One-Pot Generation of Functionalized Benzynes from Readily Available 2-Hydroxyphenylboronic Acids

Article abstract of DOI:10.1021/acs.joc.9b03169

We developed a one-pot method for the generation of benzynes from a range of readily available 2-hydroxyphenylboronic acids. This method features the in situ activation of both boronic acid and hydroxyl groups of the substrate to enhance benzyne generation at 60 °C. Such mild conditions facilitate the generation of functionalized benzynes that immediately react with diverse arynophiles to produce multisubstituted fused benzenes.

Full text of DOI:10.1021/acs.joc.9b03169

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Article
One-Pot Generation of Functionalized Benzynes from
Readily Available 2-Hydroxyphenylboronic Acids
Takashi Ikawa, JingKai Sun, Akira Takagi, and Shuji Akai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03169 • Publication Date (Web): 04 Feb 2020
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One-Pot Generation of Functionalized Benzynes from
Readily Available 2-Hydroxyphenylboronic Acids
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Takashi Ikawa,†,* JingKai Sun,† Akira Takagi,†,‡ Shuji Akai†,*
†Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-
0871, Japan.
‡Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Supporting Information.
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E-mail: ikawa@phs.osaka-u.ac.jp, akai@phs.osaka-u.ac.jp
ABSTRACT: We developed a one-pot method for the generation of benzynes from a range of readily
available 2-hydroxyphenylboronic acids. This method features the in-situ activation of both boronic acid
and hydroxyl groups of the substrate to enhance benzyne generation at 60 °C. Such mild conditions
facilitate the generation of functionalized benzynes that immediately react with diverse arynophiles to
produce multi-substituted fused benzenes.
B(OH)2
OH
1. neopentyl glycol, RT
2. NfF, NaH, Cs2CO3
arynophile, 60 °C
X
Y
FG
FG
FG
Readily available
One-pot procedure
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INTRODUCTION
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Benzynes 1 are widely used intermediates for the preparation of many multi-substituted and/or fused-
aromatic compounds through nucleophilic additions, cycloadditions, and transition-metal-catalyzed
bond-forming reactions.1 However, benzynes are too reactive to be isolated at ambient atmosphere;
hence they need to be generated in-situ in the presence of arynophiles. Therefore, the selection of
suitable precursors and conditions that effectively use benzynes for the synthesis of aromatic
compounds is very important.2 Currently, the most widely used benzyne precursors are 2-
(trimethylsilyl)aryl trifluoromethanesulfonates (2-silylaryl triflates) owing to their abilities to efficiently
generate benzynes under mild fluoride-ion-mediated conditions.1,3 However, this method is hardly
applicable to benzynes bearing reactive functional groups, such as halogens and carbonyls, as the
corresponding 2-silylaryl triflates are prepared using alkyl lithium reagents during the installation of the
silyl group on the benzene ring.
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Based on this background, Hosoya’s group,4b Greaney’s group,2c and our research group4a,c
independently discovered that 2-borylphenyl triflates 2 and 3 (Scheme 1), which are available by the
borylation of aromatic rings under much milder conditions5 than those used during silylation, serve as
new precursors for the generation of functionalized benzynes. As a result, Hosoya et al.4b and Greaney
et al.2c generated benzynes from pinacol boronates 2 with strong bases such as BuLi and t-BuOK/Pd as
the catalyst. However, the difficulty in preparing functionalized benzynes remained unsolved. In
contrast, our method enables the generation of a number of functionalized benzynes 1 from neopentyl
glycol boronates 3 using CsF. Nevertheless, this reaction requires a relatively high temperature (120 °C)
and microwave irradiation, which limits its synthetic applicability. In addition, precursors 2 and 3 are
prepared through multi-step transformations from commercially available chemicals. A new method that
produces a variety of functionalized benzynes directly from readily available materials under milder
conditions may solve all of the above-mentioned issues.
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Herein, we report the one-pot generation of benzynes 1 from readily-accessible 2-
hydroxyphenylboronic acids 4 (Scheme 1). This method features the in-situ activation of both the
boronic acid and hydroxyl groups of 4 to generate 2-[(neopentyl glycolato)boryl]phenyl nonaflates 6,
which are then converted into 1 at lower temperature (60 °C) than our previous method without any
additional fluoride source. The generated 1 are successfully used in reactions with various arynophiles
to afford substituted aromatic compounds.
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Hosoya's method
Greaney's method
Our previous method
B(pin)
B(neop)
BuLi or
CsF
OTf
Pd cat.
t-BuOK
FG
Microwave
heating
X
FG
FG
1
2
3
(X = OTf, I, Br)
This work
Me
Me
O
B(neop)
OR
B(OH)2
B(pin):
B
Me
O
Me
OH
FG
FG
4
O
O
Me
Me
Readily available
precursors
5
6
: R = H
: R = SO2(n-C4F9) (Nf)
B
B(neop):
Scheme 1. Previous Methods for the Generation of Benzynes
from Boronic Esters (2 or 3) and the Method Developed in This
Work.
RESULTS AND DISCUSSION
Our preliminary experiments revealed that the O-nonaflylation of 2-[(neopentyl glycol)boryl]phenol 5a6
with nonafluorobutanesulfonyl fluoride (NfF)7 gradually generated benzyne 1a even at 60 °C.8 We also
found that the leaving ability of other sulfonyloxyl groups, such as trifluoromethanesulfonyloxyl (TfO),
methanesulfonyloxyl (MsO), and p-toluenesulfonyloxyl (TsO), prepared by the O-sulfonylation of 5a,
was lower than that of the NfO group in 6a.8 These observations convinced us that 2-
hydroxyphenylboronic acid 4a is an ideal precursor for the one-pot generation of 1a through the double
activation of its boronic acid and hydroxyl groups. Therefore, we first searched for suitable conditions
for the one-pot generation of benzyne from 4a (Table 1). Boronic ester 5a was prepared by the reaction
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of 4a with neopentyl glycol (1.2 equiv) in CH2Cl2 at RT for 3 h followed by azeotropic dehydration
with toluene. Anhydrous THF was then added to crude 5a and the resultant solution was reacted with
different inorganic bases (3.0 equiv) and NfF (3.0 equiv) at 60 °C for 24 h in the presence of 1,3-
diphenylisobenzofuran (IBF) (7a) to trap the generated 1a. Nonaflate 6a was produced as the major
product using NaH, with only a trace amount of cycloaddition product 8a observed (entry 1). The use of
various carbonates (Li2CO3, Na2CO3, K2CO3, Rb2CO3, and Cs2CO3) increased the yield of 8a (entries
2–6) in accordance with the size of the counter cation, with Cs2CO3 giving the best yield (96%, entry 6).
However, the yield of 8a was significantly lower (45%) when these two steps were carried out in THF
in the absence of azeotropic dehydration (entry 7). Therefore, the first boronic ester should be formed in
CH2Cl2, with the generated H2O removed thereafter. The reactions also worked efficiently with Cs2CO3
in either cyclopentyl methyl ether (CPME) or MeCN to give 8a in yields of 90–94% (entries 8 and 9).
The use of a weaker or bulkier base (CsHCO3 or CsOPiv, respectively) gave poor results (entries 10 and
11). K3PO4 was also found to be inefficient since it provided only a 17% yield of 8a (entry 12).
Therefore, Cs2CO3 appears to be the best choice for generating benzyne 1a from 4a.
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However, only a trace amount of the cycloaddition product 8b was observed following the
reaction of benzyl azide (7b) and 3-methylbenzyne (1b) generated from 4b under the same reaction
conditions using Cs2CO3 (Eq 1). Under that conditions, the O-nonaflylation of the corresponding
neopentyl glycol ester 5b seems to be extremely slow and significant amount of 5b was observed after
the reaction. After extensive studies, we found that the use of NaH as an additional base dramatically
improved the yield of 8b (81%, 1.2:1 mixture of regioisomers), which is probably due to steric
hindrance associated with the methyl group that hampers O-nonaflylation. Hence, the optimum
conditions were determined to involve the combination of NaH and Cs2CO3.
