7142
Z. Hassan et al. / Tetrahedron Letters 56 (2015) 7141–7144
Langer and
co-workers
Pd (0)
Ar
O
O
The primary focus of our efforts was the selective substitution
OTf
OTf
at the C-1 and/or C-4 positions. Previous reports were disappoint-
ing, and almost none of the desired Suzuki coupling product was
observed (see Scheme 2, top).12 All efforts resulted in sluggish
reactions and low overall yields. This unexpected behavior of 1,4-
bis-triflates as evidenced by the prevalence of hydrolysis/redox
products under catalytic reaction condition was probably due to
the abstractable proton (two transferable hydrogen atoms of
1,4-dihydroxybenzenes that easily lead to stable quinones and
hydroquinones which are common redox mediators).13 Herein,
we report a highly chemo- and regioselective palladium-catalyzed
Suzuki–Miyaura reaction of 1,4-(trifluoromethanesulfonyloxy)-
2,3-chloronaphthalene, which allowed the direct synthesis of a
number of mono-, di-, and tetraphenyl substituted naphthalene
products.
Ar
Ar
Ar
Ar
Br
Br
Pd (0)
X
1,4 dioxane
1,4-dioxane
Ar
Earlier studies on the Suzuki-Miyaura coupling of 1,4-bistriflates, (hydrolysis/ redox products)
ref.12
Ar
OTf
Ar
OTf
Ar
Ar
Cl
Cl
Cl
Cl
ii
i
5
Ar
3
OTf
6
Our studies on the chemoselective Suzuki-Miyaura coupling of 1,4-bistriflates
Scheme 2. Synthesis of 5a–e and 6a–e. Reagents and conditions: (i) 3 (1.0 equiv),
ArB(OH)2 (4.5 equiv), Pd(PPh3)4 (3 mol %), KF (10.0 equiv), 1,4-dioxane, 120 °C, 8 h,
(ii) 3 (1.0 equiv), ArB(OH)2 (1.0 equiv), Pd(PPh3)4 (3 mol %), KF (3.0 equiv), 1,4-
dioxane, 50 °C, 4 h.
2,3-Dichloronaphthalene-1,4-diol 2 was synthesized in high
yield from inexpensive, commercially available 2,3-dicloro-1,4-
naphthaquinone (DCNQ) 1 by reduction with aqueous Na2S2O4
(94%), followed by transformation to the corresponding 2,3-
dichloronaphthalene-1,4-diylbis(trifluoromethanesulfonate)
(96%) (Scheme 1).
3
Table 1
2,3-Dichloronaphthalene-1,4-bistriflate (3) is stable and can be
stored for a long time (more than six months) at room tempera-
ture. In order to obtain a crystal structure, layering techniques
were applied and well-defined crystals were grown from (CH2Cl2/
EtOH, 2:1). The X-ray structure showed that both triflate groups
were twisted out of plane (Fig. 1).20
The Suzuki–Miyaura reaction of 3 with arylboronic acids 4a–e
(4.5 equiv) afforded 1,2,3,4-tetraarylnaphthalenes 5a–e in
58–76% yields (Scheme 2, Table 1). Both electron-poor and
Synthesis of 1,2,3,4-tetraarylnaphthalenes 5a–e
Entry
ArB(OH)2 (4)
5
Yield (%)
1
2
3
4
5
4-(MeO)C6H4
4-MeC6H4
4-ClC6H4
3,5-MeC6H3
3,4,5-MeC6H2
a
b
c
d
e
76
72
66
58
62
Table 2
Synthesis of 6a–c and 7a–c
OH
OTf
O
Entry
ArB(OH)2 (4)
6
Yields (%)
7
Yields (%)
Cl
Cl
Cl
Cl
Cl
Cl
i
ii
1
2
3
4-MeOC6H4
4-MeC6H4
4-ClC6H4
a
b
c
72
70
68
a
b
c
77
52
60
1
2
O
OH
3
OTf
Scheme 1. Synthesis of 2 and 3. Reagents and Conditions: (i) 1 (1.0 equiv), Na2S2O4
(3.0 equiv), 1 h; (ii) 2 (1.0 equiv), Tf2O (3.0 equiv), pyridine (2.0 equiv), CH2Cl2,
20 °C, 6 h.
electron-rich arylboronic acids were successfully employed. The
reactions were quite clean, although in some cases, small amounts
of biaryl derivatives, due to homocoupling of the organoboron
reagents, were also observed. The best yields were obtained in
1,4-dioxane at 120 °C using Pd(PPh3)4 (5 mol %) as the catalyst
and KF (10.0 equiv) as the base.
Next, the Suzuki–Miyaura coupling was examined for the
synthesis of unsymmetrical substituted naphthalenes. A highly
selective mono-coupling reaction was achieved after careful opti-
mization of the reaction parameters including base (3.0 equiv
KF), temperature (50 °C) and solvents. Selective Suzuki coupling
of 3 with various arylboronic acids (1.0 equiv) afforded the unsym-
metrical 1-aryl-2,3-dichloronaphthalene-4-trifluoromethanesul-
fonates 6a–c in 68–72% yields (Table 2). The reactions proceeded
with good selectivity for monosubstitution in favor of the triflate
at the C-1 position, while the C-4 triflate remained unreacted
under strict control of the reaction conditions. During optimiza-
tion, it proved crucial to use dried solvents, KF as base and Pd
(PPh3)4 (3 mol %) as catalyst. The reaction course was selective
and predominantly led to the product of OTf-displacement
(Scheme 3, Table 2).
The structures of the compounds were elucidated by extensive
spectral analysis; 1D and 2D (COSY, HMBC, HMQC, NOESY) NMR
spectroscopy. In order to obtain crystal structures, layering tech-
niques were applied and well-defined crystals were grown from
(CH2Cl2/EtOH, 2:1). The structure of compound 6a was unambigu-
ously confirmed by single crystal X-ray analysis (Fig. 2).20
Figure 1. Crystal structure of 3.