Synthesis of triarylmethanes by palladium-catalyzed c-h/c-o coupling of oxazoles and diarylmethanol derivatives

Article abstract of DOI:10.1021/jo5010636

A PdCl₂(MeCN)₂/PPhCy₂ catalyst couples oxazoles with diarylmethyl carbonates or pivalates to form the corresponding triarylmethanes in good yields. The catalysis involves successive secondary benzylic sp³ C-O and heteroaromatic sp² C-H cleavages and provides an effective access to heteroarene-containing triarylmethanes from nonhalogenated and nonmetalated starting materials, which is complementary to precedented cross-coupling technologies with organic halides and organometallic reagents.

Full text of DOI:10.1021/jo5010636

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Synthesis of Triarylmethanes by Palladium-Catalyzed C−H/C−O
Coupling of Oxazoles and Diarylmethanol Derivatives
Sho Tabuchi, Koji Hirano,* Tetsuya Satoh, and Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A PdCl2(MeCN)2/PPhCy2 catalyst couples
oxazoles with diarylmethyl carbonates or pivalates to form
the corresponding triarylmethanes in good yields. The catalysis
involves successive secondary benzylic sp3 C−O and hetero-
aromatic sp2 C−H cleavages and provides an effective access to
heteroarene-containing triarylmethanes from nonhalogenated
and nonmetalated starting materials, which is complementary to
precedented cross-coupling technologies with organic halides and organometallic reagents.
coupling of simple diarylmethanes and electron-rich anisoles is
INTRODUCTION
■
also achieved by the iron/DDQ catalyst system (route c).15 In
this context, we focused on the less explored fourth route with
nonfunctionalized arenes and diarylmethanol electrophiles via
aromatic sp2 C−H and benzylic sp3 C−O cleavages (route d).
Herein, we report a PdCl2(MeCN)2/PPhCy2-catalyzed C−H/C−O
coupling of oxazoles and diarylmethyl carbonates or pivalates.
This catalysis allows the rapid and concise construction of oxazole-
incorporated triarylmethanes, which are somewhat difficult to
prepare by other means (Scheme 2).16
Triarylmethanes are prevalent substructures in biologically
active compounds1 and natural products.2 Additionally, they
also constitute an important class of compounds in material
science, exemplified by their frequently occurring in dyes,3
fluorescent probes,4 and photochromic agents.5 A classical
access to the above target structure is the Lewis-acid-promoted
Friedel−Crafts-type alkylation of arenes with diarylmethyl
electrophiles.6 This reaction is well-established and practical,
but the arene substrate scope is strictly limited to the electron-
rich aromatics. Moreover, the regioselectivity is largely depen-
dent on innate electronic and steric natures of the arene employed.
To address the above problems, the transition-metal-
catalyzed cross-coupling approaches have been recently
developed (Scheme 1). Kuwano reported the palladium-
catalyzed Suzuki−Miyaura cross-coupling of diarylmethyl
carbonates with arylboronic acids (route a).7 Jarvo8 and
Watson9 independently developed relevant nickel catalysis,
in which the asymmetric synthesis becomes possible by the
stereospecific C−C bond formation with optically active
diarylmethanol derivatives. More recently, Crudden introduced
diarylmethyl sulfones as coupling partners in this type of the
reaction.10 The same group also succeeded in the enantiospe-
cific reverse cross-coupling with chiral diarylmethylboronates.11
On the other hand, metal-mediated C−H functionalization
strategies12 also have received significant attention in this
research field because they can obviate some preactivation
steps, such as halogenation and stoichiometric metalation, of
starting substrates. Yorimitsu and Oshima reported the
palladium-catalyzed arylation of aryl(azaaryl)methanes with
aryl halides, in conjunction with CsOH·OH2 as base, providing
the corresponding triarylmethanes directly (route b).13 Walsh
and co-workers successfully expanded the substrate scope into
more general diarylmethanes by the combination of stronger
metal amide bases and a Cr(CO)314a stoichiometric activator or
a uniquely deprotonatable ligand, NiXantphos.14b,c While re-
latively restricted in scope, the dehydrogenative C−H/C−H
RESULTS AND DISCUSSION
■
Previously, we reported a Pd2(dba)3/dppp/NaOAc/DMSO
system for the successful direct benzylation of oxazoles with
primary benzyl methyl carbonates (Scheme 3a).17 Unfortu-
nately, this first generation catalyst was not capable of coupling
of benzoxazole (1a) with secondary diarylmethyl carbonates.
Attempts to apply methyl diphenylmethyl carbonate gave no
desired triarylmethane, and the corresponding homocoupling
product, 1,1,2,2-tetraphenylethane, was formed exclusively
(Scheme 3b).18 Even with conceivably more reactive naphthyl-
substituted Boc carbonate 2a19 and higher catalyst loading, only
11% yield of 3aa was observed by 1H NMR analysis (Scheme 3c).
Inspired by recent advances in the nickel-catalyzed cross-
coupling reaction with C−O electrophiles,8,9,20 we then turned
our attention into Ni(0) catalysts (Scheme 4). However, we
could not obtain an acceptable yield of 3aa as far as we tested,
although the reaction proceeded to some extent in the presence
of several Ni(cod)2/bulky monodentate phosphine catalysts
and a LiO-t-Bu base in heating diglyme (see the Supporting
Information for more details). Thus, on the basis of positive
effects of LiO-t-Bu and ethereal solvents in Scheme 4, we re-
investigated Pd-based catalyst systems (Table 1). To our delight, 1a
coupled with 2a smoothly under PdCl2(MeCN)2/Cy-JohnPhos
Received: May 15, 2014
© XXXX American Chemical Society
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Scheme 1. Cross-Coupling Approaches to Triarylmethanes
Scheme 2. Palladium-Catalyzed C−H/C−O Coupling
other bases including K3PO4, NaO-t-Bu, KO-t-Bu, and Mg(O-t-Bu)2
(entries 12−15). The ancillary ligands also gave major impacts
on the reaction efficiency. While other Buchwald biarylphos-
phines did not increase the yield (entries 16−20), simpler
monodentate phosphines such as PPh3, PCy3, PPh2Cy, and
PPhCy2 showed similar or better performance (entries 21−24).
