Site-selective Suzuki-Miyaura reactions of 1,4- and 3,5- bis(trifluoromethylsulfonyloxy)-2-naphthoates

Article abstract of DOI:10.1055/s-0030-1260054

The Suzuki-Miyaura reaction of phenyl 1,4-bis(trifluoro-methylsulfonyloxy)- 2-naphthoate and ethyl 3,5-bis(trifluoromethylsulfonyloxy)-2-naphthoate afforded various 1,4- and 3,5-diaryl-2-naphthoates with very good site-selectivity, respectively. The first

Full text of DOI:10.1055/s-0030-1260054

PAPER
2101
Site-Selective Suzuki–Miyaura Reactions of 1,4- and 3,5-Bis(trifluoromethyl-
sulfonyloxy)-2-naphthoates
S
ite-Selective Couplin
u
h
3,5-Bistrifl
a
oxy-2-naph
m
thoates mad Farooq Ibad,a Nadi Eleya,a Abid Obaid-Ur-Rahman,a Ahmed Mahal,a Munawar Hussain,a
Alexander Villinger,a Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
b
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
Received 12 December 2010; revised 14 April 2011
54–88% yields (Scheme 2, Table 1). The yields of prod-
Abstract: The Suzuki–Miyaura reaction of phenyl 1,4-bis(trifluoro-
methylsulfonyloxy)-2-naphthoate and ethyl 3,5-bis(trifluorometh-
ylsulfonyloxy)-2-naphthoate afforded various 1,4- and 3,5-diaryl-
2-naphthoates with very good site-selectivity, respectively. The first
ucts derived from sterically hindered ortho-substituted
arylboronic acids were in most cases lower than the yields
of those products derived from sterically less hindered
attack occurred at the sterically more hindered positions C-1 and C- arylboronic acids. During the optimization, it proved to be
3, respectively. The selectivity can be explained by the electronic
influence of the ester group.
important to employ Pd(PPh3)4 (3 mol%) as the catalyst,
2.4 equivalents of the boronic acid, and K3PO4 as the base
Key words: catalysis, palladium, Suzuki–Miyaura reaction, site-
selectivity, naphthalene derivatives
(1,4-dioxane, 110 °C, 8 h). The use of Pd(OAc)2 in the
presence of XPhos or SPhos resulted in a decrease of the
yield. The structure of 4k was independently confirmed
by X-ray crystal structure analysis (Figure 1).8
Substituted naphthalenes are important as drugs and lead
structures in medicinal chemistry (e.g., cancerostatic ac-
tivity, antimalaria activity). In addition, they occur in sev-
eral natural products.1 In recent years, we and several
other groups studied site-selective palladium-catalyzed
cross-coupling reactions of perhalogenated hetero- and
carbacycles and of bis(triflates) of benzene derivatives.2,3
The site-selectivity is generally controlled by steric and
electronic effects. The first attack usually occurs at the
less sterically hindered and more electron-deficient car-
bon atom.4 Palladium-catalyzed cross coupling reactions
of bis(triflates) of benzene derivatives have been previ-
ously reported.5,6 Most of these reactions proceed by site
selective attack to the sterically less encumbered carbon
atom. Recently, we reported Suzuki–Miyaura (S–M) re-
actions of the bis(triflate) of phenyl 1,4-dihydroxy-2-
naphthoate which proceed with very good site-selectivity
in favor of the sterically more hindered position C-1.7
Herein, we report a comprehensive study related to the
preparative scope, which was greatly extended with re-
OTf
O
OH
O
OPh
OPh
OTf
OH
1
4 (83%)
Scheme 1 Synthesis of 2. Reagents and conditions: 1) 1 (1.0 equiv),
pyridine (4.0 equiv), CH2Cl2, –78 °C, 10 min, 2. Tf2O (2.4 equiv),
–78 → 0 °C, 4 h.
Ar
O
OTf
O
ArB(OH)2
OPh
3a–r
OPh
Ar
OTf
2
4a–r
Scheme 2 Synthesis of 4a–r. Reagents and conditions: 2 (1.0
equiv), 3a–r (2.4 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (3 mol%), 1,4-
gard to our preliminary communication. In addition, we dioxane, 110 °C, 8 h.
report, for the first time, S–M reactions of the bis(triflate)
of ethyl 3,5-dihydroxy-2-naphthoate. The reactions re-
The S–M reaction of 2 with boronic acids 3d,g,l–o,s,t (1.1
ported herein provide a convenient approach to arylated
naphthalenes, which are not readily available by other
methods.
equiv), in the presence of Pd(PPh3)4 (3 mol%), afforded
the 1-aryl-4-(trifluoromethylsulfonyloxy)-2-naphthoates
5a–h (Scheme 3, Table 2). All reactions proceeded with
excellent site-selectivity in favor of position 1 and the
products were isolated in good yields (except for 5g, pre-
sumably due to steric reasons). A small amount of the bis-
coupled product could be detected in the crude product
Phenyl 1,4-dihydroxynaphthoate (1) was transformed into
the novel bis(triflate) 2 in 83% yield (Scheme 1).
The Suzuki–Miyaura reaction of 2 with boronic acids 3a–r
(2.4 equiv) gave the 1,4-diaryl-2-naphthoates 4a–r in
1
before the purification (by H NMR and GC-MS). The
pure products were isolated by chromatography. The best
yields were obtained when 1.1 equivalents of the arylbo-
ronic acid was employed and the reactions were carried
SYNTHESIS 2011, No. 13, pp 2101–2116
Advanced online publication: 19.05.2011
DOI: 10.1055/s-0030-1260054; Art ID: N52910SS
x
x.
x
x
.
2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

2102
M. F. Ibad et al.
PAPER
Ar
O
out at 95 °C instead of 110 °C. The structures of 5a and 5g
OTf
O
ArB(OH)2
were confirmed by X-ray crystal structure analyses.7
3d,g,l–o,s,t
OPh
OPh
Table 1 Synthesis of 4a–r
OTf
OTf
3, 4
a
b
c
Ar
Yield (%)a of 4
5a–h
2
Ph
73
76
88
71
72
77
79
77
85
77
80
73
65
61
56
63
69
54
Scheme 3 Synthesis of 5a–h. Reagents and conditions: 2 (1.0
equiv), 3d,g,l–o,s,t (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3
mol%), 1,4-dioxane, 95 °C, 8 h.
4-MeC6H4
4-EtC6H4
Table 2 Synthesis of 5a–h
d
e
3,5-Me2C6H3
2-ClC6H4
5
a
b
c
d
e
f
3
d
g
l
Ar
Yield (%)a of 5
3,5-Me2C6H3
4-ClC6H4
68
73
62
69
59
66
33
52
f
3-ClC6H4
g
h
i
4-ClC6H4
2-MeOC6H4
3-MeOC6H4
2-EtOC6H4
2,4-(MeO)2C6H3
2,6-(MeO)2C6H3
4-HOC6H4
2-FC6H4
m
n
o
s
3-FC6H4
j
3-CF3C6H4
4-CF3C6H4
2-MeOC6H4
3-MeOC6H4
2-EtOC6H4
2,4-(MeO)2C6H3
3,4-(MeO)2C6H3
2,5-(MeO)2C6H3
3-HOC6H4
k
l
g
h
t
m
n
o
p
q
r
a Yields of isolated products.
1) Ar1B(OH)2
2) Ar2B(OH)2
Ar1
O
OTf
O
OPh
OPh
Ar2
OTf
a Yields of isolated products.
2
6a–h
Scheme 4 Synthesis of 6a–h. Reagents and conditions: 1) 2 (1.0
equiv), Ar1B(OH)2 (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3
mol%), 1,4-dioxane, 95 °C, 7 h; 2) Ar2B(OH)2 (1.3 equiv), K3PO4
(1.5 equiv), 110 °C, 8 h.
Table 3 Synthesis of 6a–h
6
a
b
c
d
e
f
3
Ar1
Ar2
3,4-(MeO)2C6H3 54
4-MeC6H4 63
3,4-(MeO)2C6H3 51
4-MeOC6H4 67
3,4-(MeO)2C6H3 46
Yield (%)a of 6
u,p 4-FC6H4
o,b 2,4-(MeO)2C6H3
k,p 4-CF3C6H4
v,w 4-(H2C=CH)C6H4
m,p 3-MeOC6H4
b,w 4-MeC6H4
f,w 3-ClC6H4
4-MeOC6H4
4-MeOC6H4
65
61
g
h
g,p 4-ClC6H4
3,4-(MeO)2C6H3 62
a Yields of isolated products.
Figure 1 Molecular structure of 4k
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

PAPER
Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2103
The one-pot reaction of 2 with two different arylboronic
acids gave 1,4-diaryl-2-naphthoates 6a–h containing two
different aryl groups (Scheme 4, Table 3). The boronic
acids were added in a sequential manner. During the opti-
mization it proved to be important, for the first step of the
one-pot protocol, to employ only a slight excess of the
arylboronic acid (1.1 equiv) and to carry out the reaction
at 95 °C instead of 110 °C.
O
O
OEt
OTf
OEt
ArB(OH)2
Ar
OTf
Ar
10a–i
9
Scheme 6 Synthesis of 10a–i. Reagents and conditions: 9 (1.0
equiv), ArB(OH)2 (2.4 equiv), Pd(PPh3)4 (6 mol%), K3PO4 (3.0
equiv), THF, 60 °C, 8 h.
The structure of 6h was independently confirmed by X-
ray crystal structure analysis (Figure 2).8
Ethyl 3,5-dihydroxynaphthoate (8) was prepared from the
commercially available acid 7 (Scheme 5). The bis(tri-
flate) 9 was prepared by reaction of 8 with triflic anhy-
dride. The Suzuki–Miyaura reaction of 9 with various
arylboronic acids (2.4 equiv), in the presence of Pd(PPh3)4
(6 mol%) and K3PO4 (3.0 equiv) in THF (reflux, 8 h),
gave the 3,5-diaryl-2-naphthoates 10a–i in 60–82% yields
(Scheme 6, Table 4). Surprisingly, the yield of product
10f, derived from electron-rich and highly nucleophilic
(4-methoxyphenyl)boronic acid, was lower than the
yields of the other products.
Table 4 Synthesis of 10a–i
10
a
b
c
Ar
Yield (%)a of 10
4-MeC6H4
4-t-BuC6H4
3,5-Me2C6H3
4-ClC6H4
76
80
82
76
81
60
70
80
77
d
e
3-ClC6H4
f
4-MeOC6H4
2,6-(MeO)2C6H3
4-CF3C6H4
4-FC6H4
g
h
i
a Yields of isolated products.
The Suzuki reaction of 9 with only 1.1 equivalents of aryl-
boronic acids, in the presence of Pd(PPh3)4 (3 mol%), af-
forded the 3-aryl-5-(trifluoromethylsulfonyloxy)-2-
naphthoates 11a–f in 63–82% yields (Scheme 7, Table 5).
All products were formed with very good site-selectivity
at carbon atom C-3. The yield of product 11f, derived
from (4-methoxyphenyl)boronic acid, was again relative-
ly low compared to the yields of the other products. To
avoid two-fold coupling, it proved to be very important to
carry out the reaction at 20 °C (instead of 60 °C). The pure
products were isolated by chromatographic purification
which was necessary to remove a small amount of bis-
coupled product detected (by TLC) in the crude product
mixture. Analysis of the crude product (before the separa-
tion) by 1H NMR revealed that the amount of bis-coupled
product was less than 15%. The structures of the pure
products were proved based on 2D NMR experiments
(NOESY, HMBC).
Figure 2 Molecular structure of 6h
O
O
i
OH
OEt
OH
OH
OH
OH
8 (87%)
ii
O
O
7
O
OEt
OTf
OEt
ArB(OH)2
OEt
OTf
Ar
OTf
OTf
OTf
9
11a–f
9 (77%)
Scheme 7 Synthesis of 11a–f. Reagents and conditions: 9 (1.0
equiv), ArB(OH)2 (1.0 equiv), Pd(PPh3)4 (3 mol%), K3PO4 (1.5
equiv), THF, 20 °C, 12 h.
Scheme 5 Synthesis of 9. Reagents and conditions: (i) 7 (1.0 equiv),
EtOH, reflux, 6 h; (ii) 1) 8 (1.0 equiv), pyridine (4.0 equiv), CH2Cl2,
–78 °C, 10 min, 2) Tf2O (2.4 equiv), –78 → 0 °C, 4 h.
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

2104
M. F. Ibad et al.
PAPER
Table 5 Synthesis of 11a–f
prediction of the site-selectivity of palladium(0)-cata-
lyzed cross-coupling reactions based on the H NMR
chemical shift values of the compound in which the halide
atoms or the triflate groups of the substrate are replaced by
hydrogen atoms.4This rule gives the correct prediction for
site-selective Suzuki reactions of 2 and 9.
1
11
a
b
c
Ar
Yield (%)a of 11
4-MeC6H4
4-t-BuC6H4
3,5-Me2C6H3
3-ClC6H3
4-CF3C6H4
4-MeOC6H4
70
75
80
82
65
63
d
e
more sterically hindered
1
more electron-deficient
chelation control possible
OTf
O
OPh
f
a Yields of isolated products.
less sterically hindered
less electron-deficient
chelation control not possible
OTf
2
2
Suzuki reactions of 11a and 11b afforded the 3,5-diaryl-
2-naphthoates 12a and 12b in 70 and 73% yield, respec-
tively (Scheme 8, Table 6). During the optimization, it
proved to be important to carry out the reaction at 60 °C
(as for the synthesis of 10a–i). The application of a one-
pot procedure for the synthesis of 12a (sequential addition
of two different boronic acids to 9) resulted in a decrease
of the yield (compared to the combined yields of the step-
wise process) and was, therefore, not further studied.
Scheme 9 Possible explanation for the site-selectivity of 2
O
OEt
more sterically hindered
more electron-deficient
OTf
chelation control possible
OTf
9
1
2
less sterically hindered
less electron-deficient
O
O
chelation control not possible
OEt
Ar2B(OH)2
OEt
Ar1
Scheme 10 Possible explanation for the site-selectivity of 9
Ar1
Ar2
OTf
In conclusion, we have reported site-selective Suzuki–
Miyaura reactions of phenyl 1,4-bis(trifluoromethylsulfo-
nyloxy)-2-naphthoate and of ethyl 3,5-bis(trifluorometh-
ylsulfonyloxy)-2-naphthoate. The first attack occurred at
the sterically more hindered positions C-1 and C-3, re-
spectively. This method provides a convenient access to
aryl-substituted naphthalenes, which are not readily avail-
able by other methods.
12a,b
11a,b
Scheme 8 Synthesis of 12a,b. Reagents and conditions: 11a,b (1.0
equiv), Ar2B(OH)2 (1.0 equiv), Pd(PPh3)4 (3 mol%), K3PO4 (1.5
equiv), THF, 60 °C, 8 h.
Table 6 Synthesis of 12a,b
11
a
12
a
Ar1
Ar2
Yield (%)a of 12
4-MeC6H4
4-t-BuC6H4
4-t-BuC6H4
4-CF3C6H4
70
73
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. For 1H and 13C NMR spectra
the deuterated solvents indicated were used. Mass spectrometric
data (MS) were obtained by electron ionization (EI, 70 eV), chemi-
cal ionization (CI, isobutane) or electrospray ionization (ESI). For
preparative-scale chromatography, silica gel 60 (0.063–0.200 mm,
70–230 mesh) was used.
b
b
a Yields of isolated products.
The Suzuki–Miyaura reaction of phenyl 1,4-bis(trifluo-
romethylsulfonyloxy)-2-naphthoate (2) occurs first at the
sterically more hindered position C-1 (Scheme 9). Like-
wise, the S–M reaction of ethyl 3,5-bis(trifluoromethyl-
sulfonyloxy)-2-naphthoate (9) occurs first at the sterically
more hindered position C-3. This might be explained by
electronic effects (Scheme 10). The oxidative addition of
the electron-rich palladium species usually occurs first at
the most electron deficient carbon atom.2,4 In case of 2 and
9, carbon atoms C-1 and C-3 are more electron deficient
than C-4 and C-5, respectively, due to their location ortho
to the ester group. In addition, the site-selectivity might be
controlled by chelation of the catalyst to the carbonyl
group. Handy and Zhang suggested a simple guide for the
Phenyl 1,4-Bis(trifluoromethylsulfonyloxy)-2-naphthoate (2)
To a solution of 1 (2.80 g, 10.0 mmol, 1.0 equiv) in CH2Cl2 (100
mL, 10 mL per 1 mmol of 1) was added pyridine (3.2 mL, 40.0
mmol, 4.0 equiv) at –78 °C under an argon atmosphere. After stir-
ring for 10 min, Tf2O (4.0 mL, 24.0 mmol, 2.4 equiv) was added at
–78 °C. The mixture was allowed to warm to 0 °C and stirred for 4
h. The reaction mixture was filtered and the filtrate was concentrat-
ed in vacuo. The products of the reaction mixture were isolated by
flash column chromatography (silica gel, heptanes–EtOAc); yield:
4.52 g (83%); white powder; mp 100–101 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
IR (ATR): 3068 (w), 1733 (m), 1589 (w), 1482 (w), 1427 (s), 1358
(m), 1347 (m), 1247 (m), 1203 (s), 1130 (s), 1045 (m), 1018 (m),
936 (m), 873 (s), 761 (s), 641 (s), 597 cm–1 (s).
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