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Table 1. One-Pot Benzyne Generation from 2-
Hydroxyphenylboronic Acid 4aa
HO
OH
i)
B(neop)
B(OH)2
Me Me , CH2Cl2
NfF
7a
)
ii)
, IBF (
then azeotropic
dehydration
base, solvent
60 °C
OR
OH
4a
5a
6a
: R = H
: R = Nf
9
Ph
O
Ph
O
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7a
Ph
1a
Ph
7a
IBF (
)
8a
entry
base
NaH
solvent
THF
8a (%)b
trace
nd
1
2
Li2CO3
Na2CO3
K2CO3
THF
3
THF
12
4
THF
30
5
Rb2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsHCO3
CsOPiv
K3PO4
THF
53
96c
6
7d
THF
THF
45
8
CPME
MeCN
THF
94
9
90
10
11
12
nd
THF
trace
17
THF
aConditions: i) 4a (1.0 equiv) and neopentyl glycol (1.2 equiv) in CH2Cl2 (0.10
M) at RT for 3 h, then azeotropic dehydration using toluene; ii) NfF (3.0 equiv),
base (3.0 equiv), and IBF 7a (3.0 equiv) in solvent (0.10 M) at 60 °C for 24 h.
bGC yield. Isolated yield. dAll reagents were mixed together and stirred in THF
c
for
24
h.
NfF:
nonafluorobutanesulfonyl
fluoride;
IBF:
1,3-
diphenylisobenzofuran; nd: not detected.
HO
OH
(Me)
Me
i)
, CH2Cl2;
Me Me
B(OH)2
N
Azeotropic dehydration
N
(1)
OH
N
NfF
ii)
, NaH, Cs2CO3
+ BnN3
7b
Me
Me
Bn
8b
7b
BnN3 , base
THF, 60 °C
4b
1b
Cs2CO3 (3.0 equiv): trace
NaH (2.2 equiv) + Cs2CO3 (3.0 equiv): 81%
Base
We next examined the scope of the reaction using commercially available 2-
hydroxyphenylboronic acids 4b–4g, 4j, and 4k under the optimized conditions in the presence of 7a
(Table 2, entries 1–5 and 8–10). The synthetic neopentyl glycol esters 5h and 5i4c,10 were also employed
to the second step of our optimized conditions because some boronic acids are expensive or
commercially unavailable (entries 6 and 7). All reactions of 4c–4g, 4j provided adducts 8c–8g and 8j in
yields of 62–91% (entries 1–5 and 8), whereas reactions of 3-subsituted benzynes 1b and 1k generated
from 4b and 4k provided 8k and 8l in lower yields of 43% and 48%, respectively (entries 9 and 10). The
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reaction of 5h and 5i bearing carbonyl groups in the absence of NaH gave much higher yields (62% and
65%) than those in the presence of NaH (entries 6 and 7). And NaH was not necessary for the reaction
of 4c and 4e and similar yields were obtained without NaH (entries 1 and 3). Functional groups such as
F, Cl, Br, CF3S, CN, COMe and CO2Me were tolerated under the reaction conditions, which confirmed
that functionalized benzynes 1c–1k were successfully generated.
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Table 2. Substituent Scope of 2-Hydroxyphenylboronic Acids 4 Generating Benzynes 1a
Ph
Ph
O
HO
OH
B(OH)2
i)
Me Me
Azeotropic dehydration
NfF
, CH2Cl2;
B(neop)
ONf
O
OH
FG
FG
FG
FG
ii)
, NaH, Cs2CO3
7a
Ph
4
1
Ph
8c 8l
–
7a
6
IBF , THF, 60 °C
yield (%)b
62
precursor
,
yield (%)b
4 5
1 8
,
4
1 8
4
1 8
,
entry
1
precursor
,
yield (%)b
entry
5
precursor
entry
8
B(OH)2
F
B(OH)2
NC
O
90 (90)c
1g 8g
,
B(OH)2
OH
F
F
1c 8c
,
1j 8j
,
73
OH
4c
OH
4g
4j
B(OH)2
OH
Cl
1d 8d
,
2
3
4
91
B(neop)
4d
Me
B(OH)2
6d
1h, 8h
1i, 8i
62
1k 8k
B(OH)2
9
,
43
48
Br
OH
5h
OH
81 (85)c
1e 8e
,
4k
F
OH
O
4e
B(neop)
MeO
B(OH)2
4f
CF3S
7d
40 (65)e
4b
1b 8l
,
10
1f 8f
,
77
OH
5i
OH
aConditions: i) 4 (1.0 equiv) and neopentyl glycol (1.2 equiv) in CH2Cl2 (0.10 M) at RT for 3 h; ii) After azeotropic dehydration using toluene, NfF (3.0 equiv), NaH (2.2 equiv),
Cs2CO3 (3.0 equiv), and IBF 7a (3.0 equiv) in THF (0.10 M) at 60 °C for 24 h. bIsolated yield (%) of 8. cYield without NaH. dThe reaction of 5 was started from step ii) without
NaH. eAt 80 °C.
Wider substrate scope and possible extension to other arynophiles 7 were also investigated
(Table 3). Arynophiles such as alkyl azide 7b (entry 1), furan 7c (entry 2), nitrone 7d (entry 3), nitrile
oxide 7e (entry 4), olefin 7f (entry 5), cyclic urea 7g (entry 6), amine 7h (entry 7), sydnone 7i (entry 8),
and pyrrole 7j (entry 9) reacted with benzyne 1a generated from 4a to afford the corresponding aromatic
compounds 8m–8u in yields of 75–96%. The combinations of substituted benzyne precursors 4c, 4j, 4l,
and 4m, and other arynophiles 7b, 7j, and 7k also gave cycloaddition products 8v–8y in 55–83% yields
(entries 10–13).
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Table 3. Reaction Scope of Benzynes 1 Generated from 2-Hydroxyphenylboronic Acids 4a
2
3
4
5
6
7
8
9
HO
OH
B(OH)2
i)
B(neop)
ONf
X
Y
X
Y
Me Me
, CH2Cl2;
Azeotropic dehydration
OH
FG
precursor
4a
FG
FG
FG
NfF
ii)
, NaH, Cs2CO3
4
7
6
1
8m 8y
–
7
arynophile , THF, 60 °C
yield (%)b
product
yield (%)b
4
7
arynophile
4
8
precursor
7
entry
1
product
entry
arynophile
BuNH2
8
N
N
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4a
7h
8s
8t
7
PhNHBu
N
87
N
90
7b
Ph
N
8m
8n
N
Bn
N
Ph
O
4a
8
96
Me
4-MeOC6H4
4-MeOC6H4
7i
O
O
Me
Me
2
3
4a
4a
82
91
O
Boc
7c
Boc
N
N
Me
N
4a
4c
9
81
83
–O
O
t-Bu
8u
7j
t-Bu
N
Boc
N
7d
Ph
Ph
8o
7j
10
O
8v
Boc
F
N
Me
O–
N
Me
N
B(OH)2
CF3O
4
4a
76
Me
7j
73
57
11
12
Me
Me
7e
CF3O
F
OH
8w
4l
8p
Me
OMe
N
N
N
MeO
OMe
OMe
4j
7b
5
6
4a
4a
75
75
F
8x
Bn
8q
7f
Me
O
Ph
O
O
B(OH)2
OH
Me
N
Me
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
13
55
N
N
N
4m
7k
7g
8r
Ph
8y
Me
aConditions: i) 4 (1.0 equiv) and neopentyl glycol (1.2 equiv) in CH2Cl2 (0.10 M) at RT for 3 h, then azeotropic dehydration using toluene; ii) NfF (3.0 equiv), NaH (2.2 equiv),
Cs2CO3 (3.0 equiv), and arynophile 7 (3.0 equiv) in THF (0.10 M) at 60 °C for 24 h. bIsolated yield (%) of 8.
The following reaction highlights the dominant reactivity of the 2-hydroxyphenylboronic acid 4c
in the presence of 2-(trimethylsilyl)phenyl triflate (9a)1,3 under the above-mentioned optimized
conditions. A 1:1 mixture of the two benzyne precursors 4c and 9a was subjected to the optimized
procedure in the presence of N-Boc-pyrrole (7j) (1.0 equiv), after which BuNH2 (7h) (6.0 equiv), CsF
(3.0 equiv), and 18-crown-6 (3.0 equiv) were added, and the resulting mixture was stirred at 60 °C for a
further 12 h (Eq 2). Consequently, 8v and 8s were obtained in yields of 73% and 97%, respectively. It is
worth noting that other cross-reaction products, such as 8u (available from 9a and 7j) and 3- or 4-
fluoro-N-butylaniline (available from 4c and 7h), were not obtained. These results suggest that 4-
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fluorobenzyne (1c) was generated from 4c, with 9a remaining intact under the optimized conditions. In
addition, benzyne (1a) was subsequently quantitatively formed from 9a through the addition of CsF and
18-crown-62j to the reaction mixture to give 8s in the presence of 7h. It is also worth noting that the use
of less amount of arynophile 7j (1.0 equiv) made the yield, 73% of adduct 8v, which is only 10% lower
than that using 3.0 equiv of 7j (Table 3, entry 10).
