Copper(I) bromide catalyzed arylation of cyclic enamides and naphthyl-1-acetamides using diaryliodonium salts

Article abstract of DOI:10.1021/jo501162s

Copper(I) bromide catalyzed direct C-H arylation of cyclic enamides was achieved using diaryliodonium salts in the absence of base/additive at ambient temperature with high yields. A biologically active dihydro[a]benzocarbazole scaffold was synthesized us

Full text of DOI:10.1021/jo501162s

Article
pubs.acs.org/joc
Copper(I) Bromide Catalyzed Arylation of Cyclic Enamides and
Naphthyl-1-acetamides Using Diaryliodonium Salts
Muthuraj Prakash, Subramaniam Muthusamy, and Venkitasamy Kesavan*
Chemical Biology Lab, Department of Biotechnology, Bhupat and Jyothi Mehta School of Biosciences Building, Indian Institute of
Technology Madras, Chennai-600036, India
S
* Supporting Information
ABSTRACT: Copper(I) bromide catalyzed direct C−H arylation of cyclic enamides was achieved using diaryliodonium salts in
the absence of base/additive at ambient temperature with high yields. A biologically active dihydro[a]benzocarbazole scaffold was
synthesized using the established protocol. The scope of the current methodology was further extended for the synthesis of C4-,
C7-aryl-substituted 1-naphthyl acetamides in good yields.
INTRODUCTION
■
Enamides are prevalent intermediates for synthesis of valuable
chiral amines and natural products.1,2 Although acyclic
enamides are well exploited in a number of interesting
synthetic transformations with electrophiles,3−8 exploration of
cyclic enamides as nucleophiles is very limited.9−12 Synthetic
utility of cyclic enamides in forming a C−C bond was
demonstrated by Zhou et al.,13,14 by synthesizing β-aryl cyclic
enamides 4 through Suzuki−Hiyama-type coupling. These
protocols rely on an expensive palladium(II) catalyst in
conjunction with additives such as copper or silver salts/base
at elevated temperature. Inseparable aromatized byproduct 6
Figure 1. Biologically important scaffolds can be made from β-aryl
also forms along with the expected β-aryl cyclic enamide 4 due
cyclic enamides.
to high temperature (Scheme 1).13,14 Under the established
catalytic conditions, only enamide 2 provided the expected
product in good yields. In due course, Gigant et al., reported
Although secondary enamides are stable under neutral
the first copper-catalyzed C3-arylation of cyclic enesulfonamide
conditions, the presence of trifilic acid or a triflate/
I using diaryliodonium salts in the presence of base at 80 °C.15
trifluoroborate counterion would lead to isomerization of
secondary enamides III to imines.24,25 Hence, we hypothesize
Although, β-aryl cyclic enamides (4, 5) are important
structural precursors for the synthesis of biologically important
compounds, such as indole carboline ring systems (8, 9, 10),
phenanthridine scaffolds (11), and 2-aryl-tetrahydronaphthyl-
amines (12),16−23 their preparation remains a challenge for the
aforementioned reasons (Figure 1). The importance of β-aryl
cyclic enamides 4 and drawbacks of existing methods
stimulated us to develop an operationally simple and base/
additive-free C−H arylation of cyclic enamides at ambient
temperature.
that use of a suitably activated electrophile with a triflate/
trifluoroborate counterion will facilitate the β-substitution of
secondary cyclic enamides.
Seminal contributions from Gaunt and Macmillan groups
independently showcased the ability of diaryliodonium salts in
forming C−C bonds.26−29 These reports encouraged us to use
Received: August 8, 2013
Published: August 11, 2014
© 2014 American Chemical Society
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Scheme 1. Strategies for C−H Arylation of Cyclic Enamides
Scheme 2. Hypothesis and Current Protocol
a
diaryliodonium salt as an electrophile for the C−H arylation of
secondary enamides in the presence of a copper catalyst.30,31
To the best of our knowledge, this is the first report to
demonstrate the β-arylation of cyclic enamides at ambient
conditions in the absence of additive/base using CuBr. Easy,
one-pot synthesis, air- and moisture-stable diaryliodonium
salts32−34 are an added advantage.
Table 1. Optimization of Reaction Conditions
b
entry
metal
X
mol (%)
time (h)
yield (%)
1
2
Cu(OTf)2
Cu(OAc)2
CuOTf
CuPF6
CuI
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
BF4
OTs
Cl
10
10
10
10
10
10
05
01
05
05
05
05
14
9
25
20
70
67
73
81
82
70
77
25
RESULTS AND DISCUSSION
■
3
5
Enamide derived from α-tetralone was selected to identify a
suitable copper salt to facilitate the formation of a C−C bond.
Cyclic enamide 1 was treated with various copper salts (10 mol
%) and 1.2 equiv of mesitylphenyliodonium salt 7a in
dichloromethane at ambient temperature, and the results are
tabulated in Table 1. Although copper(II) triflate catalyzed β-
arylation of cyclic enesulfonamides,15 it failed to catalyze β-
arylation of cyclic enamide 1 efficiently (Table 1, entry 1).
Copper(II) salts furnished the expected β-arylated product 4a
only in poor yields (entries 1 and 2).
Among the various Cu(I) salts screened (entries 3−6),
reaction proceeded smoothly when CuBr was employed (entry
6). Further, to emphasize the importance of the present
methodology, cyclic enamide 1 was treated with mesitylphe-
nyliodonium triflate 7a under the reported condition for ene-
sulfonamides.15 The obtained result indicates that the yield of
the expected product 4 was not only poor, aromatized
4
7
5
5
6
CuBr
3.5
7
CuBr
6
36
9
8
CuBr
9
CuBr
10
11
12
CuBr
14
36
36
CuBr
CuBr
Br
a
Reaction conditions: 1 (1 equiv), 7a (1.2 equiv), and copper catalyst
(X mol %) in CH2Cl2 at rt for the indicated time. Isolated yield after
column chromatography.
b
byproduct 6 also formed as an inseparable mixture (Scheme
2). In addition, to prove the requirement of copper(I) catalyst,
the reaction was performed in the absence of copper(I)
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bromide. No detectable arylated product 4 was observed at
room temperature; hence, the reaction was carried out in a
sealed tube at 80 °C. The arylation occurred with poor
conversion and inseparable mixture of expected product 4 and
byproduct 6, was obtained in 14% yield. This experiment
reveals that copper(I) bromide plays a vital role and it activates
the diaryliodonium salt by forming active electrophilic species.
Encouraged by the performance of copper(I) bromide, we
sought to identify the optimal catalytic loading without
compromising the yield. The yield of the reaction was
unaffected when 5 mol % of the catalyst was used (entry 7).