In particular, PPhCy2 resulted in the highest yield and good
reproducibility (entry 24). Some bidentate phosphines also
promoted the reaction, albeit with lower yields (entries
25−28). Finally, an increase in the amount of 1,4-dioxane to
3.0 mL suppressed a major side reaction, hydrolysis of 2a, to
further improve the yield to 90% (entry 29). Even with the
lower catalyst loading (5 mol % PdCl2(MeCN)2 and 10 mol %
PPhCy2), a satisfactory yield was obtained (entry 30). The
control experiments in the absence of Pd, ligand, or both
revealed no formation of 3aa, confirming Pd catalysis in the
present process (data not shown).
of Oxazoles and Diarylmethanol Derivatives
catalysis to form 3aa in 69% NMR yield (entry 1). The choice of
Pd precursors was critical: Pd(OAc)2 and Pd(acac)2 proved to be
comparable, whereas PdCl2(PhCN)2, PdCl2, [PdCl(π-allyl)]2,
Pd(OCOCF3)2, and Pd2(dba)3 were less effective (entries 2−8).
Subsequent screening of solvents (entries 9−11) identified 1,4-
dioxane to be optimal, giving 3aa in 79% NMR yield (entry 9).
On the other hand, the yield largely dropped when we employed
Scheme 3. Our Early Attempts to Apply Primary and Secondary Benzyl Carbonates in Pd2(dba)3/dppp/NaOAc/DMSO System
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Scheme 4. Representative Results of Optimization Studies for Nickel-Catalyzed C−H/C−O Coupling of Benzoxazole (1a) and
Naphthyl-Substituted Boc Carbonate 2a
Table 1. Optimization Studies for Palladium-Catalyzed C−H/C−O Coupling of Benzoxazole (1a) and Naphthyl-Substituted
a
Boc Carbonate 2a
temp yield
b
entry
Pd/ligand
base
solvent
1,4-dioxane 120
1,4-dioxane 120 10
120 10
(°C) (%)
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
PdCl2(MeCN)2/Cy-JohnPhos NaO-t-Bu
PdCl2(MeCN)2/Cy-JohnPhos KO-t-Bu
9
PdCl2(MeCN)2/Cy-JohnPhos Mg(O-t-Bu)2 DMF
PdCl2(MeCN)2/JohnPhos
PdCl2(MeCN)2/SPhos
PdCl2(MeCN)2/RuPhos
PdCl2(MeCN)2/XPhos
PdCl2(MeCN)2/DavePhos
PdCl2(MeCN)2/PPh3
PdCl2(MeCN)2/PCy3
PdCl2(MeCN)2/PPh2Cy
PdCl2(MeCN)2/PPhCy2
PdCl2(MeCN)2/dppe
PdCl2(MeCN)2/binap
PdCl2(MeCN)2/dppf
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
1,4-dioxane 120
2
1,4-dioxane 120 53
1,4-dioxane 120 60
temp yield
(°C) (%)
b
entry
Pd/ligand
base
solvent
1,4-dioxane 120
7
1,4-dioxane 120 36
1,4-dioxane 120 83
1,4-dioxane 120 77
1,4-dioxane 120 74−87
1
PdCl2(MeCN)2/Cy-JohnPhos LiO-t-Bu
PdCl2(PhCN)2/Cy-JohnPhos LiO-t-Bu
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
120 69 (60)
120 28
120 18
120 18
120 61
120 18
120 64
120 40
2
3
PdCl2/Cy-JohnPhos
[PdCl(π-allyl)]2/Cy-JohnPhos LiO-t-Bu
Pd(OAc)2/Cy-JohnPhos LiO-t-Bu
Pd(OCOCF3)2/Cy-JohnPhos LiO-t-Bu
LiO-t-Bu
c
4
1,4-dioxane 120 86 (76)
5
1,4-dioxane 120 67
6
1,4-dioxane 120 63
7
Pd(acac)2/Cy-JohnPhos
Pd2(dba)3/Cy-JohnPhos
LiO-t-Bu
LiO-t-Bu
1,4-dioxane 120 53
8
PdCl2(MeCN)2/Xantphos
PdCl2(MeCN)2/PPhCy2
PdCl2(MeCN)2/PPhCy2
1,4-dioxane 120 13
9
PdCl2(MeCN)2/Cy-JohnPhos LiO-t-Bu
PdCl2(MeCN)2/Cy-JohnPhos LiO-t-Bu
PdCl2(MeCN)2/Cy-JohnPhos LiO-t-Bu
PdCl2(MeCN)2/Cy-JohnPhos K3PO4
1,4-dioxane 120 79 (64)
d
29
1,4-dioxane 120 92 (90)
1,4-dioxane 120 90 (88)
10
11
12
DME
80 trace
100 19
de
,
30
CPME
1,4-dioxane 120
0
a
Reaction conditions: 1a (0.50 mmol), 2a (0.25 mmol), Pd (0.025 mmol), ligand (0.050 mmol for monodentate ligands, 0.025 mmol for bidentate
b
c
ligands), base (0.50 mmol), solvent (1.5 mL), N2. NMR yield. Yield is given in parentheses. Somewhat poor reproducibility. We have no
explanation for the reason at present. In 3.0 mL of 1,4-dioxane. With 5 mol % of PdCl2(MeCN)2 and 10 mol % of PPhCy2.
d
e
With the optimized conditions in hand (Table 1, entry 29),
we performed the C−H/C−O coupling of benzoxazole (1a)
with a variety of diarylmethanol derivatives 2 (Table 2). As the
leaving group, pivalate (2a′) and methyl carbonate (2a″) were
also accommodated in the synthesis of 3aa (entries 2 and 3). In
the case of electron-rich substrates, the pivalate group worked
better (entries 4−7), probably due to its higher stability under
reaction conditions. The opposite trend was observed when the
electron-withdrawing substituent was introduced (entries 8−10).
The catalysis was compatible with electron-rich heteroaromatics
C
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a
Table 2. Palladium-Catalyzed C−H/C−O Coupling of Benzoxazole (1a) with Various Diarylmethanol Derivatives (2)
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Table 2. continued
a
Reaction conditions: 1a (0.50 mmol), 2a (0.25 mmol), PdCl2(MeCN)2 (0.025 mmol), PPhCy2 (0.050 mmol), LiO-t-Bu (0.50 mmol), 1,4-dioxane
b
c
d
e
(3.0 mL), N2. NMR yield. Yield is given in parentheses. In 1.5 mL of 1,4-dioxane. In 0.50 mL of 1,4-dioxane. With Cy-JohnPhos instead of
PPhCy2. With PPh3 instead of PPhCy2.
f
such as thiophene and furan in the Ar1 ring (entries 11−13).