PAPER
Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2105
1H NMR (300 MHz, CDCl3): d = 7.20–7.27 (m, 3 H, ArH), 7.36–
7.41 (m, 2 H, ArH), 7.75–7.85 (m, 2 H, ArH), 8.08 (s, 1 H, ArH),
8.12 (dd, J = 7.1, 1.8 Hz, 1 H, ArH), 8.24 (d, J = 7.9 Hz, 1 H, ArH).
(CH), 128.3 (CH), 128.9 (2 CH), 129.2 (2 CH), 129.3 (2 CH), 129.9
(2 CH), 130.0 (2 CH), 133.2 (C), 133.4 (C), 135.9 (C), 137.0 (C),
137.2 (C), 137.5 (C), 140.2 (C), 141.0 (C), 150.8 (C), 167.1 (C=O).
13C NMR (62.90 MHz, CDCl3): d = 118.5 (CH), 118.6 (q,
MS (EI, 70 eV): m/z (%) = 428 (M+, 3), 336 (27), 335 (100), 292 (7),
289 (6), 276 (6), 145 (3), 65 (2).
1
1JC,F = 321 Hz, CF3), 118.7 (q, JC,F = 321 Hz, CF3), 121.2 (C),
121.4 (2 CH), 121.5 (CH), 123.1 (CH), 126.6 (CH), 127.9 (C),
129.6 (C), 129.7 (2 CH), 129.9 (CH), 131.4 (CH), 144.0 (C), 144.2
(C), 150.2 (C), 161.9 (C=O).
HRMS (EI): m/z calcd for C31H24O2 [M+]: 428.17708; found:
428.17783.
19F NMR (282.4 MHz, CDCl3): d = –72.27 (3 F, CF3), –72.96 (3 F,
Phenyl 1,4-Bis(4-ethylphenyl)-2-naphthoate (4c)
CF3).
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3c (179 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4c was isolated as a white viscous oil (200 mg, 88%);
Rf = 0.4 (heptane–EtOAc, 4:1).
MS (EI, 70 eV): m/z (%) = 544 (M+, 10), 453 (16), 452 (22), 451
(100), 318 (64), 234 (3), 186 (19), 185 (97), 157 (47), 129 (16), 101
(18), 75 (5), 69 (8), 64 (9), 51 (3).
IR (ATR): 3024 (w), 2962 (m), 2928 (w), 2871 (w), 1711 (s), 1591
(m), 1512 (m), 1487 (m), 1455 (m), 1379 (m), 1368 (m), 1344 (m),
1240 (s), 1214 (s), 1190 (s), 1162 (s), 1140 (s), 1098 (s), 1070 (m),
1021 (m), 985 (m), 964 (m), 900 (m), 824 (s), 763 (s), 746 (s), 687
(s), 598 (m) 533 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.25 (t, J = 7.6 Hz, 3 H, CH3),
1.26 (t, J = 7.6 Hz, 3 H, CH3), 2.65–2.72 (m, 4 H, 2 CH2), 6.64–6.70
(m, 2 H, ArH), 7.02–7.09 (m, 1 H, ArH), 7.14–7.31 (m, 8 H, ArH),
7.34–7.44 (m, 4 H, ArH), 7.66 (dd, J = 8.1, 1.2 Hz, 1 H, ArH), 7.88
(s, 1 H, ArH), 7.93 (dd, J = 8.0, 1.2 Hz, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 15.6 (CH3), 15.8 (CH3), 28.7
(CH2), 28.8 (CH2), 121.5 (2 CH), 125.6 (CH), 126.2 (CH), 126.3
(CH), 126.4 (CH), 127.7 (2 CH), 127.78 (C), 127.9 (2 CH), 128.2
(CH), 129.1 (2 CH), 129.7 (CH), 130.0 (2 CH), 130.1 (2 CH), 133.1
(C), 133.3 (C), 136.2 (C), 137.2 (C), 140.2 (C), 140.7 (C), 143.6
(C), 143.7 (C), 150.8 (C), 167.1 (C=O).
HRMS (EI): m/z calcd for C19H10F6O8S2 [M+]: 543.97158; found:
543.97051.
Suzuki–Miyaura Coupling Products 4a–r and 5a–h; General
Procedure
A 1,4-dioxane solution (4 mL per 0.5 mmol of 2) of 2, K3PO4,
Pd(PPh3)4, and arylboronic acid 3 was stirred at 110 °C or 95 °C for
8 or 7 h. After cooling to 20 °C, sat. aq NH4Cl (50 mL) was added.
The organic and the aqueous layers were separated and the latter
was extracted with CH2Cl2 (3 × 50 mL). The combined organic lay-
ers were dried (Na2SO4), filtered, and the filtrate was concentrated
in vacuo. The residue was purified by column chromatography.
Phenyl 1,4-Diphenyl-2-naphthoate (4a)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3a (146 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4a was isolated as colorless crystals (146 mg, 73%);
mp 96–97 °C; Rf = 0.4 (heptane–EtOAc, 4:1).
MS (EI, 70 eV): m/z (%) = 456 (M+, 8), 364 (42), 363 (100), 335
(15), 334 (16), 319 (17), 318 (14), 289 (15), 145 (13), 65 (2).
HRMS (EI): m/z calcd for C33H28O2 [M]+: 456.20838; found:
456.20939.
IR (ATR): 3027 (w), 2923 (w), 2850 (w), 1731 (m), 1590 (w), 1490
(w), 1379 (w), 1238 (m), 1210 (m), 1187 (s), 1096 (s), 1029 (w),
931 (w), 760 (m), 698 (s), 686 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 6.64–6.80 (m, 2 H, ArH), 7.00–
7.17 (m, 3 H, ArH), 7.28–7.48 (m, 12 H, ArH), 7.60 (dd, J = 8.2, 1.0
Hz, 1 H, ArH), 7.88 (dd, J = 8.6, 1.0 Hz, 1 H, ArH), 7.90 (s, 1 H,
ArH).
13C NMR (75.46 MHz, CDCl3): d = 121.5 (2 CH), 125.8 (CH),
126.4 (CH), 126.5 (CH), 126.8 (CH), 127.6 (C), 127.8 (CH), 127.9
(2 CH), 128.3 (2 CH), 128.4 (CH), 128.6 (2 CH), 129.4 (2 CH),
130.1 (2 CH), 130.2 (2 CH), 133.2 (C), 133.4 (C), 139.1 (C), 140.0
(C), 140.5 (C), 141.1 (C), 150.8 (C), 167.2 (C=O).
Phenyl 1,4-Bis(3,5-dimethylphenyl)-2-naphthoate (4d)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3d (180 mg, 1.2 mmol) and 1,4-dioxane (4
mL), product 4d was isolated as colorless crystals (162 mg, 71%);
mp 80–81 °C; Rf = 0.4 (heptane–EtOAc, 4:1).
IR (ATR): 3026 (w), 2916 (w), 2860 (w), 1732 (s), 1598 (m), 1487
(m), 1370 (m), 1216 (s), 1185 (s), 1160 (s), 1105 (s), 1038 (m), 848
(m), 762 (s), 704 (s), 687 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.30 (s, 6 H, 2 CH3), 2.34 (s, 6 H,
2 CH3), 6.70–6.73 (m, 2 H, ArH), 6.98–7.23 (m, 9 H, ArH), 7.32–
7.44 (m, 2 H, ArH), 7.68 (d, J = 8.4 Hz, 1 H, ArH), 7.86 (s, 1 H,
ArH), 7.91 (d, J = 8.1 Hz, 1 H, ArH).
MS (GC, 70 eV): m/z (%) = 400 (M+, 2), 308 (25), 307 (100), 278
(11), 277 (13), 276 (13), 202 (4), 138 (2), 65 (2).
HRMS (EI): m/z calcd for C29H20O2 [M+]: 400.14578; found:
400.14612.
13C NMR (62.89 MHz, CDCl3): d = 21.6 (4 CH3), 121.6 (2 CH),
125.8 (CH), 126.3 (CH), 126.5 (CH), 126.6 (CH), 127.6 (C), 127.7
(CH), 128.0 (2 CH), 128.1 (2 CH), 128.5 (CH), 129.3 (CH), 129.4
(2 CH), 129.5 (CH), 133.2 (C), 133.5 (C), 137.7 (2 C), 138.1 (2 C),
138.9 (C), 140.1 (C), 140.6 (C), 141.2 (C), 151.0 (C), 167.4 (C=O).
MS (GC, 70 eV): m/z (%) = 456 (M+, 2), 364 (30), 363 (100), 320
(5), 289 (5), 215 (2), 151 (3), 145 (3), 65 (1).
Phenyl 1,4-Di(p-tolyl)-2-naphthoate (4b)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3b (163 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4b was isolated as colorless crystals (163 mg, 76%);
mp 120–122 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3022 (w), 2921 (w), 2865 (w), 1711 (s), 1591 (w), 1511
(w), 1485 (m), 1378 (m), 1367 (m), 1241 (s), 1220 (s), 1192 (s),
1099 (m), 1020 (m), 926 (m), 814 (s), 746 (s), 687 (m), 595 cm–1
(m).
1H NMR (300 MHz, CDCl3): d = 2.37 (s, 3 H, CH3), 2.38 (s, 3 H,
CH3), 6.70–6.74 (m, 2 H, ArH), 7.02–7.08 (m, 1 H, ArH), 7.15–7.26
(m, 8 H, ArH), 7.31–7.43 (m, 4 H, ArH), 7.65 (dd, J = 8.1, 1.2 Hz,
1 H, ArH), 7.89 (s, 1 H, ArH), 7.91 (dd, J = 7.6, 1.2 Hz, 1 H, ArH).
HRMS (ESI+): m/z calcd for C33H29O2 [M + H]+: 457.21621; found:
457.21598.
Phenyl 1,4-Bis(2-chlorophenyl)-2-naphthoate (4e)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3e (187 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4e was isolated as colorless crystals (168 mg, 72%);
mp 172–174 °C; Rf = 0.4 (heptane–EtOAc, 4:1).
13C NMR (75.46 MHz, CDCl3): d = 21.3 (CH3), 21.4 (CH3), 121.5
(2 CH), 125.7 (CH), 126.3 (2 CH), 126.5 (CH), 127.5 (C), 127.6
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M. F. Ibad et al.
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IR (ATR): 3057 (w), 2915 (w), 2861 (w), 1747 (w), 1592 (m), 1564
(m), 1509 (w), 1482 (m), 1453 (m), 1434 (m), 1379 (m), 1232 (m),
1208 (m), 1187 (s), 1160 (s), 1152 (s), 1101 (s), 1054 (m), 1034 (m),
981 (m), 895 (m), 762 (s), 745 (s), 731 (s), 690 (m), 608 (m), 561
cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 6.80–6.86 (m, 2 H, ArH), 7.02–
7.08 (m, 1 H, ArH), 7.16–7.22 (m, 2 H, ArH), 7.26–7.53 (m, 12 H,
ArH), 8.03 (s, 1 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 121.5 (2 CH), 125.8 (CH),
126.3 (CH), 126.5 (C), 126.6 (CH), 126.9 (CH), 127.0 (CH), 127.2
(CH), 127.8 (CH), 128.4 (CH), 129.2 (CH), 129.3 (2 CH), 129.4
(CH), 129.5 (CH), 129.7 (CH), 131.4 (CH), 132.3 (CH), 132.4 (C),
133.7 (C), 134.1 (C), 134.2 (C), 137.9 (C), 138.1 (C), 138.5 (C),
139.9 (C), 150.8 (C), 165.6 (C=O).
MS (GC, 70 eV): m/z (%) = 468 (35Cl, M+, 1), 379 (12), 378 (16),
377 (67), 376 (26), 375 (100), 342 (6), 340 (18), 312 (16), 277 (16),
276 (40), 274 (12), 138 (6), 65 (5).
MS (GC, 70 eV): m/z (%) = 468 (35Cl, M+, 3), 378 (16), 377 (67),
376 (27), 375 (100), 342 (11), 340 (35), 312 (21), 277 (11), 276
(33), 138 (7), 65 (5).
HRMS (EI): m/z calcd for C29H18Cl2O2 [35Cl, M+]: 468.06784;
found: 468.06884.
Phenyl 1,4-Bis(2-fluorophenyl)-2-naphthoate (4h)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3h (168 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4h was isolated as colorless crystals (168 mg, 77%);
mp 137–139 °C; Rf = 0.4 (heptane–EtOAc, 4:1).
IR (ATR): 3068 (w), 2924 (w), 1750 (m), 1593 (m), 1574 (m), 1568
(m), 1492 (m), 1455 (m), 1381 (m), 1344 (m), 1241 (m), 1211 (m),
1186 (s), 1161 (s), 1149 (s), 1111 (m), 1089 (m), 983 (m), 896 (m),
749 (s), 688 (m), 607 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 6.80–6.84 (m, 2 H, ArH), 7.03–
7.30 (m, 9 H, ArH), 7.32–7.49 (m, 4 H, ArH), 7.56 (d, J = 8.2 Hz, 1
H, ArH), 7.68 (d, J = 8.2 Hz, 1 H, ArH), 8.08 (s, 1 H, ArH).
HRMS (EI): m/z calcd for C29H18Cl2O2 [35Cl, M+]: 468.06868;
found: 468.06784.
13C NMR (75.46 MHz, CDCl3): d = 115.6 (d, JC,F = 22.0 Hz, CH),
115.8 (d, JC,F = 22.0 Hz, CH), 121.4 (2 CH), 124.0 (d, JC,F = 3.0 Hz,
CH), 124.4 (d, JC,F = 3.0 Hz, CH), 125.8 (CH), 126.2 (CH), 127.0
(C), 127.07 (CH), 127.2 (C), 127.3 (C), 127.6 (CH), 127.8 (CH),
128.4 (CH), 129.4 (2 CH), 129.9 (d, JC,F = 7.7 Hz, CH), 130.1 (d,
JC,F = 7.7 Hz, CH), 131.8 (d, JC,F = 2.3 Hz, CH), 132.4 (CH), 132.8
(C), 133.7 (C), 134.9 (C), 136.3 (C), 150.7 (C), 160.1 (d, JC,F = 247
Hz, CF), 160.2 (d, JC,F = 247 Hz, CF), 166.5 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –113.58 (ArF), –114.37 (ArF).
MS (GC, 70 eV): m/z (%) = 436 (M+, 2), 344 (25), 343 (100), 314
(7), 294 (21), 220 (4).
HRMS (EI): m/z calcd for C29H18F2O2 [M+]: 436.12694; found:
Phenyl 1,4-Bis(3-chlorophenyl)-2-naphthoate (4f)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3f (187 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4f was isolated as colorless crystals (180 mg, 77%);
mp 124–125 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3061 (w), 2923 (w), 2851 (w), 2720 (w), 1747 (m), 1590
(m), 1563 (m), 1487 (m), 1478 (m), 1375 (m), 1341 (m), 1244 (m),
1213 (s), 1190 (s), 1161 (m), 1092 (s), 1079 (m), 1026 (m), 995 (m),
886 (w), 800 (w), 780 (s), 758 (s), 735 (s), 688 (s), 610 (m), 555
cm–1 (m).
1H NMR (250MHz, CDCl3): d = 6.75–6.82 (m, 2 H, ArH), 7.04–7.0
(m, 14 H, ArH), 7.81–7.88 (m, 1 H, ArH), 7.93–7.97 (m, 1 H, ArH).
436.12721.
13C NMR (75.47 MHz, CDCl3): d = 121.4 (2 CH), 125.9 (CH),
126.0 (CH), 126.6 (CH), 127.0 (C), 127.1 (CH), 127.9 (CH), 128.0
(CH), 128.1 (CH), 128.2 (CH), 128.3 (CH), 128.4 (CH), 129.4 (2
CH), 129.5 (CH), 129.8 (CH), 129.9 (CH), 130.1 (CH), 132.9 (C),
133.2 (C), 134.2 (C), 134.5 (C), 139.3 (C), 140.3 (C), 140.7 (C),
141.6 (C), 150.6 (C), 166.3 (C=O).
MS (GC, 70 eV): m/z (%) = 468 (35Cl, M+, 2), 379 (12), 378 (17),
377 (67), 376 (27), 375 (100), 342 (7), 340 (20), 312 (23), 277 (10),
276 (32), 138 (6), 65 (5).
Phenyl 1,4-Bis(3-fluorophenyl)-2-naphthoate (4i)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3i (168 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4i was isolated as colorless crystals (185 mg, 85%);
mp 143–144 °C; Rf = 0.4 (heptane–EtOAc, 4:1) .
IR (ATR): 3070 (w), 2924 (w), 2852 (w), 1750 (m), 1579 (m), 1434
(m), 1341 (w), 1251 (m), 1190 (s), 1173 (s), 1142 (s), 1094 (s), 868
(s), 762 (s), 686 (s), 570 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 6.75–6.79 (m, 2 H, ArH), 7.05–
7.28 (m, 9 H, ArH), 7.39–7.49 (m, 4 H, ArH), 7.58 (dd, J = 8.1, 1.0
Hz, 1 H, ArH), 7.87 (dd, J = 8.1, 1.0 Hz, 1 H, ArH), 7.95 (s, 1 H,
ArH).
HRMS (EI): m/z calcd for C29H18Cl2O2 [35Cl, M+]: 468.06784;
found: 468.06894.
Phenyl 1,4-Bis(4-chlorophenyl)-2-naphthoate (4g)
13C NMR (75.46 MHz, CDCl3): d = 114.9 (d, JC,F = 21.0 Hz, CH),
115.0 (d, JC,F = 21.0 Hz, CH), 117.3 (d, JC,F = 21.8 Hz, CH), 117.4
(d, JC,F = 21.8 Hz, CH), 121.5 (2 CH), 125.9 (d, JC,F = 3.0 Hz, CH),
126.0 (d, JC,F = 3.0 Hz, CH), 126.1 (CH), 126.2 (CH), 126.6 (CH),
127.2 (CH + C), 128.2 (CH), 128.4 (CH), 129.6 (2 CH), 129.9 (d,
JC,F = 8.4 Hz, CH), 130.3 (d, JC,F = 8.4 Hz, CH), 133.0 (C), 133.3
(C), 139.6 (d, JC,F = 1.8 Hz, C), 140.4 (d, JC,F = 1.8 Hz, C), 141.2 (d,
JC,F = 8.0 Hz, C), 142.1 (d, JC,F = 8.0 Hz, C), 150.8 (C), 162.8 (d,
JC,F = 247 Hz, CF), 162.9 (d, JC,F = 247 Hz, CF), 166.5 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –112.83 (ArF), –113.26 (ArF).
MS (GC, 70 eV): m/z (%) = 436 (M+, 2), 344 (26), 343 (100), 312
(12), 294 (14), 220 (6), 156 (1), 39 (1).
HRMS (EI): m/z calcd for C29H18F2O2 [M+]: 436.12694; found:
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3g (187 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4g was isolated as colorless crystals (185 mg, 79%);
mp 170–172 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3063 (w), 2919 (w), 2850 (w), 1716 (m), 1590 (w), 1488
(m), 1376 (m), 1369 (m), 1244 (m), 1218 (s), 1192 (s), 1087 (s),
1013 (m), 907 (m), 823 (s), 764 (s), 740 (s), 690 (s), 570 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.72–6.76 (m, 2 H, ArH), 7.02–
7.26 (m, 5 H, ArH), 7.32–7.45 (m, 8 H, ArH), 7.53 (dd, J = 8.4, 1.0
Hz, 1 H, ArH), 7.82 (dd, J = 8.3, 1.0 Hz, 1 H, ArH), 7.91 (s, 1 H,
ArH).
13C NMR (62.89 MHz, CDCl3): d = 121.4 (2 CH), 126.0 (CH),
126.1 (CH), 126.6 (CH), 127.1 (CH), 127.2 (C), 128.2 (CH), 128.3
(CH), 128.6 (2 CH), 128.9 (2 CH), 129.5 (2 CH), 131.3 (2 CH),
131.5 (2 CH), 133.2 (C), 133.3 (C), 133.9 (C), 134.1 (C), 137.4 (C),
138.3 (C), 139.5 (C), 140.6 (C), 150.7 (C), 166.5 (C=O).
436.12754.
Phenyl 1,4-Bis[3-(trifluoromethyl)phenyl]-2-naphthoate (4j)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3j (228 mg, 1.2 mmol), and 1,4-dioxane (4
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