Although 1 mol % of CuBr was sufficient enough to catalyze
the arylation with 70% yield, prolonged reaction time was
observed (entry 8). Hence, further optimization studies were
carried out using 5 mol % of CuBr. The effect exerted by
counteranions of diaryliodonium salt 7a was studied (entries
9−12). No improvement in either yield or rate of the reaction
was observed when the triflate ion was replaced by
tetrafluoroborate or tosylate ions (entries 9 and 10). Arylation
failed to proceed when mesitylphenyliodonium chloride or
mesitylphenyliodonium bromide salts were used (entries 11
and 12). Thus, we optimized the condition for C−C bond
formation of cyclic enamides through β-arylation using CuBr as
a catalyst at 25 °C.
The presence of sterically hindered ortho-bromo substitution
is well tolerated under our catalytic conditions (entry 7).
Moreover, halogen-substituted β-aryl enamides serve as
valuable synthetic handles for transformation, such as cross-
coupling reactions and intramolecular cyclization in the case of
ortho-bromo-substituted products. This accomplishment clearly
demonstrates the efficiency of the current methodology,
because such products are difficult to obtain using a
palladium-catalyzed method due to oxidative insertion. The
established protocol was not only limited to electron releasing
and halogen substituents; a strong electron-withdrawing group
like nitro substitution at the para-position also furnished the
expected arylated product 7h in 80% yield (entry 8). The
highlight of this methodology is that no aromatized side
product 6 was observed, unlike earlier protocols.13,14 Under the
identical conditions, chromone derived cyclic enamide 2
underwent β-arylation with ease to afford the corresponding
arylated products 5a−h in very good yields (Table 3).
a
Table 3. Substrate Scope
With these optimized reaction conditions, evaluation of the
substrate scope was undertaken. The influence of methyl
substitution at different positions was investigated initially.
Reaction proceeded with ease when compounds 7b and 7c
were employed as substrates. Corresponding arylated products
4b and 4c were isolated in good yields within 6 h (Table 2,
Table 2. Synthesis of Various Substituted β-Aryl Cyclic
a
Enamides
b
entry
(Ar =)
C6H5 (7a)
time (h)
yield (4a−h) (%)
1
2
3
4
5
6
7
8
6
6
82
81
80
72
77
83
71
80
4-CH3−C6H4 (7b)
3,5-(CH3)2-C6H3 (7c)
2,4,6-(CH3)3-C6H2 (7d)
2-F-C6H4 (7e)
9
36
24
12
36
24
3-Cl-C6H4 (7f)
2-Br-C6H4 (7g)
4-NO2-C6H4 (7h)
a
Reaction conditions: 1 (1 equiv), 7 (1.2 equiv), and Cu(I)Br (5 mol
b
%) in CH2Cl2 at rt for the indicated time. Isolated yield after column
chromatography.
a
Reaction conditions: 2 (1 equiv), 7 (1.2 equiv), and Cu(I)Br (5 mol
%) in CH2Cl2 at rt for the indicated time.
entries 2 and 3). We also examined the steric effect of methyl
substitution at ortho-positions by using dimesityliodonium
triflate 7d as the reagent. The corresponding arylated product
4d was isolated in 72% yield after 36 h (entry 4). After
examining the effect of alkyl substitutions, we moved on to
study the tolerability of halogen-substituted iodonium salts.
The examination of halogen substitutions exposed that the
position and nature of the halogen present in the aryl ring did
not affect the catalytic efficiency, and the reaction proceeded
smoothly to afford the corresponding arylated products 7e−g
in good yields (entries 5−7).
When mono- and dimethyl-substituted iodonium salts 7b
and 7c were employed as substrates, arylation occurred with
excellent yields to afford 5b and 5c, respectively. Yield of the
product was not affected in the case of sterically hindered
dimesityliodonium salt 7d. The expected arylated product 5d
was obtained in 79% yield after 32 h. The presence of halogen
substituents as well as an electron-withdrawing nitro group did
not exert any influence on the efficiency of the reaction. We
were delighted to observe that diaryliodonium salts with aryl
groups possessing electron-rich, electron-deficient and halogen
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functionalities worked well under our catalytic conditions.
Thus, we developed a copper(I) bromide catalyzed β-arylation
of cyclic enamides with no additive/base at ambient temper-
ature.
To demonstrate the applicability of β-aryl cyclic enamides,
biologically important dihydrobenzo[a]carbazole was synthe-
sized from ortho-bromo arylated product 4g through intra-
molecular cyclization. N-(3-(2-Bromophenyl)-2H-chromen-4-
yl)acetamide 4g was treated with 5 mol % of CuI and 10 mol %
of L-proline in the presence of Cs2CO3 in DMSO at 50 °C.
Dihydro[a]benzocarbazole (8) was isolated with a moderate
yield of 63% (Scheme 3). The existing protocols to synthesize
It is reasonable to anticipate that steric hindrance plays a
crucial role in determining the formation of regioisomers. An
ortho effect as well as peri-hydrogen interaction favors the
synthesis of the C7-isomer over the C2-isomer and C4-, C5-
isomers. Thus, this methodology enables directed arylation of
naphthyl-1-acetamides at either the C7- or the C4-position.
Synthesis of C7-aryl-substituted naphthyl-1-acetamides was
explored in standard reaction conditions using various
diaryliodonium salts.
We observed that the efficiency of arylation on naphthyl-1-
acetamide 13a is inferior to that of cyclic enamides (1 and 2).
TLC observation indicated the presence of starting material
13a under standard reaction conditions. Extending the reaction
time further up to 2−3 days did not improve the conversion.
For example, substrate 13a was treated with mesitylphenylio-
donium salt 7a under standard conditions to give 7-phenyl-
naphthyl-1-acetamide 15a as a major product in 68% yield
along with 22% of recovered 13a (Table4). Although only the
Scheme 3. Synthesis of Dihydrobenzo[a]carbazole via
Intramolecular Cyclization
Table 4. Synthesis of C7-, C4-Aryl-Substituted Naphthenyl-
a b
,
1-acetamides
dihydrobenzo[a]carbazole derivatives involve multistep reac-
tion processes and expensive palladium catalyst.35 This new
catalytic method paves the way to synthesize diverse substituted
dihydrobenzo[a]carbazoles effectively.
To further expand the scope of the current methodology,
arylation of naphthenyl-1-acetamide was undertaken. Despite
that various coupling strategies were employed to synthesize
arylated anilides, arylation of naphthyl-1-acetamides is not well
explored in the literature.36−39 Naphthyl-1-acetamide 13a was
treated with 5 mol % of CuBr and 1.2 equiv of diaryliodonium
salt in dichloromethane. Only a trace amount of product was
observed by TLC at ambient temperature; hence, the reaction
was carried out using 5 mol % of CuBr in dichloroethane at 50
°C (Scheme 4).
