7.14 (t, J = 1.8
Hz, 1H), 7.09 (d, J = 1.8 Hz, 2H), 7.05 (t, J = 1.8 Hz, 1H), 7.03 (t, J = 1.8 Hz, 1H), 7.00 (d, J
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= 1.8 Hz, 2H), 6.75 (d, J = 1.8 Hz, 2H), 6.72 (d, J = 1.8 Hz, 2H); C{1H} NMR (126 MHz,
CDCl3) δ 174.4, 141.8, 141.24, 141.17, 140.7, 137.9, 137.6, 136.8, 135.8, 135.2, 134.5,
134.42, 134.39, 133.0, 131.4, 130.4, 130.3, 129.9, 129.23, 129.17, 129.0, 128.5, 128.2, 127.43,
127.40, 127.3, 126.7; HRMS (ESI) calcd for C35H16Cl8O2 [M – H]– 746.8586, found
746.8573.
5,6,7,8-Tetra(thiophen-3-yl)-1-naphthoic acid (4ak). Pale yellow solid (42.4 mg, 42%):
mp >300 °C; 1H NMR (500 MHz, DMSO-d6) δ 12.20 (brs, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.59
(d, J = 6.8 Hz, 1H), 7.49–7.46 (m, 2H), 7.29 (brs, 1H), 7.20–7.18 (m, 1H), 7.10–7.07 (m, 3H),
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6.97 (brs, 1H), 6.84 (m, 1H), 6.77 (s, 1H), 6.58–6.57 (m, 2H), 6.51–6.50 (m, 1H); C{1H}
NMR (126 MHz, DMSO-d6) δ 169.7, 139.9, 139.7, 139.6, 138.6, 136.2, 135.5, 134.1, 133.9,
133.2, 132.9, 130.6, 130.2, 129.7, 128.9, 128.3, 127.6, 125.6, 125.21, 125.20, 125.0, 123.99,
123.97, 123.55, 123.52, 123.47; HRMS (ESI) calcd for C27H16O2S4 [M – H]– 498.9960, found
498.9969.
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5,7-Dimethyl-6,8-diphenyl-1-naphthoic acid (4al). Pale yellow solid (30.1 mg, 21%): mp
261–262 °C; 1H NMR (500 MHz, DMSO-d6) δ 12.01 (s, 1H), 8.20 (dd, J = 8.3, 1.1 Hz, 1H),
7.54–7.48 (m, 4H), 7.43–7.40 (m, 1H), 7.35–7.34 (m, 3H), 7.26–7.24 (m, 2H), 7.18–7.16 (m,
2H), 2.38 (s, 3H), 1.73 (s, 3H); C{1H} NMR (126 MHz, DMSO-d6) δ 170.3, 141.4, 140.3,
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139.8, 135.7, 134.0, 133.4, 131.6, 131.5, 130.8, 129.1, 128.6, 128.1, 127.4, 126.97, 126.93,
126.86, 126.4, 124.2, 20.1, 17.1.; HRMS (ESI) calcd for C25H20O2 [M – H]– 351.1391, found
351.1390.
4-Oxo-6,7-diphenyl-4H-thieno[3,2-c]pyran-3-carboxylic acid (5ma). Pale yellow solid
(85.6 mg, 82%): mp >300 °C; 1H NMR (500 MHz, DMSO-d6) δ 13.49 (brs, 1H), 8.26 (s, 1H),
7.50–7.47 (m, 3H), 7.42–7.40 (m, 2H), 7.38–7.30 (m, 5H); 13C{1H} NMR (126 MHz,
DMSO-d6) δ 163.0, 156.9, 156.2, 152.0, 133.7, 133.2, 132.8, 131.4, 129.8, 129.4, 129.1,
128.9, 128.3, 119.1, 114.9; HRMS (ESI) calcd for C20H12O4S [M – H]– 347.0384, found
347.0385.