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Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2107
mL), product 4j was isolated as colorless crystals (206 mg, 77%);
mp 124–126 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
13C NMR (62.89 MHz, CDCl3): d = 55.6 (OCH3), 55.7 (OCH3),
110.1 (CH), 111.0 (CH), 120.5 (CH), 120.7 (CH), 120.8 (CH),
121.5 (2 CH), 125.6 (CH), 126.2 (CH), 127.2 (CH), 127.4 (CH),
127.5 (C), 127.9 (CH), 128.1 (C), 128.9 (C), 129.2 (2 CH), 129.4
(CH), 131.2 (CH), 131.4 (CH), 132.1 (CH), 132.8 (C), 134.1 (C),
137.0 (C), 138.4 (C), 150.1 (C), 157.3 (C), 157.4 (C), 166.6 (C=O).
IR (ATR): 3071 (w), 2925 (w), 2853 (w), 1744 (m), 1592 (w), 1491
(w), 1322 (s), 1313 (m), 1210 (m), 1163 (m), 1119 (s), 1069 (s), 901
(m), 803 (m), 702 (s), 685 (s), 592 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 6.71–6.74 (m, 2 H, ArH), 7.00–
7.66 (m, 13 H, ArH), 7.74 (br s, 1 H, ArH), 7.78 (dd, J = 8.4, 1.1 Hz,
1 H, ArH), 7.99 (s, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 121.4 (2 CH), 124.3 (q,
JC,F = 272 Hz, CF3), 124.4 (q, JC,F = 272 Hz, CF3), 124.8 (q,
JC,F = 3.7 Hz, CH), 124.9 (q, JC,F = 3.7 Hz, CH), 126.0 (CH), 126.1
(CH), 126.7 (q, JC,F = 3.7 Hz, CH), 126.9 (CH), 127.0 (q, JC,F = 3.7
Hz, CH), 127.3 (C), 127.5 (CH), 128.2 (CH), 128.8 (CH), 128.9
(CH), 129.3 (CH), 129.6 (2 CH), 131.0 (q, JC,F = 32.4 Hz, C), 131.3
(q, JC,F = 32.4 Hz, C), 133.1 (C), 133.3 (C), 133.4 (CH), 133.6 (CH),
139.6 (C), 139.9 (C), 140.6 (C), 140.7 (C), 150.7 (C), 166.3 (C=O).
MS (GC, 70 eV): m/z (%) = 460 (M+, 2), 369 (4), 368 (27), 367
(100), 324 (5), 308 (5), 292 (4), 281 (5).
HRMS (EI): m/z calcd for C31H24O4 [M+]: 460.16691; found:
460.16758.
Phenyl 1,4-Bis(3-methoxyphenyl)-2-naphthoate (4m)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3m (182 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4m was isolated as colorless crystals (149 mg, 65%);
mp 118–120 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3064 (w), 2934 (w), 2833 (w), 1731 (m), 1575 (m), 1485
(m), 1377 (m), 1252 (m), 1217 (s), 1186 (s), 1098 (s), 1040 (s), 925
(w), 850 (m), 762 (s), 686 (s), 558 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 3 H, OCH3), 3.79 (s, 3 H,
OCH3), 6.73–6.76 (m, 2 H, ArH), 6.92–7.23 (m, 9 H, ArH), 7.32–
7.47 (m, 4 H, ArH), 7.68 (dd, J = 8.1, 1.1 Hz, 1 H, ArH), 7.92 (s, 1
H, ArH), 7.93 (dd, J = 8.3, 1.0 Hz, 1 H, ArH).
19F NMR (282.40 MHz, CDCl3): d = –62.33 (CF3), –62.39 (CF3).
MS (EI, 70 eV): m/z (%) = 536 (M+, 1), 444 (29), 443 (100), 395 (7),
346 (12), 270 (2), 269 (2), 65 (2);
HRMS (EI): m/z calcd for C31H18F6O2 [M+]: 536.12055; found:
536.12087.
Phenyl 1,4-Bis[4-(trifluoromethyl)phenyl]-2-naphthoate (4k)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3k (228 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4k was isolated as colorless crystals (214 mg, 80%);
mp 178–180 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
13C NMR (62.89 MHz, CDCl3): d = 55.5 (OCH3), 55.6 (OCH3),
113.5 (CH), 113.6 (CH), 115.7 (CH), 115.8 (CH), 121.6 (2 CH),
122.7 (2 CH), 125.9 (CH), 126.3 (CH), 126.4 (CH), 126.8 (CH),
127.4 (C), 127.9 (CH), 128.3 (CH), 129.3 (CH), 129.4 (2 CH),
129.6 (CH), 133.0 (C), 133.4 (C), 140.3 (C), 140.4 (C), 141.0 (C),
141.4 (C), 150.9 (C), 159.6 (C), 159.8 (C), 167.1 (C=O).
MS (EI, 70 eV): m/z (%) = 460 (M+, 15), 369 (13), 368 (81), 367
(100), 366 (57), 352 (14), 324 (18), 263 (11), 252 (11), 94 (14), 65
(7).
IR (ATR): 3078 (w), 2923 (w), 2853 (w), 1715 (m), 1591 (w), 1403
(w), 1323 (s), 1241 (m), 1220 (m), 1157 (s), 1102 (s), 1065 (s), 928
(w), 832 (m), 765 (s), 688 (m), 600 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 6.68–6.72 (m, 2 H, ArH), 7.03–
7.73 (m, 14 H, ArH), 7.80–7.83 (m, 1 H, ArH), 7.99 (s, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 121.3 (2 CH), 124.3 (q,
JC,F = 272 Hz, C), 124.4 (q, JC,F = 272 Hz, C), 125.4 (q, JC,F = 3.7
Hz, 2 CH), 125.7 (q, JC,F = 3.7 Hz, 2 CH), 126.1 (CH), 126.2 (CH),
126.8 (CH), 127.1 (C), 127.4 (CH), 128.2 (CH), 128.7 (CH), 129.6
(2 CH), 130.2 (q, JC,F = 32.4 Hz, C), 130.3 (q, JC,F = 32.4 Hz, C),
130.4 (2 CH), 130.6 (2 CH), 133.0 (C), 133.3 (C), 139.7 (C), 140.9
(C), 143.0 (C), 143.6 (C), 150.7 (C), 166.1 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –62.40 (ArCF3), –62.41
(ArCF3).
MS (GC, 70 eV): m/z (%) = 536 (M+, 1), 444 (29), 443 (100), 346
(13), 276 (7), 162 (1), 65 (3).
HRMS (EI): m/z calcd for C31H18F6O2 [M+]: 536.12055; found:
536.12140.
HRMS (EI): m/z calcd for C31H24O4 [M+]: 460.16691; found:
460.16645.
Phenyl 1,4-Bis(3-ethoxyphenyl)-2-naphthoate (4n)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3n (199 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4n was isolated as a colorless solid (149 mg, 61%);
mp 69–71 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3063 (m), 2978 (m), 2925 (m), 2874 (m), 2854 (m), 1732
(s), 1592 (m), 1579 (m), 1489 (s), 1444 (s), 1411 (m), 1377 (m),
1347 (m), 1288 (m), 1224 (s), 1188 (s), 1161 (s), 1122 (m), 1112
(m), 1089 (s), 1043 (s), 982 (m), 925 (m), 897 (m), 835 (m), 797
(m), 748 (s), 712 (m), 687 (m), 647 (m), 623 (w), 609 (m), 548
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.92–1.05 (m, 6 H, 2 CH3), 3.81–
3.95 (m, 4 H, 2 OCH2), 6.75–6.77 (m, 2 H, ArH), 6.92–7.06 (m, 5
H, ArH), 7.15–7.24 (m, 3 H, ArH), 7.25–7.36 (m, 5 H, ArH), 7.56–
7.63 (m, 2 H, ArH), 7.97 (s, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 14.5 (CH3), 14.6 (CH3), 63.9
(OCH2), 64.1 (OCH2), 112.3 (CH), 112.6 (CH), 120.4 (CH), 120.7
(CH), 121.5 (2 CH), 125.5 (CH), 126.0 (CH), 126.8 (CH), 127.1
(CH), 127.2 (CH), 127.3 (C), 128.0 (CH), 128.6 (C), 129.1 (CH),
129.2 (2 CH), 129.3 (CH), 129.4 (C), 131.5 (CH), 132.1 (CH),
132.7 (C), 134.0 (C), 137.0 (C), 138.4 (C), 151.0 (C), 156.6 (C),
156.8 (C), 166.8 (C=O).
MS (EI, 70 eV): m/z (%) = 488 (M+, 4), 397 (5), 396 (30), 395 (100),
368 (11), 367 (41), 366 (5), 340 (6), 339 (24), 338 (6), 337 (7), 321
(12), 295 (5), 294 (6), 292 (11), 276 (10), 252 (5), 202 (5).
Phenyl 1,4-Bis(2-methoxyphenyl)-2-naphthoate (4l)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3l (182 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4l was isolated as viscous gel (168 mg, 73%); mp
124–126 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
IR (ATR): 3062 (w), 3021 (w), 2929 (w), 2829 (w), 1741 (s), 1590
(m), 1581 (m), 1564 (m), 1493 (s), 1456 (m), 1434 (m), 1370 (m),
1343 (m), 1295 (m), 1272 (m), 1245 (s), 1227 (m), 1184 (s), 1162
(s), 1148 (s), 1130 (m), 1119 (m), 1106 (m), 1089 (s), 1046 (s), 1023
(s), 981 (m), 938 (w), 917 (m), 896 (m), 834 (w), 798 (m), 750 (s),
741 (s), 688 (s), 609 (m), 551 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.58 (s, 3 H, OCH3), 3.61 (s, 3 H,
OCH3), 6.72–6.76 (m, 2 H, ArH), 6.91–7.04 (m, 5 H, ArH), 7.09–
7.21 (m, 3 H, ArH), 7.25–7.36 (m, 5 H, ArH), 7.53–7.58 (m, 2 H,
ArH), 7.96 (s, 1 H, ArH).
HRMS (EI): m/z calcd for C33H28O4 [M+]: 488.19821; found:
488.19861.
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Phenyl 1,4-Bis(2,4-dimethoxyphenyl)-2-naphthoate (4o)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3o (218 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4o was isolated as colorless crystals (146 mg, 56%);
mp 175–177 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
7.01–7.06 (m, 1 H, ArH), 7.16–7.21 (m, 2 H, ArH), 7.28–7.38 (m,
2 H, ArH), 7.57–7.60 (m, 2 H, ArH), 7.99 (s, 1 H, ArH).
13C NMR (75.47 MHz, CDCl3): d = 54.7 (2 OCH3), 55.2 (OCH3),
55.3 (OCH3), 111.1 (CH), 111.2 (CH), 112.9 (CH), 113.2 (CH),
115.9 (CH), 116.5 (CH), 120.4 (2 CH), 124.5 (CH), 125.3 (CH),
125.6 (CH), 125.9 (CH), 126.1 (C), 126.4 (CH), 126.8 (CH), 127.8
(C), 128.1 (2 CH), 128.6 (C), 131.5 (C), 132.7 (C), 135.9 (C), 137.1
(C), 149.8 (C), 150.4 (C), 150.6 (C), 152.4 (C), 152.6 (C), 165.3
(C=O).
IR (ATR): 3011 (w), 2958 (w), 2836 (w), 1747 (m), 1609 (m), 1505
(m), 1486 (w), 1376 (w), 1304 (m), 1208 (s), 1189 (s), 1157 (s),
1092 (m), 1030 (m), 926 (w), 828 (m), 767 (m), 687 (m), 586 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 3 H, OCH3), 3.81 (s, 3 H,
OCH3), 3.84 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 6.71–6.75 (m, 2
H, ArH), 6.89–7.06 (m, 7 H, ArH), 7.14–7.20 (m, 2 H, ArH), 7.32–
7.44 (m, 2 H, ArH), 7.70 (dd, J = 8.1, 1.3 Hz, 1 H, ArH), 7.86 (s, 1
H, ArH), 7.93 (dd, J = 8.0, 1.3 Hz, 1 H, ArH).
MS (EI, 70 eV): m/z (%) = 520 (M+, 36), 429 (16), 427 (100), 413
(11), 412 (47), 397 (19), 396 (23), 381 (8), 262 (13), 206 (22), 183
(9), 94 (8).
HRMS (EI): m/z calcd for C33H28O6 [M+]: 520.18804; found:
520.188872.
13C NMR (62.89 MHz, CDCl3): d = 56.1 (4 OCH3), 111.1 (CH),
111.3 (CH), 113.4 (CH), 113.6 (CH), 121.4 (2 CH), 122.5 (2 CH),
125.8 (CH), 126.1 (CH), 126.3 (CH), 126.7 (CH), 127.7 (CH),
127.9 (C), 128.2 (CH), 129.4 (2 CH), 131.3 (C), 132.6 (C), 133.3
(C), 133.5 (C), 140.2 (C), 140.3 (C), 148.7 (C), 148.8 (2 C), 148.9
(C), 150.8 (C), 167.3 (C=O).
Phenyl 1,4-Bis(3-hydroxyphenyl)-2-naphthoate (4r)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3r (167 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4r was isolated as a white solid (117 mg, 54%); mp
170–172 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
MS (EI, 70 eV): m/z (%) = 520 (M+, 15), 428 (55), 427 (100), 412
(10), 396 (10), 384 (5), 311 (2), 283 (1), 239 (1), 206 (3), 94 (3).
HRMS (EI): m/z calcd for C33H28O6 [M+]: 520.18804; found:
520.18795.
IR (ATR): 3421–2633 (br), 3068 (w), 2930 (w), 2839 (w), 1723
(m), 1589 (w), 1515 (s), 1427 (m), 1365 (m), 1238 (s), 1220 (s),
1193 (s), 1187 (s), 1013 (s), 966 (m), 923 (w), 761 (m), 687 (m), 597
cm–1 (w).
1H NMR (250 MHz, acetone-d6): d = 6.67–6.69 (m, 1 H, ArH),
6.70–6.72 (m, 1 H, ArH), 6.75 (dt, J = 7.6, 1.3 Hz, 1 H, ArH), 6.79–
6.80 (m, 2 H, ArH), 6.81–6.83 (m, 1 H, ArH), 6.86 (dt, J = 7.6, 1.3
Hz, 1 H, ArH), 6.90 (t, J = 1.8 Hz, 1 H, ArH), 6.95–7.01 (m, 1 H,
ArH), 7.09–7.23 (m, 4 H, ArH), 7.34 (m, 1 H, ArH), 7.40 (m, 1 H,
ArH), 7.62 (dd, J = 7.9, 1.3 Hz, 1 H, ArH), 7.71 (s, 1 H, ArH), 7.85
(dd, J = 7.9, 1.3 Hz, 1 H, ArH), 8.38 (s, 1 H, ArOH), 8.40 (s, 1 H,
ArOH).
13C NMR (62.89 MHz, (acetone-d6): d = 115.7 (CH), 115.8 (CH),
117.8 (CH), 118.0 (CH), 122.1 (CH), 122.3 (CH), 122.5 (2 CH),
126.5 (CH), 126.6 (CH), 127.0 (CH), 127.7 (CH), 128.7 (CH),
128.8 (CH), 128.9 (C), 130.1 (2 CH), 130.3 (CH), 130.6 (CH),
133.6 (C), 133.8 (C), 140.9 (C), 141.0 (C), 141.1 (C), 142.0 (C),
151.9 (C), 158.2 (C), 158.5 (C), 167.7 (C=O).
Phenyl 1,4-Bis(3,4-dimethoxyphenyl)-2-naphthoate (4p)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3p (218 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4p was isolated as colorless crystals (164 mg, 63%);
mp 140–142 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
IR (ATR): 3066 (w), 2931 (w), 2834 (w), 1732 (m), 1589 (w), 1510
(s), 1461 (m), 1372 (m), 1238 (s), 1220 (s), 1187 (s), 1095 (s), 1023
(s), 923 (w), 761 (m), 687 (m), 597 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 3 H, OCH3), 3.81 (s, 3 H,
OCH3), 3.84 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 6.71–6.75 (m, 2
H, ArH), 6.89–7.06 (m, 7 H, ArH), 7.14–7.20 (m, 2 H, ArH), 7.32–
7.44 (m, 2 H, ArH), 7.70 (dd, J = 8.1, 1.3 Hz, 1 H, ArH), 7.86 (s, 1
H, ArH), 7.93 (dd, J = 8.0, 1.3 Hz, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 56.1 (4 OCH3), 111.1 (CH),
111.3 (CH), 113.4 (CH), 113.6 (CH), 121.4 (2 CH), 122.5 (2 CH),
125.8 (CH), 126.1 (CH), 126.3 (CH), 126.7 (CH), 127.7 (CH),
127.9 (C), 128.2 (CH), 129.4 (2 CH), 131.3 (C), 132.6 (C), 133.3
(C), 133.5 (C), 140.2 (C), 140.3 (C), 148.7 (C), 148.8 (2 C), 148.9
(C), 150.8 (C), 167.3 (C=O).
MS (GC, 70 eV): m/z (%) = 520 (M+, 16), 428 (27), 427 (63), 410
(11), 396 (54), 239 (7), 183 (100), 170 (21), 147 (29), 120 (89), 107
(27).
MS (EI, 70 eV): m/z (%) = 432 (M+, 1), 340 (23), 339 (100), 338
(30), 310 (7), 281 (5), 263 (5), 189 (5), 94 (21), 66 (7), 65 (8).
HRMS (EI): m/z calcd for C29H20O4 [M+]: 432.13561; found:
432.13625.
Phenyl 1-(3,5-Dimethylphenyl)-4-(trifluoromethylsulfonyloxy)-
2-naphthoate (5a)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3d (82 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5a was isolated as colorless crystals (170 mg, 68%);
mp 98–100 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
HRMS (EI): m/z calcd for C33H28O6 [M+]: 520.18804; found:
520.18900.
IR (ATR): 3030 (w), 2922 (w), 2853 (w), 1731 (m), 1598 (w), 1508
(w), 1491 (w), 1366 (w), 1243 (m), 1214 (s), 1189 (s), 1138 (s),
1009 (m), 858 (m), 762 (m), 687 (m), 598 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.48 (s, 6 H, 2 CH3), 6.92–6.96
(m, 2 H, ArH), 7.12 (s, 2 H, ArH), 7.21–7.44 (m, 4 H, ArH), 7.65
(dt, J = 8.0, 1.1 Hz, 1 H, ArH), 7.83 (dt, J = 8.0, 1.1 Hz, 1 H, ArH),
7.88 (d, J = 8.5 Hz, 1 H, ArH), 8.18 (s, 1 H, ArH), 8.29 (d, J = 8.4
Hz, 1 H, ArH).
Phenyl 1,4-Bis(2,5-dimethoxyphenyl)-2-naphthoate (4q)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3q (218 mg, 1.2 mmol), and 1,4-dioxane (4
mL), product 4q was isolated as colorless crystals (179 mg, 69%);
mp 175–177 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
IR (ATR): 3068 (w), 2942 (w), 2827 (w), 1741 (s), 1588 (m), 1497
(s), 1461 (m), 1441 (m), 1417 (m), 1369 (m), 1347 (m), 1302 (m),
1280 (m), 1268 (m), 1254 (m), 1220 (s), 1189 (s), 1093 (s), 1038 (s),
1024 (s), 1000 (m), 884 (m), 799 (m), 774 (m), 692 (s), 638 (m), 588
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.54 (s, 3 H, OCH3), 3.57 (s, 3 H,
OCH3), 3.65 (s, 3 H, OCH3), 3.69 (s, 3 H, OCH3), 6.74–6.80 (m, 3
H, ArH), 6.86 (s, 2 H, ArH), 6.88 (s, 2 H, ArH), 6.90 (s, 1 H, ArH),
13C NMR (75.46 MHz, CDCl3): d = 21.4 (2 CH3), 117.9 (CH),
1
118.9 (q, JC,F = 321 Hz, CF3), 120.9 (CH), 121.4 (2 CH), 126.1
(CH), 127.4 (C), 127.6 (2 CH), 128.0 (C), 128.3 (CH), 128.9 (CH),
129.5 (2 CH), 129.7 (CH), 129.9 (CH), 134.5 (C), 137.5 (C), 137.9
(2 C), 143.2 (C), 144.9 (C), 150.7 (C), 165.5 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –73.06 (3 F, CF3).
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Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
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MS (EI, 70 eV): m/z (%) = 500 (M+, 1), 408 (28), 407 (100), 406
(35), 275 (12), 274 (71), 273 (23), 259 (34), 231 (23), 203 (14), 202
(22), 94 (2), 65 (4).
IR (ATR): 3072 (w), 2939 (w), 2836 (w), 1729 (m), 1589 (m), 1509
(w), 1487 (m), 1419 (s), 1336 (m), 1243 (m), 1186 (s), 1134 (s),
1014 (s), 859 (m), 813 (s), 762 (s), 686 (s), 598 cm–1 (s).
HRMS (ESI+): m/z calcd for C26H20F3O5S [M + H]+: 501.0978;
found: 501.0980.
1H NMR (250 MHz, CDCl3): d = 3.71 (s, 3 H, OCH3), 6.74–6.77
(m, 2 H, ArH), 6.84–6.96 (m, 3 H, ArH), 7.06–7.25 (m, 3 H, ArH),
7.33 (t, J = 7.8 Hz, 1 H, ArH), 7.48 (dt, J = 8.6, 1.1 Hz, 1 H, ArH),
7.36–7.70 (m, 2 H, ArH), 7.98 (s, 1 H, ArH), 8.10 (d, J = 8.2 Hz, 1
H, ArH).
Phenyl 1-(4-Chlorophenyl)-4-(trifluoromethylsulfonyloxy)-2-
naphthoate (5b)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3g (86 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5b was isolated as colorless crystals (185 mg, 73%);
mp 82–84 °C; Rf = 0.4 (heptane–EtOAc, 4:1).
13C NMR (75.46 MHz, CDCl3): d = 55.5 (OCH3), 114.0 (CH),
115.5 (CH), 118.0 (CH), 119.0 (q, 1JC,F = 321 Hz, CF3), 121.0 (CH),
121.4 (2 CH), 122.4 (CH), 126.2 (CH), 127.4 (C), 128.2 (C), 128.5
(CH), 128.8 (CH), 129.5 (3 CH), 129.9 (CH), 134.5 (C), 139.0 (C),
142.7 (C), 145.1 (C), 150.6 (C), 159.7 (C), 165.3 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –73.08 (3 F, CF3).
MS (EI, 70 eV): m/z (%) = 502 (M+, 3), 410 (19), 409 (100), 408
(38), 276 (92), 275 (22), 205 (10), 176 (8), 119 (3), 94 (6), 69 (10),
43 (33).
IR (ATR): 3074 (w), 1731 (m), 1591 (w), 1490 (m), 1420 (m), 1336
(m), 1240 (m), 1186 (s), 1135 (s), 1087 (m), 1011 (s), 964 (m), 825
(s), 762 (s), 686 (m), 597 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 6.78–6.81 (m, 2 H, ArH), 7.08–
7.53 (m, 9 H, ArH), 7.68 (dt, J = 8.6, 1.8 Hz, 1 H, ArH), 8.03 (s, 1
H, ArH), 8.11 (d, J = 8.5 Hz, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 118.1 (CH), 118.9 (q,
1JC,F = 321 Hz, CF3), 121.2 (CH), 121.3 (2 CH), 126.3 (CH), 127.1
(C), 128.3 (C), 128.5 (CH), 128.7 (CH), 128.8 (2 CH), 129.7 (2
CH), 130.1 (CH), 131.1 (2 CH), 134.5 (2 C), 136.1 (C), 142.0 (C),
145.3 (C), 150.5 (C), 164.8 (C=O).
HRMS (EI): m/z calcd for C25H17F3O6S [M+]: 502.06925; found:
502.06944.
Phenyl 1-(2-Ethoxyphenyl)-4-(trifluoromethylsulfonyloxy)-2-
naphthoate (5e)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3n (91 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5e was isolated as colorless crystals (150 mg, 59%);
mp 87–89 °C; Rf = 0.2 (heptane–EtOAc, 4:1) .
19F NMR (282.40 MHz, CDCl3): d = –73.04 (3 F, CF3).
MS (GC, 70 eV): m/z (%) = 506 (M+, 35Cl, 2), 415 (40), 414 (22),
413 (100), 245 (49), 217 (28), 189 (20), 65 (4), 39 (2).
IR (ATR): 3063 (w), 2926 (w), 2854 (w), 1744 (m), 1598 (w), 1491
(m), 1421 (m), 1332 (w), 1244 (m), 1201 (s), 1185 (s), 1127 (s),
1012 (s), 925 (m), 843 (m), 753 (s), 724 (s), 687 (m), 607 cm–1 (s).
HRMS (EI): m/z calcd for C24H14ClF3O5S: [35Cl, M+]: 506.01971;
found: 506.02008.
Phenyl 1-(2-Methoxyphenyl)-4-(trifluoromethylsulfonyloxy)-2-
naphthoate (5c)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3l (84 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5c was isolated as colorless crystals (156 mg, 62%);
mp 85–87 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): d = 0.98 (t, J = 7.0 Hz, 3 H, CH3),
3.86 (q, J = 7.0 Hz, 2 H, OCH2), 6.76–6.80 (m, 2 H, ArH), 6.94 (d,
J = 8.0 Hz, 1 H, ArH), 7.00 (dt, J = 7.4, 1.0 Hz, 1 H, ArH), 7.06–
7.38 (m, 5 H, ArH), 7.46 (dt, J = 8.0, 1.2 Hz, 1 H, ArH), 7.61 (d,
J = 8.4 Hz, 1 H, ArH), 7.66 (dt, J = 7.6, 1.2 Hz, 1 H, ArH), 8.04 (s,
1 H, ArH), 8.10 (d, J = 8.4 Hz, 1 H, ArH).
IR (ATR): 3072 (w), 2917 (w), 2848 (w), 1728 (m), 1600 (w), 1492
(m), 1419 (m), 1337 (m), 1247 (m), 1186 (s), 1135 (s), 1121 (s),
1012 (s), 964 (m), 834 (s), 751 (s), 597 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 3.54 (s, 3 H, OCH3), 6.73–6.77
(m, 2 H, ArH), 6.90–7.21 (m, 6 H, ArH), 7.35 (dt, J = 8.0, 1.6 Hz, 1
H, ArH), 7.44 (d, J = 7.6 Hz, 1 H, ArH), 7.54 (s, 1 H, ArH), 7.57–
7.64 (m, 1 H, ArH), 8.03 (s, 1 H, ArH), 8.07 (d, J = 8.4 Hz, 1 H,
ArH).
13C NMR (75.46 MHz, CDCl3): d = 55.7 (OCH3), 111.1 (CH),
118.3 (CH), 118.9 (q, 1JC,F = 321 Hz, CF3), 120.7 (CH), 121.1 (CH),
121.4 (2 CH), 126.0 (CH), 126.6 (C), 127.6 (C), 128.2 (CH), 128.3
(C), 128.6 (CH), 129.5 (2 CH), 129.8 (CH), 130.7 (CH), 131.0
(CH), 134.6 (C), 140.2 (C), 145.1 (C), 150.7 (C), 157.3 (C), 165.5
(C=O).
13C NMR (75.46 MHz, CDCl3): d = 14.7 (CH3), 64.1 (OCH2),
1
112.3 (CH), 118.3 (CH), 119.0 (q, J C,F = 321 Hz, CF3), 120.6
(CH), 121.0 (CH), 121.4 (2 CH), 126.0 (CH), 126.9 (C), 127.7 (C),
128.1 (CH), 128.3 (C), 128.7 (CH), 129.5 (2 CH), 129.7 (CH),
129.9 (CH), 131.3 (CH), 134.6 (C), 140.3 (C), 145.0 (C), 150.8 (C),
156.6 (C), 165.2 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –73.16 (3 F, CF3).
MS (GC, 70 eV): m/z (%) = 516 (M+, 7), 424 (19), 423 (90), 396
(19), 395 (100), 263 (16), 262 (78), 261 (20), 234 (26), 233 (25),
205 (28), 176 (17), 65 (6).
HRMS (EI): m/z calcd for C26H19F3O6S [M+]: 516.08490; found:
516.08473.
Phenyl 1-(2,4-Dimethoxyphenyl)-4-(trifluoromethylsulfonyl-
oxy)-2-naphthoate (5f)
19F NMR (282.40 MHz, CDCl3): d = –73.16 (3 F, CF3).
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3o (100 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5f was isolated as a brownish semisolid (176 mg,
66%); Rf = 0.4 (heptane–EtOAc, 4:1) .
MS (EI, 70 eV): m/z (%) = 502 (M+, 4), 410 (20), 409 (100), 345 (5),
276 (22), 261 (14), 233 (25), 205 (8), 189 (4), 176 (5), 94 (3), 65 (3).
HRMS (ESI+): m/z calcd for C25H18F3O6S [M + H]+: 503.0771;
found: 503.0774.
IR (ATR): 3072 (w), 2937 (w), 2837 (w), 1729 (m), 1591 (m), 1512
(m), 1417 (m), 1337 (m), 1203 (s), 1186 (s), 1132 (s), 1011 (s), 965
(m), 830 (s), 762 (s), 687 (m), 597 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 3.55 (s, 3 H, OCH3), 3.77 (s, 3 H,
OCH3), 6.51–6.56 (m, 2 H, ArH), 6.81–6.86 (m, 2 H, ArH), 7.0 (d,
J = 8.1 Hz, 1 H, ArH), 7.06–7.25 (m, 3 H, ArH), 7.45 (dt, J = 7.7,
1.1 Hz, 1 H, ArH), 7.61–7.66 (m, 2 H, ArH), 8.02 (s, 1 H, ArH), 8.07
(d, J = 7.8 Hz, 1 H, ArH).
Phenyl 1-(3-Methoxyphenyl)-4-(trifluoromethylsulfonyloxy)-2-
naphthoate (5d)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3m (84 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5d was isolated as a colorless semisolid (173 mg,
69%); Rf = 0.3 (heptane–EtOAc, 4:1) .
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13C NMR (62.89 MHz, CDCl3): d = 55.6 (OCH3), 55.8 (OCH3),
99.0 (CH), 104.6 (CH), 118.2 (CH), 118.9 (C), 119.0 (q, 1JC,F = 321
Hz, CF3), 121.0 (CH), 121.5 (2 CH), 126.1 (CH), 127.9 (C), 128.2
(CH), 128.3 (C), 128.7 (CH), 129.5 (2 CH), 129.7 (CH), 131.5
(CH), 135.0 (C), 140.1 (C), 145.0 (C), 150.8 (C), 158.3 (C), 161.5
(C), 165.1 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –73.08 (3 F, CF3).
MS (EI, 70 eV): m/z (%) = 532 (M+, 17), 440 (18), 439 (100), 307
(15), 306 (52), 275 (14), 263 (21), 220 (5) 176 (4), 94 (18), 69 (11),
45 (27), 44 (40), 43 (49).
HRMS (ESI+): m/z calcd for C24H16F3O6S [M + H]+: 489.0614;
found: 489.0616.
One-Pot Synthesis of 6a–h; General Procedure
The reaction was carried out in a pressure tube. To a suspension of
2 (272 mg, 0.5 mmol), Pd(PPh3)4 (3 mol%), and Ar1B(OH)2 (0.55
mmol) in 1,4-dioxane (4 mL) was added K3PO4 (159 mg, 0.75
mmol) and the solution was degassed by bubbling argon for 10 min.
The mixture was heated at 95 °C under argon atmosphere for 7 h.
The mixture was cooled to 20 °C and Ar2B(OH)2 (0.65 mmol) and
K3PO4 (159 mg, 0.75 mmol) were added. The reaction mixture was
heated under argon atmosphere for 6 h at 110 °C. The mixture was
diluted with H2O (40 mL) and extracted with CH2Cl2 (3 × 25 mL).
The combined organic layers were dried (Na2SO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified by flash
chromatography (silica gel, EtOAc–heptanes).
HRMS (EI): m/z calcd for C26H19F3O7S [M+]: 532.07981; found:
532.07979.
Phenyl 1-(2,6-Dimethoxyphenyl)-4-(trifluoromethylsulfonyl-
oxy)-2-naphthoate (5g)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3s (100 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5g was isolated as colorless crystals (88 mg, 33%); mp
162–164 °C; Rf = 0.2 (heptane–EtOAc, 4:1).
Phenyl 4-(3,4-Dimethoxyphenyl)-1-(4-fluorophenyl)-2-naph-
thoate (6a)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3u (77 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3p (118 mg, 0.65 mmol), product 6a was isolated as white crys-
tals (129 mg, 54%); mp 136–138 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
IR (ATR): 3014 (w), 2937 (w), 2839 (w), 1723 (m), 1589 (w), 1510
(w), 1470 (m), 1413 (m), 1336 (m), 1247 (m), 1192 (s), 1109 (s),
1011 (m), 956 (m), 828 (m), 747 (m), 687 (m), 599 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.53 (s, 6 H, OCH3), 6.62 (d,
J = 8.4 Hz, 2 H, Ar), 6.79–6.84 (m, 2 H, ArH), 7.06–7.12 (m, 1 H,
ArH), 7.20–7.26 (m, 2 H, ArH), 7.33 (t, J = 8.26 Hz, 1 H, ArH),
7.41–7.48 (m, 1 H, ArH), 7.55 (d, J = 8.1 Hz, 1 H, ArH), 7.64 (dt,
J = 7.8, 1.3 Hz, 1 H, ArH), 8.07 (d, J = 8.3 Hz, 1 H, ArH), 8.08 (s,
1 H, ArH).
13C NMR (62.90 MHz, CDCl3): d = 55.9 (2 OCH3), 104.1 (2 CH),
114.8 (C), 118.3 (CH), 118.8 (q, 1J C,F = 321 Hz, CF3), 120.9 (CH),
121.3 (2 CH), 125.7 (CH), 127.7 (C), 127.9 (CH), 128.0 (CH),
128.2 (C), 129.3 (2 CH), 129.5 (CH), 129.9 (CH), 130.1 (CH),
134.3 (C), 137.0 (C), 144.9 (C), 150.7 (C), 157.8 (2 C), 164.7
(C=O).
19F NMR (282.4 MHz, CDCl3): d = –73.24 (3 F, CF3).
MS (EI, 70 eV): m/z (%) = 532 (M+, 4), 441 (7), 440 (21), 439
(100), 306 (17), 275 (25), 263 (20), 248 (4), 220 (6) 176 (2), 94 (3),
69 (4), 43 (5).
HRMS (EI): m/z calcd for C26H19F3O7S [M+]: 532.07981; found:
532.08011.
IR (ATR): 3058 (w), 2956 (w), 2831 (w), 1723 (m), 1580 (w), 1460
(m), 1381 (w), 1242 (m), 1216 (s), 1187 (s), 1141 (s), 1097 (m), 934
(w), 815 (w), 742 (s), 688 (m), 593 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.84 (s, 3 H, OCH3), 3.89 (s, 3 H,
OCH3), 6.75–6.78 (m, 2 H, ArH), 6.95 (d, J = 8.1 Hz, 1 H, ArH),
7.00 (d, J = 1.8 Hz, 1 H, ArH), 7.04 (dd, J = 8.0, 1.9 Hz, 1 H, ArH),
7.07–7.24 (m, 6 H, ArH), 7.35–7.48 (m, 3 H, ArH), 7.57 (dd,
J = 8.4, 0.9 Hz, 1 H, ArH), 7.95 (s, 1 H, ArH), 7.96 (dd, J = 7.6, 0.8
Hz, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 56.2 (2 OCH3), 111.4 (CH),
113.5 (CH), 114.8 (d, JC,F = 21.3 Hz, CH), 117.3 (d, JC,F = 21.3 Hz,
CH), 121.5 (2 CH), 122.6 (CH), 125.9 (d, JC,F = 3.0 Hz, CH), 126.0
(CH), 126.4 (CH), 126.5 (CH), 127.0 (CH), 127.2 (C), 128.1 (2
CH), 129.5 (2 CH), 129.9 (d, JC,F = 8.4 Hz, CH), 132.5 (C), 133.0
(C), 133.7 (C), 139.7 (C), 140.8 (C), 141.3 (d, JC,F = 7.9 Hz, CH),
149.0 (C), 149.1 (C), 150.8 (C), 162.8 (d, JC,F = 247 Hz, CF), 166.7
(C=O).
19F NMR (282.4 MHz, CDCl3): d = –113.35 (ArF).
MS (GC, 70 eV): m/z (%) = 478 (M+, 11), 386 (28), 385 (100), 326
(4), 283 (5), 270 (6), 192 (7), 135 (3), 122 (2), 65 (1).
HRMS (EI): m/z calcd for C31H23FO4 [M+]: 478.15749; found:
478.15783.
Phenyl 1-(4-Hydroxyphenyl)-4-(trifluoromethylsulfonyloxy)-2-
naphthoate (5h)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (160 mg, 0.75 mmol),
Pd(PPh3)4 (3 mol%), 3t (76 mg, 0.55 mmol), and 1,4-dioxane (4
mL), product 5h was isolated as colorless crystals (127 mg, 52%);
mp 117–119 °C; Rf = 0.3 (heptane–EtOAc, 4:1) .
Phenyl 1-(2,4-Dimethoxyphenyl)-4-p-tolyl-2-naphthoate (6b)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3o (100 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3b (88 mg, 0.65 mmol), product 6b was isolated as brown semi-
solid (149 mg, 63%); Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3421–2633 (br), 3069 (w), 2927 (w), 2852 (w), 1723
(m), 1589 (w), 1515 (w), 1427 (m), 1335 (m), 1240 (m), 1212 (s),
1193 (s), 1135 (s), 1013 (s), 966 (m), 830 (s), 750 (m), 642 (s), 594
cm–1 (s).
IR (ATR): 3065 (w), 2933 (w), 2834 (w), 1731 (m), 1591 (w), 1508
(m), 1414 (w), 1302 (m), 1234 (m), 1205 (s), 1186 (s), 1156 (s),
1091 (s), 1030 (s), 981 (m), 823 (m), 763 (s), 686 (m), 596 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.26 (s, 3 H, ArCH3), 3.58 (s, 3 H,
OCH3), 3.76 (s, 3 H, OCH3), 6.53–6.56 (m, 2 H, ArH), 6.79–6.82
(m, 2 H, ArH), 7.02–7.08 (m, 2 H, ArH), 7.17–7.40 (m, 7 H, ArH),
7.62 (dd, J = 7.7, 1.3 Hz, 1 H, ArH), 7.89 (d, J = 8.2 Hz, 1 H, ArH),
7.94 (s, 1 H, ArH), 8.0 (s, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 21.4 (CH3), 55.6 (OCH3), 55.9
(OCH3), 99.1 (CH), 104.5 (CH), 120.5 (C), 121.7 (2 CH), 125.7
(CH), 126.4 (CH), 126.5 (CH), 126.8 (CH), 127.7 (CH), 127.9 (C),
128.3 (CH), 129.3 (2 CH), 129.4 (2 CH), 130.2 (2 CH), 131.7 (CH),
1H NMR (250 MHz, CDCl3): d = 4.28 (br s, 1 H, OH), 6.77–6.84
(m, 4 H, ArH), 7.08–7.25 (m, 5 H, ArH), 7.47 (dt, J = 8.8, 2.0 Hz, 1
H, ArH), 7.63–7.69 (m, 2 H, ArH), 7.96 (s, 1 H, ArH), 8.09 (d,
J = 8.0 Hz, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 115.5 (2 CH), 117.9 (CH),
1
119.0 (q, JC,F = 321 Hz, CF3), 121.1 (CH), 121.4 (2 CH), 126.3
(CH), 127.6 (C), 128.2 (C), 128.4 (CH), 128.8 (CH), 129.5 (C),
129.6 (2 CH), 129.8 (CH), 131.1 (2 CH), 134.9 (C), 142.8 (C),
145.0 (C), 150.6 (C), 156.0 (C), 165.9 (C=O).
19F NMR (282.40 MHz, CDCl3): d = –73.07 (3 F, CF3).
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