Scheme 4. Phenylation of Naphthyl-1-acetamide
2D NMR studies revealed that the isolated product was not
the expected 2-phenyl-naphthyl-1-acetamide 14, but its
regioisomer 7-phenyl-naphthyl-1-acetamide 15a (see the
Supporting Information). In order to direct the phenylation
at the C2-position, we chose 7-methoxy-naphthyl-1-acetamide
13b as a substrate. Under identical reaction conditions, 4-
phenyl-7-methoxy-naphthyl-1-acetamide 17a was isolated as a
major product instead of the C2-arylated product (Scheme 5).
a
Reaction conditions: 3 (1 equiv), 7 (1.2 equiv), and Cu(I)Br (5 mol
b
%) in ClCH2CH2Cl2 at 50 °C for the indicated time. Isolated yields.
conversion was affected, the regioselectivities of the products
(15b−e) remain unchanged when halogen-substituted diary-
liodonium salts were employed as substrates. The effect of
disubstitution was also studied by employing 3,5-dimethyl
phenyliodonium salt 7c as a substrate, and the resultant arylated
product 15h was isolated in 60% yield. In all of these cases,
starting material 13a was recovered in the range of 22−36%.
Based on the recovered starting material 13a, the yields of the
products are in the range of 85−93%. Thus, we achieved C7-
Scheme 5. Phenylation of 7-Methoxynaphthyl-1-acetamide
13b
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(ESI): m/z calculated for C20H21NONa [M+ + Na] 314.1521, found:
314.1516.
arylation of naphthyl-1-acetamide under mild reaction con-
ditions using CuBr.
N-(2-Mesityl-3,4-dihydronaphthalen-1-yl)acetamide (4d). Iso-
lated as colorless solid; 59 mg, Yield 72%; Melting Point: 175−180
°C; 1H NMR (500 MHz, DMSO-d6) δ: 8.54 (bs, 1H), 7.20−7.16 (m,
3H),7.10−7.08 (m, 1H), 6.84 (s, 2H), 2.89 (t, J = 8 Hz, 2H), 2.37 (t, J
= 8 Hz, 2H), 2.28(s, 3H), 2.15(s, 6H) 1.76 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 168.8, 137.4, 135.8, 135.6, 135.0, 134.8, 133.6,
129.9, 128.2, 127.6, 127.2, 126.5, 123.1, 28.6, 28.0, 22.9, 21.0, 20.1; IR
(KBr): ν = 3234, 1656, 1531, 1278, 1035, 1015, 852, 766 cm−1;
HRMS (ESI): m/z calculated for C21H23NONa [M+ + Na] 328.1677,
found: 328.1684.
N-(2-(2-Fluorophenyl)-3,4-dihydronaphthalen-1-yl)acetamide
(4e). Isolated as colorless solid; 58 mg, Yield 77%; Melting Point:
243−247 °C; 1H NMR (500 MHz, DMSO-d6) δ: 9.01 (bs, 1H), 7.33−
7.31 (m, 2H), 7.23−7.19 (m, 6H), 2.86 (t, J = 8 Hz, 2H), 2.59 (t, J = 8
Hz, 2H), 1.82 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.2,
160.4, 158.5, 136.0, 133.2, 130.9, 130.2, 130.1, 130.0, 129.5, 129.5,
128.5, 128.4, 127.9, 127.6, 126.7, 127.4, 124.4, 123.6, 116.2, 116.0,
29.0, 27.6, 22.8; IR (KBr): ν = 3233, 1659, 1099, 1037, 1009, 805, 764
cm−1; HRMS (ESI): m/z calculated for C18H17NOF [M+ + H]
282.1294, found: 282.1293.
N-(2-(2-Chlorophenyl)-3,4-dihydronaphthalen-1-yl)acetamide
(4f). Isolated as colorless solid; 66 mg, Yield 83%; Melting Point: 238−
242 °C; 1H NMR (500 MHz, DMSO-d6) δ: 9.10 (bs, 1H), 7.41−7.38
(m, 2H), 7.34−7.30 (m, 2H), 7.21−7.16 (m, 4H), 2.87 (t, J = 8 Hz,
2H), 2.67 (t, J = 8 Hz, 2H), 1.89 (s, 3H); 13C NMR (125 MHz,
DMSO-d6) δ: 169.6, 143.3, 135.9, 133.4, 133.4, 133.1, 130.3, 129.8,
127.9, 127.6, 127.3, 127.2, 126.7, 126.2, 123.5, 29.2, 27.6, 22.8; IR
(KBr): ν = 3280, 1654, 1620, 1519, 769 cm−1; HRMS (ESI): m/z
calculated for C18H17NOCl [M+ + H] 298.0999, found: 298.1005.
N-(2-(2-Bromophenyl)-3,4-dihydronaphthalen-1-yl)acetamide
(4g). Isolated as colorless solid; 65 mg, Yield 71%; Melting Point:
203−207 °C; 1H NMR (500 MHz, DMSO-d6) δ: 8.87 (bs, 1H), 7.67−
7.65 (dd, J = 8 Hz, 1H), 7.36−7.34 (m, 1H), 7.27−7.24(m, 2H),
7.22−7.19 (m, 3H), 7.16−7.12 (m, 1H), 2.99−2.94 (m, 1H), 2.90−
2.85 (m, 1H), 2.71−2.66 (m, 1H), 2.49−2.47 (m, 1H), 1.77 (s, 3H);
13C NMR (125 MHz, DMSO-d6) δ: 169.3, 141.7, 136.0, 135.4, 133.2,
Under the identical conditions, various C4-aryl-substituted 7-
methoxynaphthyl-1-acetamides (17a−e) were successfully
synthesized with moderate yields. It is noteworthy that this is
the first method that discloses C4-, C7-arylation of naphthy-1-
acetamides using inexpensive copper(I) salt.
In summary, we established an operationally simple,
economical, and mild catalytic protocol for the direct C−H
arylation of cyclic enamides derived from tetralone and
chromonone for the first time using CuBr at ambient
temperature in the absence of base/additives. This strategy
enables the efficient synthesis of dihydrobenzo[a]carbazoles in
good yield. The scope of this catalytic system was further
extended to synthesize various C4-, C7-aryl-substituted
naphthenyl-1-acetamides in moderate yields.
EXPERIMENTAL SECTION
■
General Remarks. Solvents used for reactions and column
chromatography were commercial grade and distilled prior to use.
Toluene and THF were dried over sodium/benzophenone, whereas
CH2Cl2 and CHCl3 were dried over CaH2. Column chromatography
was performed using silica gel 60−100 mesh. Melting points were
1
determined by an open glass capillary method and uncorrected. H
NMR and 13C NMR were recorded on a 500 and 125 MHz using
DMSO-d6 or CDCl3 as solvents, and multiplicity was indicated as
follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
dd (doublet of doublet), dt (doublet of triplet) bs (broad singlet).
Coupling constants J are reported in hertz (Hz). High-resolution mass
spectra were obtained by ESI using Q-TOF and Orbitrap mass
spectrometers. IR spectra were recorded on an FT/IR-420
spectrometer and are reported in terms of frequency of absorption
(cm−1). Melting points were measured in open capillaries and are
uncorrected.
