Nickel-catalyzed Suzuki-Miyaura coupling of heteroaryl ethers with arylboronic acids

Article abstract of DOI:10.1021/jo4005537

Nickel-catalyzed Suzuki-Miyaura coupling of heteroaryl ethers with arylboronic acids was described. Selective activation of the phenol C-O bonds was achieved by converting them into the corresponding aryl 2,4-dimethoxy-1,3,5- triazine-6-yl ethers, in which aryl C-O bond could be selectively cleaved with inexpensive, air-stable NiCl₂(dppf) as a catalyst. Coupling of these readily accessible heteroaryl ethers proved tolerant of extensive functional groups.

Full text of DOI:10.1021/jo4005537

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Note
Nickel-Catalyzed Suzuki–Miyaura Coupling
of Heteroaryl Ethers with Arylboronic Acids
Xiao-Jian Li, Jin-Ling Zhang, Yu Geng, and Zhong Jin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo4005537 • Publication Date (Web): 30 Apr 2013
Downloaded from http://pubs.acs.org on May 2, 2013
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NickelꢀCatalyzed Suzuki–Miyaura Coupling of Heteroaryl Ethers with Arylboronic Acids
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XiaoꢀJian Li, JinꢀLing Zhang, Yu Geng, Zhong Jin*
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State Key Laboratory and Institute of ElementoꢀOrganic Chemistry, Nankai University, Tianjin
300071, China
Eꢀmail: zjin@nankai.edu.cn
Table of Contents
OMe
ArB(OH)2
N
N
R
R
NiCl2(dppf), K3PO4
toluene, 110 oC
O
N
OMe
Ar
Abstract
Nickelꢀcatalyzed Suzuki–Miyaura coupling of heteroaryl ethers with arylboronic acids was described.
Selective activation of the phenol C–O bonds was achieved by converting them into the corresponding
aryl 2,4ꢀdimethoxyꢀ1,3,5ꢀtriazineꢀ6ꢀyl ethers, in which aryl C–O bond could be selectively cleaved
with inexpensive, airꢀstable NiCl2(dppf) as a catalyst. Coupling of these readily accessible heteroaryl
ethers proved tolerant of extensive functional groups.
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Transition metalꢀcatalyzed Suzuki–Miyaura reactions have been recognized as a powerful and
indispensable method for biaryl synthesis because of the inherent advantages of organoboron reagents,
such as airꢀ and moistureꢀstability, good functional group tolerance, low toxicity and widely
availability.1,2 Relative to aryl halides, recently much attention has been paid to coupling with aryl
C–O electrophiles due to their ready availability from natural source and chemical synthesis.3–6 So far,
a wide array of previously unreactive substrates such as aryl methyl ethers,7 esters,8,9 carbamates,10–13
carbonates,12 sulfamates,10,12,14,15 phosphoramides,16 phosphonium salts,17,18 and phosphates19 have
been identified as competent coupling partners in the crossꢀcoupling reactions. Although significant
advances have been made in this field, for the electronically deactivated substrates,8–15,20,21
crossꢀcoupling reactions usually gave only poor to modest yields. Given low cost and readily
accessibility of the phenols, development of new methodology for crossꢀcoupling reactions of aryl
C–O electrophiles contributes greatly to the fundamental conception of the reactivity of the relative
inert C–O bonds and is, therefore, still considerably important. Herein, we report the new method for
effective activation of the phenol C–O bond through converting them into aryl
2,4ꢀdimethoxyꢀ1,3,5ꢀtriazineꢀ6ꢀyl (DMT) ethers, allowing for nickelꢀcatalyzed Suzuki–Miyaura
coupling of extensive phenol derivatives with arylboronic acids.
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In view of high efficiency of 2ꢀchloroꢀ4,6ꢀdisubstitutedꢀ1,3ꢀ5ꢀtriazines in formation of the peptide
bonds,22–25 which resulted from the excellent leaving potential of the oxygenated 1,3,5ꢀtriazines, we
envisioned that activation of the phenol C–O bond for subsequent Suzuki–Miyaura crossꢀcoupling
reactions could be achieved through converting the phenols to the corresponding heteroaryl ethers 3
(Scheme 1).
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Scheme 1. Preparation of ArꢀOꢀDMT Ethers
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The advantage to introduce such a heteroarene is obvious that two C2ꢀsymmetric ortho nitrogen
atoms may be provided to form the relative nitrogen coordinated transition metal complex,26 which
facilitated the oxidative addition of [M0Ln] species to the unreactive aryl C–O bond by ortho position
chelation assistance.27,28 Furthermore, the high leaving potential of the oxygenated 1,3ꢀ5ꢀtriazine
could also accelerate the transmetallation process in the catalytic cycles of crossꢀcoupling reactions.29
It is also worth noting that synthesis of these heteroaryl ethers was very simple and effective from the
inexpensive 2ꢀchloroꢀ4,6ꢀdimethoxyꢀ1,3,5ꢀtriazine (CDMT) 2.30 All ArꢀOꢀDMT ethers 3 are the
colorless crystals and thus could be separated and purified conveniently by recrystallization from
ethanol. They generally exhibit high airꢀ and moistureꢀstability, allowing for indefinite storage and
easy handling in air.
A
single crystal Xꢀray diffraction analysis of aryl
2,4ꢀdimethoxyꢀ1,3,5ꢀtriazineꢀ6ꢀyl ether 3a confirmed preliminarily our aforementioned hypothesis
(Figure 1).31 Analysis of the Xꢀray structure revealed that CAr–ODMT bond (C(5)–O(2)) distance is
1.411 Å, obviously larger than those of ArO–CDMT bond (O(2)–C(8)) (1.349 Å) and CAr–OMe bond
(C(2)–O(1)) (1.363 Å), which implied that the phenol C–O bond has the potential to be cleaved in
subsequent crossꢀcoupling reaction.
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Figure 1. ORTEP drawings of compound 3a. All hydrogen atoms were omitted for clarity.
With this preliminary confirmation, reactivity of these ArꢀOꢀDMT ethers in nickelꢀcatalyzed
Suzuki–Miyaura crossꢀcoupling reaction was examined subsequently. Using heteroaryl ether 3a and
phenylboronic acid 4a as the coupling partners, various reaction parameters including ligand, base,
solvent, and temperature were screened (Table 1). Base was found to show significant influence on the
coupling reaction and anhydrous K3PO4 showed the best efficiency for this transformation. In sharp
contrast, the corresponding hydrate base was completely inefficient (entries 5 vs 6, Table 1). The
effect of solvent on the coupling reaction was rather important; toluene proved to the choice of
solvent, whereas other polar solvents such as DME and DMA gave rise to no coupling product, even
though reactions were performed at elevated temperature (entry 9, Table 1). Compared with the
monodentate ligand catalyst NiCl2(PCy3)2, bidentate NiCl2(dppf) was found to be a superior catalyst
(entries 6 vs 15, Table 1). In addition, NiCl2(dppp) was also effective catalyst for the coupling reaction
although a slightly lower yield was attained (entry 13, Table 1). Under the optimal reaction conditions,
coupling with phenyl pinacolboronate, instead of phenylboronic acid, only gave trace amount of
product (entries 15 vs 16, Table 1).
Table 1. Optimization of Reaction Conditionsa
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entry
1
[Ni]/ligand
base
solvent
yield (%)b
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PCy3)2
NiCl2(PPh3)2
NiCl2(dppe)
NiCl2(dppp)
NiCl2(dppb)
NiCl2(dppf)
NiCl2(dppf)
K2CO3
Cs2CO3
KF
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
DME
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2
0
3
< 5
< 5
0
4
KOtBu
K3PO4•6H2O
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
5
6
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< 5
0c
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DMA
0d
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tBuOH
toluene
toluene
toluene
toluene
toluene
toluene
20
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38
81
< 5
90
< 5e
16
a
Reaction Conditions: 3a (1.0 mmol), 4a (4.0 mmol), [Ni]/ligand 5
mol %, base (7.0 mmol), solvent (0.15 M), T 110 oC, t 24 h. Isolated
b
yield. c T 80 oC. d T 130 oC. e Phenyl pinacolboronate instead of PhB(OH)2
was used.
