Development and Application of O-(Trimethylsilyl)aryl Fluorosulfates for the Synthesis of Arynes

Article abstract of DOI:10.1021/acs.joc.5b00923

A class of o-(trimethylsilyl)aryl fluorosulfates was synthesized by a concise method and successfully used as aryne precursors for the first time. Different trapping agents such as azides, furans, and acyl acetoacetates could successfully react with the a

Full text of DOI:10.1021/acs.joc.5b00923

Note
pubs.acs.org/joc
Development and Application of O‑(Trimethylsilyl)aryl Fluorosulfates
for the Synthesis of Arynes
Qiao Chen,† Hongmei Yu,† Zhaoqing Xu,*,† Li Lin,† Xianxing Jiang,*,‡ and Rui Wang*,†
†Institute of New Drugs Design and Synthesis, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic
Medical Sciences, Lanzhou University, Lanzhou, China
‡School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
S
* Supporting Information
ABSTRACT: A class of o-(trimethylsilyl)aryl fluorosulfates was synthesized by a
concise method and successfully used as aryne precursors for the first time.
Different trapping agents such as azides, furans, and acyl acetoacetates could
successfully react with the aryne precursors under mild conditions with good to
excellent yields.
ince the first evidence for the existence of arynes,1 they
Shave attracted chemists’ great attention because of their
very broad synthetic utilities.2 Their versatility in the synthesis
provides organic chemists with a prodigious starting point to
discover new reactions, advanced materials, and pharmaceut-
icals.3 Nevertheless, the application of these versatile synthetic
intermediates was limited due to their harsh preparing
conditions and high synthetic cost.4 Indeed, it was not until
1983 that arynes, motivated by Kobayashi’s aryne precursors,
were allowed to be generated under mild reaction conditions.5
Although the introduction of aryl triflates have turned arynes to
useful synthetic reagents from uncontrollable reactive inter-
mediates, this kind of aryne precursor still has its own
limitations, such as (i) the triflating reagents (Tf2O and
TfCl) used for the preparation of aryl triflates were relatively
expensive; (ii) the aryl triflates decomposed rapidly under
normal basic conditions, which restricted the use of this kind of
precursors as intermediates in multistep reactions;6 (iii)
fluoride promoters used for the formation of arynes showed
low selectivities over C−Si and O−Si bonds cleavage, which
means that aryne precursors bearing multiple silane groups,
such as Caryl-SiR3 and CalkylO-SiR3, will not be expected to give
highly chem- or regioselective transformation (an example is
given in the following section). In 1999, Kitamura and co-
workers disclosed a hypervalent iodine aryne precursor for the
generation of an aryne intermediate in high yield under the
treatment of Bu4NF at room temperature.4b Recently, as the o-
TMS aryl triflate analogues, a new method was developed for
the preparation of arynes by the group of Akai.7 They replaced
the traditional triflating agents with nonafluorobutanesulfonyl
fluoride (NfF) and cleverly conducted the arynes production
and trapping reaction in one-pot. In that context, the fluoride
ion released from NfF while the aryne precursor generated was
directly used for the formation of aryne, and an additional
fluorine source was needless. In 2012, o-(trimethylsilyl)aryl
Novak
́
’s group,8 and the precursors do not contain any fluorine
atoms themselves, and the potentially toxic of fluorinated side
product was eliminated. Although these excellent aryne
precursors have made notable progress in the area of aryne
chemistry, the dependence of external fluoride sources, high
fluoride content, or the expensive starting material still limited
their employment in large-scale reactions. Nowadays, with the
increasing use of arynes in synthetic chemistry, highly efficient,
relatively stable, and operationally simple aryne precursors with
low cost are still highly desired.
Sulfonyl halides, such as −SO2Cl,9 are highly polarized due
to the electron-withdrawing property of the halogen center and
can theoretically serve as leaving groups. However, the sulfur−
halogen bond in sulfonyl halides is very reactive and tends to
react with various chemicals (−SO2Br and −SO2I are even
sensitive to light), which affects the substitution of the sulfonyl
halide as a whole group in organic reactions (Figure 1, eq 1).
Unlike other sulfonyl halides, the −SO2F unit is remarkably
Figure 1. O-(TMS) phenyl fluorosulfate as precursor for the synthesis
of aryne.
Received: April 27, 2015
imidazolylsulfonates were chosen as aryne precursors by Zoltan
́
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00923
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The Journal of Organic Chemistry
Note
stable and redox-silent.10 Since fluorine is the most electro-
negative element in the periodic table, the cleavage of the
sulfonyl-fluorine bond is extremely difficult, making it hard for
−SO2F to act as halogenating agents. Considering the unique
property of the sulfonyl fluoride group, we envisioned that the
simple -OSO2F could be used as an inexpensive -OTf
alternative and serves as a leaving group for the developing of
a new type of aryne precursors 2.11−13 As shown in Figure 1
(eq 2), 2a was prepared in high yield by simply exposing the
corresponding o-TMS phenol to sulfuryl fluoride in the
presence of triethylamine.14 Sulfuryl fluoride is a broad
spectrum biocide, and its global production is about 3 million
kilograms per year,11,15 making it a very cheap starting material.
In 2014, an excellent review published by Sharpless
demonstrated the details about sulfuryl fluoride and its
application in organic syntheses.11 During the preparation of
this manuscript, a series of aryl fluorosulfates were employed as
coupling partners in a Suzuki reaction with remarkable yields.16
In this note, a family of o-(trimethylsilyl)aryl fluorosulfates were
developed and served as aryne precursors. To our delight, the
new precursor designed here could smoothly facilitate the
Huisgen cyclization,8,17 Diels−Alder reaction,7 and σ-bond
insertion reaction18 under very mild conditions. Furthermore,
o-TMS aryl fluorosulfates were proved to be air- and moisture-
stable and would not decompose for at least a month when
placed at room temperature. This class of aryne precursors will
provide economic and practical avenues toward the industrial-
ized application of arynes.