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Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2111
133.6 (C), 133.7 (C), 137.3 (C), 137.5 (C), 138.0 (C), 140.1 (C),
151.1 (C), 158.5 (C), 161.0 (C), 166.9 (C=O).
Phenyl 4-(3,4-Dimethoxyphenyl)-1-(3-methoxyphenyl)-2-naph-
thoate (6e)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3m (84 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3p (118 mg, 0.65 mmol), product 6e was isolated as white crys-
tals (113 mg, 46%); mp 143–145 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
MS (EI, 70 eV): m/z (%) = 474 (M+, 9), 382 (25), 381 (100), 323 (7),
183 (2), 149 (3), 97 (4), 69 (7), 57 (7), 44 (16), 43 (23).
HRMS (EI): m/z calcd for C32H26O4 [M+]: 474.18256; found:
474.18229.
IR (ATR): 3060 (w), 2948 (w), 2831 (w), 1737 (s), 1586 (m), 1514
(m), 1407 (w), 1316 (w), 1241 (m), 1220 (s), 1187 (s), 1135 (s),
1100 (s), 1022 (s), 935 (w), 812 (m), 766 (m), 686 (m), 595 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 3.72 (s, 3 H, OCH3), 3.83 (s, 3 H,
OCH3), 3.89 (s, 3 H, OCH3), 6.70–6.74 (m, 2 H, ArH), 6.92–7.08
(m, 7 H, ArH), 7.16–7.22 (m, 2 H, ArH), 7.31–7.39 (m, 2 H, ArH),
7.44 (dt, J = 8.3, 1.5 Hz, 1 H, ArH), 7.67 (d, J = 8.7 Hz, 1 H, ArH),
7.90 (s, 1 H, ArH), 7.94 (d, J = 8.1 Hz, 1 H, ArH).
13C NMR (62.89 MHz, CDCl3): d = 55.5 (OCH3), 56.2 (2 OCH3),
111.4 (CH), 113.5 (2 CH), 115.8 (CH), 121.5 (2 CH), 122.6 (CH),
122.7 (CH), 125.9 (CH), 126.3 (CH), 126.4 (CH), 126.8 (CH),
127.5 (C), 127.9 (CH), 128.4 (CH), 129.3 (CH), 129.4 (2 CH),
132.7 (C), 133.1 (C), 133.6 (C), 140.4 (2 C), 140.6 (C), 148.9 (C),
149.0 (C), 150.9 (C), 159.6 (C), 167.2 (C=O).
MS (EI, 70 eV): m/z (%) = 490 (M+, 14), 398 (28), 397 (100), 339
(3), 239 (3), 149 (3), 123 (5), 111 (4), 97 (7), 57 (13), 44 (19), 43
(27).
Phenyl 4-(3,4-Dimethoxyphenyl)-1-[4-(trifluoromethyl)phe-
nyl]-2-naphthoate (6c)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3k (104 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3p (118 mg, 0.65 mmol), product 6c was isolated as white crys-
tals (134 mg, 51%); mp 163–165 °C; Rf = 0.2 (heptane–
EtOAc, 4:1).
IR (ATR): 3065 (w), 2966 (w), 2838 (w), 1712 (m), 1597 (w), 1515
(m), 1406 (w), 1320 (m), 1239 (m), 1212 (m), 1159 (s), 1101 (s),
1023 (m), 923 (w), 775 (m), 744 (m), 685 (m), 623 (m), 549 cm–1
(w).
1H NMR (250 MHz, CDCl3): d = 3.85 (s, 3 H, OCH3), 3.90 (s, 3 H,
OCH3), 6.70–6.73 (m, 2 H, ArH), 6.96 (d, J = 8.2 Hz, 1 H, ArH),
7.01–7.11 (m, 3 H, ArH), 7.17–7.24 (m, 2 H, ArH), 7.40 (dd,
J = 7.3, 2.4 Hz, 1 H, ArH), 7.44–7.50 (m, 4 H, ArH), 7.68–7.71 (m,
2 H, ArH), 7.95–7.99 (m, 1 H, ArH), 8.0 (s, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 56.0 (OCH3), 56.1 (OCH3),
111.3 (CH), 113.3 (CH), 121.2 (2 CH), 122.4 (CH), 124.3 (q,
JC,F = 272 Hz, CF), 125.2 (q, JC,F = 3.8 Hz, 2 CH), 125.9 (CH),
126.4 (CH), 126.5 (CH), 126.8 (C), 126.9 (CH), 127.8 (CH), 128.1
(CH), 129.4 (2 CH), 129.9 (q, JC,F = 32.5 Hz, C), 130.3 (2 CH),
132.3 (C), 132.8 (C), 133.7 (C), 139.7 (C), 140.9 (C), 143.1 (C),
148.9 (C), 149.0 (C), 150.5 (C), 166.2 (C=O).
19F NMR (282.4 MHz. CDCl3): d = –62.38 (3 F, ArCF3).
MS (EI, 70 eV): m/z (%) = 528 (M+, 18), 436 (27), 435 (100), 376
(4), 333 (4), 252 (3), 207 (3), 153 (3), 94 (18), 69 (13), 60 (25), 43
(29).
HRMS (EI): m/z calcd for C32H23F3O4 [M+]: 528.15430; found:
528.15443.
HRMS (EI): m/z calcd for C32H26O5 [M+]: 490.17748; found:
490.17793.
Phenyl 4-(4-Methoxyphenyl)-1-p-tolyl-2-naphthoate (6f)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3b (75 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3w (99 mg, 0.65 mmol), product 6f was isolated as white crys-
tals (145 mg, 65%); mp 112–114 °C; Rf = 0.2 (heptane–
EtOAc, 4:1).
IR (ATR): 3039 (w), 2929 (w), 2835 (w), 1741 (m), 1593 (w), 1510
(m), 1414 (w), 1302 (w), 1245 (m), 1198 (s), 1181 (s), 1161 (s),
1097 (s), 1032 (m), 982 (m), 832 (m), 749 (s), 686 (m), 594 cm–1
(m).
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H, CH3), 3.77 (s, 3 H,
OCH3), 6.69–6.72 (m, 2 H, ArH), 6.92–7.05 (m, 3 H, ArH), 7.14–
7.40 (m, 10 H, ArH), 7.63 (dd, J = 8.1, 0.8 Hz, 1 H, ArH), 7.87 (s,
1 H, ArH), 7.90 (d, J = 8.3 Hz, 1 H, ArH).
13C NMR (75.46 MHz, CDCl3): d = 21.5 (CH3), 55.5 (OCH3),
114.1 (2 CH), 121.6 (2 CH), 125.8 (CH), 126.3 (CH), 126.4 (CH),
126.6 (CH), 127.7 (C), 127.8 (CH), 128.4 (CH), 129.0 (2 CH),
129.4 (2 CH), 130.0 (2 CH), 131.4 (2 CH), 132.4 (C), 133.4 (C),
133.6 (C), 136.0 (C), 137.3 (C), 140.0 (C), 141.0 (C), 150.9 (C),
159.5 (C), 167.2 (C=O).
MS (EI, 70 eV): m/z (%) = 444 (M+, 14), 352 (39), 351 (100), 308
(8), 263 (6), 215 (4), 144 (4), 111 (4), 97 (6), 69 (9), 57 (10), 44 (10),
43 (18).
Phenyl 4-(4-Methoxyphenyl)-1-(4-vinylphenyl)-2-naphthoate
(6d)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3v (81 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3w (99 mg, 0.65 mmol), product 6d was isolated as white crys-
tals (153 mg, 67%); mp 103–105 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
IR (ATR): 3065 (w), 2930 (w), 2834 (w), 1732 (m), 1606 (m), 1591
(w), 1509 (m), 1416 (w), 1303 (w), 1241 (s), 1186 (s), 1160 (s),
1095 (s), 1030 (m), 982 (m), 831 (s), 764 (s), 686 (m), 595 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.77 (s, 3 H, OCH3), 5.20 (d,
J = 11.0 Hz, 1 H, vinyl), 5.72 (d, J = 17.5 Hz, 1 H, vinyl), 6.66–
6.75 (m, 3 H, 2 ArH + 1 vinyl H), 6.93–7.04 (m, 3 H, ArH), 7.13–
7.45 (m, 10 H, ArH), 7.61 (d, J = 7.9 Hz, 1 H, ArH), 7.90 (s, 1 H,
ArH), 7.91 (dd, J = 7.7 Hz, 1 H, ArH).
HRMS (EI): m/z calcd for C31H24O3 [M+]: 444.17200; found:
444.17190.
13C NMR (75.46 MHz, CDCl3): d = 55.5 (OCH3), 114.1 (2 CH),
114.3 (CH2), 121.6 (2 CH), 125.9 (CH), 126.2 (2 CH), 126.4 (CH),
126.5 (CH), 126.7 (CH), 127.5 (C), 127.9 (CH), 128.3 (CH), 129.4
(2 CH), 130.4 (2 CH), 131.3 (2 CH), 132.3 (C), 133.2 (C), 133.7
(C), 136.7 (CH), 137.1 (C), 138.7 (C), 140.2 (C), 140.7 (C), 150.9
(C), 159.5 (C), 167.1 (C=O).
MS (GC, 70 eV): m/z (%) = 456 (M+, 7), 364 (28), 363 (100), 321
(7), 289 (8), 263 (7), 207 (27), 181 (3), 94 (5), 32 (20).
HRMS (EI): m/z calcd for C32H24O3 [M+]: 456.17200; found:
456.17161.
Phenyl 1-(3-Chlorophenyl)-4-(4-methoxyphenyl)-2-naphthoate
(6g)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3f (86 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3w (99 mg, 0.65 mmol), product 6g was isolated as a white
semisolid (142 mg, 61%); Rf = 0.3 (heptane–EtOAc, 4:1).
IR (ATR): 3040 (w), 2929 (w), 2835 (w), 1731 (m), 1591 (w), 1504
(m), 1417 (w), 1377 (m), 1242 (s), 1210 (m), 1186 (s), 1160 (s),
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