Typical Experimental Procedure for β-Arylation of Cyclic
Enamides. The solution of cyclic enamide 1 or 2 (0.267 mmol),
diaryliodonium salt 7 (0.32 mmol), and CuBr (1.91 mg, 5 mol %) in
dry CH2Cl2 (1 mL) was stirred under a nitrogen atmosphere at
ambient temperature for 5−36 h. The completion of the reaction was
ascertained by TLC. The reaction mixture was concentrated under
reduced pressure, and the residue was purified over silica gel using
hexane/EtOAc as eluent (gradient mixture ratio from 90:10 to 60:40)
to afford the corresponding arylated product 4 or 5.
132.9, 130.4, 130.3, 129.4, 127.8, 127.7, 127.6, 126.7, 123.6, 122.2,
29.1, 27.8, 22.7; IR (KBr): ν = 3268, 1665, 1498, 1024, 1009, 956, 762
cm−1; HRMS (ESI): m/z calculated for C18H17NOBr [M+ + H]
342.0494, found: 342.0494.
N-(2-(4-Nitrophenyl)-3,4-dihydronaphthalen-1-yl)acetamide
(4h). Isolated as yellow solid; 66 mg, Yield 80%; Melting Point: > 250
°C; 1H NMR (500 MHz, DMSO-d6) δ: 9.20 (bs, 1H), 8.24−8.22 (dd,
J = 7 Hz, J = 2 Hz, 2H), 7.62−7.61 (dd, J = 7 Hz, J = 2 Hz, 2H), 7.24−
7.22 (m, 4H), 2.89 (t, J = 8 Hz, 2H), 2.72 (t, J = 8 Hz, 2H), 1.91 (s,
3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.5, 148.6, 146.3, 136.2,
133.1, 132.5, 131.1, 128.7, 128.3, 127.7, 126.8, 123.8, 123.7, 29.1, 27.5,
22.9; IR (KBr): ν = 3260, 1661, 1593, 1509, 1341, 1287, 1108, 857,
774 cm−1; HRMS (ESI): m/z calculated for C18H17N2O3 [M+ + H]
309.1239, found: 309.1248.
N-(2-Phenyl-3,4-dihydronaphthalen-1-yl)acetamide (4a). Iso-
lated as colorless solid; 58 mg, Yield 83%; Melting Point: 167−171
1
°C; H NMR (500 MHz, DMSO-d6) δ: 9.05 (s, 1H), 7.36 (d, J = 4.5
Hz, 4H), 7.28−7.25 (m, 1H), 7.2−7.16 (m, 3H), 7.14−7.12 (m, 1H),
2.86 (t, J = 8 Hz, 2H), 2.67 (t, J = 8 Hz, 2H), 1.88 (s, 3H); 13C NMR
(125 MHz, DMSO-d6) δ: 169.8, 141.1, 135.8, 134.9, 133.8, 133.9,
129.0, 128.6, 128.2, 127.5, 127.4, 126.7, 123.3, 29.6, 27.7, 22.8; IR
(KBr): ν = 3279, 1653, 1622, 1523, 769, 702 cm−1.
N-(3-Phenyl-2H-chromen-4-yl)acetamide (5a). Isolated as color-
1
less solid; 65 mg, Yield 93%; Melting Point: 160−163 °C; H NMR
N-(2-(p-Tolyl)-3,4-dihydronaphthalen-1-yl)acetamide (4b). Iso-
(500 MHz, DMSO-d6) δ: 9.22 (bs, 1H), 7.41−7.38 (m, 4H), 7.33 (m,
1H), 7.20−7.17 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.11 (dd, J = 7.5 Hz, J
= 1.5 Hz, 1H), 6.96−6.93 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 6.87(dd, J =
8 Hz, 1H), 5.08 (d, J = 1.5 Hz, 2H), 1.93 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 169.9, 154.2, 136.4, 129.7, 128.8, 128.2, 128.2,
127.6, 126.6, 124.2, 122.7, 121.7, 115.9, 69.0, 22.9; IR (KBr): ν =
3235, 1665, 1600, 1537, 1208, 1037, 1005, 723 cm−1.
lated as colorless solid; 60 mg, Yield 81%; Melting Point: 181−183
1
°C; H NMR (500 MHz, DMSO-d6) δ: 9.00 (bs, 1H), 7.26 (m, 2H),
7.18−7.11 (m, 6H), 2.85 (t, J = 8 Hz, 2H), 2.65 (t, J = 8 Hz, 2H),
2.31(s, 3H) 1.89 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.7,
138.1, 136.6, 135.7, 134.7, 133.9, 129.0, 128.7, 127.5, 127.5, 127.3,
126.6, 123.3, 29.6, 27.7, 22.9, 21.2; IR (KBr):
ν =
3251,1654,1627,1520,721 cm−1.
N-(3-(p-Tolyl)-2H-chromen-4-yl)acetamide (5b). Isolated as color-
N-(2-(3,5-Dimethylphenyl)-3,4-dihydronaphthalen-1-yl)-
1
less solid; 66 mg, Yield 90%; Melting Point: 174−177 °C; H NMR
acetamide (4c). Isolated as colorless solid; 62 mg, Yield 80%; Melting
1
(500 MHz, DMSO-d6) δ: 9.17 (bs, 1H), 7.29 (d, J = 8 Hz, 2H), 7.21
(d, J = 8 Hz, 2H), 7.19−7.15 (td, J = 8 Hz, J = 1.5 Hz, 1H), 7.10 (dd, J
= 8 Hz, J = 1.5 Hz, 1H), 6.95−6.92 (td, J = 7.5 Hz, J = 1 Hz, 1H), 6.86
(dd, J = 8 Hz, J = 1 Hz, 1H), 5.05 (d, J = 1.5 Hz, 2H), 2.32(s, 3H) 1.93
(s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.8, 154.2, 137.6,
133.4, 129.5, 129.3, 128.1, 127.5, 126.2, 124.1, 122.8, 121.7, 115.8,
Point: 185−189 °C; H NMR (500 MHz, DMSO-d6) δ: 8.97 (bs,
1H), 7.18−7.11 (m, 4H), 6.97 (s, 2H), 6.90 (s, 1H), 2.84 (t, J = 8 Hz,
2H), 2.64 (t, J = 8 Hz, 2H), 2.27 (s, 6H) 1.88 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 169.7, 141.0, 137.2, 135.7, 134.8, 133.9, 128.9,
128.8, 127.5, 127.3, 126.6, 125.3, 123.3, 29.6, 27.7, 22.8, 21.4; IR
(KBr): ν = 3226, 1633, 1298, 1039, 1008, 845, 773 cm−1; HRMS
7840
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69.0, 22.9, 21.3; IR (KBr): ν = 3240, 1653, 1641, 1514, 1040, 1009,
814, 765 cm−1.