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Boc
B(OH)2
F
N
HO
OH
, CH2Cl2;
Azeotropic dehydration
i)
Me Me
OH
F
4c
9a
(1.0 equiv)
8v
(73%)
+
(2)
NfF
ii)
(3.0 equv), NaH (2.2 equiv)
+
7j
N-Boc-pyrrole ( ) (1.0 equiv)
Cs2CO3 (3.0 equiv)
THF, 60 °C, 24 h
iii) BuNH2
CsF (3.0 equiv), 18-crown-6 (3.0 equiv)
60 °C, 12 h
SiMe3
PhNHBu
8s
OTf
7h
(
) (6.0 equiv)
(97%)
(1.0 equiv)
Mechanistic studies
We examined the mechanism of this reaction with 2-borylphenyl nonaflate 6a, a key intermediate
involved in the generation of the benzyne from 4a (Figure 1). A solution of 6a and 2,5-dimethylfuran
(7c) in THF was stirred with Cs2CO3 (2 equiv) at RT, and aliquots of the crude reaction mixture were
1
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removed at selected times and subjected to H and B NMR spectroscopy. The signals of 6a almost
completely disappeared within 30 min, and a set of new signals of reaction intermediate A was observed
1
11
in both the H and B NMR spectra (Figure 1, second spectrum from the bottom, purple). These new
signals gradually disappeared as another set of signals corresponding to product 8n appearance over the
next 3 h (Figure 1, third spectrum from the bottom). This third set of signals persisted for another 24 h,
during which time the signals due to A disappeared completely; 8n was finally obtained in 97% yield
after 27 h. The same mixture was also subjected to high-resolution mass spectrometry after 0.5 h of
reaction (HRMS: DART-Orbitrap MS) in negative mode. The main peak observed (m/z 567.0528) is
consistent with the formula C16H17BF9O9S (theoretical mass: 567.0551), which is likely to be a H3O+
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adduct of A in which a carbonate ion is coordinated to the boron atom in 6a, as shown in Figure 1.
These experimental data suggest that benzyne (1a) is generated in a stepwise manner: the rapid
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coordination of a carbonate ion to the boron first forms A (Nu: OCO2 ), after which gradual C-B bond
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fission accompanied by the elimination of the NfO– ion yields 1a. The stronger electron-withdrawing
inductive effect of the NfO group than that of the TfO group increases the Lewis acidity of the boron
atom in 6a, which also enhances coordination to the carbonate ion (see Supporting Information).
This stepwise formation of 1a from the 2-borylphenyl nonaflate 6a represents a fundamental
difference from the quasi-stepwise generation of benzyne from 2-silylpheyl triflate 9a.10,11 In addition,
the higher Lewis acidity of the boron atom in 6a compared to that of the silicon in 9a, as well as the
lower steric bulkiness of the boron, most probably facilitates the dominant attack of the relatively weak
Lewis base (carbonate ion) at the boron in 6a to form intermediate A in the presence of 9a. On the other
hand, reaction of the corresponding pinacol ester provided only 11% of 8n under the same conditions,
although a similar boronate intermediate was observed.8 This result suggests that coordination of the
carboxylate ion to the more hindered boron atom of the pinacol ester may not be an issue for the
generation of the benzyne.
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Nu
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(3.0 equiv)
B(neop)
ONf
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Cs2CO3 (2.0 equiv)
O
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THF, rt
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Figure 1. 1H and 11B NMR time-course study of the reaction
of 6a with 7c in the presence of Cs2CO3, and HRMS data.
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CONCLUSION
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In summary, we developed a new one-pot method for the generation of functionalized benzynes from
readily available 2-hydroxylphenylboronic acids. Currently, 137 2-hydroxylphenylboronic acids are
commercially available12 and can be used as benzyne precursors. Additionally, benzyne can be
selectively generated in the presence of 2-(trimethylsilyl)phenyl triflate. Further studies regarding
synthetic applications and more-detailed mechanistic investigations of this method are currently
underway in our laboratory.
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EXPERIMENTAL DETAILS
General considerations
Reagents. All reactions were carried out under argon atmosphere. A round-bottomed flask with a three-
way stopcock or a Schlenk flask containing a magnetic stirrer was used as reactors and heated by an oil
bath (Riko or Techno Sigma). Anhydrous THF and MeCN were purchased from Kanto Chemical, and
purified with a Glass Contour solvent dispensing system (Nikko Hansen) using two packed columns of
activated molecular sieves. Anhydrous CPME was purchased from FUJIFILM Wako Pure Chemical. 1-
(3-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-4-hydroxyphenyl)ethan-1-one (5h),4c methyl 3-(5,5-
dimethyl-1,3,2-dioxaborinan-2-yl)-4-hydroxybenzoate (5i),4c N-tert-butylphenyl nitrone (7d),13 2,4,6-
trimethylbenzonitrile oxide (7e),14 1,1-dimethoxyethylene (7f),15 tert-butyl 1H-pyrrole-1-carboxylate
(7j),16 4-(4-methoxyphenyl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (7i),17 were prepared according to
the literature. All other reagents including phenylboronic acid derivatives (4a–4g and 4j–4m) were
purchased from FUJIFILM Wako Pure Chemical, Tokyo Chemical Industry, Sigma-Aldrich, Nacalai
tesque, Kishida Chemical, Matrix Scientific and Combi-Blocks and used without further purification.
Flash chromatography18 was performed with silica gel 60N, spherical neutral (40–50 μm), purchased
from Kanto Chemical. Gel permeation chromatography (GPC) was performed with JAIGEL-2HR,
purchased from Japan Analytical Industry. All reactions were monitored by thin-layer chromatography
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(TLC) on glass-backed silica gel 60F254, 0.2 mm plates (Merck), and compounds were visualized under
UV light (254 nm).
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Analytical methods. Melting points were recorded on Yanagimoto melting point apparatus and are
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uncorrected. IR spectra were obtained on a SHIMADZU IRAffinity-1S. H NMR and C{1H} NMR
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spectra were recorded on a JEOL JMN-ECA-500 (1H: 500 MHz, 13C{1H}: 125 MHz, 19F{1H}: 470 MHz,
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11B: 160 MHz), a JEOL JMN-ECS-400 (1H: 400 MHz, C{1H}: 100 MHz, F{1H}: 376 MHz, Si: 79
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MHz), a JEOL AL-300 (1H: 300 MHz, C{1H}: 75 MHz). Instrument with chemical shifts reported in
ppm relative to the residual deuterated solvent. GC spectra were taken on SHIMADZU GC-2010. The
mass spectra were recorded on a JEOL JMS-S3000 (MALDI, TOF), a JEOL JMS-700 (FAB), a Thermo
Fisher Scientific LTQ-Orbitrap XL spectrometer equipped with DART apprication (Direct Analysis in
Real Time) made by JEOL instead of using standard ESI (APCI, Orbitrap). “Yield” refers to the
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isolated yields of compounds showing at most only trace peaks in the H NMR spectra that are not
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attributable to the assigned structure. H NMR and melting points (where applicable) of all known
compounds were taken. All new products were further characterized by high resolution mass spectrum
(HRMS).