In regard to transition metalꢀcatalyzed Suzuki–Miyaura crossꢀcoupling reactions, it is well
established that the electrophiles with electronꢀdonating groups are electronically deactivated and
generally less susceptible to oxidative addition. For examples, crossꢀcoupling of electronically
deactivated aryl pivalates,8,9 carbamates,10–13 and sulfamates10,12,14,15 with arylboronic acids commonly
gave poor to modest yields. A comparison of nickelꢀcatalyzed crossꢀcoupling of various
4ꢀanisoleꢀcontaining C–O electrophiles with phenylboronic acid was outlined in Table 2. The
electronꢀrich aryl methyl ether was completely inactive under the catalytic conditions employed in this
study. Coupling with electronꢀrich aryl mesylate, tosylate, pivalate and carbamate only gave the
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desired biaryl in poor to modest yields, although increased yield was obtained when using the
corresponding aryl sulfamate as an electrophile. In contrast, coupling of electronꢀrich ArꢀOꢀDMT
ether 3a with phenylboronic acid gave rise to the biaryl in excellent yield under the present condition.
Table 2. NickelꢀCatalyzed CrossꢀCoupling of ElectronꢀRich Aryl C–O Electrophiles with
Phenylboronic Acida
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OP(O)(OEt)2
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Reaction Conditions: Aryl C–O electrophile (1.0 mmol), PhB(OH)2 (4.0 equiv), NiCl2(dppf) (5 mol %), K3PO4 (7.0 equiv), toluene (0.15 M), T 110 oC, t 24 h.
Isolated yield. c Literature yield (ref. 32). d Literature yield (ref. 9). e Literature yield (ref. 12). f Literature yield (ref. 19).
Next, the generality of Suzuki coupling with respect to ArꢀOꢀDMT ethers has been investigated. As
shown in Table 3, under the present catalytic system, those substrates with electronꢀdonating group(s)
exhibited very good compatibility and all gave excellent yields (5a–e, Table 3). Coupling with
ArꢀOꢀDMT ethers was also found to be tolerant of a variety of functional groups (5j–p, Table 3), such
as amide, ester, nitrile, aldehyde, ketone, etc. To our surprise, electronically activated ArꢀOꢀDMT ether
3s bearing a strong electronꢀwithdrawing nitro group failed to couple with phenylboronic acid (5r,
Table 3). The reactions proved also tolerant of a lactone or α,βꢀunsaturated lactone group (5t, 5u,
Table 3). In addition, double crossꢀcoupling proceeded in good yield (5u, Table 3). It should be
emphasized that aryl fluoride was chemically inert under the coupling conditions (5m, Table 3).
Table 3. Scope and Limitations of Suzuki Coupling with ArꢀOꢀDMT Ethersa,b
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MeO
OMe
R
5
6
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8
R
OMe
5a (R = H), 90 %
5e
, 85 % 5a
(R = H), 92 %
5b (R = 2-Me), 89 %
5c (R = 4-Me), 87 %
5b (R = 2-Me), 89 %
5c (R = 4-Me), 91 %
5d (1-naphthyl), 87 %
5d
(1-naphthyl), 89 %
9
NHAc
R
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R
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OMe
5f (R = 3-Me), 90 % 5j, 81 % 5k (R = CO2Me), 89 %
5g (2-naphthyl), 81 %
5h (R = 3,5-dimethyl), 87 %
5i (R = 4-tBu), 85 %
5l (R = CN), 86 %
5n
(R = CHO), 88 %
5o (R = COCH3), 89 %
5r
(R = NO2), 0 %
R
OHC
N
OMe
OMe
5m (R = F), 88 %
5p (R = CF3), 84 %
5q, 51 %
5s, 61 %
O
O
Me
Me
O
H
H
H
Ph
O
O
Ph
Ph
Ph
5v, 82 %
5t, 84 %
5u, 78 %
a Reaction Conditions: ArꢀOꢀDMT ether (1.0 mmol), ArB(OH)2 (4.0 mmol),
NiCl2(dppf) (5 mol %), K3PO4 (7.0 mmol), toluene (0.15 M), T 110 oC, t 24
h. b Isolated yield.
Notably, crossꢀcoupling of 3ꢀhydroxypyridineꢀderived ether with phenylboronic acid also afforded a
PhꢀDMT derivative 6a in an isolated yield of 9 % in addition to the desired 3ꢀphenylpyridine (5s,
Table 3). However, when its 2ꢀpyridinyl congener 3x was used as the coupling partner, only product
6a was obtained in a yield of 51 % (Scheme 2). Coupling of ether 3x with 4ꢀmethylphenylboronic acid
proceeded in a similar manner.
Scheme 2. Suzuki Coupling with 2ꢀHydroxypyridineꢀDerived Ether 3x
OMe
N
OMe
N
N
N
NiCl2(dppf)
N
N
Ar
ArB(OH)2
K3PO4, toluene
O
N
OMe
4
OMe
110 o
C
Ar = Ph, 6a, 51 %
3x
Ar = p-Tol, 6b, 55 %
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Unlike that of 2ꢀ and 3ꢀhydroxy pyridines, reaction of 4ꢀhydroxy pyridine with
1ꢀchlorideꢀ3,5ꢀdimethoxyꢀ2,4,6ꢀtriazine did not give the corresponding 4ꢀpyridinylꢀOꢀDMT ether and
an unexpected isomer was isolated. After careful examination of its 1H and 13C NMR spectra data, its
structure was identified as NꢀDMT 4ꢀpyridinone 3y. A single crystal Xꢀray diffraction analysis further
validated the proposed structure.31 Unexpectedly, when this NꢀDMT 4ꢀpyridinone 3y was subjected to
subsequent crossꢀcoupling with arylboronic acids, the corresponding ArꢀDMT derivatives 6 were also
obtained in good yields (Scheme 3). Meanwhile, reaction performed without catalyst NiCl2(dppf)
failed to give the corresponding coupling products. Although several classes of Nꢀleaving groups, such
as diazonium salts,33 ammonium salts,34 aryltriazene,35 azoles,36 and anilines with an ortho position
carbonyl group as the ligating group,37,38 have been reported in the Suzuki–Miyaura coupling, this
represented the first example of catalytic Suzuki coupling with an enamine as the leaving group.
Scheme 3. Suzuki Coupling with NꢀDMT 4ꢀPyridinone 3y
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Furthermore, scope of Suzuki coupling with various arylboronic acids was investigated. As
illustrated in Table 4, arylboronic acids incorporating electronꢀwithdrawing groups coupled smoothly
with a variety of ArꢀOꢀDMT ethers to afford biaryl products in good to excellent yields. To our
disappointment, under the coupling conditions heteroaryl boronic acids are less reactive (5k′ and 5l′,
Table 4).39 Additionally, aryl chloride was not able to survive in the coupling reaction. When reaction
was performed using 4ꢀchloride phenylboronic acid as the coupling partner, a pꢀtetraphenyl derivative
was obtained in a yield of 27 % (5m′, Table 4).
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Table 4. Scope and Limitations of Suzuki Coupling with Arylboronic Acidsa,b
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a
Reaction Conditions: ArꢀOꢀDMT ether 3 (1.0 mmol), ArB(OH)2 (4.0
mmol), NiCl2(dppf) (5 mol %), K3PO4 (7.0 mmol), toluene (0.15 M), T 110
oC, t 24 h. b Isolated yield.
To investigate the scope of other types of heteroaryl ether, crossꢀcoupling of 2ꢀphenoxypyridine
with 4ꢀmethoxyphenylboronic acid was therefore carried out. The corresponding biaryl 5a was
obtained in an isolated yield of 26 % by employing the present catalytic condition. Meanwhile,
coupling with the simple diphenyl ether gave rise to no desired product (Scheme 4).