Notably, the more remarkable positive effect of Piv was observed
in the reaction of the thiophene-containing substrate (entry 11 vs
12). The product was not a target triarylmethane, but methyl-
substituted diarylmethane 3ah was also accessible (entry 14),
despite the possibility of β-hydrogen elimination from an alkyl
Pd intermediate (vide infra).21 We next tested fused aromatics
other than the 2-naphthyl group (Ar2). The diarylmethanol deriv-
atives that bear 1-naphthyl, 3-benzothienyl, and 2-benzofuryl
substituents reacted with 1a to afford 3ai−ak with synthetically
valuable levels (entries 15−17). The biphenyl-type system 2l
also underwent the direct coupling, and the corresponding 3al
was produced in an acceptable yield (entry 18). On the other
hand, expectedly, the simpler diphenylmethyl Boc carbonate
2m and phenyl(2-thienyl)methyl pivalate 2n′ afforded
moderate yields of 3am and 3an (entries 19 and 22).19 Even
with Cy-JohnPhos or PPh3 instead of PPhCy2, the yield of 3am
was not improved (entries 20 and 21).22
In addition to the simple benzoxazole (1a), monocyclic
5-substituted oxazoles could be employed for the catalytic
C−H/C−O coupling. In these cases, slight modifications were
essential for obtaining the successful conversion: (1) the use of
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a
Scheme 5. Palladium-Catalyzed C−H/C−O Coupling of Various 5-Substituted Oxazoles
a
Reaction conditions: 1 (0.25 mmol), 2 (0.50 mmol), PdCl2(MeCN)2 (0.025 mmol), PPhCy2 (0.050 mmol), LiO-t-Bu (1.0 mmol), 1,4-dioxane
b
c
(3.0 mL), N2. The coupling partner is given in parentheses. With 1.5 mmol of LiO-t-Bu. With PPh3 instead of PPhCy2.
oxazoles as a limiting agent; (2) higher loading of LiO-t-Bu.
Representative results are illustrated in Scheme 5. Both
electron-donating methyl and methoxy and electron-with-
drawing trifluoromethyl groups on the phenyl ring of the
parent 5-phenyloxazole were well tolerated for the coupling
with 2a (3ba−fa). Only in the reaction of chloro-substituted
oxazole, the replacement of PPhCy2 with PPh3 was necessary,
due to the competitive protodechlorination under the stan-
dard conditions (3ga). Bulky naphthyl and conjugated styryl
moieties did not interfere with this catalysis to furnish 3ha and 3ia
in 80 and 64% yields, respectively. The 5-phenyloxazole also effec-
tively coupled with the methoxyphenyl-, thienyl-, and benzothienyl-
substituted pivalates 2b′, 2f′, and 2j′, leading to 3bb, 3bf, and 3bj
in good yields. The current major limitation is inaccessibility to
other heteroarenes including thiazoles and imidazoles. While the
exact reason is not clear at this stage, the acidity of C−H may play a
pivotal role in the C−H cleavage step.23
On the basis of literature information and our findings, we
are tempted to assume the reaction mechanism of 1a with 2a
as follows (Scheme 6). Initial off-cycle reduction of Pd(II)
by the action of the PPhCy2, LiO-t-Bu,24 or LiO-t-Bu/1a25 and
coordination of PPhCy2 forms the starting Pd(0) species 4.
Subsequent oxidative addition of 2a (4 → 5) is followed by
decarboxylation to generate the alkyl(tert-butoxy)palladium
intermediate 6. With the pivalate 2a′ in place of the Boc
carbonate 2a, the decarboxylation step is skipped and the
oxidative addition of 2a′ directly affords the alkyl(pivaloyloxy)
palladium 6′ corresponding to 6. Base-assisted C−H pallada-
tion of 1a26 with 6 occurs to form the alkyl(heteroaryl)
palladium 7. Final productive reductive elimination provides
the desired triarylmethane 3aa along with the regeneration of
the starting Pd(0) complex 4 to close the catalytic cycle. Given
the better reactivity of higher fused aromatic systems observed
in Table 2 (for example, entry 1 vs 19 and entry 12 vs 22), the
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Scheme 6. Plausible Mechanism
participation of π-benzyl intermediate is likely.19 The overall
stereochemistry (retention or inversion of configuration of
starting diarylmethanols) remains elusive at present. The facile
racemization of the triarylmethane product associated with
higher acidity of the benzylic C−H increased difficulties to
study the mechanistic details.27 Further efforts on modification
of the catalyst system were essential.
was stirred for a few minutes to activate Mg. A solution of
bromobenzene (3.15 mL, 30 mmol) in THF (27 mL) was then
added slowly to the flask via an addition funnel. After the addition
completion, the resulting suspension was stirred for additional 30 min
at room temperature. A solution of 2-naphthaldehyde (3.12 g,
20 mmol) in THF (10 mL) was added dropwise, and the suspension
was stirred for 24 h. The resulting mixture was quenched with aq.
NH4Cl and then extracted three times with ethyl acetate. The
combined organic layer was dried over sodium sulfate. Concentration
in vacuo and subsequent purification by column chromatography on
silica gel with hexane/ethyl acetate (5/1 v/v) as an eluent gave (2-
naphthyl)(phenyl)methanol (3.95 g, 17 mmol) in 85% yield.
To a solution of the above (2-naphthyl)(phenyl)methanol (3.95 g,
17 mmol) in THF (30 mL), n-BuLi (1.6 M hexane solution, 10.6 mL,
17 mmol) was added dropwise at −78 °C, and the solution was stirred
at −78 °C. After 30 min, Boc2O (3.9 mL, 17 mmol) was added drop-
wise at 0 °C, and the suspension was stirred for 2 h at room tem-
perature. The resulting mixture was quenched with water and then
extracted three times with ethyl acetate. The combined organic layer
was dried over sodium sulfate. Concentration in vacuo and subsequent
purification by column chromatography on silica gel with hexane/ethyl
acetate (20/1 v/v) as an eluent gave tert-butyl (2-naphthyl)(phenyl)-
methyl carbonate (2a; 5.11 g, 15.3 mmol) in 90% yield.