One-pot generation of benzyne from 2-borylphenol 4 (Tables 1–3, Eq 1):
General Procedure I: i) An oven-dried Schlenk tube was charged with 2-hydroxyphenylboronic acid 4
(1.0 equiv), neopentyl glycol (1.2 equiv), and a stirrer bar. The tube was capped with a rubber septum,
and then evacuated and back-filled with argon. Anhydrous CH2Cl2 (0.10 M) was added into the tube
through the septum by a syringe, after which the mixture was stirred until the mixture turned to be a
clear solution. After adding ca. 2 mL of toluene to the mixture, all solvents were removed under reduced
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pressure (this process was repeated three times). ii) Cs2CO3 (3.0 equiv) and NaH (60%, dispersion in
paraffin liquid) (2.2 equiv) were added to the mixture. If arynophile 7 (3.0 equiv) was a solid, it was
added at this time. The tube was evacuated and filled-back with argon (this process was repeated three
times). THF (0.10 M) and NfF (3.0 equiv) were added by a syringe sequentially at room temperature. If
arynophile 7 (3.0 equiv) was a liquid, it was added to the tube at this time along with THF. The mixture
was stirred at 60 °C for 24 h. An aquous solution of NH4Cl was added to the reaction mixture, after
which it was extracted three times with CH2Cl2. The combined organic phase was dried over Na2SO4,
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filtered, and concentrated under reduced pressure. The crude mixture was examined by H NMR
spectroscopy to determine NMR yield using 1,1,2,2-tetrachloroethane as an internal standard. This
crude mixture was purified by flash column chromatography on silica gel to afford product 8.
General Procedure II: i) An oven-dried Schlenk tube was charged with 2-hydroxyphenylboronic acid
4 (1.0 equiv), neopentyl glycol (1.2 equiv), and a stirrer bar. The tube was capped with a rubber septum,
and then evacuated and back-filled with argon. CH2Cl2 (0.10 M) was added into the tube through the
septum by a syringe, after which the mixture was stirred until the mixture turned to be a clear solution.
After adding ca. 2 mL of toluene to the mixture, all solvents were removed under reduced pressure (this
process was repeated three times). ii) Cs2CO3 (3.0 equiv) and NaH (60%, dispersion in paraffin liquid)
(2.2 equiv) were added to the mixture, then evacuated and back-filled with argon (This process was
repeated three times). THF (0.10 M), NfF (3.0 equiv) and arynophile 7 (3.0 equiv) were added by a
syringe sequentially at room temperature. The mixture was stirred at 60 °C for 24 h. A saturated
solution of NH4Cl was added to the reaction mixture, after which it was extracted three times with
CH2Cl2. The combined organic phase was dried over Na2SO4, filtered, and concentrated under reduced
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pressure. The crude mixture was examined by H NMR spectroscopy to determine NMR yield using
1,1,2,2-tetrachloroethane as an internal standard. This crude mixture was purified by flash column
chromatography on silica gel to afford product 8.
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9,10-Diphenyl-9,10-dihydro-9,10-epoxyanthracene (8a) (Table 1, entry 6):2b Following General
Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a)
(29 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue
was mixed with Cs2CO3 (0.21 g, 0.63 mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in
THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol) was added by syringe. The reaction mixture was stirred
for 24 h at 60 °C. The crude product was purified by column chromatography on silica gel
(hexane/CH2Cl2 = 5:2) to provide the titled compound 8a as a colorless solid [71 mg (2% CH2Cl2),
96%]. Mp: 185–186 °C (187.5–180 °C, lit).2b 1H NMR (400 MHz, CDCl3) δ: 7.94 (dd, J = 7.5, 1.5 Hz, 4
H), 7.59 (dd, J = 7.5, 7.5 Hz, 4 H), 7.49 (tt, J = 7.5, 1.5 Hz, 2 H), 7.36 (dd, J = 5.5, 3.0 Hz, 4 H), 7.03
(dd, J = 5.5, 3.0 Hz, 4 H).
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Following General Procedure I, a mixture of neopentyl glycol (0.12 g, 1.2 mmol), and 2-
hydroxyphenylboronic acid (4a) (0.14 g, 1.0 mmol) in CH2Cl2 (10 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with Cs2CO3 (1.0 g, 3.2 mmol) and 1,3-
diphenylisobenzofuran (7a) (0.57 g, 2.1 mmol) in THF (10 mL). Then, NfF (0.55 mL, 3.0 mmol) was
added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by
column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled compound 8a as a
colorless solid (0.27 g, 78%).
1-Benzyl-4-methyl-1H-benzo[d][1,2,3]triazole (8b) (Eq 1): Following General Procedure I, a mixture of
neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-3-methylphenylboronic acid (4b) (32 mg, 0.21
mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was mixed
with NaH (20 mg, 0.46 mmol), and Cs2CO3 (0.21 mg, 0.63 mmol) in THF (2.0 mL). Then, benzyl azide
(7b) (0.078 mL, 0.63 mmol) and NfF (0.12 mL, 0.63 mmol) were added by syringe sequentially. The
reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by column
chromatography on silica gel (hexane/EtOAc = 5:1) to provide a mixture of the titled compound 8b (18
mg, 81 µmol) and 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-methylphenol (5b) (4.1 mg, 19 µmol) as
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a colorless oil, and a mixture of 8b (1.8 mg, 7.9 µmol), 1-benzyl-7-methyl-1H-benzo[d][1,2,3]triazole
(8b’) (17 mg, 78 µmol) and 5b (4.2 mg, 19 µmol) as a colorless oil [total 81% of regioisomers, 8b (20
mg, 89 µmol, 43%) and 8b’ (17 mg, 78 µmol, 38%)]. 8b: 1H NMR (500 MHz, CDCl3) δ: 7.34–7.26 (m,
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6 H), 7.16 (d, J = 8.5 Hz, 1 H), 7.10 (d, J = 7.0 Hz, 1 H), 5.84 (s, 2 H), 2.80 (s, 3 H). 13C{1H} NMR (125
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MHz, CDCl3) δ: 146.3, 134.9, 130.9, 128.9, 128.3, 127.5, 127.4, 124.3, 123.7, 107.0, 52.2, 16.7. IR:
3033 cm-1. HRMS (MALDI, TOF): m/z Calcd for C14H14N3 [M+H]+: 224.1182, Found: 224.1184.
1-Benzyl-7-methyl-1H-benzo[d][1,2,3]triazole (8b’) (Eq 1) (17 mg, 78 µmol) was obtained by above-
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mentioned column chromatography as a mixure with 5b (4.2 mg, 19 µmol). H NMR (500 MHz,
CDCl3) δ: 7.92 (brd, J = 8.5 Hz, 1 H), 7.34–7.25 (m, 3 H), 7.23 (dd, J = 7.5, 1.5 Hz, 1 H), 7.15–7.14 (m,
1 H), 7.06–7.04 (m, 2 H), 6.05 (s, 2 H), 2.52 (s, 3 H). 13C{1H} NMR (125 MHz, CDCl3) δ: 146.8, 136.8,
132.7, 132.5, 129.0, 128.7, 128.0, 126.1, 120.8, 117.8, 53.1, 18.4. IR: 3035 cm-1. HRMS (MALDI,
TOF): m/z Calcd for C14H14N3 [M+H]+: 224.1182, Found: 224.1185.
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2-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-6-methylphenol (5b) was synthesized to obtain H and
13C{1H} NMR spectra data, which was used to identify products from the above mentioned crude
mixture. A mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-3-methylphenylboronic
acid (4b) (32 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. After 3 h,
H2O (ca. 5 mL) was added to the reaction and water phase was extracted with CH2Cl2 (ca. 5 mL) three
times. Without further purification, the titled compound (5b) was obtained as a colorless solid (46 mg,
quant). Mp: 94–96 °C. 1H NMR (500 MHz, CDCl3) δ: 8.50 (s, OH), 7.48 (dd, J = 7.5, 1.5 Hz, 1 H), 7.20
(brd, J = 7.5 Hz, 1 H), 6.78 (dd, J = 7.5, 7.5 Hz 1 H), 3.82 (s, 4 H), 2.23 (s, 3 H), 1.05 (s, 6 H). 13C{1H}
NMR (125 MHz, CDCl3) δ: 161.8, 134.2, 132.7, 124.3, 119.0, 72.3, 32.0, 21.8, 16.0 (insufficient
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number of signals because of signal overlapping). IR: 3367 cm-1. HRMS (MALDI, TOF): m/z Calcd for
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4
C12H17BO3 [M]+: 220.1265, Found: 220.1269.