1-(5,6,7,8-Tetraphenylnaphthalen-1-yl)ethanone (9aa). Pale yellow solid (45.5 mg, 32%):
mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.68 (dd, J = 8.4, 1.4 Hz, 1H), 7.41 (dd, J = 7.0,
1.4 Hz, 1H), 7.35 (dd, J = 8.4, 7.0 Hz, 1H), 7.25–7.22 (m, 2H), 7.20–7.17 (m, 3H), 7.13–7.10
(m, 3H), 7.08–7.06 (m, 2H), 6.87–6.82 (m, 6H), 6.79–6.77 (m, 2H), 6.74–6.72 (m, 2H), 2.01
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(s, 3H); C{1H} NMR (126 MHz, CDCl3) δ 204.4, 142.2, 141.1, 141.0, 140.4, 140.3, 140.0,
139.5, 139.1, 137.4, 133.6, 132.9, 131.4, 131.3, 131.1, 129.8, 129.3, 127.7, 127.5, 127.0,
126.77, 126.74, 126.71, 125.7, 125.6, 125.5, 124.6, 30.7; HRMS (ESI) calcd for C36H26O [M
+ H]+ 475.2056, found 475.2052.
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Procedure for Synthesis of 6. To a 50 mL Schlenk flask equipped with a magnetic stirrer,
4aa (190.6 mg, 0.4 mmol), 16 mL DCM, and 4 mL MeNO2 were added sequentially. The
flask was charged with N2 and SOCl2 (120 μL, 1.6 mmol) was added. The flask was stirred at
room temperature for 6 h. The reaction mixture was then diluted with DCM and washed with
NaHCO3 aqueous solution and water. After purification by flash column chromatography on
silica gel with petroleum ether/EtOAc (gradient mixture ratio from 1:0 to 15:1) as eluant, 6aa
(168.3 mg, 92%) was obtained as a yellow solid. Similarly, 6fa was synthesized from 4fa.
1,2,3-Triphenyl-7H-benzo[de]anthracen-7-one (6aa).19 Yellow solid (168.3 mg, 92%): mp
260–261 °C; 1H NMR (500 MHz, CDCl3) δ 8.78 (dd, J = 7.2, 1.1 Hz, 1H), 8.46 (dd, J = 7.8,
1.1 Hz, 1H), 7.93 (dd, J = 8.3, 1.1 Hz, 1H), 7.67–7.64 (m, 1H), 7.34–7.31 (m, 1H), 7.25–7.20
(m, 3H), 7.17–7.08 (m, 7H), 7.06–7.04 (m, 2H), 6.90–6.88 (m, 3H), 6.75–6.74 (m, 2H);
13C{1H} NMR (126 MHz, CDCl3) δ 184.5, 142.0, 141.9, 141.25, 141.22, 139.6, 138.9, 137.5,
134.4, 132.9, 132.0, 131.7, 131.4, 131.2, 131.1, 130.2, 129.7, 128.8, 128.5, 128.4, 127.7,
127.6, 127.4, 127.1, 127.0, 126.9, 126.4, 125.8, 125.3.
5-Bromo-1,2,3-triphenyl-7H-benzo[de]anthracen-7-one (6fa). Yellow solid (183.2 mg,
85%): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 8.80 (d, J = 2.2 Hz, 1H), 8.41 (d, J = 7.7
Hz, 1H), 8.02 (d, J = 2.2 Hz, 1H), 7.34–7.31 (m, 1H), 7.26–7.22 (m, 3H), 7.17–7.10 (m, 7H),
7.03–7.02 (m, 2H), 6.90–6.89 (m, 3H), 6.73–6.71 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3)
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δ 183.4, 142.4, 142.1, 141.7, 140.4, 139.3, 138.1, 137.3, 135.7, 133.8, 132.4, 132.3, 132.1,
131.2, 131.03, 130.99, 130.3, 130.0, 128.5, 127.9, 127.8, 127.7, 127.31, 127.25, 126.9, 125.9,
125.6, 121.1; HRMS (ESI) calcd for C35H21BrO [M + H]+ 537.0849, found 537.0845.