in 20 h at 60 °C (entry 1). Gratifyingly, a remarkable
enhancement of reactivity was detected when KOH was used
instead of NaOH, given the desired product 4a with a
promising yield (57%, entry 2). Further screening of other
bases revealed that cesium salts are better candidates than
potassium-containing bases (entries 3, 4, and 9 vs entries 2, and
5−7), and Cs2CO3 was proved to be optimal for this
cycloaddition. An organic base DBU was also tested under
the same conditions; however, only a trace amount of the
desired product was observed (entry 8). It should be noted that
the generally used F− promoters, namely, CsF and TBAF, were
also effective for the reaction (entries 9 and 10). Subsequently,
Cs2CO3 was chosen for further investigation of the reaction
conditions. Reducing the reaction temperature to 30 °C only
slightly decreased the yield of 4a (entry 11). We were happy to
find that when 18-crown-6 (18-c-6) was used as an additive, the
product yield was dramatically improved to 89% (entry 12).19
A
solvent survey indicated that CH3CN is the best choice for this
transformation. Modification of the ration of 2a/3a to 1.5/1
improved the yield sharply (entry 13). At last, a complete
conversion of 3a was obtained by using 2a (1.5 equiv), Cs2CO3
(1.5 equiv), and 18-c-6 (1 equiv) in 0.2 M CH3CN at 30 °C for
8 h (entry 14).
Armed with the optimized conditions, several symmetrical or
nonsymmetrical aryne precursors were subjected to the
cycloaddition reaction with the benzyl azide 3a (Table 2). As
a,b
Table 2. Reaction Scope with Different Aryne Precursors
At the outset of our investigations, by using CH3CN as the
solvent, a series of nonfluorinated bases was evaluated for the
Huisgen 2 + 3 cycloaddition between o-TMS phenyl
fluorosulfate 2a and benzyl azide 3a (Table 1). It was found
that two equivalents of NaOH can hardly catalyze the reaction
a
Table 1. Optimization of the Reaction Conditions
b
entry
base
solvent
temperature
yield (%)
1
NaOH
KOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
60 °C
30 °C
30 °C
30 °C
30 °C
60 °C
<5
2
57
3
CsOH
Cs2CO3
K3PO4
KOtBu
K2CO3
DBU
76
4
82
5
17
6
40
7
29
a
Method A: All of the reactions were carried out with 0.3 mmol of 2,
0.2 mmol of 3a, 0.3 mmol of Cs2CO3, 0.2 mmol of 18-c-6, and 1 mL of
MeCN, at 30 °C, and stirred for 12 h. Method B: 0.2 mmol of 2, 0.3
mmol of 3a, 0.4 mmol of CsF, and 1 mL of MeCN, at 60 °C and 36 h.
8
<5
9
CsF
75
10
11
12
13
14
15
TBAF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsF
75
78
b
Isolated yields. Ratios in parentheses refer to the 5-:6-substituted
c
c
c
f
89
product.
,
,
d
d
97
,
e
97 (90)
88 (80)
expected, the symmetrical aryne precursors such as 2a, 2b, 2d,
and 2h afforded the single regioisomer of the products (4a, 4b,
4d and 4h), while the nonsymmetrical aryne precursors
resulted in inseparable regioisomeric mixtures of 5- and 6-
substituted benzotriazoles20 (4c and 4e−4g). Aryne precursors
with different substituent groups as well as disubstituted and
heterocyclic substituted were well tolerated in the trans-
formation and provided the desired products in good yields. It
should be noted that, an aryne precursor bearing two silane-
a
Unless otherwise noted, the reactions were carried out by using 0.24
mmol of 2a, 0.2 mmol of 3a, 0.4 mmol of base, and 2 mL of solvent,
b
1
and stirred for 20 h. Yields were detected by H NMR with isolated
yield indicated in parentheses. 1 equiv of 18-c-6 (1,4,7,10,13,16-
hexaoxacyclooctadecane) was used. 0.3 mmol of 2a was used, and the
reaction was completed in 8 h. 0.3 mmol of Cs2CO3 and 1 mL of
CH3CN were used. 0.2 mmol of 2a, 0.3 mmol of 3a, and 1 mL of
CH3CN, and 36 h.
c
d
e
f
B
DOI: 10.1021/acs.joc.5b00923
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Note
protected groups was synthesized and directly subjected to the
aryne cycloaddition reaction with azide 3a. To our delight, the
corresponding 4g was obtained in 78% yield with the para-
silane protecting group untouched. In fact, when 4g was
exposed to one equiv of CsF, it completely desilylated to the
corresponding alcohol 4g′ within 2 h. Further research
indicated that the silyl substituent on the ortho-position of
the aryne precursor was not limited to TMS, and 2h with a
TBDPS (tert-butyldiphenylsilyl) group also lead to the
formation of 4a with good result. Since CsF is one of the
most classic desilylation reagents, the yields of the reactions
catalyzed by CsF are also depicted in the table (method B).
Different azides bearing electron-donating as well as electron-
withdrawing substituents also permitted an efficient access to
the benzotriazoles 5a−5j in good to excellent yields (Table 3).
Following the successful cycloaddition between the new
aryne precursors and azides, we continued our investigations
with other types of reactions to confirm the synthetic
applicability of this novel precursor (Figure 2). To our delight,
a,b
Table 3. Reaction Scope with Different Azides
Figure 2. Application of 2a in other reactions under the established
conditions.
the Diels−Alder reaction of 2a and furan proceeded smoothly
under the standard conditions (method A), giving the
corresponding Diels−Alder adducts 6a and 6b in 82% and
60% yields, respectively. The σ-bond insertion reaction of acetyl
acetic ether or ethyl benzoyl acetate with 2a were also achieved
under established conditions and afforded the desired product
7a or 7b in good yields.
Notably, the reactivity and stability differences between
Kobayashi’s aryne precursor and our precursor 2a were
examined (Table 4). We were glad to find that our precursor
Table 4. Reactivity and Stability Difference between
a
Precursors 2a and 8
b
yield (%)
entry
precursor
base
CsF
precursor
1a
4a
1
2
2a
8
8 (2a)
10 (8)
92 (2a)
32 (8)
0
85
80
4
CsF
6
c
a
3
2a
8
NaOH
NaOH
0
Method A: 0.3 mmol of 2a, 0.2 mmol of 3, 0.3 mmol of Cs2CO3, 0.2
mmol of 18-c-6, and 1 mL of MeCN, at 30 °C, and stirred for 12 h.