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2-Fluoro-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8c) (Table 2, entry 1): Following General
Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-fluorophenylboronic
acid (4c) (33 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant
residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63 mmol) and 1,3-
diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol)
was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product was
purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled compound
8c as a colorless solid [71 mg (3% hexane), 90%]. Mp: 83–84 °C. 1H NMR (500 MHz, CDCl3) δ: 7.91
(dd, J = 7.0, 7.0 Hz, 2 H), 7.91 (dd, J = 7.0, 7.0 Hz, 2 H), 7.62–7.58 (m, 4 H), 7.52–7.48 (m, 2 H), 7.39–
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7.34 (m, 2 H), 7.29–7.26 (m, 1 H), 7.09–7.04 (m, 3 H), 6.69 (ddd, J = 9.5, 7.5, 1.5 Hz, 1 H). C{1H}
NMR (125 MHz, CDCl3) δ: 160.9 (d, J = 247.0 Hz), 153.2 (d, J = 8.5 Hz), 150.3, 149.8, 145.8, 134.7,
134.5, 128.9, 128.8, 128.5, 128.4, 126.6, 126.5, 126.1, 125.9, 121.3 (d, J = 8.5 Hz), 120.5, 120.3, 111.6
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(d, J = 23.0 Hz), 109.2 (d, J = 25.0 Hz), 90.5, 90.4. F{1H} NMR (470 MHz, CDCl3) δ: –115.8. IR:
3064, 3033 cm-1. HRMS (MALDI, TOF): m/z Calcd for C26H18OF [M+H]+: 365.1336, Found:
365.1339.
2-Chloro-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8d) (Table 2, entry 2): Following General
Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-chlorophenylboronic
acid (4d) (37 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant
residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63 mmol) and 1,3-
diphenylisobenzofuran (7a) (0.17 g, 63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol) was
added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by
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column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled compound 8d as a
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colorless solid [75 mg (3% hexane), 91%]. Mp: 74–75 °C. H NMR (500 MHz, CDCl3) δ: 7.92 (d, J =
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8.5 Hz, 2 H), 7.92 (d, J = 8.5 Hz, 2 H), 7.62 (dd, J = 8.5, 8.5 Hz, 2 H), 7.61 (dd, J = 8.5, 8.5 Hz, 2 H),
7.54–7.49 (m, 2 H), 7.41–7.35 (m, 2 H), 7.33 (d, J = 1.5 Hz, 1 H), 7.27 (d, J = 7.5 Hz, 1 H), 7.07 (dd, J
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= 5.5, 3.0 Hz, 1 H), 7.07 (dd, J = 3.0, 5.5 Hz, 1 H), 7.01 (dd, J = 7.5, 1.5 Hz, 1 H). 13C{1H} NMR (125
MHz, CDCl3) δ: 152.7, 149.9, 149.6, 149.0, 134.5, 134.4, 131.6, 128.9, 128.8, 128.5, 128.4, 126.6,
126.5, 126.1, 126.0, 125.6, 121.3, 121.2, 120.5, 120.4, 90.4, 90.3. IR: 3065, 3033 cm-1. HRMS
(MALDI, TOF): m/z Calcd for C26H18O35Cl [M+H]+: 381.1041, Found: 381.1032.
2-Bromo-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8e) (Table 2, entry 3):2b Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-
bromophenylboronic acid (4e) (45 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63
mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL,
0.63 mmol) was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product
was purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled
compound 8e as a colorless solid [75 mg (1% hexane, 1% CH2Cl2), 81%]. Mp: 170–171 °C (164–166
°C, lit).2b 1H NMR (500 MHz, CDCl3) δ: 7.91 (d, J = 7.5 Hz, 2 H), 7.91 (d, J = 7.5 Hz, 2 H), 7.62 (dd, J
= 7.5, 7.5 Hz, 2 H), 7.60 (dd, J = 7.5, 7.5 Hz, 2 H), 7.53–7.49 (m, 2 H), 7.46 (d, J = 1.5 Hz, 1 H), 7.40–
7.35 (m, 2 H), 7.22 (d, J = 8.0 Hz, 1 H), 7.17 (dd, J = 8.0, 1.5 Hz, 1 H), 7.08–7.05 (m, 2H).
9,10-Diphenyl-2-((trifluoromethyl)thio)-9,10-dihydro-9,10-epoxyanthracene (8f) (Table 2, entry 4):
Following General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-
((trifluoromethyl)thio)phenylboronic acid (4f) (50 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3
h at room temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g,
0.63 mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12
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mL, 0.63 mmol) was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude
product was purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the
titled compound 8f as a colorless oil [74 mg (3% hexane), 77%]. 1H NMR (400 MHz, CDCl3) δ: 7.93–
7.90 (m, 4 H), 7.65–7.59 (m, 5 H), 7.55–7.50 (m, 2 H), 7.43–7.39 (m, 3 H), 7.37 (dd, J = 7.5, 1.0 Hz, 1
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H), 7.09 (dd, J = 5.0, 3.5 Hz, 1 H), 7.09 (dd, J = 5.0, 3.5 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ:
153.7, 152.2, 149.6, 149.3, 134.6, 134.2, 134.1, 129.1 (q, J = 308.0 Hz), 128.93, 128.88, 128.6, 128.5,
127.6, 126.6, 126.3, 126.2, 121.6, 121.2, 120.74, 120.72, 90.42, 90.38 (insufficient number of signals
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because of signal overlapping). F{1H} NMR (470 MHz, CDCl3) δ: –42.6. IR: 3066, 3034, 1602 cm-1.
HRMS (MALDI, TOF): m/z Calcd for C27H18OF3S [M+H]+: 447.1025, Found: 447.1022.
9,10-Diphenyl-9,10-dihydro-9,10-epoxyanthracene-2-carbonitrile (8g) (Table 2, entry 5):2b Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-
cyanophenylboronic acid (4g) (34 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63
mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL,
0.63 mmol) was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product
was purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled
compound 8g as a colorless solid [49 mg (1% CH2Cl2), 62%]. Mp: 220–222 °C (216–218 °C, lit).2b 1
H
NMR (400 MHz, CDCl3) δ: 7.89 (d, J = 7.0 Hz, 2 H), 7.89 (d, J = 7.0 Hz, 2 H), 7.64 (t, J = 7.0 Hz, 2 H),
7.62 (t, J = 7.0 Hz, 2 H), 7.58 (brs, 1 H), 7.56–7.51 (m, 2 H), 7.44 (d, J = 7.0 Hz, 1 H), 7.42–7.38 (m, 3
H), 7.12–7.07 (m, 2 H).
2-Acetyl-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8h) (Table 2, entry 6): Following General
Procedure I [from ii)], 1-(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-hydroxyphenyl)ethan-1-one (5h)
(26 mg, 0.11 mmol) was mixed with Cs2CO3 (0.10 g, 0.32 mmol) and 1,3-diphenylisobenzofuran (7a)
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(60 mg, 0.22 mmol) in MeCN (1.0 mL). Then NfF (60 µL, 0.32 mmol) was added by syringe. The
reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by column
chromatography on silica gel (hexane/EtOAc = 5:1) and Gel Permeation Chromatography (Chloroform)
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to provide the titled compound 8h as a colorless solid (25 mg, 62%). Mp: 82–83 °C. H NMR (500
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MHz, CDCl3) δ: 7.96–7.92 (m, 5 H), 7.68 (dd, J = 4.5, 1.5 Hz, 1 H), 7.64–7.60 (m, 4 H), 7.53–7.50 (m,
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2 H), 7.43 (d, J = 4.5 Hz, 1 H), 7.40–7.38 (m, 2 H), 7.07–7.06 (m, 2 H), 2.52 (s, 3 H). C{1H} NMR
(101 MHz, CDCl3) δ: 197.4, 155.6, 151.3, 149.9, 149.2, 135.2, 134.4, 134.3, 128.93, 128.86, 128.5,
127.6, 126.7, 126.2, 126.1, 120.74, 120.66, 120.2, 119.4, 90.5, 90.4, 26.8 (insufficient number of signals
because of signal overlapping). IR: 1681 cm-1. HRMS (MALDI, TOF): m/z Calcd for C28H21O2
[M+H]+: 389.1536, Found: 389.1539.