Procedure for One-pot Synthesis of 7aa. To a 10 mL tube with a branch pipe, a magnetic
stirrer, [Ru(p-cymene)Cl2]2 (6.1 mg, 0.01 mmol), phthalic acid 1a (39.9 mg, 0.24 mmol),
diphenylacetylene 3a (71.3 mg, 0.4 mmol), TBAB (12.9 mg, 0.04 mmol), 900 μL GVL and
100 μL DMF were added sequentially. The top of the tube was sealed and leave the branch
pipe open to air. After reaction at 100 °C for 12 h, the tube was cool down, following by
addition of KOAc (19.6 mg, 0.20 mmol) and ethyl acrylate (44 μL, 0.40 mmol). After reaction
at 100 °C for additional 16 h, the reaction mixture was cool down, diluted with EtOAc and
washed with water. After purification by flash column chromatography on silica gel with
petroleum ether/EtOAc (gradient mixture ratio from 1:0 to 12:1) as eluant, 7aa (64.6 mg, 56%)
was obtained as a pale yellow solid.
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Ethyl 2-(1-oxo-6,7,8,9-tetraphenyl-1,3-dihydronaphtho[1,2-c]furan-3-yl)acetate (7aa). Pale
yellow solid (64.6 mg, 56%): mp >300 °C; 1H NMR (500 MHz, CDCl3) δ 7.94 (d, J = 8.7 Hz,
1H), 7.37 (d, J = 8.7 Hz, 1H), 7.25–7.15 (m, 5H), 7.12–7.07 (m, 5H), 6.87–6.82 (m, 6H),
6.79–6.69 (m, 4H), 5.81 (dd, J = 7.0, 5.9 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 2.90 (dd, J = 16.2,
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5.8 Hz, 1H), 2.84 (dd, J = 16.2, 7.2 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H); C{1H} NMR (126
MHz, CDCl3) δ 169.5, 166.9, 152.5, 143.1, 141.6, 140.8, 140.04, 139.96, 139.5, 139.3, 137.6,
135.3, 133.8, 131.31, 131.29, 131.26, 131.22, 131.18, 131.03, 130.99, 130.97, 128.8, 127.85,
127.83, 127.1, 127.0, 126.8, 126.7, 126.4, 125.7, 125.6, 121.8, 118.4, 74.8, 61.4, 40.1, 14.3;
HRMS (ESI) calcd for C40H30O4 [M + H]+ 575.2217, found 575.2214.
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Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at
DOI: 10.1021/acs.joc.xxxxxxx.
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X-ray structural details, mechanism studies, and copies of NMR spectra (PDF)
X-ray crystallography data for compound 4da (CIF)
X-ray crystallography data for compound 4al (CIF)
Corresponding Author
*E-mail: zlychem@gzhu.edu.cn.
ORCID ID
Liyao Zheng: 0000-0002-1996-7727
Author Contributions
† H.C. and L.O. contributed equally.
Notes
The authors declare no competing financial interest.
Acknowledgments
We thank Start-up Grant from Guangzhou University, Science and Technology Research
Project of Guangzhou (Grant No. 201707010483), Natural Science Foundations of
Guangdong Province (Grant No. 2018A030310064), and the Open Sharing Funds for
Instruments of Guangzhou University for financial support.
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Notes and References
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(1) (a) Brummond, K. M.; Kocsis, L. S. Intramolecular Didehydro-Diels–Alder Reaction and
Its Impact on the Structure–Function Properties of Environmentally Sensitive Fluorophores.
Acc. Chem. Res. 2015, 48, 2320; (b) Xu, F.; Hershey, K. W.; Holmes, R. J.; Hoye, T. R.