CONCLUSION
■
We have developed a second generation palladium-based
catalyst system, PdCl2(MeCN)2/PPhCy2/LiO-t-Bu/1,4-diox-
ane for the C−H/C−O coupling of oxazoles and diary-
lmethanol derivatives. The present catalysis allows the relatively
challenging secondary benzyl carbonates and pivalates to be
adopted in the direct coupling with oxazoles and provides a
concise access to heteroarene-containing triarylmethanes,
which are interesting scaffolds in medicinal and material
chemistry. Further development of more mild and reactive
catalysts and clarification of the stereochemistry are currently
underway in our laboratory.
Typical Procedure for Preparation of Diarylmethyl Pivalates 2′.
The synthesis of 2a′ is representative: to a solution of (2-naphthyl)-
(phenyl)methanol (3.95 g, 17 mmol), which is synthesized by the
same procedure as for the preparation of the carbonate 2a, in THF
(30 mL), n-BuLi (1.6 M hexane solution, 10.6 mL, 17 mmol) was
added dropwise at −78 °C, and the solution was stirred at −78 °C.
After 30 min, pivaloyl chloride (2.0 mL, 17 mmol) was added
dropwise at 0 °C, and the mixture was stirred for 2 h at room tem-
perature. The resulting mixture was quenched with water and then
extracted three times with ethyl acetate. The combined organic layer
was dried over sodium sulfate. Concentration in vacuo and subsequent
purification by column chromatography on silica gel with hexane/ethyl
acetate (20/1 v/v) as an eluent gave (2-naphthyl)(phenyl)methyl
pivalate (2a′; 4.65 g, 14.6 mmol) in 86% yield.
EXPERIMENTAL SECTION
■
Instrumentation and Chemicals. 1H and 13C NMR spectra were
recorded at 400 and 100 MHz, respectively, for CDCl3 solutions.
HRMS data were obtained by APCI using a TOF. GC analysis was
carried out using a silicon OV-17 column (i.d. 2.6 mm × 1.5 m) or a
CBP-1 capillary column (i.d. 0.5 mm × 25 m). TLC analyses were
performed on commercial glass plates bearing a 0.25 mm layer of
Merck silica gel 60F254. Silica gel was used for column chromatog-
raphy. Gel permeation chromatography (GPC) was performed with a
CHCl3 eluent (3.5 mL/min, UV detector). Unless otherwise noted,
materials obtained from commercial suppliers were used without
further purification. Anhydrous THF was purchased and used out of
the bottle without further purification, and 1,4-dioxane was dried on a
Glass Contour Solvent dispending system (Nikko Hansen & Co.,
Ltd.) prior to use. 5-Substituted oxazoles 1 were prepared by the van
Leusen reaction with TosMIC and the corresponding aldehydes.28
Diarylmethyl Boc carbonates 2 and pivalates 2′ were synthesized
from the corresponding secondary carbinols and Boc2O or PivCl,
respectively.8,9 Unless otherwise noted, all reactions were carried out
under N2 conditions.
Typical Procedure for Pd-Catalyzed Direct C−H/C−O
Coupling of Oxazoles and Diarylmethanol Derivatives. The
synthesis of 3aa is representative (Table 2, entry 1): PdCl2(MeCN)2
(6.5 mg, 0.025 mmol), PCy2Ph (13.7 mg, 0.050 mmol), and LiO-t-Bu
(40.0 mg, 0.50 mmol) were placed in a 20 mL two neck flask equipped
with a reflux condenser, which was filled with nitrogen. 1,4-Dioxane
(2.0 mL) was added to the flask, and suspension was stirred for 2 min
at room temperature. A solution of benzoxazole (1a; 59.5 mg,
0.50 mmol) and tert-butyl (2-naphthyl)(phenyl)methyl carbonate (2a;
83.5 mg, 0.25 mmol) in 1,4-dioxane (1.0 mL) was then added to the
flask, and the suspension was stirred for 6 h at 120 °C. The resulting
mixture was quenched with water and then extracted three times with
Typical Procedure for Preparation of tert-Butyl Diarylmethyl
Carbonates 2. The synthesis of 2a is representative: Mg turnings
(875 mg, 36 mmol) were placed in a 100 mL three neck flask, which
was filled with nitrogen. A solution of 1,2-dibromoethane (0.2 mL,
2.3 mmol) in THF (3 mL) was added to the flask, and the suspension
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ethyl acetate. The combined organic layer was dried over sodium
sulfate. Concentration in vacuo and subsequent purification by column
chromatography on silica gel with hexane/ethyl acetate (20/1 v/v) as
an eluent gave 2-[naphthalen-2-yl(phenyl)methyl]benzo[d]oxazole
(3aa; 75.5 mg, 0.23 mmol) in 90% yield.
2.6 Hz, 1H), 7.30 (dd, J = 4.3, 3.3 Hz, 1H), 7.33 (dd, J = 4.4, 3.0 Hz,
1H), 7.44 (dd, J = 1.8, 0.76 Hz, 1H), 7.45−7.52 (m, 3H), 7.57 (dd, J =
8.5, 1.1 Hz, 1H), 7.73−7.77 (m, 1H), 7.79−7.85 (m, 4H) ; 13C{1H}
NMR (100 MHz, CDCl3) δ 46.0, 108.9, 110.6, 110.7, 120.4, 124.4,
125.1, 126.3 (overlapped), 126.4, 127.6, 127.7, 128.1, 128.7, 132.9,
133.4, 134.2, 141.2, 142.7, 151.0, 151.6, 164.7; HRMS (APCI) m/z
([M + H]+) calcd for C22H16NO2 326.1176, found 326.1176.
2-[1-(Naphthalen-2-yl)ethyl]benzo[d]oxazole (3ah). Purified by
column chromatography on silica gel with ethyl acetate/hexane (1/20
v/v) as an eluent; 53 mg (77%): mp 115−116 °C (from ethyl acetate/
hexane); 1H NMR (400 MHz, CDCl3) δ 1.92 (d, J = 7.2 Hz, 3H), 4.58
(q, J = 7.2 Hz, 1H), 7.27 (ddd, J = 7.4, 4.7, 1.6 Hz, 1H), 7.30 (ddd, J =
7.4, 4.7, 1.6 Hz, 1H), 7.42−7.50 (m, 4H), 7.72−7.75 (m, 1H), 7.79−
7.82 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ 19.8, 40.3, 110.5,
119.9, 124.2, 124.7, 125.6, 125.9, 126.1, 126.3, 127.7, 127.9,
128.6, 132.6, 133.5, 138.6, 141.2, 150.9, 168.8; HRMS (APCI) m/z
([M + H]+) calcd for C19H16NO 274.1236, found 274.1226.