Scheme 4. Comparative Suzuki Coupling of 2ꢀPhenoxypyridine and Diphenyl Ether
In summary, we have demonstrated that activation of the phenol C–O bond could conveniently be
achieved through converting them into the corresponding aryl triazinyl ethers. These readily
accessible heteroaryl ethers showed prominent reactivity in the Suzuki–Miyaura coupling reactions.
Coupling reactions with ArꢀOꢀDMT ethers proved tolerant of extensive functional groups, including
ester, amide, aldehyde, ketone, nitrile, and so on.
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EXPERIMENTAL SECTION
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General. All solvents were dried prior to use using the standard methods. The phenols, CDMT 2, and
arylboronic acids were used as received from commercial availability. CDMT 2 was also prepared
from cyanuric chloride with methanol on a large scale according to the literature method.30 HRMS
were recorded on Varian 7.0T FTICRꢀMS. NMR spectroscopy data of the known compounds matches
with those reported in the corresponding references. All new compounds were further characterized by
elemental analysis or HRMS.
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General Procedure for Synthesis of ArꢀOꢀDMT Ethers 3. A mixture of the phenol 1 (20 mmol),
CDMT 2 (3.50 g, 20 mmol), and KOH (1.12 g, 20 mmol) in THF (80 mL) was stirred at room
temperature overnight. After reaction completion monitoring by TLC, the mixture was filtrated
through a short pad of silica gel and washed exhaustively with CH2Cl2. The solvent was removed off
under vacuum. Recrystallization from ethanol gave the title compounds.
2,4ꢀDimethoxyꢀ6ꢀ(4′ꢀmethoxyphenoxy)ꢀ1,3,5ꢀtriazine (3a) (CAS no. 33950ꢀ61ꢀ7). Yield 97%, 5.10 g;
m.p. 76–78 oC, 1H NMR (400 MHz, CDCl3) δ: 7.10 (d, J = 8 Hz, 2H), 6.91 (d, J = 8 Hz, 2H), 4.00 (s,
6H), 3.82 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.7, 173.5, 157.3, 145.2, 122.2, 114.4, 55.5, 55.4.
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H13N3O4Na 286.0798; Found 286.0795.
o
1
2,4ꢀDimethoxyꢀ6ꢀ(2′ꢀmethoxyphenoxy)ꢀ1,3,5ꢀtriazine (3b). Yield 93%, 4.89 g; m.p. 96–98 C, H
NMR (400 MHz, CDCl3) δ: 7.27–7.23 (m, 1H), 7.15 (d, J = 12 Hz, 1H), 6.98 (d, J = 12 Hz, 2H), 3.98
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(s, 6H), 3.78(s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.7, 173.2, 151.1, 140.7, 126.9, 122.4, 120.7,
112.5, 55.8, 55.3. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H13N3O4Na 286.0798; Found
286.0802.
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2,4ꢀDimethoxyꢀ6ꢀphenoxyꢀ1,3,5ꢀtriazine (3c) (CAS no. 21002ꢀ15ꢀ3). Yield 96%, 4.33 g; m.p. 103–104
oC, 1H NMR (400 MHz, CDCl3) δ: 7.41 (t, J = 8.8 Hz, 2H), 7.28 (d, J = 8 Hz, 1H), 7.18 (d, J = 8Hz,
2H), 3.99 (s, 6H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 173.2, 151.7, 129.5, 125.9, 121.5, 55.4.
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C11H11N3O3Na 256.0693; Found 256.0693.
2,4ꢀDimethoxyꢀ6ꢀ(2′ꢀmethylphenoxy)ꢀ1,3,5ꢀtriazine (3d) (CAS no. 42030ꢀ81ꢀ9). Yield 95%, 4.69 g;
m.p. 90–92 oC, 1H NMR (400 MHz, CDCl3) δ: 7.27–7.17 (m, 3H), 7.07 (d, J = 8 Hz, 1H), 3.98 (s, 6H),
2.19 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 173.1, 150.3, 131.2, 130.16, 127.0, 126.1, 121.6,
55.4, 16.2. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H13N3O3Na 270.0849; Found 270.0849.
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2,4ꢀDimethoxyꢀ6ꢀ(3′ꢀmethylphenoxy)ꢀ1,3,5ꢀtriazine (3e). Yield 91%, 4.50 g; m.p. 68–70 C, H NMR
(400 MHz, CDCl3) δ: 7.30–7.26 (m, 1H), 7.07 (d, J = 8 Hz, 1H), 6.99– 6.97 (m, 2H), 4.00 (s, 6H),
2.37 (s, 6H). 13C NMR (100 MHz, CDCl3) δ: 173.7, 173.3, 151.6, 139.7, 129.2, 126.8, 121.9, 118.5,
55.4, 21.3. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H13N3O3Na 270.0849; Found 270.0849.
2,4ꢀDimethoxyꢀ6ꢀ(4′ꢀmethylphenoxy)ꢀ1,3,5ꢀtriazine (3f) (CAS no. 33950ꢀ59ꢀ3) Yield 93%, 4.59 g; m.p.
88–90 oC, 1H NMR (400 MHz, CDCl3) δ: 7.19 (d, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz, 2H), 3.99 (s, 6H),
2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 173.4, 149.5, 135.5, 130.0, 121.1, 55.4, 20.9.
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H13N3O3Na 270.0849; Found 270.0849.
2,4ꢀDimethoxyꢀ6ꢀ(naphthaleneꢀ1′ꢀyloxy)ꢀ1,3,5ꢀtriazine (3g) (CAS no. 42030ꢀ87ꢀ5). Yield 90%, 5.10 g;
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m.p. 89–91 C, H NMR (400 MHz, CDCl3) δ: 7.88 (d, J = 8 Hz, 2H), 7.77 (d, J = 8 Hz, 1H),
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7.52–7.45 (m, 3H), 7.30 (d, J = 8 Hz, 1H), 3.95 (s, 6H). 13C NMR (100 MHz, CDCl3) δ: 173.9, 173.8,
147.7, 134.7, 128.0, 126.8, 126.5, 126.2, 125.4, 121.4, 117.9, 55.4. HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd. for C15H13N3O3Na 306.0849; Found 306.0846.
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2,4ꢀDimethoxyꢀ6ꢀ(naphthaleneꢀ2′ꢀyloxy)ꢀ1,3,5ꢀtriazine (3h) (CAS no. 41735ꢀ95ꢀ9). Yield 96%, 5.43 g;
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m.p. 120–122 C, H NMR (400 MHz, CDCl3) δ: 7.88–7.8 (m, 3H), 7.62 (s, 1H ), 7.5–7.47 (m, 2H),
7.33–7.30 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 173.4, 149.3, 133.84, 131.5, 129.5, 127.8,
127.7, 126.6, 125.8, 121.1, 118.4, 55.5. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C15H13N3O3Na
306.0849; Found 306.0846.
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2ꢀ(3′,5′ꢀDimethylphenoxy)ꢀ4,6ꢀdimethoxyꢀ1,3,5ꢀtriazine (3i). Yield 94%, 4.90 g; m.p. 75–77 C, H
NMR (400 MHz, CDCl3) δ: 6.88 (s, 1H), 6.77(s, 2H), 4.00 (s, 6H), 2.32 (s, 6H). 13C NMR (100 MHz,
CDCl3) δ: 173.8, 173.4, 151.6, 139.3, 127.7, 119.0, 55.4, 21.3. HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd. for C13H15N3O3Na 284.1006; Found 284.1003.
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2ꢀ(4′ꢀtertꢀButylphenoxy)ꢀ4,6ꢀdimethoxyꢀ1,3,5ꢀtriazine (3j). Yield 95%, 5.48 g; m.p. 90–93 C, H
NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 8 Hz, 2H), 7.10 (d, J = 8 Hz, 2H), 4.01 (s, 6H), 1.33 (s, 9H).
13C NMR (100 MHz, CDCl3) δ: 173.7, 173.3, 149.3, 148.6, 126.3, 120.7, 55.4, 34.4, 31.4. HRMS
(ESIꢀTOF) m/z: [M+Na]+ Calcd. for C15H19N3O3Na 312.1319; Found 312.1313.