Cs2CO3 (97 mg, 0.3 mmol), and CuI (1.94 mg, 5 mol %) in DMSO (3
mL) was heated at 50 °C for 12 h under an inert atmosphere. The
reaction mixture was cooled to room temperature, and 5 mL of water
was added. The aqueous layer was extracted with AcOEt (10 mL × 2).
The combined organic layer was washed with brine (10 mL × 2) and
dried over MgSO4. The organic layer was concentrated in vacuo. The
obtained crude product was purified with column chromatography on
silica gel (elution with hexane/AcOEt = 70:30) to give 8 (20 mg, 63%
yield) as a colorless solid. Melting Point: 162−165 °C; 1H NMR (500
MHz, DMSO- d6): δ 11.41 (br s, 1H), 7.63−7.64 (m, 1H), 7.63−7.64
(m, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8 Hz, 1H), 7.27−7.29
(m, 2H), 7.14−7.17 (m, 1H), 7.08−7.11 (m, 1H), 6.98−7.01 (m, 1H),
2.98−3.01 (m, 2H), 2.88−2.91 (m, 2H); 13C NMR (125 MHz,
DMSO- d6): δ 137.5, 136.3, 133.5, 129.5, 128.7, 127.1, 127.1, 126.9,
122.0, 121.3, 119.3, 118.8, 111.8, 111.2, 29.4, 19.7; IR (KBr): ν =
3410, 3048, 1451, 1319, 743 cm−1.
Typical Experimental Procedure for Synthesis of Various
Substituted 7-Aryl-1-naphthenyl Acetamides 15a−f. To the
stirred solution of 1-naphthenyl acetamide 13a (50 mg, 0.27 mmol)
and diaryliodonium salt 7 (0.32 mmol) in dry dichloroethane (1 mL)
was added CuBr (1.93 mg, 5 mol %) under a nitrogen atmosphere,
and the mixture was heated at 50 °C for 7−9 h. The reaction progress
was monitored by TLC. After 7−9 h, the crude mixture was
concentrated under reduced pressure, and the residue was purified to
afford the corresponding 7-aryl-1-naphthenyl acetamides 15a−f and
unreacted substrate 13a.
N-(3-(3,5-Dimethylphenyl)-2H-chromen-4-yl)acetamide (5c). Iso-
lated as colorless solid; 67 mg, Yield 87%; Melting Point: 179−183 °C;
1H NMR (500 MHz, DMSO-d6) δ: 9.16 (bs, 1H), 7.17 (td, J = 8 Hz, J
= 1.5 Hz, 1H), 7.09 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 6.99 (s, 2H), 6.96
(s, 1H), 6.95−6.91 (td, J = 7.5 Hz, J = 1 Hz, 1H), 6.86 (dd, J = 8 Hz, J
= 1 Hz, 1H), 5.03 (d, J = 1 Hz, 2H), 2.27(s, 6H) 1.92 (s, 3H); 13C
NMR (125 MHz, DMSO-d6) δ: 169.9, 154.2, 137.7, 136.2, 129.7,
129.5, 128.3, 126.4, 125.3, 124.2, 122.8, 121.7, 115.8, 69.0, 22.8, 21.4;
IR (KBr): ν = 3238, 1652, 1646, 1598, 1038, 1015, 848, 753 cm−1;
HRMS (ESI): m/z calculated for C19H20NO2 [M+ + H] 294.1494,
found: 294.1507.
N-(3-Mesityl-2H-chromen-4-yl)acetamide (5d). Isolated as color-
1
less solid; 66 mg, Yield 79%; Melting Point: 170−175 °C; H NMR
(500 MHz, DMSO-d6) δ: 8.76 (bs, 1H), 7.16 (td, J = 7.5 Hz, J = 1.5
Hz, 1H), 7.07 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 6.92 (m, 1H), 6.86 (s,
3H), 4.76 (s, 2H), 2.23(s, 3H), 2.19(s, 6H), 1.79 (s, 3H); 13C NMR
(125 MHz, DMSO-d6) δ: 169.0, 154.3, 136.7, 136.2, 132.5, 129.3,
129.0, 128.4, 127.5, 124.0, 122.3, 121.5, 115.9, 68.3, 22.9, 21.0, 19.9; IR
(KBr): ν = 3235, 1663, 1651, 1511, 1036, 1005, 803, 756 cm−1;
HRMS (ESI): m/z calculated for C20H22NO2 [M+ + H] 308.1651,
found: 308.1644.
N-(3-(2-Fluorophenyl)-2H-chromen-4-yl)acetamide (5e). Isolated
1
as colorless solid; 60 mg, Yield 80%; Melting Point: 200−204 °C; H
NMR (500 MHz, DMSO-d6) δ: 9.21 (bs, 1H), 7.41−7.34 (m, 1H),
7.27−7.21 (m, 3H), 7.17 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 6.97 (td, J =
7.5 Hz, J = 1 Hz, 1H), 6.90 (dd, J = 8 Hz, J = 1 Hz, 1H), 4.94 (s, 2H),
1.87 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.3, 160.9, 158.9,
154.6, 130.4, 130.3, 130.2, 130.2, 130.1, 128.8, 124.8, 124.7, 124.4,
124.3, 124.1, 122.8, 122.3, 121.8, 116.3, 116.1, 68.3, 68.3, 22.9; IR
(KBr): ν = 3234, 1664, 1575, 1272, 1039, 1005, 790, 759 cm−1;
HRMS (ESI): m/z calculated for C17H14NO2FNa [M+ + Na]
306.0902, found: 306.0906.
N-(7-Phenylnaphthalen-1-yl)acetamide (15a). The crude product
was purified by flash chromatography using hexane/AcOEt as eluent
(gradient mixture ratio from 95:05 to 80:20) to provide the
compounds in order of elution, arylated product 15a as a colorless
solid (48 mg, 68%) and the recovered starting material 13a (11 mg,
1
22%). Melting Point: 161−165 °C; H NMR (500 MHz, DMSO-d6)
δ: 10.01 (bs, 1H), 8.35 (s, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.86 (dt, J =
7.5, 1 Hz, 3H), 7.79 (d, J = 7.5, 1H), 7.77 (d, J = 8.5, 1H), 7.55 (t, J =
8 HZ, 2H), 7.50 (t, J = 8 HZ, 1H), 7.42 (t, J = 7.5 HZ, 1H), 2.23 (s,
3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.4, 140.7, 137.9, 134.4,
133.3, 129.5, 129.4, 128.1, 127.9, 127.6, 126.2, 125.6, 125.0, 121.9,
120.7, 24.1; IR (KBr): ν = 3266, 3052, 2926, 1672, 1606, 1547, 1517,
1467, 1388, 1291, 1188, 1131, 1099, 1042, 889, 798, 772 cm−1. HRMS
(ESI): m/z calculated C18H16ON [M+ + H] 262.1226, found:
262.1221.