2-[Naphthalen-2-yl(phenyl)methyl]benzo[d]oxazole (3aa). Puri-
fied by column chromatography on silica gel with ethyl acetate/hexane
(1/20 v/v) as an eluent; 76 mg (90%): mp 114−115 °C (from ethyl
1
acetate/hexane); H NMR (400 MHz, CDCl3) δ 5.93 (s, 1H), 7.27−
7.40 (m, 7H), 7.43−7.51 (m, 4H), 7.74−7.79 (m, 3H), 7.80−7.83 (m,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 51.7, 110.7, 120.3, 124.3,
124.9, 126.1, 126.3, 126.9, 127.52, 127.53, 127.6, 128.0, 128.5, 128.8,
128.9, 132.6, 133.4, 136.7, 139.1, 141.3, 151.0, 166.7; HRMS (APCI)
m/z ([M + H]+) calcd for C24H18NO 336.1387, found 336.1383.
2-[(4-Methoxyphenyl)(naphthalen-2-yl)methyl]benzo[d]oxazole
(3ab). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent; 76 mg (83%): mp 113−114 °C
1
(from ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 3.79 (s,
2-[Naphthalen-1-yl(phenyl)methyl]benzo[d]oxazole (3ai). Puri-
fied by column chromatography on silica gel with ethyl acetate/hexane
(1/20 v/v) as an eluent; 68 mg (82%): mp 155−156 °C (from ethyl
3H), 5.89 (s, 1H), 6.89 (dd, J = 8.8, 2.1 Hz, 2H), 7.29−7.34 (m, 4H),
7.43−7.52 (m, 4H), 7.72−7.83 (m, 5H); 13C{1H} NMR (100 MHz,
CDCl3) δ 50.9, 55.3, 110.7, 114.2, 120.2, 124.3, 124.9, 126.1, 126.3,
126.8, 127.3, 127.6, 128.0, 128.5, 130.0, 131.2, 132.6, 133.4, 137.0,
141.3, 151.0, 158.9, 167.0; HRMS (APCI) m/z ([M + H]+) calcd for
C25H20NO2 366.1494, found 366.1489.
1
acetate/hexane); H NMR (400 MHz, CDCl3) δ 6.54 (s, 1H), 7.27−
7.38 (m, 8H), 7.39−7.48 (m, 4H), 7.71−7.74 (m, 1H), 7.82 (d, J = 8.4
Hz, 1H), 7.86−7.89 (m, 1H), 8.03−8.06 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 48.0, 110.7, 120.3, 123.3, 124.3, 124.9, 125.4,
125.8, 126.7, 126.9, 127.5, 128.4, 128.8, 128.98, 129.02, 131.5, 134.0,
135.0, 138.8, 141.4, 151.0, 167.0; HRMS (APCI) m/z ([M + H]+)
calcd for C24H18NO 336.1383, found 336.1383.
2-[Naphthalen-2-yl(2-methylphenyl)methyl]benzo[d]oxazole
(3ac). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent; 50 mg (58%): mp 125−126 °C
1
(from ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 2.34 (s,
2-[Benzo[b]thiophen-3-yl(phenyl)methyl]benzo[d]oxazole(3aj).
Purified by column chromatography on silica gel with ethyl acetate/
hexane (1/20 v/v) as an eluent; 65 mg (76%): mp 154−155 °C (from
3H), 6.10 (s, 1H), 7.16−7.24 (m, 4H), 7.29−7.34 (m, 2H), 7.40−7.49
(m, 4H), 7.64 (s, 1H), 7.73−7.79 (m, 2H), 7.80−7.83 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 19.8, 48.4, 110.7, 120.3,
1
ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 6.07 (s, 1H),
7.27−7.36 (m, 8H), 7.43−7.45 (m, 2H), 7.45−7.50 (m, 1H), 7.62 (d,
J = 7.7 Hz, 1H), 7.71−7.74 (m, 1H), 7.85 (dd, J = 7.2, 1.2 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 46.0, 110.7, 120.3, 121.9, 123.0,
124.3, 124.4, 124.6, 125.0, 125.4, 127.8, 128.7, 128.9, 133.3, 137.8,
137.9, 140.5, 141.3, 150.9, 165.9; HRMS (APCI) m/z ([M + H]+)
calcd for C22H16NOS 342.0947, found 342.0953.
124.3, 124.9, 126.1, 126.2, 126.4, 127.1, 127.7 (three signals were
overlapped.), 128.0, 128.5, 128.8, 130.9, 132.6, 133.4, 136.1, 136.5,
137.4, 141.4, 151.0, 166.9; HRMS (APCI) m/z ([M + H]+) calcd for
C25H20NO 350.1539, found 350.1539.
2-[(4-Chlorophenyl)(naphthalen-2-yl)methyl]benzo[d]oxazole
(3ad). Purified by column chromatography on silica gel with
ethyl acetate/hexane (1/20 v/v) as an eluent followed by GPC with
chloroform; 43 mg (47%), oil: 1H NMR (400 MHz, CDCl3) δ 5.89 (s,
1H), 7.30−7.33 (m, 6H), 7.43−7.50 (m, 4H), 7.72−7.82 (m, 5H);
13C{1H} NMR (100 MHz, CDCl3) δ 51.2, 110.7, 120.3, 124.5, 125.1,
2-[Benzofuran-2-yl(phenyl)methyl]benzo[d]oxazole (3ak). Puri-
fied by column chromatography on silica gel with ethyl acetate/hexane
1
(1/20 v/v) as an eluent; 32 mg (39%), oil: H NMR (400 MHz,
CDCl3) δ 5.89 (s, 1H), 6.66 (s, 1H), 7.18−7.27 (m, 2H), 7.31−7.44
(m, 6H), 7.49−7.53 (m, 4H), 7.73−7.77 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 46.3, 105.8, 110.8, 111.3, 120.4, 121.1, 122.9,
123.3, 124.3, 124.5, 125.2, 128.2, 128.7, 129.0, 136.2, 141.2, 151.0,
154.7, 155.2, 164.1; HRMS (APCI) m/z ([M + H]+) calcd for
C22H16NO2 326.1176, found 326.1176.