Method B: 0.2 mmol of 2a, 0.3 mmol of 3, 0.4 mmol of CsF, and 1 mL
4
65
1
a
The reactions were carried out with 0.2 mmol 2a or 8, 0.3 mmol 3a,
and 0.2 mmol base in 1 mL of MeCN at 30 °C; stirred for 24 h.
b
of MeCN, at 60 °C and 36 h. Isolated yields.
b
c
Determined by 1H NMR using mesitylene as an internal standard. A
week later, still no 1a was detected.
It is worth noting that benzyl azides bearing a methyl group
exhibited even higher reactivity and yielded the corresponding
benzotriazoles with outstanding results (5a and 5b). While the
unsubstituted azidobenzene and the methoxyl substituted
azidobenzene gave slightly lower yields of the desired products,
they afforded 5d and 5h with 82% and 80% yields, respectively.
Disubstituted and allylic azides were found to be competent in
the cycloaddition reaction with 2a, thus delivering 5i and 5j
with remarkable yields. We also examined the use of
trimethylsilyl azide in this reaction; however, the desired
product seems to be desilylated and then phenylated under the
standard conditions and led to 5d in a moderate yield (39%).
Summarizing the results of Tables 2 and 3 (method B), we can
see that CsF is also competent to generate aryne from o-
(trimethylsilyl)aryl fluorosulfates.
demonstrated a slightly higher reactivity under the same
conditions. What’s more, when treated with NaOH, Kobaya-
shi’s aryne precursor seriously decomposed, while our
precursor 2a was undamaged even in a week. In order to
investigate the potential of this precursor in industrial
application, the Huisgen cyclization was conducted on a larger
scale (10 mmol). As we had expected, both of the methods give
the desired product in good yields (Figure 3).
In summary, a new class of aryne precursors was developed
and successfully applied to the preparation of arynes under mild
conditions. These precursors were easily approached from o-
trimethylsilyl aryl phenols and readily available sulfuryl fluoride.
Moreover, the arynes could be generated with or without an
external fluoride source which smoothly underwent the
C
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Note
the organic phase was dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash column
chromatography on silica gel (petroleum ether) to give 2i as a
colorless oil; 85% yield.
General Procedure for the Synthesis of 4−7. Method A. An oven-
dried flask was charged with Cs2CO3 (0.3 mmol, 1.5 equiv) and 18-c-6
(0.2 mmol, 1 equiv) and capped with a rubber septum and then
evacuated and backfilled with argon. Anhydrous MeCN (1 mL, 0.2
M), 2 (0.3 mmol, 1.5 equiv), and 3 (0.2 mmol, 1equiv) were added via
syringes, and the reaction mixture was stirred at 30 °C for a given
reaction time. After the reaction, saturated aqueous solution of NH4Cl
was added into the reaction mixture for quenching. The mixture was
extracted with ethyl acetate, and the combined organic phase was dried
over Na2SO4 and concentrated under reduced pressure. The residue
was purified by flash column chromatography on silica gel (petroleum
ether/ethyl acetate 10:1−6:1) to give the desired product 4 or 5.
Products 6 and 7 were synthesed using method A with the
corresponding aryne trapping reagents instead of 3.
Method B. An oven-dried flask was charged with CsF (0.4 mmol, 2
equiv) and capped with a rubber septum and then evacuated and
backfilled with argon. Anhydrous MeCN (1 mL, 0.2 M), 2 (0.2 mmol,
1 equiv), and 3 (0.3 mmol, 1.5 equiv) were added via syringes, and the
reaction mixture was stirred at 60 °C for 36 h. After cooling down to
room temperature, the reaction mixture was concentrated in vacuo.
The crude products were purified through flash chromatography on
silica gel (petroleum ether/ethyl acetate 10:1−6:1) to afford the
desired product 4 or 5.
General Procedure for the Synthesis of 4g′. An oven-dried flask
was charged with 4g (35.3 mg, 0.10 mmol) and CsF (15.2 mg, 0.10
mmol) and capped with a rubber septum. The flask was evacuated and
backfilled with argon. MeCN (1.0 mL) was charged via syringes, and
the reaction mixture was stirred at room temperature for 2 h. Water
was added into the reaction mixture for quenching. The mixture was
extracted from ethyl acetate, and the combined organic phase was
dried over Na2SO4. The organic phase was filtered and concentrated
under reduce pressure. The residue was purified by flash column
chromatography (petroleum ether/ethyl acetate 2:1) to provide the
titled compound 4g′ as a white solid (23.6 mg, 99%). The 5- and 6-
substitued 4g′ were separable and were characterized separately. It
should be noted that when one equivalent of CsF was added to the
mixture of the 4g formation reaction after 4g was fully generated, 4g′
could also be acquired.
2-(Trimethylsilyl)phenyl Sulfofluoridate (2a). Colorless oil, Rf = 0.5
(PE), 90% yield (2.23 g). 1H NMR (300 MHz, CDCl3) δ 7.55 (dd, J =
7.5, 1.8 Hz, 1H), 7.52−7.42 (m, 1H), 7.41−7.32 (m, 2H), 0.37 (s,
9H). 13C NMR (75 MHz, CDCl3) δ 155.7, 136.2, 132.1, 131.3, 127.8,
119.0, −0.9. 19F NMR (282 MHz, CDCl3) δ 42.34. IR (CHCl3): 2960,
1599, 1449, 1233, 1143, 925, 845, 575 cm−1. HRMS (EI):
C9H13FO3SSi calcd, 248.0339; found, 248.0336.
Figure 3. Peparation of 4a with a 10 mmol scale reaction by methods
A and B.
Huisgen cyclization reactions with a uniformly high yields. We
believe that the design of these simple, efficient aryne
precursors will benefit the application of arynes on an industrial
scale. Further investigations of the applicability of the new
aryne precursor as well as the mechanism studies are currently
underway.