2112
M. F. Ibad et al.
PAPER
1102 (s), 1031 (m), 992 (m), 833 (m), 764 (s), 686 (m), 582 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 3.77 (s, 3 H, OCH3), 6.75–6.78
(m, 2 H, ArH), 6.95 (td, J = 8.7, 2.1 Hz, 1 H, ArH), 7.02–7.43 (m,
11 H, ArH), 7.53 (dd, J = 8.4, 0.9 Hz, 1 H, ArH), 7.92 (d, J = 8.1
Hz, 1 H, ArH), 7.93 (br s, 2 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 14.2 (CH3), 61.8 (CH2O), 106.2,
111.1 (CH), 114.8 (C), 121.8, 123.7 (CH), 128.2, 129.0 (C), 132.1
(CH), 150.0, 156.1 (C), 169.8 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 232 ([M]+, 46), 187 (18), 186 (100),
158 (60), 130 (19).
HRMS (EI, 70 eV): m/z calcd for C13H12O4 [M]+: 232.07301; found:
13C NMR (75.46 MHz, CDCl3): d = 55.6 (OCH3), 114.1 (2 CH),
121.5 (2 CH), 126.0 (CH), 126.5 (CH), 126.6 (CH), 127.0 (CH),
127.2 (C), 127.9 (CH), 128.0 (CH), 128.1 (CH), 128.4 (CH), 129.5
(2 CH), 129.6 (CH), 130.1 (CH), 131.3 (2 CH), 132.2 (C), 133.0
(C), 133.7 (C), 134.3 (C), 139.5 (C), 140.7 (C), 141.1 (C), 150.8
(C), 159.6 (C), 166.6 (C=O).
MS (GC, 70 eV): m/z (%) = 464 (M+, 35Cl, 7), 372 (26), 371 (100),
336 (32), 308 (15), 276 (4), 263 (18), 237 (3), 132 (9), 65 (4).
HRMS (EI): m/z calcd for C30H21ClO3 [35Cl, M+]: 464.11737;
found: 464.11658.
232.07313.
Ethyl 3,5-Bis(trifluoromethylsulfonyloxy)-2-naphthoate (9)
To a CH2Cl2 solution (65 mL) of 8 (1.50 g, 6.4 mmol) was added
pyridine (2.0 mL, 25.8 mmol) and the solution was stirred at 20 °C
for 10 min under argon atmosphere. Then Tf2O (2.6 mL, 15.3
mmol) was added at –78 °C and the reaction mixture was allowed
to warm to r.t. and was stirred for 14 h. The reaction mixture was
filtered and the filtrate was concentrated in vacuo. The product 9
was isolated by flash column chromatography (silica gel, heptanes–
EtOAc) as a white solid (2.80 g, 87%); mp 75–77 °C; Rf = 0.2 (hep-
tane–EtOAc, 4:1).
Phenyl 1-(4-Chlorophenyl)-4-(3,4-dimethoxyphenyl)-2-naph-
thoate (6h)
Starting from 2 (272 mg, 0.5 mmol), K3PO4 (318 mg, 1.5 mmol),
Pd(PPh3)4 (3 mol%), 3g (86 mg, 0.55 mmol), 1,4-dioxane (4 mL),
and 3p (118 mg, 0.65 mmol), product 6h was isolated as white crys-
tals (153 mg, 62%); mp 181–183 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
IR (KBr): 1708 (s), 1640, 1606, 1501, 1476, 1458 (w), 1426, 1395
(s), 1375, 1322, 1302 (w), 1274, 1242 (m), 1200 (s), 1161 (m), 1128
(s), 1094 (m), 1078, 1058 (s), 1018, 974 (m), 946 (s), 905 (s), 886
(m), 869, 814, 805 (s), 781 (m), 766 (s), 746, 720, 709 (m), 674,
651, 614, 595, 576 (s), 574, 529 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.1 Hz, 3 H, CH3),
4.35 (q, J = 7.1, 2 H, CH2), 7.43–7.51 (m, 2 H, ArH), 7.77 (s, 1 H,
ArH), 7.80 (d, J = 7.5 Hz, 1 H, ArH), 8.50 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 12.8 (CH3), 61.5 (CH2), 113.8
(CH), 117.7 (q, JC,F = 320.2 Hz, CF3), 117.9 (q, JC,F = 320.8 Hz,
CF3), 120.6 (CH), 123.3 (C), 126.7 (CH), 126.8 (C), 128.4 (CH),
131.6 (C), 133.7 (CH), 143.6, 145.2 (C), 162.1 (C=O).
IR (ATR): 3055 (w), 2959 (w), 2832 (w), 1728 (s), 1597 (w), 1516
(m), 1408 (w), 1317 (w), 1243 (m), 1211 (m), 1192 (s), 1142 (s),
1099 (s), 925 (w), 813 (m), 741 (s), 687 (m), 593 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.84 (s, 3 H, OCH3), 3.89 (s, 3 H,
OCH3), 6.76–6.79 (m, 2 H, ArH), 6.95 (d, J = 8.1 Hz, 1 H, ArH),
7.00–7.11 (m, 3 H, ArH), 7.19–7.30 (m, 4 H, ArH), 7.35–7.42 (m,
3 H, ArH), 7.46 (dt, J = 6.9, 1.5 Hz, 1 H, ArH), 7.55 (dd, J = 8.2, 0.9
Hz, 1 H, ArH), 7.95 (d, J = 7.7 Hz, 1 H, ArH), 7.96 (s, 1 H, ArH).
19F NMR (282.4, MHz): d = –73.6, –73.3.
GC-MS (EI, 70 eV): m/z (%) = 496 ([M]+, 32), 451 (11), 364 (09),
13C NMR (75.46 MHz, CDCl3): d = 56.2 (2 OCH3), 111.4 (CH),
113.5 (CH), 121.5 (2 CH), 122.6 (CH), 126.0 (CH), 126.4 (CH),
126.6 (CH), 127.0 (CH), 127.2 (C), 128.1 (2 CH), 128.6 (2 CH),
129.6 (2 CH), 131.4 (2 CH), 132.5 (C), 133.2 (C), 133.8 (C), 133.9
(C), 137.6 (C), 140.0 (C), 140.7 (C), 149.0 (C), 149.1 (C), 150.8
(C), 166.7 (C=O).
MS (GC, 70 eV): m/z (%) = 494 (M+, 14), 403 (35), 402 (29), 401
(100), 367 (15), 366 (56), 276 (4), 263 (6), 250 (7), 125 (5), 65 (2).
HRMS (EI): m/z calcd for C31H23O4Cl [M+]: 494.12794; found:
494.12780.
363 (61), 291 (11).
HRMS (EI, 70 eV): m/z calcd for C15H10F6O8S2 [M]+: 495.97158;
found: 495.97131.
Products 10, 11, and 12 by Suzuki–Miyaura Reactions; General
Procedure
A suspension of 9 (100 mg, 0.2 mmol), K3PO4 (1.5 mmol per cross-
coupling step), Pd(PPh3)4 (3 mol% per cross-coupling step), and
arylboronic acid (1.0–1.2 equiv per cross-coupling step) in THF (4
mL) was stirred at 20–60 °C for 8–12 h. To the reaction mixture was
added H2O (25 mL) and CH2Cl2 (25 mL) at 20 °C. The organic and
the aqueous layers were separated and the latter was extracted with
CH2Cl2 (2 × 25 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The
residue was purified by column chromatography.
Ethyl 3,5-Dihydroxy-2-naphthoate (8)
To a solution of 7 (1.00 g, 4.9 mmol) in absolute EtOH (20 mL) was
carefully added concd H2SO4 (1 mL). The reaction mixture was
heated under reflux for 6 h and poured into H2O (250 mL). Sat. aq
NaHCO3 (100 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 50 mL). The aqueous and the organic layer were sepa-
rated and the latter was dried (Na2SO4), and filtered. The filtrate was
concentrated in vacuo. The residue was purified by flash column
chromatography (silica gel, heptanes–EtOAc) to give 2 as a yellow
solid (0.88 g, 77%); mp 160–162 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
Ethyl 3,5-Bis(4-methylphenyl)-2-naphthoate (10a)
Starting from 9 (100 mg, 0.2 mmol), 4-methylphenylboronic acid
(64 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10a was isolated as a yellow
oil (58 mg, 76%); Rf = 0.3 (heptane–EtOAc, 4:1).
IR (KBr): 1713 (s), 1619, 1589, 1566 (w), 1512 (m), 1478 (w), 1443
(m), 1389 (w), 1366, 1297 (m), 1269, 1235 (s), 1211 (w), 1192 (s),
1211 (w), 1192 (s), 1173, 1121, 1111 (m), 1086 (s), 1052 (w), 1022
(s), 984 (m), 944, 919, 902, 863, 849 (w), 816, 797 (s), 780, 752 (m),
722, 702, 684, 658, 644, 608, 593 (w), 563, 532 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.97 (t, J = 7.1 Hz, 3 H, CH3),
2.25 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 4.06 (q, J = 7.1 Hz, 2 H,
CH2O), 7.05 (d, J = 7.5 Hz, 2 H, ArH), 7.10–7.13 (m, 3 H, ArH),
7.16 (s, 1 H, ArH), 7.26 (d, J = 8.0 Hz, 2 H, ArH), 7.37 (dd, J = 1.5,
IR (KBr): 1671 (s), 1633, 1579 (w), 1528 (m), 1478, 1469, 1454,
1396 (w), 1370 (m), 1324 (w), 1289 (m), 1274, 1222, 1161, 1105
(s), 1066, 1058 (w), 1003 (s), 964, 926, 911 (w), 871, 791 (s), 761
(m), 741 (s), 719, 671, 657 (m), 594 (w), 580 (s), 547 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.41 (t, J = 7.1 Hz, 3 H, CH3),
4.42 (q, J = 7.1 Hz, 2 H, CH2), 5.20 (s, 1 H, OH), 6.78 (dd, J = 0.8,
7.4 Hz, 1 H, ArH), 7.09 (t, J = 8.3 Hz, 1 H, ArH), 7.34 (d, J = 8.4
Hz, 1 H, ArH), 7.55 (s, 1 H, ArH), 8.39 (s, 1 H, ArH), 10.46 (s, 1 H,
OH).
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