1-Methoxycarbonyl-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8i) (Table 2, entry 7):
Following General Procedure I [from ii)], methyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-
hydroxybenzoate (5i) (28 mg, 0.11 mmol) was mixed with Cs2CO3 (0.10 g, 0.32 mmol) and 1,3-
diphenylisobenzofuran (7a) (60 mg, 0.22 mmol) in MeCN (1.0 mL). Then NfF (60 µL, 0.32 mmol) was
added by syringe. The reaction mixture was stirred for 24 h at 80 °C. The crude product was purified by
column chromatography on silica gel (hexane/EtOAc = 5:1) and (Chloroform, HP column) to provide
the titled compound 8i as a colorless solid (27 mg, 65%). Mp: 79–80 °C. 1H NMR (500 MHz, CDCl3) δ:
7.97–7.92 (m, 5 H), 7.79 (dd, J = 4.5, 1.5 Hz, 1 H), 7.64–7.59 (m, 4 H), 7.54–7.49 (m, 2 H), 7.42 (d, J =
4.5 Hz, 1 H), 7.40–7.38 (m, 2 H), 7.07–7.05 (m, 2 H), 3.85 (s, 3 H). 13C{1H} NMR (101 MHz, CDCl3) δ:
166.7, 155.5, 151.0, 149.9, 149.4, 134.4, 128.9, 128.8, 128.5, 128.0, 126.72, 126.69, 126.2, 126.1,
121.0, 120.7, 120.6, 120.1, 90.5, 52.1 (insufficient number of signals because of signal overlapping). IR:
1721 cm-1. HRMS (MALDI, TOF): m/z Calcd for C28H21O3 [M+H]+: 405.1485, Found: 405.1485.
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2,3-Difluoro-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8j) (Table 2, entry 8): Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-4,5-
difluorophenylboronic acid (4j) (36 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63
mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL,
0.63 mmol) was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product
was purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled
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compound 8j as a colorless solid [61 mg (3% CH2Cl2), 73%]. Mp: 55–57 °C. H NMR (500 MHz,
CDCl3) δ: 7.88 (d, J = 8.0 Hz, 4 H), 7.61 (dd, J = 8.0, 8.0 Hz, 4 H), 7.51 (t, J = 8.0 Hz, 2 H), 7.37 (dd, J
= 5.5, 3.0 Hz, 2 H), 7.17 (dd, J = 8.0, 8.0 Hz, 2 H), 7.07 (dd, J = 5.5, 3.0 Hz, 2 H). 13C{1H} NMR (125
MHz, CDCl3) δ: 149.7, 148.0 (dd, J = 249.5, 14.5 Hz), 146.7 (dd, J = 4.0, 4.0 Hz), 134.2, 128.9, 128.6,
126.4, 126.1, 120.4, 110.8 (dd, J = 14.5, 7.0 Hz), 90.3. 19F{1H} NMR (470 MHz, CDCl3) δ: –140.2. IR:
3065, 3033 cm-1. HRMS (MALDI, TOF): m/z Calcd for C26H17OF2 [M+H]+: 383.1242, Found:
383.1245.
1-Fluoro-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8k) (Table 2, entry 9):2b Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-3-
fluorophenylboronic acid (4i) (33 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63
mmol) and 1,3-diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL,
0.63 mmol) was added by a syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude
product was purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the
titled compound 8k as a colorless solid [34 mg (2% CH2Cl2), 43%]. Mp: 196–198 °C (200.5–200.7 °C,
lit).2b 1H NMR (500 MHz, CDCl3) δ: 8.00 (dd, J = 7.5, 2.0 Hz, 2 H), 7.90 (dd, J = 8.5, 1.0 Hz, 2 H),
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7.59–7.54 (m, 4 H), 7.51–7.47 (m, 3 H), 7.39 (d, J = 6.5 Hz, 1 H), 7.15 (d, J = 7.0 Hz, 1 H), 7.13–7.02
(m, 3 H), 6.74 (dd, J = 8.5, 8.5 Hz, 1 H).
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1-Methyl-9,10-diphenyl-9,10-dihydro-9,10-epoxyanthracene (8l) (Table 2, entry 10): Following General
Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-3-methylphenylboronic
acid (4b) (32 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant
residue was mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63 mmol) and 1,3-
diphenylisobenzofuran (7a) (0.17 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol)
was added by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product was
purified by column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled compound
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8l as a colorless solid [38 mg (2% hexane), 48%]. Mp: 81–83 °C. H NMR (400 MHz, CDCl3) δ: 7.98
(d, J = 6.5 Hz, 2 H), 7.89 (d, J = 7.5 Hz, 2 H), 7.63 (d, J = 7.0 Hz, 1 H), 7.56–7.43 (m, 6 H), 7.35 (d, J =
7.0 Hz, 1 H), 7.18 (d, J = 7.0 Hz, 1 H), 7.12 (dd, J = 7.0, 7.0 Hz, 1 H), 7.04 (dd, J = 7.0, 7.0 Hz, 1 H),
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6.94 (dd, J = 7.0, 7.0 Hz, 1 H), 6.79 (dd, J = 7.0 Hz, 1 H), 1.96 (s, 3 H). C{1H} NMR (100 MHz,
CDCl3) δ: 152.3, 151.0, 148.73, 148.68, 135.2, 134.8, 131.6, 129.6, 129.0, 128.8, 128.61, 128.57, 128.2,
127.2, 125.9, 125.8, 125.5, 121.6, 120.8, 118.0, 91.9, 90.1, 19.0. IR: 3060, 2955, 2924, 2854 cm–1.
HRMS (MALDI, TOF): m/z Calcd for C27H21O [M+H]+: 361.1587, Found: 361.1577.
1-Benzyl-1H-benzo[d][1,2,3]triazole (8m) (Table 3, entry 1):19 Following General Procedure I, a
mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg, 0.21
mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was mixed
with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (2.0 mL). Then, benzyl azide
(7b) (0.078 mL, 0.63 mmol) and NfF (0.12 mL, 0.63 mmol) were added by syringe sequentially. The
reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by column
chromatography on silica gel (hexane/EtOAc = 5:1) to provide the titled compound 8m as a colorless
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solid (40 mg, 83%). Mp: 113–115 °C (114–115 °C, lit).19 1H NMR (500 MHz, CDCl3) δ: 8.07 (d, J =
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8.0 Hz, 1 H), 7.43–7.26 (m, 8 H), 5.86 (s, 2 H).
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1,4-Dimethyl-1,4-dihydro-1,4-epoxynaphthalene (8n) (Table 3, entry 2):4c Following General Procedure
II, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg,
0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. NaH (20 mg, 0.46 mmol) was
added to the mixture. THF (2.0 mL) and NfF (0.12 mL, 0.63 mmol) were added by syringe into the tube
and the reaction mixture was stirred for 20 minutes at 60 °C. Cs2CO3 (0.21 g, 0.63 mmol) and 2,5-
dimethylfuran (7c) (0.068 mL, 0.63 mmol) were then added sequentially and the reaction mixture was
stirred at 60 °C for 24 h. The crude product was purified by column chromatography on silica gel
(hexane/EtOAc = 8:1) to provide the titled compound 8n as a colorless oil (30 mg, 82%). 1H NMR (400
MHz, CDCl3) δ: 7.13 (dd, J = 5.0, 3.0 Hz, 2 H), 6.98 (dd, J = 5.0, 3.0 Hz, 2 H), 6.78 (s, 2 H), 1.90 (s, 6
H).
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2-(tert-Butyl)-3-phenyl-2,3-dihydrobenzo[d]isoxazole (8o) (Table 3, entry 3):2n Following General
Procedure II, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a)
(29 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue
was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (1.0 mL). Then, NfF
(0.12 mL, 0.63 mmol) was added by a syringe at room temperature, and the mixture was warmed to 60
°C. 1.0 mL of a THF solution of N-tert-butyl-α-phenylnitrone (7d) (0.11g, 0.63 mmol) was added to the
mixture dropwise in 3 min, and the mixture was stirred at 60 °C for 24 h. The crude product was
purified by column chromatography on silica gel (hexane/EtOAc = 5:1) to provide the titled compound
8o as a colorless solid (51 mg, 96%). Mp: 92–94 °C (92–94 °C, lit).2n 1H NMR (400 MHz, CDCl3) δ:
7.39 (d, J = 7.0, Hz, 2 H), 7.32 (dd, J = 7.0, 7.0 Hz, 2 H), 7.26–7.22 (m, 1 H), 7.14 (t, J = 7.0 Hz, 1 H),
6.88 (d, J = 7.5 Hz, 1 H), 6.81–6.77 (m, 2 H), 5.59 (s, 1 H), 1.17 (s, 9 H).