EXPERIMENTAL SECTION
■
General. All commercially available reagents were used without
further purification unless otherwise stated. 18-c-6 was purified by
recrystallization from CH3CN. All solvents were dried according to
1
established procedures. H, 13C, and 19F NMR spectra were recorded
on a spectrometer (300 MHz, 75 and 282 MHz, respectively). The
1
regioselectivities were determined by H NMR spectra of the crude
reaction mixtures. IR spectra were recorded on a FT-IR spectrometer,
and only major peaks were reported in cm−1. High resolution mass
spectra (HRMS) were obtained by the ESI (Q-TOF or Orbitrap) or
EI (TOF) ionization sources. Noncommercial azides 3 were prepared
according to known procedures.17d
General Procedure for the Preparation of Aryne Precursors 2.
Starting material 2-bromophenols are commercially available, and
bromosesamol21a was prepared from commercially available sesamol
according to a literature procedure. 2-(Trimethylsilyl)phenols were
prepared from the corresponding 2-bromophenols according to
literature procedures.21b 4-(((tert-Butyldimethylsilyl)oxy)methyl)-2-
(trimethylsilyl)phenol was prepared according to a literature
procedure.7 Aryne precursors 2 were prepared according to a modified
literature procedure.11,14 An oven-dried flask with a magnetic stirring
bar, and the corresponding 2-(trimethylsilyl)phenols 1 (10 mmol) was
capped with a rubber septum and then evacuated and backfilled with
argon. CH2Cl2 (10 mL) and Et3N (12 mmol) were added via syringes,
and the mixture was stirred at room temperature for 2 h. Then the
atmosphere above the solution was removed with gentle vacuum, and
SO2F2 gas (1−1.5 equiv sulfuryl fluoride was enough. CAUTION:
Sulfuryl fluoride is a chemical mainly used as a fumigant insecticide.
Ingestion and other exposures to the chemical might be harmful.) was
introduced by needle from a balloon filled with the gas. For large scale
reactions, depletion of the sulfuryl fluoride from the balloon was easily
observed, and more reagents were introduced with a fresh balloon
when required. For small scale reactions, SO2F2 was used in excess.
The reaction mixture was vigorously stirred at room temperature for
0.5−12 h, monitoring by TLC. After completion, the solvent was
removed under vacuum, and the residue was purified by chromatog-
raphy on silica gel (petroleum ether−petroleum ether/ethyl acetate
10:1) to give the desired product 2a−2g.
4,5-Dimethyl-2-(trimethylsilyl)phenyl Sulfofluoridate (2b). Color-
1
less oil, Rf = 0.5 (PE), 85% yield (2.35 g). H NMR (300 MHz,
CDCl3) δ 7.24 (s, 1H), 7.13 (d, J = 1.8 Hz, 1H), 2.29 (s, 3H), 2.27 (s,
3H), 0.34 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 153.9, 140.4, 136.9,
136.4, 128.4, 119.9, 19.9, 19.2, −0.8. 19F NMR (282 MHz, CDCl3) δ
41.90. IR (CHCl3): 2957, 1607, 1447, 1229, 1003, 842, 803, 629 cm−1.
HRMS (EI): C11H17FO3SSi calcd, 276.0652; found, 276.0650.
4-Methyl-2-(trimethylsilyl)phenyl Sulfofluoridate (2c). Colorless
oil, Rf = 0.5 (PE), 96% yield (2.52 g). 1H NMR (300 MHz, CDCl3) δ
7.30 (s, 1H), 7.25 (s, 2H), 2.37 (s, 3H), 0.35 (s, 9H). 13C NMR (75
MHz, CDCl3) δ 153.7, 137.6, 136.6, 131.7, 118.7, 20.9, −0.8. 19F
NMR (282 MHz, CDCl3) δ 41.95. IR (CHCl3): 2959, 1596, 1448,
1233, 926, 842, 803, 608 cm−1. HRMS (EI): C10H15FO3SSi calcd,
262.0495; found, 262.0490.
6-(Trimethylsilyl)benzo[d][1,3]dioxol-5-yl Sulfofluoridate (2d).
Colorless oil, Rf = 0.3 (PE), 80% yield (2.34 g). 1H NMR (300
MHz, CDCl3) δ 6.89 (d, J = 1.8 Hz, 1H), 6.88 (s, 1H), 6.04 (s, 2H),
0.33 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 149.6, 149.3, 147.2,
124.3, 113.1, 102.4, 101.7, −0.7. 19F NMR (282 MHz, CDCl3) δ
41.51. IR (CHCl3): 2959, 1622, 1450, 1250, 1231, 993, 903, 844 cm−1.
2-(tert-Butyldiphenylsilyl)phenyl Sulfofluoridate (2h). 2-(tert-
Butyldiphenylsilyl)phenol (1h) was prepared according to a literature
procedure.21c Compound 2h was prepared from 1h following the
general procedure. White solid, 86% yield.
2-(Trimethylsilyl)phenyl sulfochloridate (2i). An oven-dried 100
mL round-bottomed flask equipped with a magnetic stirring bar was
charged with 2-(trimethylsilyl)phenol (1.66 g, 10 mmol, 1.0 equiv).
The vessel was evacuated and backfilled with nitrogen. CH2Cl2 (20
mL) and pyridine (0.97 mL, 12 mmol, 1.2 equiv) were then added via
syringes, and the solution was cooled to −40 °C. After the mixture was
stirred for 1 h at −40 °C, sulfuryl chloride (0.97 mL, 12 mmol, 1.2
equiv) was added via syringe. The reaction was stirred for 2 h at this
temperature and then warmed to room temperature and stirred for
one more hour. After the reaction, water was added into the reaction
mixture for quenching. The mixture was extracted with CH2Cl2, and
D
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The Journal of Organic Chemistry
Note
HRMS (ESI-Orbitrap): C10H14FO5SSi [M + H]+ calcd, 293.0310;
found, 293.0313.
of 5-chloro and 6-chloro isomers with 7:3 ratio). mp 105−106 °C. 1H
NMR (300 MHz, CDCl3) δ 8.16−7.89 (m, 1H), 7.37−7.22 (m, 6H),
5.82 (s, 1.4H), 5.80 (s, 0.6H). 13C NMR (75 MHz, CDCl3) δ 146.9,
144.8, 134.5, 134.2, 134.2, 133.8, 133.3, 131.4, 129.8, 129.1, 129.03,
128.6, 128.3, 127.5, 125.1, 122.9, 120.9, 120.6, 119.3, 110.7, 109.5,
52.5, 52.3. IR (CHCl3): 3345, 2926, 1595, 1421, 1104, 1061, 845
cm−1. HRMS (ESI-Q-TOF): C13H11ClN3 [M + H]+ calcd, 244.0636;
found, 244.0646.