PAPER
Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2113
7.1 Hz, 1 H, ArH), 7.40 (t, J = 8.0 Hz, 1 H, ArH), 7.79–7.81 (m, 2
Ethyl 3,5-Bis(4-chlorophenyl)-2-naphthoate (10d)
H, ArH), 8.30 (s, 1 H, ArH).
Starting from 9 (100 mg, 0.2 mmol), 4-chlorophenylboronic acid
(75 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol) and THF (4 mL), product 10d was isolated as a white sol-
id (64 mg, 76%); mp 104–106 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
13C NMR (62.9 MHz, CDCl3): d = 13.8 (CH3), 21.2, 21.3 (2 CH3),
61.0 (CH2O), 125.0 (CH), 126.7, 126.9 (C), 127.4, 127.6, 127.9,
128.0, 128.4, 128.7, 130.0 (CH), 131.0 (C), 131.6 (CH), 135.5,
136.0, 136.1, 137.6, 137.8, 139.2 (C), 167.6 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 380 ([M]+, 100), 335 (13), 317 (11),
292 (9).
IR (KBr): 1714 (s), 1682, 1622, 1596, 1493 (w), 1480, 1472, 1454,
1443 (m), 1397, 1363, 1352, 1310 (w), 1278, 1246, 1191 (s), 1174
(w), 1126 (m), 1089 (s), 1054, 1023 (w), 1013, 985 (s), 969, 958,
929, 918 (w), 902, 896 (m), 866 (w), 850, 836, 824, 819 (m), 797,
786 (s), 754, 743, 735 (m), 721, 693, 663, 635, 624, 597, 583 (w),
569, 531 cm–1 (m).
HRMS (EI, 70 eV): m/z calcd for C27H24O2 [M]+: 380.17708; found:
380.17674.
1H NMR (300 MHz, CDCl3): d = 1.0 (t, J = 7.1 Hz, 3 H, CH3), 4.07
(q, J = 7.1 Hz, 2 H, CH2O), 7.12–7.13 (m, 1 H, ArH), 7.22–7.27 (m,
3 H, ArH), 7.30–7.32 (m, 4 H, ArH), 7.38 (dd, J = 1.1, 7.0 Hz, 1 H,
ArH), 7.41 (t, J = 8.0 Hz, 1 H, ArH), 7.66 (s, 1 H, ArH), 7.85 (d,
J = 8.1 Hz, 1 H, ArH), 8.37 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.8 (CH3), 61.2 (CH2O), 126.4,
127.5, 128.1, 128.6, 128.7 (CH), 129.2 (C), 129.3, 129.9, 131.1,
131.6 (CH), 132.1, 132.3, 133.2, 133.7, 138.0, 138.3, 139.0, 140.1
(C), 168.1 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 420 ([M]+, 35Cl, 100), 340 (15), 276
(34), 138 (15).
HRMS (EI, 70 eV): m/z calcd for C25H18Cl2O2 ([M]+, 35Cl):
420.06784; found: 420.06781.
Ethyl 3,5-Bis(4-tert-butylphenyl)-2-naphthoate (10b)
Starting from 9 (100 mg, 0.2 mmol), 4-tert-butylphenylboronic acid
(86 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10b was isolated as a white
solid (74 mg, 80%); mp 239–238 °C; Rf = 0.4 (heptane–
EtOAc, 4:1).
IR (KBr): 1723 (s), 1687, 1671, 1653, 1638, 1619, 1575, 1560,
1543, 1525 (w), 1508, 1476, 1461, 1443, 1397, 1361 (m), 1297 (s),
1262 (s), 1242, 1189, 1172 (m), 1127 (w), 1104 (m), 1081 (s), 1053,
1024, 984 (m), 947, 928 (w), 904 (m), 876, 853 (w), 832, 824 (m),
800 (s), 787, 750 (m), 699, 666, 641, 634 (w), 597, 571 (m), 531
cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.87 (t, J = 7.1 Hz, CH3), 1.25 (s,
9 H, 3 CH3), 1.30 (s, 9 H, 3 CH3), 4.05 (q, J = 7.1 Hz, CH2O), 7.19
(d, J = 8.5 Hz, 2 H, ArH), 7.31 (d, J = 8.3 Hz, 2 H, ArH), 7.34–7.48
(m, 5 H, ArH), 7.82 (d, J = 7.7 Hz, 1 H, ArH), 7.90 (s, 1 H, ArH),
7.90 (s, 1 H, ArH), 8.32 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 13.6 (CH3), 31.2, 31.5 (3 CH3),
33.4, 33.5 (C), 61.0 (CH2O), 123.8, 124.3, 125.1, 126.6, 126.9,
127.3, 128.1, 128.5 (CH), 128.7, 129.9 (C), 130.9 (CH), 131.5,
136.1, 137.4, 137.8, 139.2, 148.8, 149.2 (C), 168.0 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 464 ([M]+, 100), 449 (83), 347 (7),
217 (17).
Ethyl 3,5-Bis(3-chlorophenyl)-2-naphthoate (10e)
Starting from 9 (100 mg, 0.2 mmol), 4-chlorophenylboronic acid
(75 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10e was isolated as a yellow
oil (68 mg, 81%); Rf = 0.3 (heptane–EtOAc, 4:1).
IR (KBr): 1713 (s), 1621 (w), 1592, 1563, 1470, 1442 (m), 1408,
1367, 1297 (w), 1269, 1234, 1192 (s), 1176, 1127 (m), 1088, 1078,
1019 (s), 997 (m), 940, 921 (w), 883 (m), 854, 833, 805 (w), 782,
754, 747, 696, 689 (s), 677, 604, 556 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.98 (t, J = 7.1 Hz, 3 H, CH3),
4.08 (q, J = 7.1 Hz, 2 H, CH2O), 7.16–7.21 (m, 3 H, ArH), 7.23–
7.31 (m, 4 H, ArH), 7.36–7.38 (m, 1 H, ArH), 7.40 (dd, J = 1.3, 7.2
Hz, 1 H, ArH), 7.47 (t, J = 8.1 Hz, 1 H, ArH), 7.67 (s, 1 H, ArH),
7.87 (d, J = 8.1 Hz, 1 H, ArH), 8.38 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.0 (CH3), 60.1 (CH2O), 125.4,
125.8, 126.0, 126.3, 126.7, 127.0, 127.7, 127.7, 128.1, 128.3, 128.6,
128.8 (CH), 130.6 (C), 131.1 (CH), 132.7, 133.4, 136.7, 137.8,
140.6, 142.4 (C), 166.9 (C=O).
HRMS (EI, 70 eV): m/z calcd for C33H36O2 [M]+: 464.27098; found:
464.27024.
Ethyl 3,5-Bis(3,5-dimethylphenyl)-2-naphthoate (10c)
Starting from 9 (100 mg, 0.2 mmol), 3,5-dimethylphenylboronic
acid (72 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127
mg, 0.6 mmol), and THF (4 mL), product 10c was isolated as a
white solid (67 mg, 82%); mp 89–90 °C; Rf = 0.4 (heptane–
EtOAc, 4:1).
IR (KBr): 1718 (s), 1620 (w), 1598 (m), 1462, 1443 (m), 1389 (s),
1369 (m), 1316, 1295 (w), 1265, 1248, 1195 (s), 1126 (w), 1106 (s),
1052, 1052, 1023 (m), 970, 950, 917, 893, 870 (s), 845, 812 (s), 798,
775, 763, 754 (m), 719 (s), 705 (m), 686 (s), 656 (w), 619 (m), 588,
568, 557, 536, 528 cm–1 (w).
GC-MS (EI, 70 eV): m/z (%) = 420 ([M]+, 35Cl, 100), 375 (29), 312
(24), 276 (48).
HRMS (EI, 70 eV): m/z calcd for C25H18Cl2O2 ([M]+, 35Cl):
420.06784; found: 420.06670.
1H NMR (300 MHz, CDCl3): d = 0.96 (t, J = 6.0 Hz, 3 H, CH3),
2.22 (s, 6 H, 2 CH3), 2.27 (s, 6 H, 2 CH3), 4.07 (q, J = 6.0 Hz, 2 H,
CH2O), 6.85 (br, 3 H, ArH), 6.93 (s, 1 H, ArH), 7.01 (br, 2 H, ArH),
7.35 (dd, J = 1.5, 7.1 Hz, 1 H, ArH), 7.43 (t, J = 6.0 Hz, 1 H, ArH),
7.79–7.82 (m, 2 H, ArH), 8.20 (s, 1 H, ArH).
Ethyl 3,5-Bis(4-methoxyphenyl)-2-naphthoate (10f)
Starting from 9 (100 mg, 0.2 mmol), 4-methoxyphenylboronic acid
(73 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10f was isolated as a yellow
oil (63 mg, 76%); Rf = 0.2 (heptane–EtOAc, 4:1).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 21.3, 21.4 (CH3),
61.0 (CH2O), 126.0, 126.5, 127.8, 127.9, 128.0, 128.5, 128.8, 129.0
(CH), 129.7 (C), 130.8 (CH), 131.9, 132.6, 137.3, 137.8, 138.7,
140.0, 140.6, 141.6 (C), 169.0 (C=O).
IR (KBr): 1713, 1607 (s), 1573 (w), 1510 (s), 1480, 1453, 1438 (m),
1411, 1389, 1366 (w), 1270, 1236, 1192, 1172 (s), 1122, 1108,
1087, 1030 (m), 982, 919, 901, 850 (w), 830, 800, 786 (m), 753,
730, 703, 684, 658, 641, 594 (w), 573, 545 cm–1 (m).
GC-MS (EI, 70 eV): m/z (%) = 408 ([M]+, 100), 363 (17).
HRMS (EI, 70 eV): m/z calcd for C29H28O2 [M]+: 408.20838; found:
1H NMR (300 MHz, CDCl3): d = 1.01 (t, J = 7.1 Hz, 3 H, CH3),
3.73 (s, 3 H, CH3O), 3.77 (s, 3 H, CH3O), 4.09 (q, J = 7.1 Hz, 2 H,
CH2O), 6.79–6.81 (m, 2 H, ArH), 6.84–6.89 (m, 2 H, ArH), 7.14–
7.19 (m, 2 H, ArH), 7.29–7.34 (m, 2 H, ArH), 7.39 (dd, J = 1.4, 7.0
Hz, 1 H, ArH), 7.45 (t, J = 7.7 Hz, 1 H, ArH), 7.80–7.83 (m, 2 H,
ArH), 8.30 (s, 1 H, ArH).
408.20727.
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