126.3, 126.4, 126.6, 127.5, 127.7, 128.0, 128.7, 129.0, 130.3, 132.7,
133.4, 133.5, 136.2, 137.6, 141.2, 151.0, 166.2; HRMS (APCI) m/z
([M + H]+) calcd for C24H17ClNO 370.0993, found 370.0993.
4-[Benzo[d]oxazol-2-yl(naphthalen-2-yl)methyl]benzonitrile
(3ae). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent; 48 mg (53%): mp 53−54 °C
2-([1,1′-Biphenyl]-4-yl(phenyl)methyl)benzo[d]oxazole (3al). Pu-
rified by column chromatography on silica gel with ethyl acetate/
hexane (1/20 v/v) as an eluent; 37 mg (42%): mp 126−127 °C (from
1
(from ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 5.96 (s,
1H), 7.33−7.37 (m, 2H), 7.43 (dd, J = 8.6, 1.8 Hz, 1H), 7.47−7.52
(m, 5H), 7.65 (d, J = 8.4 Hz, 2H), 7.73 (s, 1H), 7.75−7.86 (m, 4H);
13C{1H} NMR (100 MHz, CDCl3) δ 51.5, 110.8, 111.6, 118.6, 120.4,
124.6, 125.4, 126.4, 125.55, 126.63, 127.68, 127.71, 128.0, 129.0,
129.8, 132.6, 132.8, 133.3, 135.3, 141.1, 144.4, 150.9, 165.3; HRMS
(APCI) m/z ([M + H]+) calcd for C25H17N2O 361.1335, found
361.1335.
1
ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 5.81 (s, 1H),
7.29−7.44 (m, 12H), 7.48−7.50 (m, 1H), 7.56−7.58 (m, 4H), 7.72−
7.77 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 51.3, 110.7, 120.3,
124.3, 124.9, 127.1, 127.4, 127.5 (overlapped), 128.77, 128.82, 128.83,
129.2, 138.3, 139.2, 140.4, 140.6, 141.3, 151.0, 166.7; HRMS (APCI)
m/z ([M + H]+) calcd for C26H20NO 362.1539, found 362.1539.
2-[(Diphenyl)methyl]benzo[d]oxazole (3am). Purified by column
chromatography on silica gel with ethyl acetate/hexane (1/20 v/v) as
an eluent; 22 mg (31%): mp 62−63 °C (from ethyl acetate/hexane);
1H NMR (400 MHz, CDCl3) δ 5.77 (s, 1H), 7.27−7.35 (m, 12H),
7.46−7.50 (m, 1H), 7.71−7.76 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 51.6, 110.7, 120.2, 124.3, 124.9, 127.4, 128.76, 128.81,
139.2, 141.3, 151.0, 166.7; HRMS (APCI) m/z ([M + H]+) calcd for
C20H16NO 286.1226, found 286.1232.
2-[Naphthalen-2-yl(thiophen-2-yl)methyl]benzo[d]oxazole (3af).
Purified by column chromatography on silica gel with ethyl acetate/
hexane (1/20 v/v) as an eluent; 53 mg (62%): mp 102−103 °C (from
1
ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 6.12 (s, 1H),
6.99 (dd, J = 5.1, 3.6 Hz, 1H), 7.04−7.05 (m, 1H), 7.29 (dd, J = 5.1,
1.1 Hz, 1H), 7.31−7.35 (m, 2H), 7.45−7.51 (m, 3H), 7.58 (dd, J =
8.5, 1.1 Hz, 1H), 7.75−7.86 (m, 5H); 13C{1H} NMR (100 MHz,
CDCl3) δ 47.1, 110.8, 120.4, 124.4, 125.1, 125.7, 126.28, 126.31,
126.4, 126.9, 127.0, 127.3, 127.7, 128.1, 128.7, 132.8, 133.4, 136.4,
141.2, 141.7, 151.0, 165.8; HRMS (APCI) m/z ([M + H]+) calcd for
C22H16NOS 342.0958, found 342.0947.
2-(Phenyl(thiophen-2-yl)methyl)benzo[d]oxazole (3an). Purified
by column chromatography on silica gel with ethyl acetate/hexane
(1/20 v/v) as an eluent followed by GPC with chloroform; 26 mg
1
2-[Furan-2-yl(naphthalen-2-yl)methyl]benzo[d]oxazole (3ag).
(35%), oil: H NMR (400 MHz, CDCl3) δ 5.96 (s, 1H), 6.97−7.02
Purified by column chromatography on silica gel with ethyl acetate/
(m, 2H), 7.25−7.38 (m, 6H), 7.43−7.45 (m, 2H), 7.48−7.52 (m, 1H),
7.71−7.77 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 46.9, 110.7,
120.3, 124.4, 125.1, 125.5, 126.82, 126.84, 127.9, 128.4, 128.9, 139.0,
1
hexane (1/20 v/v) as an eluent; 33 mg (40%), oil: H NMR (400
MHz, CDCl3) δ 5.94 (s, 1H), 6.30−6.31 (m, 1H), 6.38 (dd, J = 2.9,
H
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141.1, 141.8, 151.0, 165.9; HRMS (APCI) m/z ([M + H]+) calcd for
C18H14NOS 292.0791, found 292.0788.
5-(Naphthalen-1-yl)-2-[naphthalen-2-yl(phenyl)methyl]oxazole
(3ha). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent followed by GPC with
2-[Naphthalen-2-yl(phenyl)methyl]-5-phenyloxazole (3ba). Puri-
fied by column chromatography on silica gel with ethyl acetate/hexane
(1/5 v/v) as an eluent followed by GPC with chloroform; 62 mg
(69%): mp 150−151 °C (from CHCl3); 1H NMR (400 MHz, CDCl3)
δ 5.84 (s, 1H), 7.28−7.32 (m, 2H), 7.35−7.41 (m, 7H), 7.44−7.48 (m,
3H), 7.59−7.61 (m, 2H), 7.72 (s, 1H), 7.77−7.83 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 51.3, 122.2, 124.2, 126.1, 126.2, 126.9,
127.3 (overlapped), 127.6, 128.0 (overlapped), 128.4, 128.5, 128.7,
128.8, 128.9, 132.6, 133.4, 137.4, 139.8, 151.6, 164.1; HRMS (APCI)
m/z ([M + H]+) calcd for C26H20NO 362.1548, found 362.1539.