N-(3-(3-Chlorophenyl)-2H-chromen-4-yl)acetamide (5f). Isolated
1
as colorless solid; 67 mg, Yield 85%; Melting Point: 186−192 °C; H
NMR (500 MHz, DMSO-d6) δ: 9.26 (bs, 1H), 7.44−7.42 (m, 2H),
7.40−7.38 (dt, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.35−7.33 (dt, J = 7.5 Hz, J
= 1.5 Hz, 1H), 7.22−7.19 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.14 (dd, J
= 7.5 Hz, J = 1.5 Hz, 1H), 6.97−6.94 (td, J = 7.5 Hz, J = 1 Hz, 1H),
6.87 (dd, J = 8 Hz, J = 1 Hz, 1H), 5.07 (d, J = 1 Hz, 2H), 1.93 (s, 3H);
13C NMR (125 MHz, DMSO-d6) δ: 169.8, 154.4, 138.6, 133.5, 130.6,
130.1, 128.0, 127.5, 127.4, 126.7, 126.3, 124.3, 122.4, 121.8, 116.0,
68.6, 22.9; IR (KBr): ν = 3238, 1651, 1633, 1523, 1278, 1038, 1009,
877, 750 cm−1; HRMS (ESI): m/z calculated for C17H15NO2Cl [M+ +
H] 300.0791, found: 300.0792.
N-(7-(3-Fluorophenyl)naphthalen-1-yl)acetamide (15b). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 15b as a
colorless solid (51 mg, 67%) and the recovered starting material 13a
N-(3-(2-Bromophenyl)-2H-chromen-4-yl)acetamide (5g). Isolated
1
(10 mg, 20%). Melting Point: 182−187 °C; H NMR (500 MHz,
1
as colorless solid; 70 mg, Yield 77%; Melting Point: 176−181 °C; H
DMSO-d6) δ: 10.01 (bs, 1H), 9.71 (s, 1H), 8.01−7.94 (m, 3H), 7.59−
7.58 (m, 2H), 7.56−7.49 (m, 2H), 7.30−7.26 (m, 2H), 2.19 (s, 3H);
13C NMR (125 MHz, DMSO-d6) δ: 170.0, 162.4 (d, J = 241 Hz),
142.6 (d, J = 8.75 Hz), 135.9, 133.7, 131.4, 131.3, 130.6 (d, J = 8.75
Hz), 128.4, 128.1, 127.9, 127.3, 126.9, 125.5 (d, J = 3.75 Hz), 124.4,
116.0 (d, J = 22.5 Hz), 114.4 (d, J = 21.25 Hz), 23.0; IR (KBr): ν =
3253, 3046, 2327, 1667, 1607, 1590, 1537, 1501, 1456, 1433, 1271,
1185, 1161, 1131, 1185, 1131, 869, 832, 753, 699 cm−1. HRMS (ESI):
m/z calculated C18H15ONF [M+ + H] 280.1132, found: 280.1130.
N-(7-(3-Chlorophenyl)naphthalen-1-yl)acetamide (15c). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 15c as a
colorless solid (49 mg, 61%) and the recovered starting material 13a
NMR (500 MHz, DMSO-d6) δ: 9.09 (bs, 1H), 7.68 (dd, J = 8 Hz, J =
1.5 Hz, 1H), 7.39 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.30−7.28 (m, 2H),
7.23 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.14 (dd, J = 7.5 Hz, J = 1.5 Hz,
1H), 6.97 (td, J = 7.5 Hz, J = 1 Hz, 1H), 6.89 (dd, J = 5 Hz, J = 0.5 Hz,
1H), 5.01 (d, J = 15 Hz, 1H), 4.84 (d, J = 13.5 Hz, 1H), 1.82 (s, 3H);
13C NMR (125 MHz, DMSO-d6) δ: 169.4, 154.6, 137.5, 133.1, 131.2,
130.2, 130.1, 128.4, 128.1, 128.0, 124.5, 122.5, 122.2, 121.8, 116.1,
68.3, 22.8; IR (KBr): ν = 3268, 1670, 1604, 1485, 1366, 1036, 1002,
856, 756 cm−1; HRMS (ESI): m/z calculated for C17H15NO2Br [M+ +
H] 344.0286, found: 344.0293.
N-(3-(4-Nitrophenyl)-2H-chromen-4-yl)acetamide (5h). Isolated
1
as yellow solid; 68 mg, Yield 83%; Melting Point: 229−235 °C; H
NMR (500 MHz, DMSO-d6) δ: 9.39 (bs, 1H), 8.25 (d, J = 7 Hz, 2H),
7.64 (d, J = 7 Hz, 2H), 7.25−7.20 (m, 2H), 6.99 (td, J = 7.5 Hz, J = 1
Hz, 1H), 6.90 (dd, J = 7.5 Hz, J = 1 Hz, 1H), 5.11 (d, J = 1 Hz, 2H),
1.95 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.6, 154.7, 146.7,
143.7, 130.6, 128.9, 128.8, 125.3, 124.7, 124.0, 122.2, 121.9, 116.1,
68.4, 23.0; IR (KBr): v = 3260, 1666, 1594, 1278, 1039, 1008, 757
cm−1; HRMS (ESI): m/z calculated for C17H14N2O4Na [M+ + Na]
333.0851, found: 333.0868.
1
(14 mg, 28%). Melting Point: 187−192 °C; H NMR (500 MHz,
DMSO-d6) δ: 10.03 (bs, 1H), 8.39 (s, 1H), 8.04 (d, J = 8.5 Hz, 1H),
7.94 (t, J = 2 Hz, 1H), 7.88 (dd, J = 8.5, 2 Hz, 1H), 7.85−7.82 (m,
2H), 7.77 (d, J = 8 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H), 7.54−7.49 (m,
2H), 2.25 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.4, 142.9,
136.3, 134.5, 134.3, 133.6, 131.3, 130.5, 129.6, 127.9, 127.3, 126.5,
126.4, 125.4, 124.9, 121.9, 121.0, 24.2; IR (KBr): ν 3293, 3066, 2961,
2934, 2868, 1739, 1676, 1621, 1548, 1476, 1391, 1278, 1133, 1103,
Synthesis of Dihydrobenzo[a]carbazole (8). The mixture of 0.2
mmol of enamide 4g (35 mg, 0.2 mmol), proline (2.35 mg, 10 mol %),
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Article
1083, 1057, 1021, 978, 898, 834, 743 cm−1. HRMS (ESI): m/z
calculated C18H15ONCl [M+ + H] 296.0837, found: 296.0832.
N-(7-(4-Bromophenyl)naphthalen-1-yl)acetamide (15d). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 15d as a
colorless solid (53 mg, 58%) and the recovered starting material 13a
764, 742, 698 cm−1. HRMS (ESI): m/z calculated C19 H18 O2 N
[M+ + H] 292.1332, found: 292.1330.