2114
M. F. Ibad et al.
PAPER
13C NMR (62.9 MHz, CDCl3): d = 13.9 (CH3), 55.3, 55.2 (2 CH3O),
61.0 (CH2O), 113.4, 113.9, 126.1, 127.7, 127.8, 129.0 (CH), 129.5
(C), 129.6, 131.0, 131.1 (CH), 131.9, 132.4, 132.7, 134.2, 138.3,
139.9, 158.8, 159.0 (C), 168.8 (C=O).
Ethyl 3,5-Bis(4-fluorophenyl)-2-naphthoate (10i)
Starting from 9 (100 mg, 0.2 mmol), 4-fluorophenylboronic acid
(67 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10i was isolated as a yellow
solid (60 mg, 77%); mp 89–90 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
GC-MS (EI, 70 eV): m/z (%) = 412 ([M]+, 100), 384 (17), 367 (16),
349 (10).
IR (KBr): 1716 (s), 1670, 1661, 1653, 1638, 1621 (w), 1603 (m),
1560, 1543 (w), 1508 (s), 1480, 1453, 1443 (m), 1404, 1390, 1367
(w), 1269, 1219, 1193 (s), 1174 (m), 1157 (s), 1122 (w), 1090 (s),
1053 (w), 1016 (m), 985, 921, 901, 854 (w), 836, 798 (s), 781, 753
(m), 723, 701, 685, 657, 641, 605, 591 (w), 561, 537 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.9 (t, J = 7.1 Hz, 3 H, CH3), 4.06
(q, J = 7.1 Hz, 2 H, CH2O), 6.92–6.99 (m, 2 H, ArH), 7.02–7.09 (m,
2 H, ArH), 7.13–7.21 (m, 2 H, ArH), 7.30–7.35 (m, 2 H, ArH), 7.38
(dd J = 1.3, 7.1 Hz, 1 H, ArH), 7.46 (t, J = 8.0 Hz, 1 H, ArH), 7.67
(s, 1 H, ArH), 7.84 (d, J = 8.0 Hz, 1 H, ArH), 8.35 (s, 1 H, ArH).
HRMS (EI, 70 eV): m/z calcd for C27H24O4 [M]+: 412.16691; found:
412.16641.
Ethyl 3,5-Bis(2,6-dimethoxyphenyl)-2-naphthoate (10g)
Starting from 9 (100 mg, 0.2 mmol), 2,6-dimethoxyphenylboronic
acid (87 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127
mg, 0.6 mmol), and THF (4 mL), product 10g was isolated as a
white solid (66 mg, 70%); mp 212–214 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
IR (KBr): 1715 (s), 1679, 1621 (w), 1587, 1467 (s), 1428 (m), 1391,
1367, 1310, 1296, 1284 (w), 1265 (m), 1243 (s), 1188, 1168 (m),
1145 (w), 1101, 1074 (s), 1035, 1028, 978 (m), 952, 938, 916, 909,
900, 884, 873, 845 (w), 808 (m), 789 (w), 778 (m), 760, 746 (w),
725 (s), 696, 683, 671, 636, 601, 588, 566, 540 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.95 (t, J = 7.1 Hz, 3 H, CH3),
3.53 (s, 6 H, 2 CH3O), 3.54 (s, 6 H, 2 CH3O), 4.03 (q, J = 7.1 Hz, 2
H, CH2O), 6.50 (d, J = 8.3 Hz, 2 H, ArH), 7.11–7.26 (m, 2 H, ArH),
7.31 (s, 1 H, ArH), 7.33 (dd, J = 1.7, 7.6 Hz, 1 H, ArH), 7.47 (t,
J = 7.1 Hz, 1 H, ArH), 7.85 (d, J = 8.2 Hz, 1 H, ArH), 8.44 (s, 1 H,
ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.8 (CH3), 55.8, 55.9 (4 CH3O),
60.30 (CH2O), 104.1, 104.2 (CH), 117.3, 120.2 (C), 125.8, 128.2,
128.3, 129.1 (CH), 129.7 (C), 129.8, 129.9 (CH), 130.0 (C), 130.9
(CH), 131.9, 132.6, 133.9, 157.5, 158.4 (C), 167.9 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 472 ([M]+, 100), 413 (25), 321 (17).
HRMS (EI, 70 eV): m/z calcd for C29H28O6 [M]+: 472.18804; found:
13C NMR (62.9 MHz, CDCl3): d = 13.8 (CH3), 61.1 (CH2O), 115.2
(d, J = 21.4 Hz), 115.4 (d, J = 21.4 Hz), 126.3, 127.6, 128.4, 129.4,
130.1 (d, J = 8.0 Hz), 131.4, 131.4 (d, J = 8.0 Hz) (CH), 132.0,
132.5, 135.9 (d, J = 3.3 Hz), 137.7 (d, J = 3.3 Hz), 138.0, 139.2 (C),
162.1 (d, JC,F = 246.2 Hz) (CF), 162.4 (d, JC,F = 246.8 Hz) (CF),
168.3 (C=O).
19F NMR (282 MHz, CDCl3): d = –115.07, –114.85.
GC-MS (EI, 70 eV): m/z (%) = 388 ([M]+, 100), 343 (29), 325 (16),
294 (16).
HRMS (EI, 70 eV): m/z calcd for C25H18F2O2 [M]+: 388.12694;
found: 388.12670.
Ethyl 3-(4-Methylphenyl)-5-(trifluoromethylsulfonyloxy)-2-
naphthoate (11a)
Starting from 9 (100 mg, 0.2 mmol), 4-methylphenylboronic acid
(27 mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63 mg, 0.3
mmol), and THF (4 mL), product 11a was isolated as a yellow oil
(61 mg, 70%); Rf = 0.2 (heptane–EtOAc, 4:1).
472.18810.
IR (KBr): 1713 (s), 1638, 1602, 1563, 1517, 1487, 1475, 1446 (w),
1416 (s), 1399, 1382, 1367, 1320, 1306 (w), 1277, 1254, 1241 (m),
1206, 1199 (s), 1156 (w), 1138, 1100 (s), 1063 (w), 1027 (m), 1007
(s), 967 (w), 955 (m), 885 (s), 840 (w), 817, 796 (s), 779, 764, 744
(m), 728, 713, 696, 660 (w), 636 (m), 597 (s), 572, 558, 540 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 1.00 (t, J = 7.1 Hz, 3 H, CH3), 2.3
(s, 3 H, ArH), 4.11 (q, J = 7.1 Hz, 2 H, CH2O), 7.16–7.24 (m, 4 H,
ArH), 7.50–7.43 (m, 2 H, ArH), 7.88 (dd, J = 2.0, 7.0 Hz, 1 H,
ArH), 7.96 (s, 1 H, ArH), 8.30 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.7, 21.2 (CH3), 61.4 (CH2O),
118.7 (q, JC,F = 320.4 Hz, CF3), 119.8, 122.3, 125.8 (CH), 127.1
(C), 128.4, 129.0, 130.4 (CH), 131.6, 132.9, 137.4, 137.7, 140.8,
145.4 (C), 168.2 (C=O).
Ethyl 3,5-Bis(4-trifluoromethylphenyl)-2-naphthoate (10h)
Starting from 9 (100 mg, 0.2 mmol), 4-trifluoromethylboronic acid
(91 mg, 0.48 mmol), Pd(PPh3)4 (14 mg, 6 mol%), K3PO4 (127 mg,
0.6 mmol), and THF (4 mL), product 10h was isolated as a yellow
solid (78 mg, 80%); mp 123–125 °C; Rf = 0.2 (heptane–
EtOAc, 4:1).
IR (KBr): 1721 (s), 1615 (m), 1592, 1573, 1474, 1455, 1446, 1407,
1365, 1356 (w), 1319 (s), 1283 (m), 1247, 1192, 1177, 1156 (m),
1115, 1105, 1093, 1063, 1017 (s), 986 (m), 968, 931, 919, 905, 897,
867 (w), 851, 841, 832, 800, 789 (m), 774, 751, 719, 704, 689, 648,
639, 619, 591, 579, 561 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.96 (t, J = 7.1 Hz, 3 H, CH3),
4.06 (q, J = 7.1 Hz, 2 H, CH2O), 7.32 (d, J = 8 Hz, 2 H, ArH), 7.44
(dd, J = 1.2, 7.1 Hz, 1 H, ArH), 7.49–7.58 (m, 5 H, ArH), 7.64–7.67
(m, 3 H, ArH), 7.93 (d, J = 8.1 Hz, 1 H, ArH), 8.46 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.6 (CH3), 61.2 (CH2O), 118.2
(q, JC,F = 320.3 Hz, CF3), 122.0 (q, JC,F = 272.4 Hz, CF3), 124.9 (q,
J = 3.7 Hz, CH), 125.5 (q, J = 3.7 Hz, CH), 126.6, 127.4, 128.9
(CH), 129.0, 129.0 (C), 129.1 (CH), 129.5 (C), 129.6, 130.2, 131.9
(CH), 132.0, 132.3, 138.1, 138.8, 143.5, 145.3 (C), 167.7 (C=O).
19F NMR (282.4 MHz, CDCl3): d = –73.09.
GC-MS (EI, 70 eV): m/z (%) = 438 ([M]+, 35), 305 (100), 202 (10),
189 (10).
HRMS (EI, 70 eV): m/z calcd for C21H17F3O5S [M]+: 438.07433;
found: 438.07449.
Ethyl 3-(4-tert-Butylphenyl)-5-(trifluoromethylsulfonyloxy)-2-
naphthoate (11b)
Starting from 9 (100 mg, 0.2 mmol), 4-tert-butylphenylboronic acid
(36 mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63 mg, 0.3
mmol), and THF (4 mL), product 11b was isolated as a white solid
(73 mg, 75%); mp 124–126 °C; Rf = 0.3 (heptane–EtOAc, 4:1) .
19F NMR (282 MHz, CDCl3): d = –62.69, –62.37.
GC-MS (EI, 70 eV): m/z (%) = 488 ([M]+, 100), 489 ([M + H]+, 29),
443 (37), 423 (23), 346 (18), 276 (11).
HRMS (EI, 70 eV): m/z calcd for C27H18F6O2 [M]+: 488.12055;
found: 488.12080.
IR (KBr): 1708 (s), 1636, 1600, 1562, 1518, 1477, 1462 (w), 1446
(m), 1395 (s), 1366 (m), 1318, 1309 (w), 1277, 1259, 1241 (m),
1213, 1202, 1192, 1153, 1130, 1120, 1099 (s), 1060, 1022 (m),
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