Nꢀ(3ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)phenyl)acetamide (3k). Yield 96%, 5.56 g; m.p.
131–133 oC, 1H NMR (400 MHz, CDCl3) δ: 8.38 (s, 1H), 7.51 (s 1H), 7.30–7.19 (m, 2H), 6.84 (d, J =
8 Hz, 1H), 4.03 (s, 6H), 1.98 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.7, 173.3, 168.7, 151.7,
140.0, 129.6, 117.2, 116.2, 113.0, 55.7, 24.3. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for
C13H14N4O4Na 313.0907; Found 313.0901.
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Methyl 4ꢀ((4′,6′ꢀdimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)benzoate (3l). Yield 95%, 5.53 g; m.p. 122–124 oC,
1H NMR (400 MHz, CDCl3) δ: 8.11 (d, J = 8 Hz, 2H), 7.26 (d, J = 8 Hz, 2H), 4.00 (s, 6H), 3.93 (s,
3H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 172.8, 166.2, 155.2, 131.3, 127.9, 121.6, 55.6, 52.2.
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C13H13N3O5Na 314.0747; Found 314.0753.
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4ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)benzonitrile (3m). Yield 94%, 4.85 g; m.p. 135–137 C,
1H NMR (400 MHz, CDCl3) δ: 7.77 (d, J = 8 Hz, 2H), 7.33 (d, J = 8 Hz, 2H), 4.02 (s, 6H). 13C NMR
(100 MHz, CDCl3) δ: 173.8, 154.8, 133.8, 122.8, 118.1, 110.0, 55.7. HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd. for C12H10N4O3Na 281.0645; Found 281.0651.
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2ꢀ(4′ꢀFluorophenoxy)ꢀ4,6ꢀdimethoxyꢀ1,3,5ꢀtriazine (3n). Yield 91%, 4.56 g; m.p. 80–82 C, H NMR
(400 MHz, CDCl3) δ: 7.17–7.14 (m, 2H), 7.12–7.07 (m, 2H), 4.01 (s, 6H). 13C NMR (100 MHz,
CDCl3) δ: 173.8, 173.2, 161.5, 159.1, 147.5, 123.0, 122.9, 116.3, 116.0, 55.5. HRMS (ESIꢀTOF) m/z:
[M+Na]+ Calcd. for C11H10FN3O3Na 274.0598; Found 274.0602.
4ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)benzaldehyde (3o) (CAS no. 42030ꢀ76ꢀ2). Yield 95%,
4.96 g; m.p. 150–152 oC, 1H NMR (400 MHz, CDCl3) δ: 10.02 (s, 1H), 7.96 (d, J = 8 Hz, 2H), 3.37 (d,
J = 8 Hz, 2H), 4.02 (s, 6H). 13C NMR (100 MHz, CDCl3) δ: 190.8, 173.8, 172.7, 156.2, 134.1, 131.3,
122.4, 55.6. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H11N3O4Na 284.0642; Found 284.0641.
1ꢀ(4ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)phenyl)ethanone (3p) (CAS no. 42030ꢀ75ꢀ1). Yield
92%, 5.06 g; m.p. 120–121 oC, 1H NMR (400 MHz, CDCl3) δ: 8.03 (d, J = 8 Hz, 2H), 7.29 (d, J = 8
Hz, 2H), 4.01 (s, 6H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 196.7, 173.8, 172.7, 155.2, 134.8,
130.1, 121.8, 55.6, 26.6. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C13H13N3O4Na 298.0798; Found
298.0797.
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2,4ꢀDimethoxyꢀ6ꢀ(3′ꢀ(trifluoromethyl)phenoxy)ꢀ1,3,5ꢀtriazine (3q). Yield 90%, 5.42 g; m.p. 51–53 C,
1H NMR (400 MHz, CDCl3) δ: 7.58–7.56 (m, 2H), 7.51 (s, 1H), 7.43–7.41 (m, 1H), 4.03 (s, 6H). 13C
NMR (100 MHz, CDCl3) δ: 173.8, 172.8, 151.7, 132.2, 131.8, 130.1, 125.2, 124.8, 122.8, 122.1, 119.0,
55.5. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C12H10F3N3O3Na 324.0567; Found 324.0573.
4ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)ꢀ3ꢀmethoxybenzaldehyde (3r). Yield 93%, 5.40 g; m.p.
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149–151 C, H NMR (400 MHz, CDCl3) δ: 9.97 (s, 1H), 7.52 (d, J = 8 Hz, 2H), 7.33 (d, J = 8 Hz,
1H), 3.99 (s, 6H), 3.86 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 191.0, 173.8, 172.7, 152.0, 135.3,
124.9, 123.1, 111.0, 56.1, 55.5. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C13H13N3O5Na 314.0747;
Found 314.0753.
2,4ꢀDimethoxyꢀ6ꢀ(4′ꢀnitrophenoxy)ꢀ1,3,5ꢀtriazine (3s) (CAS no. 28690ꢀ95ꢀ1). Yield 92%, 5.10 g; m.p.
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135–137 C, H NMR (400 MHz, CDCl3) δ: 8.32 (d, J = 8 Hz, 2H), 7.38 (d, J = 8 Hz, 2H), 4.03 (s,
6H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 172.4, 156.2, 145.4, 125.4, 122.5, 55.7. HRMS (ESIꢀTOF)
m/z: [M+Na]+ Calcd. for C11H10N4O5Na 301.0543; Found 301.0541.
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2,4ꢀDimethoxyꢀ6ꢀ(pyridineꢀ3′ꢀyloxy)ꢀ1,3,5ꢀtriazine (3t). Yield 91%, 4.25 g; m.p. 98–100 C, H NMR
(400 MHz, CDCl3) δ: 8.55–8.53 (m, 2H), 7.56 (d, J = 8 Hz, 1H), 7.40–7.36 (m, 1H), 4.01 (s, 6H). 13
C
NMR (100 MHz, CDCl3) δ: 173.8, 172.9, 148.4, 147.16, 143.6, 129.1, 123.9, 55.6. HRMS (ESIꢀTOF)
m/z: [M+Na]+ Calcd. for C10H10N4O3Na 257.0645; Found 257.0648.
7ꢀ((4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)ꢀ4ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (3u). Yield 91%, 5.72 g;
m.p. 204–206 C, 1H NMR (400 MHz, CDCl3) δ: 7.67 (d, J = 8 Hz, 1H), 7.27 (m, 1H), 7.18 (dd, J =
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4.4 Hz, 1H), 6.32 (s, 1H), 4.05 (s, 6H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 172.7,
160.4, 154.2, 153.9, 151.9, 125.6, 118.1, 114.6, 110.6, 55.7, 18.7. HRMS (ESIꢀTOF) m/z: [M+Na]+
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Calcd. for C15H13N3O5Na 338.0747; Found 338.0747.
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3,3ꢀBis(4′ꢀ((4′′,6′′ꢀdimethoxyꢀ1′′,3′′,5′′ꢀtriazinꢀ2′′ꢀyl)oxy)phenyl)isobenzofuranꢀ1(3H)ꢀone (3v). Yield
88%, 10.50 g; m.p. 207–209 oC, 1H NMR (400 MHz, CDCl3) δ: 7.97 (d, J = 8 Hz, 1H), 7.76–7.72 (m,
1H), 7.61–7.58 (m, 2H), 7.41 (d, J = 8 Hz, 4H), 7.18 (d, J = 8 Hz, 4H), 4.00 (s, 12H). 13C NMR (100
MHz, CDCl3) δ: 173.7, 172.9, 169.4, 151.8, 151.5, 138.1, 134.4, 129.6, 128.5, 126.2, 124.1, 121.6,
115.1, 90.7, 55.6. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C30H24N6O8Na 619.1548; Found
619.1539.