Blue-Emitting Arylalkynyl Naphthalene Derivatives via a Hexadehydro-Diels–Alder
Cascade Reaction. J. Am. Chem. Soc. 2016, 138, 12739; (c) Kobaisi, M. A.; Bhosale, S. V.;
Latham, K.; Raynor, A. M.; Bhosale, S. V. Functional Naphthalene Diimides: Synthesis,
Properties, and Applications. Chem. Rev. 2016, 116, 11685; (d) Su, L.; Ren, T.; Dong, J.;
Liu, L.; Xie, S.; Yuan, L.; Zhou, Y.; Yin, S.-F. Cu(I)-Catalyzed 6-endo-dig Cyclization of
Terminal Alkynes, 2-Bromoaryl Ketones, and Amides toward 1-Naphthylamines:
Applications and Photophysical Properties. J. Am. Chem. Soc. 2019, 141, 2535.
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(2) (a) Hein, S. J.; Lehnherr, D.; Arslan, H.; Uribe-Romo, F. J.; Dichtel, W. R. Alkyne
Benzannulation Reactions for the Synthesis of Novel Aromatic Architectures. Acc. Chem.
Res. 2017, 50, 2776; (b) Han, T.; Zhao, Z.; Deng, H.; Kwok, R. T. K.; Lam, J. W. Y.; Tang,
B. Z. Iridium-Catalyzed Polymerization of Benzoic Acids and Internal Diynes: A New
Route for Constructing High Molecular Weight Polynaphthalenes without the Constraint of
Monomer Stoichiometry. Polym. Chem. 2017, 8, 1393; (c) Kumar, S.; Tao, Y.-T. Contorted
Naphtho- and Fluorenocoronenes: Syntheses and Properties of Polycyclic Aromatics
beyond Benzo- and Thiophenocoronenes. Org. Lett. 2018, 20, 2320; (d) Yang, W.; Bam, R.;
Catalano, V. J.; Chalifoux, W. A. Highly Regioselective Domino Benzannulation Reaction
of Buta-1,3-diynes To Construct Irregular Nanographenes. Angew. Chem., Int. Ed. 2018, 57,
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14773; (e) Kong, W. J.; Finger, L. H.; Oliveira, J. C. A.; Ackermann, L.
Rhodaelectrocatalysis for Annulative C−H Activation: Polycyclic Aromatic Hydrocarbons
through Versatile Double Electrocatalysis. Angew. Chem., Int. Ed. 2019, 58, 6342.
(3) (a) Zhang, Q.; Pang, B.; Ding, W.; Liu, W. Aromatic Polyketides Produced by Bacterial
Iterative Type I Polyketide Synthases. ACS Catal. 2013, 3, 1439; (b) Tian, Y.; Jiang, N.;
Zhang, A. H.; Chen, C. J.; Deng, X. Z.; Zhang, W. J.; Tan, R.-X. Muta-mycosynthesis of
Naphthalene Analogs. Org. Lett. 2015, 17, 1457; (c) Abdissa, N.; Pan, F.; Gruhonjic, A.;
Gräfenstein, J.; Fitzpatrick, P. A.; Landberg, G.; Rissanen, K.; Yenesew, A.; Erdélyi, M.
Naphthalene Derivatives from the Roots of Pentas parvifolia and Pentas bussei. J. Nat.
Prod. 2016, 79, 2181; (d) Singh, S.; Samineni, R.; Pabbaraja, S.; Mehta, G. Nitromethane
as a Carbanion Source for Domino Benzoannulation with Ynones: One-Pot Synthesis of
Polyfunctional Naphthalenes and a Total Synthesis of Macarpine. Angew. Chem., Int. Ed.
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(4) For recent reviews on alkyne annulations via C–H activation, see: (a) Boyarskiy, V. P.;
Ryabukhin, D. S.; Bokach, N. A.; Vasilyev, A. V. Alkenylation of Arenes and Heteroarenes
with Alkynes. Chem. Rev. 2016, 116, 5894; (b) Gulías, M.; Mascareñas, J. L.
Metal-Catalyzed Annulations through Activation and Cleavage of C−H Bonds. Angew.
Chem., Int. Ed. 2016, 55, 11000; (c) Loginov, D. A.; Konoplev, V. E. Oxidative Coupling
of Benzoic Acids with Alkynes: Catalyst Design and Selectivity. J. Organomet. Chem.