PAPER
Site-Selective Couplings of 1,4- and 3,5-Bistrifloxy-2-naphthoates
2115
1007, 958 (s), 922 (w), 898 (m), 885 (s), 847, 842 (m), 815, 799 (s),
784, 766, 744, 736, 714, 693 (m), 655 (s), 633 (m), 603, 583, 572
(s), 552 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 7.1 Hz, 3 H, CH3),
1.30 (s, 9 H, 3 CH3), 4.06 (q, J = 7.1 Hz, 2 H, CH2O), 7.27 (d,
J = 8.7 Hz, 2 H, ArH), 7.39 (d, J = 8.5 Hz, 2 H, ArH), 7.46–7.48 (m,
2 H, ArH), 7.88 (dd, J = 0.5, 7.0 Hz, 1 H, ArH), 7.99 (s, 1 H, ArH),
8.30 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 13.5 (CH3), 31.3 (3 CH3), 34.6
(C), 61.3 (CH2O), 118.7 (q, JC,F = 320.5 Hz, CF3), 119.7, 122.3,
125.2, 125.8 (CH), 127.1 (C), 128.1, 129.0, 130.4 (CH), 131.8,
133.0, 137.6, 140.7, 145.4, 150.6 (C), 168.0 (C=O).
19F NMR (282.4 MHz, CDCl3): d = –73.03.
GC-MS (EI, 70 eV): m/z (%) = 458 ([M]+, 31), 325 (100), 245 (9),
217 (13).
HRMS (EI, 70 eV): m/z calcd for C20H14ClF3O5S [M]+: 458.01971;
found: 458.01984.
Ethyl 3-(4-Trifluoromethylphenyl)-5-(trifluoromethylsulfonyl-
oxy)-2-naphthoate (11e)
Starting from 9 (100 mg, 0.2 mmol), 4-trifluoromethylphenylboron-
ic acid (38 mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63
mg, 0.3 mmol), and THF (4 mL), product 11e was isolated as a yel-
low oil (64 mg, 65%); Rf = 0.4 (heptane–EtOAc, 4:1).
19F NMR (282.4 MHz, CDCl3): d = –73.07.
GC-MS (EI, 70 eV): m/z (%) = 480 ([M]+, 54), 465 (68), 347 (100),
IR (KBr): 1720 (s), 1681, 1619, 1596, 1500, 1481, 1455 (w), 1425
(s), 1408 (m), 1367, 1354 (s), 1425 (s), 1408 (m), 1367, 1354 (w),
1327, 1284, 1277 (s), 1249, 1240 (m), 1199 (s), 1157 (m), 1133,
1126, 1104, 1069, 1045, 1015 (s), 952 (w), 940, 907 (m), 849, 883
(s), 842 (m), 826, 801 (s), 773, 765, 757, 724 (m), 706 (w), 662, 647,
635 (m), 608, 598, 585 (s), 544 cm–1 (w).
332 (73).
HRMS (EI, 70 eV): m/z calcd for C24H23F3O5S [M]+: 480.12128;
found: 480.12190.
1H NMR (300 MHz, CDCl3): d = 1.39 (t, J = 7.1 Hz, 3 H, CH3),
4.44 (q, J = 7.1 Hz, 2 H, CH2O), 7.51 (d, J = 7.9 Hz, 2 H, ArH), 7.56
(dd, J = 1.2, 7.1 Hz, 1 H, ArH), 7.61–7.66 (m, 2 H, ArH), 7.73 (d,
J = 8.0 Hz, 2 H, ArH), 7.97 (d, J = 8.1 Hz, 1 H, ArH), 8.66 (s, 1 H,
ArH).
13C NMR (75.4 MHz, CDCl3): d = 14.1 (CH3), 62.32 (CH2O), 117.0
(q, JC,F = 321.0 Hz, CF3), 119.1 (CH), 122.7 (C), 123.1 (q,
JC,F = 271.3 Hz, CF3), 125.6 (q, J = 3.8 Hz, CH), 126.0 (C), 127.6,
129.3, 130.1, 130.4 (CH), 131.8, 132.9 (C), 135.1 (CH), 138.9,
142.5, 145.3 (C), 163.7 (C=O).
Ethyl 3-(3,5-Dimethylphenyl)-5-(trifluoromethylsulfonyloxy)-
2-naphthoate (11c)
Starting from 9 (100 mg, 0.2 mmol), 3,5-dimethyllboronic acid (30
mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63 mg, 0.3
mmol), and THF (4 mL), product 11c was isolated as a yellow oil
(73 mg, 80%); Rf = 0.2 (heptane–EtOAc, 4:1).
IR (KBr): 1717 (s), 1635 (w), 1597 (m), 1562, 1455, 1447 (w), 1420
(s), 1367, 1322, 1300 (w), 1270 (m), 1246, 1198 (s), 1198 (s), 1156
(w), 1137 (s), 1105, 1074, 1049 (m), 1020, 991, 966 (w), 886 (m),
859, 848 (w), 813 (m), 765, 742, 712, 687, 648, 625 (w), 599 (m),
534 cm–1 (w).
19F NMR (282.4 MHz, CDCl3): d = –73.24, –62.55.
1H NMR (300 MHz, CDCl3): d = 0.99 (t, J = 7.1 Hz, 3 H, CH3),
2.30 (s, 6 H, 2 CH3), 4.01 (q, J = 7.1 Hz, 2 H, CH2O), 6.94–6.97 (m,
3 H, ArH), 7.43–7.51 (m, 2 H, ArH), 7.88 (dd, J = 2.0, 7.0 Hz, 1 H,
ArH), 7.96 (s, 1 H, ArH), 8.28 (s, 1 H, ArH).
GC-MS (EI, 70 eV): m/z (%) = 492 ([M]+, 54), 313 (100), 257 (36).
HRMS (EI, 70 eV): m/z calcd for C21H14F6O5S [M]+: 492.04606;
found: 492.04653.
13C NMR (62.9 MHz, CDCl3): d = 13.6 (CH3), 21.2 (2 CH3), 61.3
(CH2O), 118.6 (q, JF,C = 320.5 Hz, CF3), 119.7, 122.2 (CH), 125.8
(C), 126.3 (CH), 127.0 (C), 128.8, 129.2, 130.2, 131.8 (CH), 132.9,
137.7, 140.4, 140.9, 145.5 (C), 168.3 (C=O).
19F NMR (282.4 MHz, CDCl3): d = –73.06.
GC-MS (EI, 70 eV): m/z (%) = 452 ([M]+, 34), 319 (100), 202 (10).
Ethyl 3-(4-Methoxyphenyl)-5-(trifluoromethylsulfonyloxy)-2-
naphthoate (11f)
Starting from 9 (100 mg, 0.2 mmol), 4-methoxyboronic acid (30
mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63 mg, 0.3
mmol), and THF (4 mL), product 11f was isolated as a yellow oil
(57 mg, 63%); Rf = 0.3 (heptane–EtOAc, 4:1).
IR (KBr): 1716 (s), 1621 (m), 1592, 1574, 1553, 1514 (w), 1496
(m), 1467, 1453, 1440 (w), 1410, 1397 (s), 1365, 1354, 1315, 1305
(w), 1276, 1245, 1206, 1177, 1137, 1109 (s), 1059 (w), 1044 (m),
1030 (s), 1014, 1008 (m), 966, 960, 945, 939 (w), 929, 906 (m), 881,
823, 802 (s), 788, 775, 767 (m), 752 (s), 719 (m), 684 (w), 669 (m),
639 (w), 607, 587, 572 (m), 546, 538 cm–1 (w).
HRMS (EI, 70 eV): m/z calcd for C22H19F3O5S [M]+: 452.08998;
found: 452. 08986.
Ethyl 3-(3-Chlorophenyl)-5-(trifluoromethylsulfonyloxy)-2-
naphthoate (11d)
Starting from 9 (100 mg, 0.2 mmol), 3-chlorophenylboronic acid
(31 mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%), K3PO4 (63 mg, 0.3
mmol), and THF (4 mL), product 11d was isolated as a white solid
(75 mg, 82%); mp 102–103 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): d = 1.38 (t, J = 7.1 Hz, 3 H, CH3),
3.83 (s, 3 H, CH3O), 4.42 (q, J = 7.1 Hz, 2 H, CH2O), 6.97–7.00 (m,
2 H, ArH), 7.18, 7.51–7.54 (m, 2 H, ArH), 7.53 (dd, J = 1.5, 7.1 Hz,
1 H, ArH), 7.58 (t, J = 7.8 Hz, 1 H, ArH), 7.77 (s, 1 H, ArH), 7.89
(d, J = 7.8 Hz, 1 H, ArH), 8.61 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 14.1 (CH3), 55.3 (CH3O), 62.1
(CH2O), 114.1 (CH), 118.6 (q, JF,C = 321.1 Hz, CF3), 119.7 (CH),
122.2 (C), 127.6, 128.2, 130.2, 130.8 (CH), 131.1, 131.9, 133.5 (C),
134.9 (CH), 140.2, 145.0, 159.5 (C), 163.9 (C=O).
IR (KBr): 1712 (s), 1639 (w), 1593, 1567 (m), 1475 (w), 1443 (m),
1414 (s), 1396, 1368 (m), 1302, 1280 (w), 1258, 1240 (m), 1211,
1199 (s), 1157 (w), 1135 (m), 1106, 1092, 1064 (m), 1016 (s), 959,
923, 914, 897 (w), 880 (s), 842 (w), 818, 793, 786 (s), 758, 741, 715,
706, 684, 670 (w), 642 (m), 618 (w), 600 (s), 575, 555 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.01 (t, J = 7.1 Hz, 3 H, CH3),
4.11 (q, J = 7.1 Hz, 2 H, CH2O), 7.18–7.23 (m, 1 H, ArH), 7.30–
7.32 (m, 3 H, ArH), 7.51 (d, J = 2.5 Hz, 1 H, ArH), 7.52 (s, 1 H,
ArH), 7.90–7.93 (m, 2 H, ArH), 8.38 (s, 1 H, ArH).
19F NMR (282.4 MHz, CDCl3): d = –73.20.
GC-MS (EI, 70 eV): m/z (%) = 454 ([M]+, 75), 275 (100), 248 (19),
205 (13), 176 (23).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 61.5 (CH2O), 119.3
(q, JC,F = 320.6 Hz, CF3), 120.1, 122.6, 126.3, 126.7 (CH), 127.1
(C), 127.7, 128.6, 129.0, 129.4, 131.1 (CH), 133.2, 134.0, 139.3,
142.5, 145.4 (C), 167.5 (C=O).
HRMS (EI, 70 eV): m/z calcd for C21H17F3O6S [M]+: 454.06925;
found: 454.06977.
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York

2116
M. F. Ibad et al.
PAPER
Ethyl 3-(4-Methylphenyl)-5-(4-tert-butylphenyl)-2-naphthoate
(12a)
Starting from 11a (100 mg, 0.23 mmol), Pd(PPh3)4 (7 mg, 3 mol%),
K3PO4 (63 mg, 0.3 mmol), 4-tert-butylphenylboronic acid (41 mg,
0.23 mmol), and THF (4 mL), product 12a was isolated as a white
solid (67 mg, 70%); mp 142–145 °C; Rf = 0.3 (heptane–
EtOAc, 4:1).
References
(1) For cancerostatic activity of 1,4-dihydroxy-2-naphthoates,
see: (a) Kongkathip, N.; Luangkamin, S.; Kongkathip, B.;
Sangma, C.; Grigg, R.; Kongsaeree, P.; Prabpai, S.;
Pradidphol, N.; Piyaviriyagul, S.; Siripong, P. J. Med. Chem.
2004, 47, 4427. (b) Jiang, Z.-H.; Tanaka, T.; Inutsuka, C.;
Kouno, I. Chem. Pharm. Bull. 2001, 49, 737. Foranticancer
activity of 4-aryl-2-naphthoates, see: (c) Cullmann, F.;
Schmidt, A.; Schuld, F.; Trennheuser, M. L.; Becker, H.
Phytochemistry 1999, 52, 1647. (d) Fedoreyev, S. A.;
Veselova, M. V.; Krivoschekova, O. E.; Mischenko, N. P.;
Denisenko, V. A.; Dmitrenok, P. S.; Glazunov, V. P.;
Bulgakov, V. P.; Tchernoded, G. K.; Zhuravlev, Y. N.
Planta Med. 2005, 71, 446. (e) Ovenden, S. P. B.; Yu, J.;
Wan, S. S.; Sberna, G.; Tait, R. M.; Rhodes, D.; Cox, S.;
Coates, J.; Walsh, N. G.; Meurer-Grimes, B. M.
IR (KBr): 1702 (s), 1621, 1589, 1510, 1471, 1453, 1441, 1393, 1366
(w), 1277, 1266 (s), 1238, 1194 (m), 1129 (w), 1106, 1096, 1025,
1016 (m), 985, 973, 937, 908, 897, 865, 853 (w), 833 (m), 801 (s),
784, 755 (m), 724, 699, 666, 645, 637 (w), 607, 597 (m), 565 cm–1
(s).
1H NMR (300 MHz, CDCl3): d = 1.00 (t, J = 7.1 Hz, 3 H, CH3),
1.30 (s, 9 H, 3 CH3), 2.29 (s, 3 H, CH3), 4.08 (q, J = 7.1 Hz, 2 H,
CH2O), 7.09–7.11 (m, 2 H, ArH), 7.14–7.17 (m, 2 H, ArH), 7.32–
7.36 (m, 2 H, ArH), 7.38–7.41 (m, 2 H, ArH), 7.42 (d, J = 1.6 Hz, 1
H, ArH), 7.48 (t, J = 7.7 Hz, 1 H, ArH), 7.84 (dd, J = 1.2, 7.6 Hz, 1
H, ArH), 7.87 (s, 1 H, ArH), 8.33 (s, 1 H, ArH).
Phytochemistry 2004, 65, 3255 . For anti-malaria activity of
naphthyltetrahydroisoquinoline alkaloids, see:
(f) Bringmann, G. The Naphthyl Isoquinoline Alkaloids, In
The Alkaloids, Vol. 29; Brossi, A., Ed.; Academic Press:
New York, 1986, 141–184.
13C NMR (62.9 MHz, CDCl3): d = 13.6 (CH3), 21.1 (CH3), 31.4 (3
CH3), 33.5 (C), 61.0 (CH2O), 124.3, 125.1, 126.8, 126.9, 127.5,
127.6, 128.1 (CH), 128.4 (C), 128.5, 130 (CH), 130.9, 131.5, 135.6,
136.0, 137.6, 137.9, 139.2, 149.2 (C), 167.7 (C=O).
GC-MS (EI, 70 eV): m/z (%) = 422 ([M]+, 100), 407 (36).
HRMS (EI, 70 eV): m/z calcd for C30H30O2 [M]+: 422.22403; found:
(2) For reviews of cross-coupling reactions of polyhalogenated
heterocycles, see: (a) Schröter, S.; Stock, C.; Bach, T.
Tetrahedron 2005, 61, 2245. (b) Schnürch, M.; Flasik, R.;
Khan, A. F.; Spina, M.; Mihovilovic, M. D.; Stanetty, P. Eur.
J. Org. Chem. 2006, 3283.
422.22406.
(3) For palladium-catalyzed reactions from our group, see for
example: (a) Dang, T. T.; Dang, T. T.; Ahmad, R.; Reinke,
H.; Langer, P. Tetrahedron Lett. 2008, 49, 1698. (b) Dang,
T. T.; Villinger, A.; Langer, P. Adv. Synth. Catal. 2008, 350,
2109. (c) Hussain, M.; Nguyen, T. H.; Langer, P.
Tetrahedron Lett. 2009, 50, 3929. (d) Dang, T. T.; Dang, T.
T.; Rasool, N.; Villinger, A.; Langer, P. Adv. Synth. Catal.
2009, 351, 1595.
(4) Handy, S. T.; Zhang, Y. Chem. Commun. 2006, 299.
(5) (a) Takeuchi, M.; Tuihiji, T.; Nishimura, J. J. Org. Chem.
1993, 58, 7388. (b) Sugiura, H.; Nigorikawa, Y.; Saiki, Y.;
Nakamura, K.; Yamaguchi, M. J. Am. Chem. Soc. 2004, 126,
14858. (c) Akimoto, K.; Suzuki, H.; Kondo, Y.; Endo, K.;
Akiba, U.; Aoyama, Y.; Hamada, F. Tetrahedron 2007, 63,
6887. (d) Akimoto, K.; Kondo, Y.; Endo, K.; Yamada, M.;
Aoyama, Y.; Hamada, F. Tetrahedron Lett. 2008, 49, 7361.
(e) Hosokawa, S.; Fumiyama, H.; Fukuda, H.; Fukuda, T.;
Seki, M.; Tatsuta, K. Tetrahedron Lett. 2007, 48, 7305.
(6) (a) Nawaz, M.; Farooq Ibad, M.; Obaid-Ur-Rahman, A.;
Khera, R. A.; Villinger, A.; Langer, P. Synlett 2010, 150.
(b) Nawaz, M.; Khera, R. A.; Malik, I.; Ibad, M. F.; Obaid-
ur-Rahman, A.; Villinger, A.; Langer, P. Synlett 2010, 979.
(c) Obaid-ur-Rahman, A.; Ibad, M. F.; Nawaz, M.; Adeel,
M.; Rama, N. H.; Villinger, A.; Langer, P. Tetrahedron Lett.
2010, 51, 657.
Ethyl 3-(4-tert-Butylphenyl)-5-(4-trifluoromethylphenyl)-2-
naphthoate (12b)
Starting with 11b (100 mg, 0.2 mmol), Pd(PPh3)4 (7 mg, 3 mol%),
K3PO4 (63 mg, 0.3 mmol), 4-(trifluoromethyl)phenylboronic acid
(41 mg), and THF (4 mL), product 12b was isolated as a white solid
(72 mg, 73%); mp 212–214 °C; Rf = 0.3 (heptane–EtOAc, 4:1).
IR (KBr): 1715 (s), 1616, 1591, 1514, 1475, 1454, 1403, 1365 (w),
1322, 1269 (s), 1238, 1194 (m), 1163, 1122, 1107, 1089, 1066,
1017 (s), 985 (m), 921 (w), 901, 854 (m), 839, 800 (s), 786, 752 (m),
707, 652, 640 (w), 610, 587, 570 (m), 534 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 7.1 Hz, 3 H, CH3),
1.26 (s, 9 H, 3 CH3), 4.05 (q, J = 7.1 Hz, 2 H, CH2O), 7.18–7.19 (m,
2 H, ArH), 7.33 (d, J = 8.4 Hz, 2 H, ArH), 7.42 (d, J = 1.2, 7.1 Hz,
1 H, ArH), 7.52–7.55 (m, 3 H, ArH), 7.67 (d, J = 8.1 Hz, 2 H, ArH),
7.73 (s, 1 H, ArH), 7.92 (d, J = 8.1 Hz, 1 H, ArH), 8.35 (s, 1 H,
ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.5 (CH3), 31.3 (3 CH3), 34.5
(C), 61.0 (CH2O), 122.4 (q, JC,F = 272.2 Hz, CF3), 124.9, 125.4 (q,
J = 3.8 Hz), 126.0, 127.0, 128.2, 128.9, 129.1 (CH), 129.7 (q,
JC,F = 32.3 Hz), 130.2 (C), 130.3, 131.0 (CH), 132.0, 132.1, 138.5,
138.7, 139.1, 143.8, 150.1 (C), 168.8 (C=O).
19F NMR (282.4 MHz, CDCl3): d = –62.4.
GC-MS (EI, 70 eV): m/z (%) = 476 ([M]+, 53), 462 (32), 461 (100).
HRMS (EI, 70 eV): m/z calcd for C30H27F3O2 [M]+: 476.19577;
found: 476.19558.
(7) Obaid-ur-Rahman, A.; Ibad, M. F.; Nawaz, M.; Sher, M.;
Rama, N. H.; Villinger, A.; Langer, P. Tetrahedron Lett.
2010, 51, 1541.
(8) CCDC-818524 (4k) and CCDC-818525 (6h) contain all
crystallographic details of this publication and are available
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html
or can be ordered from the following address: Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: +44(1223)336033; or e-mail:
deposit@ccdc.cam.ac.uk.
Acknowledgment
Financial support by the DAAD (scholarships for M.F.I., O.-u.-
R.A., N.E., and A.M.) and by the State of Pakistan (scholarships for
A.O.-u.-R. and M.H.) and by the State of Mecklenburg-Vorpom-
mern (scholarship for M.H.) is gratefully acknowledged.
Synthesis 2011, No. 13, 2101–2116 © Thieme Stuttgart · New York