N-(4-(3-Fluorophenyl)-7-methoxynaphthalen-1-yl)acetamide-
(17b). The crude product was purified by flash chromatography using
hexane/AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20)
to provide the compounds in order of elution, arylated product 17b as
a colorless solid (37 mg, 52%) and the recovered starting material 13b
1
1
(15 mg, 30%). Melting Point: 214−219 °C; H NMR (500 MHz,
(18 mg, 36%). Melting Point: 194−197 °C; H NMR (500 MHz,
DMSO-d6) δ: 9.66 (bs, 1H), 7.93 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 8.5
Hz, 1H), 7.52−7.48 (m, 1H), 7.36 (d, J = 8.5 Hz, 1H), 7.29−7.22 (m,
5H), 3.88 (s, 3H); 1.99 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ:
169.9, 162.4 (d, J = 241 Hz), 158.5, 142.7 (d, J = 7.5 Hz), 136.5, 132.7,
130.5 (d, J = 8.75 Hz), 130.3, 130.2, 129.2, 127.6, 125.6, 125.4 (d, J =
2.5 Hz), 119.0, 115.9 (d, J = 22.5 Hz), 114.3 (d, J = 21.25 Hz), 103.0,
55.6, 23.0; IR (KBr): v = 3293, 3085, 3030, 3005, 2983, 2928, 1643,
1616, 1538, 1509, 1472, 1390, 1280, 1256, 1226, 1190, 1056, 1027,
752, 737 cm-1. HRMS (ESI): m/z calculated C19H17O2NF [M+ + H]
310.1238, found: 310.1237.
DMSO-d6) δ: 10.02 (bs, 1H), 8.36 (s, 1H), 8.03 (d, J = 8.5 Hz, 1H),
7.87−7.82 (m, 3H), 7.76−7.73 (m, 3H), 7.54−7.49 (m, 2H), 2.23 (s,
3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.4, 139.9, 137.4, 133.5,
132.4, 129.7, 129.5, 128.6, 126.4, 125.3, 125.0, 123.2, 122.0, 121.6,
120.7, 24.2; IR (KBr): ν = 3274, 3041, 2944, 2917, 2847, 1719, 1651,
1598, 1527, 1439, 1363, 1259, 1112, 1081, 1059, 1028, 1001, 947, 875,
807, 738 cm−1. HRMS (ESI): m/z calculated C18H15ONBr [M+ + H]
340.0332, found: 340.0327.
N-(7-(4-Chlorophenyl)naphthalen-1-yl)acetamide (15e). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 15e as a
colorless solid (52 mg, 65%) and the recovered starting material 13a
N-(4-(4-Chlorophenyl)-7-methoxynaphthalen-1-yl)acetamide
(17c). The crude product was purified by flash chromatography using
hexane/AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20)
to provide the compounds in order of elution, arylated product 17c as
a colorless solid (42 mg, 55%) and the recovered starting material 13b
1
(15 mg, 30%). Melting Point: 220−225 °C; H NMR (500 MHz,
DMSO-d6) δ: 10.04 (bs, 1H), 8.33 (s, 1H), 8.03 (d, J = 8.5 Hz, 1H),
7.89−7.84 (m, 3H), 7.77 (d, J = 8.0 Hz, 2H), 7.61−7.59 (m, 2H), 7.51
(dd, J = 7.5, 8.0 Hz, 1H), 3.10 (s, 3H); 13C NMR (125 MHz, DMSO-
d6) δ: 169.4, 139.5, 136.5, 134.5, 133.5, 133.0, 129.5, 129.5, 129.4,
127.8, 126.4, 125.3, 125.0, 122.0, 120.7, 24.2; IR (KBr): ν = 3280,
3056, 2957, 2926, 2856, 1728, 1664, 1608, 1537, 1461, 1377, 1272,
1125, 1094, 1070, 1041, 1009, 962, 881, 821, 751 cm−1. HRMS (ESI):
m/z calculated C18H15ONCl [M+ + H] 296.0837, found: 296.0827
N-(7-(3,5-Dimethylphenyl)naphthalen-1-yl)acetamide (15f). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 15f as a
colorless solid (52 mg, 66%) and the recovered starting material 13a
1
(16 mg, 32%). Melting Point: 205−212 °C; H NMR (500 MHz,
DMSO-d6) δ: 9.63 (bs, 1H), 7.92 (d, J = 9 Hz, 1H), 7.89 (d, J = 8.5
Hz, 1H), 7.52 (d, J = 9 Hz, 2H), 7.46 (d, J = 8 Hz, 2H), 7.34 (d, J =
8.5 Hz, 1H), 7.26−7.24 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 7.22 (d, J =
1.5 Hz, 1H), 3.88 (s, 3H), 1.99 (s, 3H); 13C NMR (125 MHz, DMSO-
d6) δ: 169.8, 158.5, 139.4, 136.5, 132.7, 132.4, 131.0, 130.2, 130.1,
129.1, 128.6,127.6,125.6, 118.9, 103.0, 55.6, 23.0. IR (KBr): v = 3240,
3010, 2961, 2832, 1657, 1627, 1513, 1492, 1460, 1424, 1390, 1334,
1275, 1225, 1180, 1141, 1095, 1032, 1015, 831, 760 cm−1. HRMS
(ESI): m/z calculated C19H17O2NCl [M+ + H] 326.0942, found:
326.0944.
N-(4-(4-Bromophenyl)-7-methoxynaphthalen-1-yl)acetamide
(17d). The crude product was purified by flash chromatography using
hexane/AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20)
to provide the compounds in order of elution, arylated product 17d as
a colorless solid (49 mg, 57%) and the recovered starting material 13b
1
(13 mg, 26%). Melting Point: 179−182 °C; H NMR (500 MHz,
DMSO-d6) δ: 10.01 (bs, 1H), 8.30 (s, 1H), 8.00 (d, J = 8.5 Hz, 1H),
7.82 (dd, J = 8.5, 1.5 Hz, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.76 (d, J = 8.5
Hz, 1H), 7.49 (dd, J = 8,8 Hz 1H), 7.44 (s, 2H), 7.06 (s, 1H), 2.39 (s,
6H), 2.23 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.4, 140.7,
138.4, 138.2, 137.5, 134.4, 133.3, 129.5, 129.2, 127.1, 126.0, 125.8,
125.0, 122.0, 120.4, 24.2, 21.6; IR (KBr): v =3254, 3073, 3030, 3012,
2972, 2927, 2809, 2302, 1603, 1587, 1521, 1485, 1442, 1417, 1364,
1350, 1319, 1223, 1225, 1200, 1133, 1107, 1011, 942, 958, 801, 733,
721, 676 cm-1. HRMS (ESI): m/z calculated C20H20ON [M+ + H]
290.1539, found: 290.1534.