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(8R,9S,13S,14S)ꢀ3ꢀ((4′,6′ꢀdimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)oxy)ꢀ13ꢀmethylꢀ7,8,9,11,12,13,15,16ꢀoctahyd
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roꢀ6Hꢀcyclopenta[a]phenanthrenꢀ17(14H)ꢀone (3w). Yield 94%, 7.69 g; m.p. 155–157 C, 1H NMR
(400 MHz, CDCl3) δ: 7.30 (d, J = 8 Hz, 1H), 6.95 (dd, J = 4.8 Hz, 1H), 6.89 (d, J = 4 Hz, 1H), 4.01 (s,
6H), 2.92–2.90 (m, 2H), 2.55–2.48 (m, 1H), 2.43–2.39 (m, 1H), 2.2–2.13 (m, 1H), 2.09–1.99 (m, 3H),
1.69–1.62 (m, 2H), 1.59–1.48 (m, 4H), 1.46–1.40 (m, 1H), 0.92 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ: 220.8, 173.7, 173.3, 149.6, 138.0, 137.4, 126.4, 121.2, 118.6, 55.4, 50.4, 47.9, 44.1, 37.9, 35.8, 31.5,
29.4, 26.3, 25.7, 21.5, 13.8. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C23H27N3O4Na 432.1894;
Found 432.1903.
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2,4ꢀDimethoxyꢀ6ꢀ(pyridineꢀ2′ꢀyloxy)ꢀ1,3,5ꢀtriazine (3x). Yield 90%, 4.21 g; m.p. 68–70 C, 1H NMR
(400 MHz, CDCl3) δ: 8.43 (d, J = 4 Hz, 1H), 7.86–7.81 (m, 1H), 7.28–7.24 (m, 1H), 7.13 (d, J = 8 Hz,
1H), 4.00 (s, 6H). 13C NMR (100 MHz, CDCl3) δ: 173.8, 172.8, 158.7, 148.5, 139.8, 122.1, 115.9,
55.5. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C10H10N4O3Na 257.0645; Found 257.0648.
1ꢀ(4′,6′ꢀDimethoxyꢀ1′,3′,5′ꢀtriazinꢀ2′ꢀyl)pyridineꢀ4(1H)ꢀone (3y). Yield 92%, 4.30 g; m.p. 179–181 oC,
1H NMR (400 MHz, CDCl3) δ: 8.78 (d, J = 8 Hz, 2H), 6.44 (d, J = 8 Hz, 2H), 4.14 (s, 6H). 13C NMR
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(100 MHz, CDCl3) δ: 181.0, 173.1, 164.3, 134.0, 118.7, 56.0. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd.
for C10H10N4O3Na 257.0645; Found 257.0648.
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General Procedure for Suzuki Coupling of ArꢀOꢀDMT Ethers with Arylboronic Acids. To a
Schlenk tube were added in turn ether 3 (1.0 mmol), arylboronic acid 4 (4.0 mmol), NiCl2(dppf) (0.05
mmol), and K3PO4 (7.0 mmol) in Ar2. Toluene (7 mL) was injected by syringe. The mixture was
stirred at a preꢀheated oil bath (110 oC) for 24 h. The reaction mixture was cooled to room temperature
and CH2Cl2 (25 mL) added. After filtration via a short pad of celite, the filtrate was condensed under
vacuum and the residue was purified by flash column chromatography to provide the biaryl products.
4ꢀMethoxyꢀ1,1'ꢀbiphenyl (5a) (CAS no. 613ꢀ37ꢀ6). 1H NMR (400 MHz, CDCl3) δ: 7.56–7.52 (m, 4H),
7.42 (t, J = 8 Hz, 2H), 7.30 (t, J = 8 Hz, 1H), 6.98 (d, J = 8 Hz, 2H), 3.85 (s, 3H).
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4'ꢀMethoxyꢀ2ꢀmethylꢀ1,1'ꢀbiphenyl (5b) (CAS no. 92495ꢀ54ꢀ0). H NMR (400 MHz, CDCl3) δ:
7.24–7.20 (m, 6H), 6.92 (d, J = 8 Hz, 2H), 3.80 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) δ:
158.6, 141.6, 135.5, 134.4, 130.4, 130.3, 130.0, 127.1, 125.8, 113.6, 55.3, 20.6.
4ꢀMethoxyꢀ4'ꢀmethylꢀ1,1'ꢀbiphenyl (5c) (CAS no. 53040ꢀ92ꢀ9). 1H NMR (400 MHz, CDCl3) δ: 7.42 (d,
J = 8 Hz, 2H), 7.34 (d, J = 8 Hz, 2H), 7.14 (d, J = 8Hz, 2H), 6.88 (d, J = 8 Hz, 2H), 3.75 (s, 3H), 2.30
(s, 3H). 13C NMR (100 MHz, CDCl3) δ: 157.8, 136.9, 135.3, 132.6, 128.4, 126.9, 125.5, 113.1, 54.2,
20.0.
1ꢀ(4′ꢀMethoxyphenyl)naphthalene (5d) (CAS no. 27331ꢀ33ꢀ5). 1H NMR (400 MHz, CDCl3) δ:
7.85–7.80 (m, 2H), 7.74 (d, J = 8 Hz, 1H), 7.44–7.39 (m, 2H), 7.36–7.31 (m, 4H), 6.94 (d, J = 8 Hz,
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2H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 157.8, 138.8, 132.8, 132.0, 130.7, 130.0, 127.2,
126.2, 125.8, 125.0, 124.8, 124.6, 124.3, 112.6, 54.3.
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2H), 7.42–7.38 (m, 2H), 7.33–7.29 (m, 3H),7.04–6.97 (m, 2H)，3.80 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 156.4, 138.5, 130.9, 130.7, 129.5, 128.6, 128.0, 126.9, 120.8, 111.2, 55.5.
4'ꢀMethoxyꢀ3ꢀmethylꢀ1,1'ꢀbiphenyl (5f) (CAS no. 17171ꢀ17ꢀ4). 1H NMR (400 MHz, CDCl3) δ: 7.55 (d,
J = 8 Hz, 2H), 7.4–7.34 (m, 3H), 7.15(d, J = 4 Hz, 1H), 7.00 (d, J = 8 Hz, 2H), 3.88 (s, 3H), 2.44 (s,
3H). 13C NMR (100 MHz, CDCl3) δ: 158.0, 139.7, 137.2, 132.8, 127.6, 127.1, 126.5, 126.3, 122.8,
113.1, 54.3, 20.5.
2ꢀ(4'ꢀMethoxyphenyl)naphthalene (5g) (CAS no. 59115ꢀ45ꢀ6). 1H NMR (400 MHz, CDCl3) δ: 7.99 (s,
1H), 7.91–7.84 (m, 3H), 7.73–7.65 (m, 3H), 7.50–7.46 (m, 2H), 7.03 (d, J = 12 Hz, 2H), 3.88 (s, 3H).
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4'ꢀMethoxyꢀ3,5ꢀdimethylꢀ1,1'ꢀbiphenyl (5h) (CAS no. 473774ꢀ78ꢀ6). H NMR (400 MHz, CDCl3) δ:
7.51 (d, J = 12 Hz, 2H), 7.16 (s, 2H), 6.96–6.94 (m, 3H), 3.83 (s, 3H), 2.36 (s, 6H). 13C NMR (100
MHz, CDCl3) δ: 159.0, 140.8, 138.2, 134.0, 128.3, 128.2, 124.7, 114.1, 55.3, 21.4.
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4ꢀ(tertꢀButyl)ꢀ4'ꢀmethoxyꢀ1,1'ꢀbiphenyl (5i) (CAS no. 19812ꢀ91ꢀ0). H NMR (400 MHz, CDCl3) δ:
7.52–7.42 (m, 6H), 6.95 (d, J = 12 Hz, 2H), 3.81 (s, 3H), 1.35 (s, 9H). 13C NMR (100 MHz, CDCl3) δ:
159.0, 149.6, 138.0, 133.7, 128.0, 126.4, 125.7, 114.2, 55.3, 34.54, 31.4.