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3-Mesitylbenzo[d]isoxazole (8p) (Table 3, entry 4): Following General Procedure II, a mixture of
neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg, 0.21 mmol) in
CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was mixed with NaH (20
mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol)
was added by syringe. The reaction mixture was warmed to 60 °C. After 10 minutes, 2,4,6-
trimethylbenzonitrile oxide (7e) (0.10 g, 0.63 mmol) was added into the tube and the mixture was stirred
at 60 °C for 24 h. The crude product was purified by column chromatography on silica gel
(hexane/EtOAc = 10:1), followed by GPC to provide the titled compound 8p as a colorless liquid (38
mg, 76%). 1H NMR (500 MHz, CDCl3) δ: 7.66 (d, J = 7.5 Hz, 1 H), 7.58 (dd, J = 7.5, 7.5 Hz, 1 H), 7.39
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(d, J = 7.5 Hz, 1 H), 7.29 (dd, J = 7.5, 7.5 Hz, 1 H), 7.01 (s, 2 H), 2.37 (s, 3 H), 2.09 (s, 6 H). 13C{1H}
NMR (125 MHz, CDCl3) δ: 163.1, 157.9, 139.3, 137.7, 129.8, 128.5, 124.2, 123.6, 122.2, 121.9, 110.1,
21.2, 20.1. IR: 2920, 1613 cm-1. HRMS (MALDI, TOF): m/z Calcd for C16H16NO [M+H]+: 238.1226,
Found: 238.1226.
7,7-Dimethoxybicyclo[4.2.0]octa-1(6),2,4-triene (8q) (Table 3, entry 5):20 Following General Procedure
II, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg,
0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was
mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (2.0 mL). Then, NfF
(0.12 mL, 0.63 mmol) was added by syringe. The reaction mixture was warmed to 60 °C. After 10
minutes, 1,1-dimethoxyethylene (7f) (0.060 mL, 0.63 mmol) was added into the tube by syringe and the
mixture was stirred at 60 °C for 24 h. The crude product was purified by column chromatography on
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NMR (400 MHz, CDCl3) δ: 7.31–7.34 (m, 1 H), 7.22–7.28 (m, 3 H), 3.45 (s, 6 H), 3.37 (s, 2 H).
1,4-Dimethyl-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one (8r) (Table 3, entry 6):21 Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic
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acid (4a) (29 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant
residue was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (1.0 mL).
Then, 1,3-dimethyl-2-imidazolidinone (7g) (1.0 mL, 9.2 mmol) and NfF (0.12 mL, 0.63 mmol) were
added by syringe sequentially. The reaction mixture was stirred for 24 h at 60 °C. The crude product
was purified by column chromatography on silica gel (EtOAc), followed by GPC to provide the titled
compound 8r as a colorless liquid (75%). 1H NMR (500 MHz, CDCl3) δ: 7.63 (dd, J = 7.5, 2.0 Hz, 1 H),
7.36 (ddd, J = 7.0, 7.0, 2.0 Hz, 1 H), 6.98 (dd, J = 7.0, 7.0 Hz, 1 H), 6.86 (d, J = 7.0 Hz, 1 H), 3.42 (dd,
J = 6.0, 6.0 Hz, 2 H), 3.30 (dd, J = 6.0, 6.0 Hz, 2 H), 3.21 (s, 3 H), 2.83 (s, 3 H).
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N-Butylaniline (8s) (Table 3, entry 7):22 Following General Procedure II, a mixture of neopentyl glycol
(24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg, 0.21 mmol) in CH2Cl2 (2.0 mL)
was stirred for 3 h at room temperature. NaH (20 mg, 0.46 mmol) was added to the mixture. THF (2.0
mL) was added by a syringe and the mixture at 0 °C. NfF (0.12 mL, 0.63 mmol) was added to the tube
and the mixture was stirred for 1 h and warmed to room temperature. Cs2CO3 (0.21 g, 0.63 mmol) was
added at room temperature and the mixture was warmed to 60 °C. Butylamine (7h) (0.068 mL, 0.63
mmol) was then added by a syringe and the mixture was stirred at 60 °C for 24 h. The crude product
was purified by column chromatography on silica gel (hexane/EtOAc = 10:1) to provide the titled
compound 8s as a colorless oil (28 mg, 87%). 1H NMR (300 MHz, CDCl3) δ: 7.17 (dd, J = 7.5, 7.5 Hz,
2 H), 6.68 (t, J = 7.5 Hz, 1 H), 6.61 (d, J = 7.5 Hz, 2 H), 3.59 (brs, 1 H), 3.11 (t, J = 7.0 Hz, 2 H), 1.66–
1.55 (m, 2 H), 1.43 (tq, J = 7.0, 7.0 Hz, 2 H), 0.96 (t, J = 7.0 Hz, 3 H).
3-(4-Methoxyphenyl)-2-phenyl-2H-indazole (8t) (Table 3, entry 8):23 Following General Procedure I, a
mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic acid (4a) (29 mg, 0.21
mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was mixed
with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63 mmol) and 3-phenyl-4-(4-methoxyphenyl)sydnone
(7i) (0.17 mg, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol) was added by syringe.
The reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by column
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chromatography on silica gel (hexane/EtOAc = 5:1) to provide the titled compound 8t as a colorless
solid (60 mg, 96%). Mp: 120–122 °C (103–105 °C, lit).23 1H NMR (400 MHz, CDCl3) δ: 7.79 (d, J =
9.0 Hz, 1 H), 7.70 (dd, J = 8.5, 1.0 Hz, 1 H), 7.46–7.34 (m, 7 H), 7.29 (d, J = 9.0 Hz, 2 H), 7.13 (ddd, J
= 8.5, 6.5, 1.0 Hz, 1 H), 6.93 (d, J = 9.0 Hz, 2 H), 3.83 (s, 3 H).
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tert-Butyl-1,4-dihydro-1,4-epiminonaphthalene-9-carboxylate (8u) (Table 3, entry 9):2f Following
General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxyphenylboronic
acid (4a) (29 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant
residue was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63 mmol) in THF (2.0 mL).
Then, tert-butyl 1H-pyrrole-1-carboxylate (7j) (0.11 mL, 0.63 mmol) and NfF (0.12 mL, 0.63 mmol)
were added by syringe sequentially. The reaction mixture was stirred for 24 h at 60 °C. The crude
product was purified by column chromatography on silica gel (hexane/EtOAc = 8:1) to provide the
titled compound 8u as a colorless solid (41 mg, 81%). Mp: 67–68 °C (70–72 °C, lit).2f 1H NMR (500
MHz, CDCl3) δ: 7.25 (brs, 1 H), 7.00 (brs, 1 H), 6.97–6.94 (m, 4 H), 5.50 (brs, 1 H), 5.47 (brs, 1 H),
1.37 (s, 9 H).
tert-Butyl-6-fluoro-1,4-dihydro-1,4-epiminonaphthalene-9-carboxylate (8v) (Table 3, entry 10):
Following General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-
fluorophenylboronic acid (4c) (33 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63
mmol) in THF (2.0 mL). Then, tert-butyl 1H-pyrrole-1-carboxylate (7j) (0.11 mL, 0.63 mmol) and NfF
(0.12 mL, 0.63 mmol) were added by syringe sequentially. The reaction mixture was stirred for 24 h at
60 °C. The crude product was purified by column chromatography on silica gel (hexane/EtOAc = 8:1)
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to provide the titled compound 8v as a colorless solid (45 mg, 83%). Mp: 49–51 °C, H NMR (500
MHz, CDCl3) δ: 7.15 (brs, 1 H), 7.06–6.90 (m, 3 H), 6.62 (ddd, J = 10.0, 9.0, 2.0 Hz, 1 H), 5.47 (brs, 1
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H), 5.45 (brs, 1 H), 1.38 (s, 9 H). C{1H} NMR (125 MHz, CDCl3) δ: 160.3 (d, J = 244.5 Hz), 154.9,
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existence of their amide rotamers). 19F{1H} NMR (376 MHz, CDCl3) δ: –117.6, –117.8 (two signals
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because of the existence of their amide rotamers). IR: 2979, 1709 cm-1. HRMS (MALDI, TOF): m/z
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Calcd for C15H16NO2FNa [M+Na]+: 284.1057, found: 284.1061.
tert-Butyl-6-(trifluoromethoxy)-1,4-dihydro-1,4-epiminonaphthalene-9-carboxylate (8w) (Table 3, entry
11): Following General Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-
5-(trifluoromethoxy)phenylboronic acid (4l) (46 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h
at room temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21
g, 0.63 mmol) in THF (2.0 mL). Then, tert-butyl 1H-pyrrole-1-carboxylate (7j) (0.11 mL, 0.63 mmol)
and NfF (0.12 mL, 0.63 mmol) were added by syringe sequentially. The reaction mixture was stirred for
24 h at 60 °C. The crude product was purified by column chromatography on silica gel (hexane/EtOAc
= 8:1) to provide the titled compound 8w as a colorless oil (50 mg, 73%). 1H NMR (400 MHz, CDCl3)
δ: 7.23 (brs, 0.5 H), 7.22 (brs, 0.5 H), 7.13 (brs, 1 H), 7.00 (brs, 1 H), 6.99 (brs, 1 H), 6.81 (dq, J = 8.0,
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1.0 Hz, 1 H), 5.50 (brs, 2 H), 1.37 (s, 9 H). C{1H} NMR (400 MHz, CDCl3) δ: 154.9, 150.7, 146.9,
146.3, 143.6, 143.3, 142.5, 142.1, 121.5, 120.9, 120.4 (q, J = 256.5 Hz), 117.2, 115.3, 114.8, 81.0, 66.8,
66.4, 66.8, 65.8, 28.1 (too much number of signals because of the existence of their amide rotamers).