2018, 867, 14; (d) Zheng, L.; Hua, R. C–H Activation and Alkyne Annulation via
Automatic or Intrinsic Directing Groups: Towards High Step Economy. Chem. Rec. 2018,
18, 556.
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(5) (a) Ueura, K.; Satoh, T.; Miura, M. Rhodium- and Iridium-Catalyzed Oxidative Coupling
of Benzoic Acids with Alkynes via Regioselective C−H Bond Cleavage. J. Org. Chem.
2007, 72, 5362; (b) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Fluorescent Naphthyl-
and Anthrylazoles from the Catalytic Coupling of Phenylazoles with Internal Alkynes
through the Cleavage of Multiple C–H Bonds. Angew. Chem., Int. Ed. 2008, 47, 4019; (c)
Yamashita, M.; Horiguchi, H.; Hirano, K.; Satoh, T.; Miura, M. Fused Ring Construction
around Pyrrole, Indole, and Related Compounds via Palladium-Catalyzed Oxidative
Coupling with Alkynes. J. Org. Chem. 2009, 74, 7481; (d) Fukutani, T.; Hirano, K.; Satoh,
T.; Miura, M. Synthesis of Highly Substituted Naphthalene and Anthracene Derivatives by
Rhodium-Catalyzed Oxidative Coupling of Arylboronic Acids with Alkynes. Org. Lett.
2009, 11, 5198. See also: (e) Kawasaki, S.; Satoh, T.; Miura, M.; Nomura, M. Synthesis of
Tetrasubstituted Naphthalenes by Palladium-Catalyzed Reaction of Aryl Iodides with
Internal Alkynes. J. Org. Chem. 2003, 68, 6836.
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(6) For selected examples, see: (a) Wu, Y. T.; Huang, K. H.; Shin, T. C.; Wu, T. C.
Palladium-Catalyzed Formation of Highly Substituted Naphthalenes from Arene and
Alkyne Hydrocarbons. Chem. - Eur. J. 2008, 14, 6697; (b) Wu, J.; Cui, X.; Mi, X.; Li, Y.;
Wu, Y. Palladium Catalyzed Synthesis of Highly Substituted Naphthalenes via Direct Ring
Construction from Amides with Alkynes. Chem. Commun. 2010, 46, 6771; (c) Pham, M. V.;
Cramer, N. Aromatic Homologation by Non-Chelate-Assisted RhIII-Catalyzed C–H
Functionalization of Arenes with Alkynes. Angew. Chem., Int. Ed. 2014, 53, 3484; (d)
Annamalai, P.; Chen, W.-Y.; Raju, S.; Hsu, K.-C.; Upadhyay, N. S.; Cheng, C.-H.; Chuang,
S.-C. Palladium-Catalyzed Selective Aryl Ring C–H Activation of N-Acyl-2-aminobiaryls:
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Efficient Access to Multiaryl-Substituted Naphthalenes. Adv. Synth. Catal. 2016, 358, 3642;
(e) Wang, L.; Yu, Y.; Yang, M.; Kuai, C.; Cai, D.; Yu, J.; Cui, X. Rhodium-Catalyzed
Synthesis of Multiaryl-substituted Naphthols via a Removable Directing Group. Adv. Synth.
Catal. 2017, 359, 3818; (f) Honjo, Y.; Shibata, Y.; Kudo, E.; Namba, T.; Masutomi, K.;
Tanaka, K. Room Temperature Decarboxylative and Oxidative [2+2+2] Annulation of
Benzoic Acids with Alkynes Catalyzed by an Electron-Deficient Rhodium(III) Complex.
Chem. - Eur. J. 2018, 24, 317.