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Nꢀ([1,1'ꢀBiphenyl]ꢀ3ꢀyl)acetamide (5j) (CAS no. 2113ꢀ54ꢀ4). H NMR (400 MHz, CDCl3) δ: 7.72 (s,
1H), 7.57 (d, J = 8 Hz, 2H), 7.50 (d, J = 8Hz, 1H), 7.4–7.32 (m, 6H), 2.19 (m, 3H). 13C NMR (100
MHz, CDCl3) δ: 168.4, 144.7, 142.1, 138.3, 129.4, 128.7, 127.5, 127.2, 123.1, 118.8, 118.6, 24.7.
Methyl [1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylate (5k) (CAS no. 720ꢀ75ꢀ2). 1H NMR (400 MHz, CDCl3) δ: 8.11(d,
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J = 8 Hz, 2H), 7.68–7.62 (m, 4H), 7.47 (dd, J = 8.4 Hz, 2H), 7.41 (d, J = 4 Hz, 1H), 3.94 (s, 3H). 13
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[1,1'ꢀBiphenyl]ꢀ4ꢀcarbonitrile (5l) (CAS no. 2920ꢀ38ꢀ9). 1H NMR (400 MHz, CDCl3) δ: 7.69 (dd, J =
12 Hz, 4H), 7.58(d, J = 12 Hz, 2H), 7.5–7.42 (m, 3H). 13C NMR (100MHz, CDCl3) δ: 145.6, 139.1,
132.6, 129.1, 128.6, 127.7, 127.2, 118.9, 110.9.
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4ꢀFluoroꢀ4'ꢀmethoxyꢀ1,1'ꢀbiphenyl (5m) (CAS no. 450ꢀ39ꢀ5). 1H NMR (400 MHz, CDCl3) δ: 7.5–7.45
(m, 4H), 7.09 (t, J = 8 Hz, 2H), 6.97 (d, J = 12 Hz, 2H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3) δ:
163.3, 160.9, 159.1, 137.0, 132.8, 128.2, 128.1, 128.0, 127.7, 115.6, 115.4, 114.2, 55.3.
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[1,1'ꢀBiphenyl]ꢀ4ꢀcarbaldehyde (5n) (CAS no. 3218ꢀ36ꢀ8). H NMR (400 MHz, CDCl3) δ: 10.04 (s,
1H), 7.94 (d, J = 8 Hz, 2H), 7.74 (d, J = 8 Hz, 2H), 7.62 (d, J = 4 Hz, 2H)，7.47 (t, J = 8 Hz, 2H), 7.41
(t, J = 8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 190.8, 146.1, 138.6, 134.1, 129.2, 127.9, 127.4,
126.6, 126.3.
1ꢀ([1,1'ꢀBiphenyl]ꢀ4ꢀyl)ethanone (5o) (CAS no. 92ꢀ91ꢀ1). 1H NMR (400 MHz, CDCl3) δ: 8.04 (d, J =
12 Hz, 2H), 7.68 (d, J = 12 Hz, 2H), 7.63 (d, J = 4 Hz, 2H), 7.47 (t, J = 8 Hz, 2H), 7.40 (t, J = 8 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ: 197.6, 145.8, 139.9, 135.8, 128.9, 128.9, 128.2, 127.2, 127.2,
26.67.
4'ꢀMethoxyꢀ3ꢀ(trifluoromethyl)ꢀ1,1'ꢀbiphenyl (5p) (CAS no. 194873ꢀ98ꢀ8). 1H NMR (400 MHz,
CDCl3) δ: 7.79 (s, 1H), 7.72 (d, J = 8 Hz, 1H), 7.55–7.52 (m, 4H), 6.99 (d, J = 12 Hz, 2H), 3.86 (s,
3H). 13C NMR (100 MHz, CDCl3) δ: 159.7, 141.6, 132.2, 131.2, 130.9, 129.9, 129.1, 128.2, 123.5,
123.4, 123.4, 123.3, 123.2, 123.2, 114.4, 55.3.
2ꢀMethoxyꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarbaldehyde (5q) (CAS no. 248263ꢀ04ꢀ9). 1H NMR (400 MHz, CDCl3)
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δ: 10.05 (s, 1H), 7.60–7.29 (m, 8H), 3.93 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 191.8, 156.9, 137.2,
136.8, 136.8, 131.3, 129.4, 128.1, 127.9, 124.4, 109.6, 55.7.
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3ꢀPhenylpyridine (5s) (CAS no. 1008ꢀ88ꢀ4). 1H NMR (400 MHz, CDCl3) δ: 8.85 (s, 1H), 8.59 (d, J =
4 Hz, 1H), 7.87 (d, J = 8 Hz, 1H), 7.59 (d, J = 12 Hz, 2H), 7.51–7.46 (m, 2H), 7.43–7.34 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ: 149.2, 149.0, 138.5, 137.3, 135.0, 129.8, 128.8, 127.8, 124.2.
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4ꢀMethylꢀ7ꢀphenylꢀ2Hꢀchromenꢀ2ꢀone (5t). M.p. 99–101 C, 1H NMR (400 MHz, CDCl3) δ: 7.7–7.65
(m, 3H), 7.58–7.56 (m, 2H), 7.52 (t, J = 8.8 Hz, 2H), 7.45 (t, J = 8.8 Hz, 1H), 6.32 (s, 1H), 2.5 (s, 3H).
13C NMR (100MHz, CDCl3) δ: 160.9, 153.9, 152.2, 144.9, 139.1, 129.1, 128.5, 127.2, 124.9, 123.0,
118.9, 115.1, 114.8, 18.6. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C16H12O2Na 259.0730; Found
259.0735.
3,3ꢀDi([1,1'ꢀbiphenyl]ꢀ4ꢀyl)isobenzofuranꢀ1(3H)ꢀone (5u). 1H NMR (400 MHz, CDCl3) δ: 7.91 (d, J =
8 Hz, 1H), 7.67 (t, J = 4.8 Hz, 1H), 7.59 (d, J = 8 Hz, 1H), 7.54–7.49 (m, 9H), 7.37–7.28 (m, 10). 13C
NMR (100 MHz, CDCl3) δ: 168.7, 150.9, 140.5, 139.2, 138.7, 133.2, 128.4, 127.8, 126.6, 126.5,
126.2, 126.1, 125.1, 124.6, 123.1, 90.4. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C32H22O2Na
461.1512; Found 461.1518.
(8R,9S,13S,14S)ꢀ13ꢀMethylꢀ3ꢀphenylꢀ7,8,9,11,12,13,15,16ꢀoctahydroꢀ6Hꢀcyclopenta[a]phenanthrenꢀ1
o
7(14H)ꢀone (5v). M.p. 178–180 C, 1H NMR (400 MHz, CDCl3) δ: 7.58 (d, J = 8 Hz, 2H), 7.44–7.32
(m, 6H), 2.99 (dd, J = 4.8 Hz, 2H), 2.55–2.44 (m, 2H), 2.38–2.32 (m, 1H), 2.19–1.97 (m, 4H),
1.69–1.45 (m, 6H), 0.92 (s,3H). 13C NMR (100 MHz, CDCl3) δ: 220.9, 141.0, 138.9, 138.8, 136.9,
128.7, 127.7, 127.1, 127.0, 125.8, 124.6, 50.5, 48.0, 44.4, 38.2, 35.9, 31.6, 29.5, 26.5, 25.7, 21.6, 13.9.
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C24H26ONa 353.1876; Found 353.1874.
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3'ꢀ(Trifluoromethyl)ꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarbaldehyde (5a′). H NMR (400 MHz, CDCl3) δ: 10.09 (s,
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1H), 8.00 (d, J = 8 Hz, 2H), 7.88 (s, 1H), 7.82 (d, J = 8 Hz, 1H), 7.77 (d, J = 8 Hz, 2H), 6.68 (d, J = 8
Hz, 1H), 7.63 (m, 1H).13C NMR (100 MHz, CDCl3) δ: 191.7, 145.5, 140.5, 135.7, 130.8, 130.6, 130.4,
129.5, 127.8, 125.3, 125.1, 125.1, 125.0, 125.0, 124.2, 124.2, 124.1, 124.1. MS m/z: 250(M+). Anal.