19F{1H} NMR (376 MHz, CDCl3) δ: –57.9. IR: 2980, 1369 cm-1. HRMS (MALDI, TOF): m/z Calcd for
C16H16NO3F3Na [M+Na]+: 350.0974, Found: 350.0973.
1-Benzyl-5,6-difluoro-1H-benzo[d][1,2,3]triazole (8x) (Table 3, entry 12):2f Following General
Procedure I, a mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-4,5-
difluorophenylboronic acid (4j) (36 mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room
temperature. The resultant residue was mixed with NaH (20 mg, 0.46 mmol) and Cs2CO3 (0.21 g, 0.63
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mmol) in THF (2.0 mL). Then, benzyl azide (7b) (0.078 mL, 0.63 mmol) and NfF (0.12 mL, 0.63
mmol) were added by syringe sequentially. The reaction mixture was stirred for 24 h at 60 °C. The
crude product was purified by column chromatography on silica gel (hexane/EtOAc = 5:1) to provide
the titled compound 8x as a colorless solid (29 mg, 57%). Mp: 119–121 °C (120–122 °C, lit).2f 1H NMR
(400 MHz, CDCl3) δ: 7.82 (dd, J = 9.0, 7.0 Hz, 1 H), 7.38–7.33 (m, 3 H), 7.26–7.24 (m, 2 H), 7.07 (dd,
J = 9.0, 7.0 Hz, 1 H), 5.80 (s, 2 H).
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6-Methyl-1,2,3,4-tetraphenylnaphthalene (8y) (Table 3, entry 13):24 Following General Procedure I, a
mixture of neopentyl glycol (24 mg, 0.25 mmol), and 2-hydroxy-5-methylphenylboronic acid (4m) (32
mg, 0.21 mmol) in CH2Cl2 (2.0 mL) was stirred for 3 h at room temperature. The resultant residue was
mixed with NaH (20 mg, 0.46 mmol), Cs2CO3 (0.21 g, 0.63 mmol) and 2,3,4,5-tetraphenylcyclopenta-
2,4-dien-1-one (7k) (0.24 g, 0.63 mmol) in THF (2.0 mL). Then, NfF (0.12 mL, 0.63 mmol) was added
by syringe. The reaction mixture was stirred for 24 h at 60 °C. The crude product was purified by
column chromatography on silica gel (hexane/CH2Cl2 = 5:2) to provide the titled compound 8y as a
colorless solid (51 mg, 55%). Mp: 217–219 °C (220.4–222.4 °C, lit).24 1H NMR (500 MHz, CDCl3) δ:
7.54 (d, J = 8.5 Hz, 1 H), 7.40 (s, 1 H), 7.26–7.17 (m, 11 H), 6.87–6.80 (m, 10 H), 2.39 (s, 3 H).
Precursor selective benzyne generation (Eq 2):
An oven-dried Schlenk tube was charged with 2-hydroxy-5-fluorophenylboronic acid (4c) (33 mg, 0.21
mmol, 1.0 equiv), neopentyl glycol (24 mg, 0.25 mmol, 1.2 equiv), and a stirrer bar. The tube was
capped with a rubber septum, and then evacuated and back-filled with argon. Anhydrous CH2Cl2 (2.0
mL, 0.10 M) was added into the tube through the septum by a syringe as well as 2-
(trimethylsilyl)phenyl triflate (9a) (49 µL, 0.21 mmol, 1.0 equiv), after which the mixture was stirred
until the mixture turned to be a clear solution. After adding ca. 2 mL of toluene to the mixture, all
solvents were removed under reduced pressure (this process was repeated three times). Cs2CO3 (0.21 g,
0.63 mmol, 3.0 equiv) and NaH (20 mg, 0.46 mmol, 2.2 equiv, 60% dispersion in mineral oil) were
added to the mixture, then evacuated and filled-back with argon; this process was repeated three times.
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THF (2.0 mL, 0.10 M), NfF (0.12 mL, 0.63 mmol, 3.0 equiv) and tert-butyl 1H-pyrrole-1-carboxylate
(7j) (0.11 mL, 0.63 mmol, 3.0 equiv) were added by a syringe sequentially at room temperature. The
mixture was stirred at 60 °C for 24 h. After 24 h, butylamine (7h) (0.13 mL, 1.3 mol, 6.0 equiv) was
added by syringe. CsF (95 mg, 0.63 mmol, 3.0 equiv) and 18-crown-6 (0.17 g, 0.63 mmol, 3.0 equiv)
were added afterwards. Then the reaction mixture was put back into the oil bath again and stirred for 12
h. After reaction, an aquous solution of NH4Cl was added to the reaction mixture, after which it was
extracted three times with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered, and
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concentrated under reduced pressure. The crude mixture was examined by H NMR spectroscopy to
determine NMR yield using tetrachloroethane as an internal standard. This crude mixture was purified
by flash column chromatography on silica gel (hexane/EtOAc = 5:1) to afford product 8v (40 mg, 0.15
mmol, 73%), another column afford 8s (30 mg, 0.20 mmol, 97%).
ASSOCIATED CONTENT
Supporting Information
The supporting information is available free of charge on the ACS Publication website at DOI:
xxxxxxxxxxxxxxxxx
Preliminary experiments, additional experiments and NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding authors
*E-mail: ikawa@phs.osaka-u.ac.jp
*E-mail: akai@phs.osaka-u.ac.jp
ORCID
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Takashi Ikawa: 0000-0002-1642-3273
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Shuji Akai: 0000-0001-9149-8745
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS
This work was financially supported by the JSPS KAKENHI (grant number 16K08164), a Grant-in-Aid
for JSPS (grant number 15J06024), AMED (grant number JP19am0101084), the Research Foundation
for Pharmaceutical Sciences, and the Kobayashi International Scholarship Foundation. We acknowledge
Dr. Akihiro Ito of the Department of Science, Osaka University for his help in acquiring and analyzing
mass spectral data of the intermediate. We also thank Dr. Kazunobu Igawa of the Institute for Materials
Chemistry and Engineering, Kyushu University for his helpful suggestion about 29Si NMR
measurement.
REFERENCES
(1) For selected recent reviews on benzynes, see: (a) Pellisier, H.; Santelli, M. The use of arynes in
organic synthesis. Tetrahedron 2003, 59, 701. (b) Wenk, H. H.; Winkler, M.; Sander, W. One Century
of Aryne Chemistry. Angew. Chem. Int. Ed. 2003, 42, 502. (c) Sanz, R. Recent Applications of Aryne
Chemistry to Organic Synthesis. A Review. Org. Prep. Proced. Int. 2008, 40, 215. (d) Kitamura, T.
Synthetic Methods for the Generation and Preparative Application of Benzyne. Aust. J. Chem. 2010, 63,
987. (e) Tadross, P. M.; Stoltz, B. M. A Comprehensive History of Arynes in Natural Product Total
Synthesis. Chem. Rev. 2012, 112, 3550. (f) Bhunia, A.; Yetra, S. R.; Biju, A. T. Recent advances in
transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions using arynes. Chem.
Soc. Rev. 2012, 41, 3140. (g) Bhojgude, S. S.; Biju, A. T. Arynes in Transition-Metal-Free
Multicomponent Coupling Reactions. Angew. Chem. Int. Ed. 2012, 51, 1520. (h) Dubrovskiy, A. V.;
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