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(7) For recent examples using heterocyclic substrates, see: (a) Fukuzumi, K.; Unoh, Y.; Nishii,
Y.; Satoh, T.; Hirano, K.; Miura, M. Synthesis of Benzo[c]thiophenes by
Rhodium(III)-Catalyzed Dehydrogenative Annulation. J. Org. Chem. 2016, 81, 2474; (b)
Li, S.-S.; Liu, C.-F.; Zhang, G.-T.; Xia, Y.-Q.; Li, W.-H.; Dong, L. A Convenient One-Pot
Route to Screw-Shaped [5]Azahelicenes via Rhodium(III)-Catalyzed Multiple C−H Bond
Activation. Chem. - Asian J. 2017, 12, 415; (c) Xu, X.; Zhao, H.; Xu, J.; Chen, C.; Pan, Y.;
Luo, Z.; Zhang, Z.; Li, H.; Xu, L. Rhodium(III)-Catalyzed Oxidative Annulation of
2,2’-Bipyridine N-Oxides with Alkynes via Dual C–H Bond Activation. Org. Lett. 2018, 20,
3843; (d) Bettadapur, K. R.; Kapanaiah, R.; Lanke, V.; Prabhu, K. R. Weak Directing
Group Steered Formal Oxidative [2+2+2]-Cyclization for Selective Benzannulation of
Indoles. J. Org. Chem. 2018, 83, 1810; (e) Yang, X.; Jiang, L.; Yang, M.; Zhang, H.; Lan,
J.; Zhou, F.; Chen, X.; Wu, D.; You, J. Pd-Catalyzed Direct C–H Functionalization/
Annulation of BODIPYs with Alkynes to Access Unsymmetrical Benzo[b]-Fused
BODIPYs: Discovery of Lysosome-Targeted Turn-On Fluorescent Probes. J. Org. Chem.
2018, 83, 9538.
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(8) For reviews on Ru-catalyzed C–H functionalization, see: (a) Arockiam, P. B.; Bruneau, C.;
Dixneuf, P. H. Ruthenium(II)-Catalyzed C–H Bond Activation and Functionalization.
Chem. Rev. 2012, 112, 5879; (b) Ackermann, L. Carboxylate-Assisted Ruthenium-
Catalyzed Alkyne Annulations by C–H/Het–H Bond Functionalizations. Acc. Chem. Res.
2014, 47, 281; (c) De Sarkar, S.; Liu, W.; Kozhushkov, S. I.; Ackermann, L. Weakly
Coordinating Directing Groups for Ruthenium(II)-Catalyzed C–H Activation. Adv. Synth.
Catal. 2014, 356, 1461; (d) Manikandan, R.; Jeganmohan, M. Recent Advances in the
Ruthenium(II)-Catalyzed Chelation-Assisted C–H Olefination of Substituted Aromatics,
Alkenes and Heteroaromatics with Alkenes via the Deprotonation Pathway. Chem.
Commun. 2017, 53, 8931; (e) Duarah, G.; Kaishap, P. P.; Begum, T.; Gogoi, S. Recent
Advances in Ruthenium(II)-Catalyzed C−H Bond Activation and Alkyne Annulation
Reactions. Adv. Syn. Catal. 2019, 361, 654.
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(9) For examples of Ru-catalyzed coupling of benzoic acids and alkynes, see: (a) Warratz, S.;
Kornhaaß, C.; Cajaraville, A.; Niepötter, B.; Stalke, D.; Ackermann, L. Ruthenium(II)-
Catalyzed C−H Activation/Alkyne Annulation by Weak Coordination with O2 as the Sole
Oxidant. Angew. Chem., Int. Ed. 2015, 54, 5513; (b) Miura, H.; Tsutsui, K.; Wada, K.;
Shishido, T. Coupling of Carboxylic Acids with Internal Alkynes by Supported Ruthenium
Catalysts: Direct and Selective Syntheses of Multi-Substituted Phthalide Derivatives.
Chem. Commun. 2015, 51, 1654; (c) Zhang, J.; Shrestha, R.; Hartwig, J. F.; Zhao, P. A
Decarboxylative Approach for Regioselective Hydroarylation of Alkynes. Nat. Chem. 2016,
8, 1144; (d) Kumar, N. Y.; Bechtoldt, A.; Raghuvanshi, K.; Ackermann, L.
Ruthenium(II)-Catalyzed Decarboxylative C−H Activation: Versatile Routes to meta-
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