1
(14 mg, 28%). Melting Point: 211−216 °C; H NMR (500 MHz,
DMSO-d6) δ: 9.63 (bs, 1H), 7.92 (d, J = 9 Hz, 1H), 7.89 (d, J = 8.5
Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H), 7.34 (d, J
= 8 Hz, 1H), 7.26−7.24 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 7.22 (d, J =
2.5 Hz, 1H), 3.88 (s, 3H), 1.99 (s, 3H); 13C NMR (125 MHz, DMSO-
d6) δ: 169.9,158.5, 139.7, 136.52, 132.7, 131.5, 131.3, 130.2, 130.2,
129.1, 127.6, 125.6, 121.1, 118.9, 103.0, 55.6, 23.0. IR (KBr): v = 3262,
2958, 2927, 2855, 1723, 1658, 1605, 1511, 1490, 1373, 1275, 1226,
1180, 829, 752 cm−1. HRMS (ESI): m/z calculated C19H17O2NBr [M+
+ H] 370.0437, found: 370.0439.
Typical Experimental Procedure for Synthesis of Various
Substituted 7-Methoxy-4-aryl-1-naphthenyl Acetamides 17a−
e. To the stirred solution of 7-methoxy-1-naphthenyl acetamide 13b
(50 mg, 0.23 mmol) and diaryliodonium salt 7 (0.28 mmol) in dry
dichloroethane (1 mL) was added CuBr (1.66 mg, 5 mol %) under a
nitrogen atmosphere, and the mixture was heated at 50 °C for 7−12 h.
The reaction completion was monitored by TLC. After completion,
the crude mixture was concentrated and purified to the corresponding
7-methoxy-4-aryl-1-naphthenyl acetamides 17a−e.
N-(7-Methoxy-4-p-tolylnaphthalen-1-yl)acetamide (17e). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 17e as a
colorless solid (45 mg, 59%) and the recovered starting material 13b
1
(10 mg, 20%). Melting Point: 224−227 °C; H NMR (500 MHz,
N-(7-Methoxy-4-phenylnaphthalen-1-yl)acetamide (17a). The
crude product was purified by flash chromatography using hexane/
AcOEt as eluent (gradient mixture ratio from 95:05 to 80:20) to
provide the compounds in order of elution, arylated product 17a as a
colorless solid (38 mg, 56%) and the recovered starting material 13b
(16 mg, 32%). Melting Point: 223−226 °C; Isolated as a colorless
DMSO-d6) δ: 9.55 (bs, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.5
Hz, 1H), 7.35−7.32 (m, 3H), 7.26 (d, J = 8 Hz, 2H), 7.23−7.21 (dd, J
= 8.5 Hz, J = 2.5 Hz, 1H), 7.18 (d, J = 2.5 Hz, 1H), 3.86 (s, 3H), 2.36
(s, 3H), 1.99 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.9,
158.4, 137.7, 137.5, 136.7, 132.9, 130.1, 130.1, 129.2, 129.1, 128.9,
127.4, 126.0, 118.6, 103.1, 55.6, 23.0, 21.2. (KBr): v = 3260, 2957,
2924, 2856, 1725, 1659, 1626, 1576, 1505, 1459, 1423, 1373, 1334,
1273, 1225, 1182, 1137, 1121, 1073, 1033, 968, 892, 841, 823 cm−1.
HRMS (ESI): m/z calculated C20H20O2N [M+ + H] 306.1489, found:
306.1488
Typical Procedure for (2-Bromophenyl)(mesityl)iodonium
Trifluoromethanesulfonate (7g). To the stirred solution of m-
CPBA (∼55% assay, dried under high vacuum for 2−3 h prior to use)
(2.4 g, 7.77 mmol) in dry CH2Cl2 (70 mL) were added 2-bromo
iodobenzene (2.0 g, 7.07 mmol) and mesitylene (0.935 g, 7.77 mmol)
1
solid; 60 mg, Yield 81%; Melting Point: 181−183 °C; H NMR (500
MHz, DMSO-d6) δ: 9.59 (bs, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.88 (d, J
= 8.5 Hz, 1H), 7.46−7.45 (m, 4H), 7.35 (d, J = 8.5 Hz, 2H), 7.25−
7.23 (dd, J = 8 Hz, J = 2.5 Hz, 1H), 7.20 (d, J = 4 Hz, 1H), 3.87 (s,
3H), 1.98 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 169.8, 158.4,
140.5, 137.8, 132.8, 130.2, 130.1, 129.2, 129.0, 128.6, 127.5, 127.5,
126.0, 118.7, 103.1, 55.6, 23.0. IR (KBr): v = 3266, 3085, 3050, 3026,
2999, 2938, 2829, 2330, 1633, 1602, 1534, 1501, 1468, 1434, 1390,
1370, 1330, 1273, 1250, 1218, 1162, 1134, 1034, 1010, 961, 914, 824,
7842
dx.doi.org/10.1021/jo501162s | J. Org. Chem. 2014, 79, 7836−7843

The Journal of Organic Chemistry
Article
under an argon atmosphere. The resulting solution was cooled to 0 °C,
and trifluoromethanesulfonic acid (1.9 mL, 22 mmol) was added
dropwise over a period of 10−15 min. The reaction mixture was
stirred at room temperature for 8 h. Volatiles are removed under
vacuum and titurated with Et2O. This process was repeated 3−4 times
until detectable formation of precipitate was observed. Once
precipitation initiated, the solution was cooled to −20 °C for 30
min to obtain (2-bromophenyl)(mesityl)iodonium trifluoromethane-
sulfonate 7g (3.4 g, 87%). Melting Point: 155−157 °C; 1H NMR (500
MHz, CDCl3) δ: 7.77 (dd, J = 8 Hz, J = 1.5 Hz, 1H), 7.47 (td, J = 8
Hz, J = 1.5 Hz, 1H), 7.35 (td, J = 8 Hz, J = 1.5 Hz, 1H), 7.23 (s, 2H),
6.88 (dd, J = 8 Hz, J = 1.5 Hz, 1H), 2.64 (s, 6H), 2.43 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ: 145.4, 142.8, 134.5, 133.2, 131.4, 131.0,
130.9, 124.6, 121.6, 120.2 (q, J = 318 Hz), 115.4, 27.1, 21.0; IR (KBr):
ν = 2919, 1619, 1443, 1251, 1159, 1026 cm−1; HRMS (ESI): m/z
calculated for C15H15BrI [M+] 400.9402, found: 400.9402. All other
aryliodonium salts were prepared according to the literature
procedure.32−34,40−44
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ASSOCIATED CONTENT
* Supporting Information
■
(27) Bigot, A.; Williamson, A. E.; Gaunt, M. J. J. Am. Chem. Soc.
2011, 133, 13778.
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S
General information and NMR spectra are given for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: vkesavan@iitm.ac.in.
Notes
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■
2011, 370.
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge DST (SR/S1/OC-60/2006), Government of
India, New Delhi, for financial support. M.P. thanks CSIR and
S.M. thanks UGC for a research fellowship. We thank
Sophisticated Analytical Instrument Facility (SAIF) and the
Department of Chemistry, IIT Madras, for the analytical data.
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