4-Chloro-2-(trimethylsilyl)phenyl Sulfofluoridate (2e). Colorless
1
oil, Rf = 0.4 (PE), 78% yield (2.2 g). H NMR (300 MHz, CDCl3) δ
7.49−7.38 (m, 2H), 7.32 (dd, J = 8.7, 1.8 Hz, 1H), 0.37 (s, 9H). 13C
NMR (75 MHz, CDCl3) δ 153.6, 135.8, 134.9, 133.9, 131.1, 120.5,
−1.01. 19F NMR (282 MHz, CDCl3) δ 42.26. IR (CHCl3): 2961,
1589, 1452, 1233, 1150, 924, 844, 595 cm−1. HRMS (EI):
C9H12ClFO3SSi calcd, 281.9949; found, 281.9948.
1-Benzyl-5(6)-fluoro-1H-benzo[d][1,2,3]triazole (4f).8 Yellow
solid, Rf = 0.4 (PE/EA = 10:1), 86% yield (39.0 mg), (unseparable
mixture of 5-fluoro and 6-fluoro isomers with a 7:3 ratio). mp 88−89
4-Fluoro-2-(trimethylsilyl)phenyl Sulfofluoridate (2f). Light blue
1
oil, Rf = 0.4 (PE), 75% yield (2.0 g). H NMR (300 MHz, CDCl3) δ
1
7.36 (ddd, J = 9.0, 4.0, 1.9 Hz, 1H), 7.20 (dd, J = 8.0, 3.1 Hz, 1H), 7.12
(ddd, J = 9.0, 7.4, 3.2 Hz, 1H), 0.37 (s, 9H). 13C NMR (75 MHz,
CDCl3, C−F coupling not assigned) δ 162.9, 159.6, 150.9, 135.5,
122.5, 122.2, 121.0, 120.9, 118.0, 117.7, −1.1. 19F NMR (282 MHz,
CDCl3) δ 41.66, −113.80. IR (CHCl3): 2960, 1583, 1452, 1233, 1135,
844, 806, 538 cm−1. HRMS (EI): C9H12F2O3SSi calcd, 266.0244;
found, 266.0240.
4-(((tert-Butyldimethylsilyl)oxy)methyl)-2-(trimethylsilyl)phenyl
Sulfofluoridate (2g). Colorless oil, Rf = 0.4 (PE), 80% yield (3.16 g).
1H NMR (300 MHz, CDCl3) δ 7.50 (s, 1H), 7.45−7.28 (m, 2H), 4.76
°C (literature reported: 92−93 °C). H NMR (300 MHz, CDCl3) δ
8.00 (dd, J = 9.1, 4.6 Hz, 0.3H), 7.73−7.63 (m,0.7 H), 7.41−7.23 (m,
5.7H), 7.22−7.68 (m, 1H), 6.97 (dd, J = 7.9, 2.2 Hz, 0.3H), 5.83 (s,
1.4H), 5.79 (s, 0.6H). 13C NMR (75 MHz, CDCl3, C−F coupling not
assigned) δ 163.6, 161.2, 160.4, 158.0, 146.6, 146.4, 143.1, 134.3,
134.2, 129.7, 129.0, 128.6, 127.5, 127.5, 121.5, 121.4, 117.5, 117.2,
114.1, 113.7, 110.8, 110.6, 104.6, 104.3, 95.6, 95.3, 52.5, 52.3.
1-Benzyl-5(6)-(((tert-butyldimethylsilyl)oxy)methyl)-1H-benzo[d]-
[1,2,3]triazole (4g). Yellow wax, Rf = 0.2 (PE/EA = 10:1), 78% yield
(55.1 mg), (unseparable mixture of 5-substituted and 6-substituted
isomers with 1:1 ratio). 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 0.5H),
7.91 (d, J = 8.6 Hz, 0.5H), 7.34−7.10 (m, 7H), 5.76 (s, 2H), 4.78 (s,
1H), 4.76 (s, 1H), 0.88 (s, 4.5H), 0.86 (s, 4.5H), 0.05 (s, 3H), −0.00
(s, 3H). 13C NMR (75 MHz, CDCl3) δ 146.6, 145.7, 141.6, 137.8,
134.7, 133.0, 132.10, 128.9, 128.4, 127.6, 127.5, 126.3, 122.3, 119.5,
116.7, 109.4, 106.2, 64.6, 64.4, 52.2, 25.9, 25.9, 18.4, 18.3, −5.3, −5.4.
IR (CHCl3): 3371, 2926, 2372, 1595, 1458, 1220, 1115, 779 cm−1.
HRMS (ESI-Q-TOF): C20H28N3OSi [M + H]+ calcd, 354.1996;
found, 354.2007.
(s, 2H), 0.95 (s, 9H), 0.36 (s, 9H), 0.12 (s, 6H). 13C NMR (75 MHz,
CDCl3) δ 154.5, 141.0, 133.4, 131.7, 128.7, 118.7, 64.0, 25.9, 18.3,
−0.9, −5.4. 19F NMR (282 MHz, CDCl3) δ 42.07. IR (CHCl3): 2956,
1597, 1450, 1233, 1105, 926, 842, 804 cm−1. HRMS (ESI-Orbitrap):
C16H33FO4SSi2 N [M + NH4]+ calcd, 410.1647; found, 410.1652.
2-(tert-Butyldiphenylsilyl)phenyl Sulfofluoridate (2h). White solid,
Rf = 0.6 (PE/EA = 10:1), 86% yield (3.56 g), mp 90−92 °C. 1H NMR
(300 MHz, CDCl3) δ 7.71 (dd, J = 7.4, 1.8 Hz, 1H), 7.59−7.50 (m,
5H), 7.47−7.31 (m, 8H), 1.21 (s, 9H). 13C NMR (75 MHz, CDCl3) δ
156.0, 139.2, 136.1, 133.3, 131.9, 129.6, 127.9, 127.1, 118.7, 29.1, 18.9.