5-(4-Methylphenyl)-2-[naphthalen-2-yl(phenyl)methyl]oxazole
(3ca). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent followed by GPC with
chloroform; 53 mg (57%): mp 149−150 °C (from CHCl3); 1H NMR
(400 MHz, CDCl3) δ 2.34 (s, 3H), 5.83 (s, 1H), 7.18 (d, J = 7.9, 2H),
7.26−7.29 (m, 2H), 7.34−7.35 (m, 4H), 7.43−7.49 (m, 5H), 7.71 (s,
1H), 7.76−7.81 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 21.4,
51.3, 121.6, 124.2, 125.3, 126.0, 126.2, 126.9, 127.3, 127.3, 127.6,
128.0, 128.4, 128.7, 128.8, 129.5, 132.6, 133.4, 137.5, 138.4, 139.9,
151.8, 163.7; HRMS (APCI) m/z ([M + H]+) calcd for C27H22NO
376.1699, found 376.1696.
5-(4-Methoxyphenyl)-2-[naphthalen-2-yl(phenyl)methyl]oxazole
(3da). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent followed by GPC with
chloroform; 61 mg (62%): mp 183−184 °C (from CHCl3); 1H NMR
(400 MHz, CDCl3) δ 3.81 (s, 3H), 5.82 (s, 1H), 6.91 (dd, J = 8.7, 1.4
Hz, 2H), 7.21 (s, 1H), 7.26−7.29 (m, 1H), 7.34−7.35 (m, 4H), 7.43−
7.47 (m, 3H), 7.52 (d, J = 8.7 Hz, 2H), 7.71 (s, 1H), 7.76−7.82 (m,
3H); 13C NMR (100 MHz, CDCl3) δ 51.2, 55.4, 114.3, 120.7, 120.9,
125.7, 126.0, 126.2, 126.9, 127.28, 127.31, 127.6, 128.0, 128.4, 128.7,
128.8, 132.5, 133.4, 137.5, 139.9, 151.6, 159.7, 163.4; HRMS (APCI)
m/z ([M + H]+) calcd for C27H22NO2 392.1644, found 392.1645.
5-(3,4-Dimethoxyphenyl)-2-[naphthalen-2-yl(phenyl)methyl]-
4,5-dihydrooxazole (3ea). Purified by column chromatography on
silica gel with ethyl acetate/hexane (1/5 v/v) as an eluent followed by
GPC with chloroform; 66 mg (63%): mp 147−148 °C (from CHCl3);
1H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), 3.91 (s, 3H), 5.83 (s,
1
chloroform; 82 mg (80%): mp 52−53 °C (from CHCl3); H NMR
(400 MHz, CDCl3) δ 5.92 (s, 1H), 7.28−7.35 (m, 1H), 7.35−7.53 (m,
11H), 7.69 (d, J = 7.2 Hz, 1H), 7.79−7.88 (m, 6H), 8.18 (d, J = 0.76
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 51.4, 125.0, 125.28,
125.34, 125.6, 126.1, 126.2, 126.3, 126.4, 126.9, 127.0, 127.39, 127.43,
127.7, 128.0, 128.5, 128.7, 128.8, 128.9, 129.6, 130.1, 132.6, 133.4,
133.9, 137.4, 139.9, 150.9, 164.4; HRMS (APCI) m/z ([M + H]+)
calcd for C30H22NO 412.1702, found 412.1696.
(E)-2-[Naphthalen-2-yl(phenyl)methyl]-5-styryloxazole (3ia). Pu-
rified by column chromatography on silica gel with ethyl acetate/
hexane (1/5 v/v) as an eluent followed by GPC with chloroform; 62
1
mg (64%): mp 146−147 °C (from CHCl3); H NMR (400 MHz,
CDCl3) δ 5.81 (s, 1H), 6.86 (d, J = 16.2 Hz, 1H), 6.99 (d, J = 16.2 Hz,
1H), 7.06 (s, 1H), 7.24−7.36 (m, 8H), 7.42−7.46 (m, 5H), 7.71 (s,
1H), 7.77−7.83 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 51.3,
113.1, 125.1, 126.1, 126.3, 126.5, 126.9, 127.35, 127.36, 127.7, 128.0,
128.2, 128.5, 128.76, 128.78, 128.81, 129.5, 132.6, 133.4, 136.3, 137.3,
139.7, 150.7, 164.1; HRMS (APCI) m/z ([M + H]+) calcd for
C28H22NO, 388.1706, found 388.1706.
2-[(4-Methoxyphenyl)(naphthalen-2-yl)methyl]-5-phenyloxazole
(3bb). Purified by column chromatography on silica gel with ethyl
1
acetate/hexane (1/5 v/v) as an eluent; 63 mg (64%), oil: H NMR
(400 MHz, CDCl3) δ 3.79 (s, 3H), 5.79 (s, 1H), 6.88 (d, J = 11.7 Hz,
2H), 7.26−7.31 (m, 3H), 7.34 (s, 1H), 7.36−7.40 (m, 2H), 7.43−7.47
(m, 3H), 7.57−7.61 (m, 2H), 7.69 (s, 1H), 7.76−7.82 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 50.5, 55.3, 114.1, 122.2, 124.2,
126.0, 126.2, 126.8, 127.1, 127.6, 128.0 (overlapped), 128.3, 128.4,
128.9, 129.9, 131.9, 132.5, 133.4, 137.7, 151.5, 158.8, 164.4; HRMS
(APCI) m/z ([M + H]+) calcd for C27H22NO2 392.1645, found
392.1645.