Calcd for C14H9F3O: C, 67.20; H, 3.63. Found: C 67.28, H, 3.61.
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1ꢀ(3'ꢀ(Trifluoromethyl)ꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀyl)ethanone (5b′) (CAS no. 709667ꢀ96ꢀ9). H NMR (400
MHz, CDCl3) δ: 8.07 (d, J = 8 Hz, 2H), 7.87 (s, 1H), 7.80 (d, J = 8 Hz, 2H), 7.70–7.65 (m, 3H),
7.61–7.57 (s, 1H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 197.5, 144.1, 140.6, 136.4, 131.5,
130.5, 129.4, 129.0, 127.3, 124.8, 124.8, 124.0, 123.9, 122.7, 26.6.
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Ethyl 4'ꢀacetylꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylate (5c′) (CAS no. 119838ꢀ61ꢀ8). H NMR (400 MHz,
CDCl3) δ: 8.14 (d, J = 8 Hz, 2H), 8.06 (d, J = 8 Hz, 2H), 7.73–7.68 (m, 4H), 4.41 (q, J = 8 Hz, 2H),
2.66 (s, 3H), 1.43 (t, J = 8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ: 197.6, 166.3, 144.5, 144.1, 136.4,
130.2, 130.1, 129.0, 127.4, 127.2, 61.1, 26.7, 14.3.
Ethyl 3'ꢀacetamidoꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylate (5d′). M.p. 117–119 oC, 1H NMR (400 MHz, CDCl3)
δ: 8.09 (d, J = 8 Hz, 2H), 7.80 (s, 1H), 7.63 (d, J = 8 Hz, 2H), 7.53 (d, J = 8 Hz, 1H), 7.48–7.35 (m,
3H), 4.40 (q, J = 8 Hz, 2H), 2.21 (s, 3H), 1.41 (t, J = 8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ: 168.4,
166.5, 145.0, 140.9, 138.5, 130.0, 129.5, 129.4, 127.0, 123.2, 119.5, 118.7, 61.0, 24.7, 14.3. HRMS
(ESIꢀTOF) m/z: [M–H]– Calcd. for C17H16NO3 282.1134; Found 282.1137.
Ethyl 4'ꢀcyanoꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylate (5e′) (CAS no. 89409ꢀ89ꢀ2). 1H NMR (400 MHz, CDCl3)
δ: 8.15 (d, J = 8 Hz, 2H), 7.76 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H), 7.66 (d, J = 8 Hz, 2H), 4.42 (q,
J = 8 Hz, 2H), 1.42 (t, J = 8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ: 166.1, 144.4, 143.2, 132.7,
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130.5, 130.3, 127.9, 127.1, 118.6, 111.7, 61.2, 14.3.
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4ꢀFluoroꢀ4'ꢀmethylꢀ1,1'ꢀbiphenyl (5f′) (CAS no. 72093ꢀ43ꢀ7). 1H NMR (400 MHz, CDCl3) δ:
7.53–7.50 (m, 2H), 7.43 (d, J = 8 Hz, 2H), 7.23 (d, J = 8 Hz, 2H), 7.10 (t, J = 8 Hz, 2H), 2.38 (s, 3H).
13C NMR (100 MHz, CDCl3) δ: 163.5, 161.1, 137.4, 137.3, 137.2, 137.0, 129.5, 128.5, 128.4, 126.8,
115.6, 115.4, 21.0.
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4'ꢀFluoroꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarbaldehyde (5g′) (CAS no. 60992ꢀ98ꢀ5). 1H NMR (400 MHz, CDCl3) δ:
10.06 (s, 1H), 7.95 (d, J = 12 Hz, 2H), 7.72 (d, J = 12 Hz, 2H), 7.63–7.59 (m, 2H), 7.20–7.15 (m, 2H).
13C NMR (100 MHz, CDCl3) δ: 191.8, 164.3, 157.8, 146.1, 135.8, 135.1, 130.3, 129.1, 129.0, 127.5,
116.1, 115.9.
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Methyl 4'ꢀfluoroꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxylate (5h′) (CAS no. 80254ꢀ87ꢀ1). H NMR (400 MHz,
CDCl3) δ: 8.10 (d, J = 12 Hz, 2H), 7.63–7.57 (m, 4H), 7.18–7.13 (m, 2H), 3.94 (s, 3H). 13C NMR (100
MHz, CDCl3) δ: 166.9, 164.1, 161.7, 144.6, 136.1, 136.1, 130.1, 128.9, 128.9, 126.9, 116.0, 115.7,
52.1.
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1ꢀ(4'ꢀFluoroꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀyl)ethanone (5i′) (CAS no. 720ꢀ74ꢀ1). H NMR (400 MHz, CDCl3) δ:
8.03 (d, J = 12 Hz, 2H), 7.65–7.57 (m, 4H), 7.16 (t, J = 12 Hz, 2H), 2.64 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 197.7, 164.2, 161.7, 144.7, 136.0, 135.9, 135.8, 128.9, 128.9, 127.0, 116.0, 115.8, 26.69.
(8R,9S,13S,14S)ꢀ3ꢀ(4ꢀFluorophenyl)ꢀ13ꢀmethylꢀ7,8,9,11,12,13,15,16ꢀoctahydroꢀ6Hꢀcyclopenta[a]phe
o
nanthrenꢀ17(14H)ꢀone (5j′). M.p. 181–183 C, 1H NMR (400 MHz, CDCl3) δ: 7.54–7.50 (m, 2H),
7.37–7.32 (m, 2H), 7.28 (s, 1H), 7.13–7.07 (m, 2H), 2.99 (dd, J = 4.4 Hz, 2H), 2.55–2.44 (m, 2H),
2.38–2.31 (m, 1H), 2.20–1.96 (m, 4H), 1.69–1.45 (m, 6H), 0.92 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ: 220.8, 163.5, 161.1, 138.9, 137.8, 137.1, 137.0, 128.5, 128.4, 127.6, 125.9, 124.4, 115.6, 115.4,
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50.5, 48.0, 44.3, 38.2, 35.8, 31.6, 29.5, 26.5, 25.7, 21.6, 13.8. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd.
for C24H25FONa 371.1782; Found 371.1784.
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3ꢀ(pꢀTolyl)thiophene (5k′) (CAS no. 16939ꢀ05ꢀ2). H NMR (400 MHz, CDCl3) δ: 7.50 (d, J = 12 Hz,
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2H), 7.40–7.34 (m, 3H), 7.21 (d, J = 12 Hz, 2H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 142.3,
136.8, 133.0, 129.4, 126.3, 126.3, 126.0, 119.6, 21.1.
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1ꢀ(4ꢀ(Thiophenꢀ3ꢀyl)phenyl)ethanone (5l′) (CAS no. 172035ꢀ84ꢀ6). H NMR (400 MHz, CDCl3) δ:
8.00 (d, J = 12 Hz, 2H), 7.69 (d, J = 12 Hz, 2H), 7.59–7.58 (m, 1H), 7.44–7.43 (m, 3H), 2.62 (s, 3H).
13C NMR (100 MHz, CDCl3) δ: 197.5, 141.1, 140.2, 135.6, 129.0, 126.7, 126.3, 126.1, 122.0, 26.6.
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Methyl 4'''ꢀchloroꢀ[1,1':4',1'':4'',1'''ꢀquaterphenyl]ꢀ4ꢀcarboxylate (5m′). H NMR (400 MHz, CDCl3)
δ: 8.12 (d, J = 8 Hz, 2H), 7.71–7.63 (m, 8H), 7.56 (m, 3H), 7.43 (m, 3H), 3.95 (s, 3H). 13C NMR (100
MHz, CDCl3) δ: 165.9, 143.9, 138.7, 138.1, 137.8, 132.6, 129.1, 128.0, 127.8, 127.3, 127.2, 126.7,
126.6, 126.4, 126.3, 126.0, 125.8, 51.1. ESIꢀMS [M–Cl]+: 362.5. Anal. Calcd for C26H19ClO2: C,
78.29; H, 4.80. Found: C 78.20, H, 4.79.