19F NMR (282 MHz, CDCl3) δ 45.49. IR (CHCl3): 3387, 2929, 1452,
1429, 1232, 1145, 1106, 1060, 702 cm−1. HRMS (ESI-Orbitrap):
C22H27FO3SSiN [M + NH4]+ calcd, 432.1459; found, 432.1464.
2-(Trimethylsilyl)phenyl Sulfochloridate(2i). Colorless oil, Rf = 0.6
(PE), 85% yield (2.24 g). 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J =
8.3 Hz, 1H), 7.57 (dt, J = 7.2, 1.8 Hz, 1H), 7.53−7.43 (m, 1H), 7.42−
7.33 (m, 1H), 0.37 (d, J = 1.8 Hz, 9H). 13C NMR (75 MHz, CDCl3) δ
156.1, 136.3, 132.4, 131.2, 127.8, 118.7, −0.6. IR (CHCl3): 2959,
1597, 1414, 1140, 1061, 843, 594, 542 cm−1. HRMS (EI):
C9H13ClO3SSi calcd, 264.0043; found, 264.0039.
(1-Benzyl-1H-benzo[d][1,2,3]triazol-5-yl)methanol (5-Substituted
4g′).21d White solid, Rf = 0.4 (PE/EA = 1:1), 45% yield. mp 156−157
°C. 1H NMR (300 MHz, CDCl3) δ 8.03 (s, 1H), 7.45 (dd, J = 8.6, 1.2
Hz, 1H), 7.37−7.29 (m, 4H), 7.29−7.23 (m, 2H), 5.85 (s, 2H), 4.83
(s, 2H). 13C NMR (75 MHz, CDCl3) δ 146.5, 137.3, 134.6, 132.4,
129.0, 128.5, 127.5, 127.2, 117.8, 109.9, 65.0, 52.3. IR (CHCl3): 3366,
2924, 1655, 1596, 1458, 1098, 1030, 714 cm−1. HRMS (ESI-Q-TOF):
C14H14N3O [M + H]+ calcd, 240.1131; found, 240.1143.
(1-Benzyl-1H-benzo[d][1,2,3]triazol-6-yl)methanol (6-Substituted
4g′).21d White solid, Rf = 0.5 (PE/EA = 1:1), 45% yield. mp 119−120
°C. 1H NMR (300 MHz, CDCl3) δ 8.03 (d, J = 8.6 Hz, 1H), 7.42 (s,
1H), 7.37−7.26 (m, 6H), 5.84 (s, 2H), 4.83 (d, J = 4.6 Hz, 2H). 13C
NMR (75 MHz, CDCl3) δ 145.8, 141.0, 134.7, 133.1, 129.0, 128.4,
127.5, 123.2, 120.0, 107.0, 64.8, 52.1. IR (CHCl3): 3365, 2923, 2373,
1595, 1458, 1265, 1117, 716 cm−1. HRMS (ESI-Q-TOF): C14H14N3O
[M + H]+ calcd, 240.1131; found, 240.1142.
Benzyl-1H-benzo[d][1,2,3]triazole (4a).8 Yellow solid, Rf = 0.3
(PE/EA = 10:1), 90% yield (37.6 mg). mp 108−110 °C (literature
1
reported: 114−116 °C). H NMR (300 MHz, CDCl3) δ 8.05 (d, J =
8.0 Hz, 1H), 7.40−7.22 (m, 8H), 5.83 (s, 2H). 13C NMR (75 MHz,
CDCl3) δ 146.2, 134.6, 132.7, 128.9, 128.3, 127.5, 127.3, 123.8, 119.9,
109.6, 52.1.
1-(2-Methylbenzyl)-1H-benzo[d][1,2,3]triazole (5a).21e White
solid, Rf = 0.3 (PE/EA = 10:1), 97% yield (43.2 mg). mp 77−78
1-Benzyl-5,6-dimethyl-1H-benzo[d][1,2,3]triazole (4b).17d Yellow
solid, Rf = 0.3 (PE/EA = 10:1), 84% yield (39.8 mg). mp 156−157 °C
1
°C (literature reported: 80−81 °C). H NMR (300 MHz, CDCl3) δ
1
7.99−7.91 (m, 1H), 7.31−7.01 (m, 6H), 6.95 (d, J = 7.5 Hz, 1H), 5.74
(s, 2H), 2.23 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 146.1, 136.4,
132.9, 132.5, 130.8, 128.6, 128.4, 127.2, 126.3, 123.8, 119.9, 109.8,
50.7, 19.2.
(literature reported: 158−161 °C). H NMR (300 MHz, CDCl3) δ
7.78 (s, 1H), 7.37−7.21 (m, 5H), 7.10 (s, 1H), 5.78 (s, 2H), 2.36 (s,
3H), 2.34 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 145.5, 137.7, 135.0,
133.7, 131.8, 128.9, 128.2, 127.4, 119.0, 109.0, 51.9, 20.9, 20.4.
1-Benzyl-5(6)-methyl-1H-benzo[d][1,2,3]triazole (4c).8 Yellow
solid, Rf = 0.3 (PE/EA = 10:1), 77% yield (34.2 mg), (unseparable
mixture of 5- methyl and 6- methyl isomers with a 1:1 ratio). mp 95−
96 °C (literature reported: 97−98 °C). 1H NMR (300 MHz, CDCl3)
δ 7.91 (d, J = 8.5 Hz, 0.5H), 7.80 (s, 0.5H), 7.35−7.12 (m, 7H), 5.79
(s, 1H), 5.78 (s, 1H), 2.46 (s, 1.5H), 2.44 (s, 1.5H). 13C NMR (75
MHz, CDCl3) δ 146.8, 144.8, 137.9, 134.9, 134.8, 133.8, 133.2, 131.2,
129.5, 128.8, 128.3, 128.2, 127.4, 127.3, 126.1, 119.3, 118.8, 109.1,
108.7, 52.1, 51.8, 21.9, 21.3.