2-[Naphthalen-2-yl(thiophen-2-yl)methyl]-5-phenyloxazole
(3bf). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/20 v/v) as an eluent followed by GPC with
chloroform; 53 mg (58%): mp 122−123 °C (from CHCl3); 1H NMR
(400 MHz, CDCl3) δ 6.03 (s, 1H), 6.97−7.01 (m, 2H), 7.26−7.41 (m,
5H), 7.45−7.49 (m, 2H), 7.54−7.62 (m, 3H), 7.80−7.85 (m, 4H);
13C{1H} NMR (100 MHz, CDCl3) δ 46.7, 122.2, 124.2, 125.5, 126.2,
1H), 6.87 (d, J = 7.2 Hz, 1H), 7.07 (d, J = 2.0 Hz, 1H), 7.18 (dd, J =
8.3, 2.0 Hz, 1H), 7.23 (s, 1H), 7.27- 7.33 (m, 1H), 7.34−7.36 (m, 4H),
7.43−7.47 (m, 3H), 7.72 (s, 1H), 7.76−7.82 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 51.2, 55.99, 56.03, 107.5, 111.4, 117.2, 121.1
(overlapped), 126.0, 126.2, 126.9, 127.3 (overlapped), 127.6, 128.0,
128.4, 128.7, 128.8, 132.5, 133.4, 137.5, 139.9, 149.26, 149.34, 151.6,
163.5; HRMS (APCI) m/z ([M + H]+) calcd for C28H24NO3
422.1750, found 422.1751.
126.26, 126.31, 126.6, 126.8, 127.0, 127.7, 127.9, 128.1, 128.5, 128.6,
128.9, 132.8, 133.4, 137.0, 142.5, 151.7, 163.2; HRMS (APCI) m/z
([M + H]+) calcd for C24H18NOS 368.1104, found 368.1104.
2-(Benzo[b]thiophen-3-yl(phenyl)methyl)-5-phenyloxazole (3bj).
Purified by column chromatography on silica gel with ethyl acetate/
hexane (1/20 v/v) as an eluent; 70 mg (76%): mp 137−138 °C (from
1
ethyl acetate/hexane); H NMR (400 MHz, CDCl3) δ 5.97 (s, 1H),
2-[Naphthalen-2-yl(phenyl)methyl]-5-[4-(trifluoromethyl)-
phenyl]oxazole (3fa). Purified by column chromatography on silica
gel with ethyl acetate/hexane (1/5 v/v) as an eluent followed by GPC
7.26−7.42 (m, 12H), 7.56−7.64 (m, 3H), 7.71−7.74 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 45.6, 122.0, 122.3, 122.9, 124.2,
124.3, 124.5, 125.1, 127.6, 127.9, 128.4, 128.5, 128.86, 128.88, 134.1,
137.9, 138.4, 140.6, 151.6, 163.4; HRMS (APCI) m/z ([M + H]+)
calcd for C24H18NOS 368.1104, found 368.1104.
1
with chloroform; 54 mg (50%), oil: H NMR (400 MHz, CDCl3) δ
5.85 (s, 1H), 7.27−7.33 (m, 1H), 7.33−7.38 (m, 4H), 7.45 (ddd, J =
3.6, 3.2, 1.6 Hz, 2H), 7.47 (dd, J = 3.6, 3.0 Hz, 2H), 7.63 (d, J = 8.4
Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 7.72 (s, 1H), 7.76−7.83 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 51.3, 123.9 (q, J = 270 Hz),
124.1, 124.3, 125.3 (q, J = 3.8 Hz), 126.2, 126.3, 126.7, 127.4, 127.5,
127.7, 128.0, 128.6, 128.77, 128.81, 130. 0 (q, J = 32 Hz), 131.2, 132.6,
133.4, 137.1, 139.5, 150.3, 165.0; HRMS (APCI) m/z ([M + H]+)
calcd for C27H19F3NO 430.1412, found 430.1413.
5-(4-Chlorophenyl)-2-[naphthalen-2-yl(phenyl)methyl]oxazole
(3ga). Purified by column chromatography on silica gel with ethyl
acetate/hexane (1/5 v/v) as an eluent followed by GPC with
chloroform; 31 mg (31%), oil: 1H NMR (400 MHz, CDCl3) δ 5.83 (s,
1H), 7.27−7.32 (m, 1H), 7.33−7.36 (m, 7H), 7.44−7.47 (m, 3H),
7.50−7.54 (m, 2H), 7.71 (s, 1H), 7.77−7.83 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 51.3, 121.6, 124.2, 125.3, 126.0, 126.2, 126.9,
127.31, 127.33, 127.6, 128.0, 128.4, 128.7, 128.8, 129.5, 132.6, 133.4,
137.5, 138.4, 139.9, 151.8, 163.9; HRMS (APCI) m/z ([M + H]+)
calcd for C26H19ClNO 396.1149, found 396.1150.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
More detailed results of nickel-catalyzed reactions and H and
13C{1H} NMR spectra for products. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: k_hirano@chem.eng.osaka-u.ac.jp.
*E-mail: miura@chem.eng.osaka-u.ac.jp.
Notes
The authors declare no competing financial interest.
I
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The Journal of Organic Chemistry
Featured Article
J.; Dreher, S. D.; Tudge, M. T.; Yin, H.; Robinson, J. R.; Schelter, E. J.;
Walsh, P. J. J. Am. Chem. Soc. 2014, 136, 6276.
(15) Li, Y.-Z.; Li, B.-J.; Lu, X.-Y.; Lin, S.; Shi, Z.-J. Angew. Chem., Int.
ACKNOWLEDGMENTS
■
This work was supported by Grants-in-Aid for Scientific
Research from the MEXT and JSPS, Japan.
Ed. 2009, 48, 3817.
(16) Wang reported a copper-catalyzed direct coupling of oxazoles
with diaryl N-tosylhydrazones for the synthesis of similar triaryl-
methanes: Zhao, X.; Wu, G.; Zhang, Y.; Wang, J. J. Am. Chem. Soc.
2011, 133, 3296.
(17) Mukai, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12,
1360.
(18) Similar trends were often observed in the cross-coupling
reaction with diarylmethyl electrophiles. For example, see: Molander,
G. A.; Elia, M. D. J. Org. Chem. 2006, 71, 9198.
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J
dx.doi.org/10.1021/jo5010636 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
2010, 132, 6900. (f) Tamba, S.; Okubo, Y.; Tanaka, S.; Monguchi, D.;
Mori, A. J. Org. Chem. 2010, 75, 6998. (g) Yao, T.; Hirano, K.; Satoh,
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(27) Actually, the product 3ba underwent the facile deuterium
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the following scheme). Development of much milder conditions and
detailed stereochemical studies under modified catalysis are ongoing
and will be reported in due course.
(28) van Leusen, A. M.; Hoogenboom, B. E.; Sinderius, H.
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K
dx.doi.org/10.1021/jo5010636 | J. Org. Chem. XXXX, XXX, XXX−XXX