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2,4ꢀDimethoxyꢀ6ꢀphenylꢀ1,3,5ꢀtriazine (6a) (CAS no. 18213ꢀ73ꢀ5). H NMR (400 MHz, CDCl3) δ:
8.52 (d, J = 8 Hz, 2H), 7.59 (t, J = 8 Hz, 1H), 7.50 (t, J = 8.8 Hz, 2H), 4.15 (s, 6H). 13C NMR (100
MHz, CDCl3) δ: 174.9, 172.9, 135.0, 132.8, 129.0, 128.4, 55.2.
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2,4ꢀDimethoxyꢀ6ꢀ(pꢀtolyl)ꢀ1,3,5ꢀtriazine (6b) (CAS no. 42010ꢀ75ꢀ3). H NMR (400 MHz, CDCl3) δ:
8.39 (d, J = 8 Hz, 2H), 7.27 (d, J = 8 Hz, 2H), 4.12 (s, 6H), 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ: 174.9, 172.8, 143.5, 132.3, 129.2, 129.0, 55.1, 21.6.
ACKNOWLEDGMENT
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This research was supported by the National Natural Science Foundation of China (grant nos.
21172111 and 20502012).
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Supporting Information
1H and 13C NMR spectra copies of compounds 3a–y, 5a–q, 5s–v, 5a′–m′, 6a and 6b; crystallographic
data of compounds 3a and 3y. This material is available free of charge via the Internet at
http://pubs.acs.org.
RERERENCES
(1) de Meijere, A.; Diederich, F. Eds. MetalꢀCatalyzed CrossꢀCoupling Reactions; WileyꢀVCH:
Weinheim, 2004; Vols. 1–2.
(2) Miyaura, N. Top. Curr. Chem. 2002, 219, 11–59.
(3) Mesganaw, T.; Garg, N. K. Org. Process Res. Dev. 2013, 17, 29–39.
(4) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.; Garg, N. K.; Percec,
V. Chem. Rev. 2011, 111, 1346–1416.
(5) Li, B.ꢀJ.; Yu, D.ꢀG.; Sun, C.ꢀL.; Shi, Z.ꢀJ. Chem. Eur. J. 2011, 17, 1728–1759.
(6) Yu, D.ꢀG.; Li, B.ꢀJ.; Shi, Z.ꢀJ. Acc. Chem. Res. 2010, 43, 1486–1495.
(7) Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866–4869.
(8) Guan, B.ꢀT.; Wang, Y.; Li, B.ꢀJ.; Yu, D.ꢀG.; Shi, Z.ꢀJ. J. Am. Chem. Soc. 2008, 130,
14468–14470.
(9) Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008, 130, 14422–14423.
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7
8
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(10) Quasdorf, K. W.; AntoftꢀFinch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.;
Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352–6363.
(11) Xu, L.; Li, B.ꢀJ.; Wu, Z.ꢀH.; Lu, X.ꢀY.; Guan, B.ꢀT.; Wang, B.ꢀQ.; Zhao, K.ꢀQ.; Shi, Z.ꢀJ. Org.
Lett. 2010, 12, 884–887.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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54
55
56
57
58
59
60
(12) Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009, 131,
17748–17749.
(13) AntoftꢀFinch, A.; Blackburn, T.; Snieckus, V. J. Am. Chem. Soc. 2009, 131, 17750–17752.
(14) Baghbanzadeh, M.; Pilger, C.; Kappe, C. O. J. Org. Chem. 2011, 76, 1507–1510.
(15) Chen, G.ꢀJ.; Han, F.ꢀS. Eur. J. Org. Chem. 2012, 3575–3579.
(16) Zhao, Y.ꢀL.; Li, Y.; Li, Y.; Gao, L.ꢀX.; Han, F.ꢀX. Chem. Eur. J. 2010, 16, 4991–4994.
(17) Li, S.ꢀM.; Huang, J.; Chen, G.ꢀJ.; Han, F.ꢀS. Chem. Commun. 2011, 47, 12840–12842.
(18) Chen, G.ꢀJ.; Huang, J.; Gao, L.ꢀX.; Han, F.ꢀS. Chem. Eur. J. 2011, 17, 4038–4042.
(19) Chen, H.; Huang, Z.; Hu, X.; Tang, G.; Xu, P.; Zhao, Y.; Cheng, C.ꢀH. J. Org. Chem. 2011, 76,
2338–2344.
(20) Leowanawat, P.; Zhang, N.; Safi, M.; Hoffman, D. J.; Fryberger, M. C.; George, A.; Percec, V.
J. Org. Chem. 2012, 77, 2885–2892.
(21) Gao, H.; Li, Y.; Zhou, Y.ꢀG.; Han, F.ꢀS.; Lin, Y.ꢀJ. Adv. Synth. Catal. 2011, 353, 309–314.
(22) Blotny, G. Tetrahedron 2006, 62, 9507–9522.
(23) Kaminski, Z. J.; Paneth, P.; Rudzinski, J. J. Org. Chem. 1998, 63, 4248–4255.
(24) Kaminski, Z. J. Int. J. Peptide Protein Res. 1994, 43, 312–319.
(25) Kaminski, Z. J.; Paneth, P.; O’Leary, M. J. Org. Chem. 1991, 56, 5716–5719.
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(26) Munakata, M.; Wen, M.; Suenaga, Y.; KurodaꢀSowa, T.; Maekawa, M.; Anahata, M.
Polyhedron 2001, 20, 2321–2327.
8
9
(27) Ueno, S.; Mizushima, E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128,
16516–16517.
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(28) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126,
2706–2707.
(29) Li, Z.; Zhang, S.ꢀL.; Fu, Y.; Guo, Q.ꢀX.; Liu, L. J. Am. Chem. Soc. 2009, 131, 8815–8823.
(30) Although the commercially available 2ꢀchloroꢀ4,6ꢀdimethoxyꢀ1,3,5ꢀtriazine 2 is somewhat
costly (RMB 3682/100 g, Alfa Aesa, CAS # 3140ꢀ73ꢀ6), it is readily prepared from more cheap
cyanuric chloride (RMB 463/1.0 kg, Alfa Aesa, CAS # 108ꢀ77ꢀ0) and methanol on a large scale (see:
Cronin, J. S.; Ginah, F. O.; Murray, A. R.; Copp, J. D. Synth. Commun. 1996, 26, 3491–3494).
Relatively, the approximate reagent costs: N,Nꢀdimethylsulfamoyl chloride (RMB 5530/500 g, Alfa
Aesa, CAS # 13360ꢀ57ꢀ1), N,Nꢀdimethylcarbamyl chloride (RMB 1159/500 g, Sigma–Aldrich, CAS #
79ꢀ44ꢀ7), and methanesulfonyl chloride (RMB 1048/500 mL, Sigma–Aldrich, CAS # 124ꢀ63ꢀ0).
(31) See Supporting Information for crystallographic data of compounds 3a and 3y.
(32) Fan, X.ꢀH.; Yang, L.ꢀM. Eur. J. Org. Chem. 2010, 2457–2460.
(33) For using aryl diazonium salts as substrates in crossꢀcoupling reactions, see: Roglans, A.;
PlaꢀQuintana, A.; MorenoꢀManas, M. Chem. Rev. 2006, 106, 4622–4643 and references cited therein.
(34) Blakey, S. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 6046–6047.
(35) Saeki, T.; Son, Eꢀ.C.; Tamao, K. Org. Lett. 2004, 6, 617–619.
(36) Liu, J.; Robins, M. J. Org. Lett. 2004, 6, 3421–3423.
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(37) Koreeda, T.; Kochi, T.; Kakiuchi, F. J. Am. Chem. Soc. 2009, 131, 7238–7239.
(38) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129, 6098–6099
(39) Other heteroaryl boronic acids, such as 2ꢀfurylboronic acid, 3ꢀ and 4ꢀpyridinylboronic acids,
5ꢀpyrimidinylboronic acid, etc., were also examined under the present catalytic system. All of them
afforded the responding biaryl in poor yields.
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