1-(3Methylbenzyl)-1H-benzo[d][1,2,3]triazole (5b).21e White solid,
Rf = 0.3 (PE/EA = 10:1), 99% yield (44.2 mg). mp 118−120 °C
1
(literature reported: 119−121 °C). H NMR (300 MHz, CDCl3) δ
8.05 (d, J = 8.1 Hz, 1H), 7.43−7.27 (m, 3H), 7.24−7.15 (m, 1H), 7.08
(t, J = 8.2 Hz, 3H), 5.78 (s, 2H), 2.28 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 146.2, 138.7, 134.6, 132.7, 129.1, 128.7, 128.2, 127.3, 124.6,
123.8, 119.9, 109.7, 52.1, 21.2.
1-(4-Chlorobenzyl)-1H-benzo[d][1,2,3]triazole (5c).21e White
solid, Rf = 0.2 (PE/EA = 10:1), 86% yield (41.8 mg). mp 92−94
1
°C (literature reported: 87−89 °C). H NMR (300 MHz, CDCl3) δ
1-Benzyl-1H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d][1,2,3]triazole
(4d).8 White solid, Rf = 0.2 (PE/EA = 5:1), 92% yield (46.6 mg). mp
148−149 °C (literature reported: 148−151 °C). 1H NMR (300 MHz,
CDCl3) δ7.35−7.20 (m, 6H), 6.61 (s, 1H), 6.01 (s, 2H), 5.71 (s, 2H).
13C NMR (75 MHz, CDCl3) δ 149.5, 146.9, 142.1, 134.5, 129.3, 128.9,
128.4, 127.4, 102.1, 97.0, 88.3, 52.2.
1-Benzyl-5(6)-chloro-1H-benzo[d][1,2,3]triazole (4e). Yellow solid,
8.09−7.02 (m, 1H), 7.46−7.24 (m, 5H), 7.20 (d, J = 8.5 Hz, 2H), 5.80
(s, 2H). 13C NMR (75 MHz, CDCl3) δ 146.2, 134.3, 133.2, 132.5,
129.1, 128.8, 127.5, 124.0, 120.0, 109.4, 51.3.
1-Phenyl-1H-benzo[d][1,2,3]triazole (5d).17d Yellow solid, Rf = 0.4
(PE/EA = 10:1), 82% yield (32.0 mg). mp 90−92 °C (literature
reported: 86−87 °C). 1H NMR (300 MHz, CDCl3) δ 8.15 (d, J = 8.3
Hz, 1H), 7.79 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.61 (t, J =
Rf = 0.5 (PE/EA = 10:1), 79% yield (38.4 mg), (unseparable mixture
E
DOI: 10.1021/acs.joc.5b00923
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
7.7 Hz, 2H), 7.58−7.47 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H). 13C NMR
(75 MHz, CDCl3) δ 146.4, 136.9, 132.2, 129.8, 128.6, 128.2, 124.3,
122.8, 120.2, 110.3.
MHz, CDCl3) δ 198.0, 171.2, 138.2, 137.8, 134.0, 132.9, 131.7, 130.8,
130.4, 130.0, 128.3, 126.5, 60.8, 38.9, 14.0.
1-(o-Tolyl)-1H-benzo[d][1,2,3]triazole (5e).21f White solid, Rf = 0.3
(PE/EA = 10:1), 90% yield (37.6 mg). mp 60−63 °C (literature
reported: 66−67 °C). 1H NMR (300 MHz, CDCl3) δ 8.15 (d, J = 8.2
Hz, 1H), 7.54−7.25 (m, 7H), 2.13 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 145.5, 135.1, 135.1, 133.8, 131.6, 129.9, 127.9, 126.9, 126.8,
124.1, 119.9, 110.0, 17.7.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for the products, and single crystal
data of 2h. The Supporting Information is available free of
charge on the ACS Publications website at DOI: 10.1021/
acs.joc.5b00923.
1-(3-chlorophenyl)-1H-benzo[d][1,2,3]triazole (5f). Pale gray solid,
Rf = 0.3 (PE/EA = 10:1), 92% yield (42.0 mg). mp 108−110 °C
1
(literature reported: 108−109 °C). H NMR (300 MHz, CDCl3) δ
AUTHOR INFORMATION
Corresponding Authors
*(Z.X.) E-mail: zqxu@lzu.edu.cn
*(X.J.) E-mail: jiangxx5@mail.sysu.edu.cn
*(R.W.) E-mail: wangrui@lzu.edu.cn
■
8.15 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 1.7 Hz, 1H), 7.75 (d, J = 8.4 Hz,
1H), 7.71 (d, J = 7.9 Hz, 1H), 7.62−7.40 (m, 4H). 13C NMR (75
MHz, CDCl3) δ 146.5, 137.9, 135.5, 131.9, 130.8, 128.6, 124.6, 122.8,
120.6, 120.4, 110.1. IR (CHCl3): 3381, 2924, 2371, 1594, 1126, 1062,
790, 740 cm−1. HRMS (ESI-Q-TOF): C12H9ClN3 [M + H]+ calcd,
230.0480; found, 230.0490.
Notes
1-(4-Chlorophenyl)-1H-benzo[d][1,2,3]triazole (5g).21g White
solid, Rf = 0.4 (PE/EA = 10:1), 91% yield (41.6 mg). mp 148−150
°C (literature reported: 151−152 °C). 1H NMR (300 MHz, CDCl3) δ
8.14 (d, J = 8.3 Hz, 1H), 7.72 (t, J = 8.2 Hz, 3H), 7.56 (t, J = 8.3 Hz,
3H), 7.44 (t, J = 7.6 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 146.4,
135.4, 134.3, 132.0, 130.0, 128.4, 124.5, 123.8, 120.3, 110.0.
1-(4-Methoxyphenyl)-1H-benzo[d][1,2,3]triazole (5h).17c Yellow
solid, Rf = 0.2 (PE/EA = 10:1), 80% yield (36.2 mg). mp 100−101 °C
(literature reported: 98−99 °C). 1H NMR (300 MHz, CDCl3) δ 8.12
(d, J = 8.3 Hz, 1H), 7.69−7.60 (m, 3H), 7.52 (t, J = 7.6 Hz, 1H), 7.41
(t, J = 7.6 Hz, 1H), 7.14−7.06 (m, 2H), 3.89 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 159.7, 146.2, 132.5, 129.8, 127.9, 124.4, 124.1, 120.0,
114.8, 110.2, 55.5.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the grants from the NSFC (Nos. 21202072,
21102141, and 21432003) and the Fundamental Research
Funds for the Central Universities (Nos. 860976 and 861966).
REFERENCES
■
(1) Roberts, J. D.; Simmons, H. E., Jr.; Carlsmith, L. A.; Vaughan, C.
W. J. Am. Chem. Soc. 1953, 75, 3290−3291.
(2) (a) Goetz, A. E.; Garg, N. K. J. Org. Chem. 2014, 79, 846−851.
(b) Wu, C.; Shi, F. Asian J. Org. Chem. 2013, 2, 116−125.
(c) Dubrovskiy, A. V.; Markina, N. A.; Larock, R. C. Org. Biomol.
Chem. 2013, 11, 191−218. (d) Yeoman, J. T. S.; Reisman, S. E. Nature
2012, 490, 179−180. (e) Bhunia, A.; Yetra, S. R.; Biju, A. T. Chem. Soc.
Rev. 2012, 41, 3140−3152. (f) Bhojgude, S. S.; Biju, A. T. Angew.
Chem., Int. Ed. 2012, 51, 1520−1522. (g) Yoshida, H.; Takaki, K.
Synlett 2012, 23, 1725−1732. (h) Bronner, S. M.; Goetz, A. E.; Garg,
N. K. Synlett 2011, 2599−2604. (i) Wentrup, C. Aust. J. Chem. 2010,
63, 979−986. (j) Sanz, R. Org. Prep. Proced. Int. 2008, 40, 215−291.
1-(3,5-Dimethylphenyl)-1H-benzo[d][1,2,3]triazole (5i).17d Yellow
solid, Rf = 0.4 (PE/EA = 15:1), 96% yield (42.8 mg). mp 58−60 °C
(literature reported: 60−62 °C). 1H NMR (300 MHz, CDCl3) δ 8.13
(d, J = 8.3 Hz, 1H), 7.74 (d, J = 8.3 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H),
7.42 (d, J = 7.8 Hz, 1H), 7.38 (s, 2H), 7.13 (s, 1H), 2.44 (s, 6H). 13C
NMR (75 MHz, CDCl3) δ 146.3, 139.7, 136.7, 132.2, 130.3, 128.0,
124.2, 120.5, 120.1, 110.5, 21.3.
1-Cinnamyl-1H-benzo[d][1,2,3]triazole (5j).17d Yellow solid, Rf =
0.3 (PE/EA = 5:1), 94% yield (44.2 mg). mp 68−71 °C (literature
reported: 72−73 °C). 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J = 8.3
Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.48−7.40 (m, 1H), 7.40−7.19 (m,
6H), 6.66 (d, J = 15.9 Hz, 1H), 6.37 (dt, J = 15.8, 6.3 Hz, 1H), 5.42
(dd, J = 6.3, 1.3 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 146.2, 135.4,
134.3, 132.8, 128.6, 128.3, 127.26, 126.5, 123.8, 122.1, 119.9, 109.7,
50.4.
(k) Butenschon, H. Angew. Chem., Int. Ed. 2007, 46, 4012−4014.
̈
́ ́
(l) Pena, D.; Perez, D.; Guitian, E. Heterocycles 2007, 74, 89−100.
̃
(m) Pellisier, H.; Santelli, M. Tetrahedron 2003, 59, 701−730.
(n) Sander, W. Acc. Chem. Res. 1999, 32, 669−676. (o) Kauffmann, T.;
Wirthwein, R. Angew. Chem., Int. Ed. Engl. 1971, 10, 20−33.
(p) Kauffmann, T. Angew. Chem., Int. Ed. Engl. 1965, 4, 543−557.
(3) (a) Goetz, A. E.; Shah, T. K.; Garg, N. K. Chem. Commun. 2015,
51, 34−45. (b) Gampe, C. M.; Carreira, E. M. Angew. Chem., Int. Ed.
2012, 51, 3766−3778. (c) Tadross, P. M.; Stoltz, B. M. Chem. Rev.
2012, 112, 3550−3577.
1,4-Dihydro-1,4-epoxynaphthalene (6a).8 White solid, Rf = 0.5
(PE/EA = 10:1), 82% yield (23.6 mg). mp 55−56 °C (literature
1
reported: 53−54 °C). H NMR (300 MHz, CDCl3) δ 7.29−7.19 (m,
2H), 7.01 (s, 2H), 7.00−6.91 (m, 2H), 5.70 (s, 2H). 13C NMR (75
MHz, CDCl3) δ 148.9, 143.0, 124.9, 120.2, 82.2.
(4) (a) Kitamura, T. Aust. J. Chem. 2010, 63, 987−1001.
(b) Kitamura, T.; Yamabe, M.; Inoue, K.; Todaka, M.; Fukatsu, N.;
Meng, Z.; Fujiwara, Y. J. Am. Chem. Soc. 1999, 121, 11674−11679. (c)
For a mechanistic study, see: Buxton, P. C.; Fensome, M.; Heaney, H.;
Mason, K. G. Tetrahedron 1995, 51, 2959−2968. (d) Matsumoto, T.;
Hosoya, T.; Katsuki, M.; Suzuki, K. Tetrahedron Lett. 1991, 32, 6735−
6736. (e) Campbell, C. D.; Rees, C. W. J. Chem. Soc. 1969, 742−747.
(f) Friedman, L.; Logullo, F. M. J. Am. Chem. Soc. 1963, 85, 1549−
1549.
1-Methoxy-1,4-dihydro-1,4-epoxynaphthalene (6b). Clear crystal,
1
Rf = 0.2 (PE/EA = 10:1), 60% yield (20.8 mg). mp 130−132 °C. H
NMR (300 MHz, CDCl3) δ 8.25−8.17 (m, 1H), 8.16−8.08 (m, 1H),
7.56−7.45 (m, 2H), 6.72 (d, J = 8.1 Hz, 1H), 6.62 (d, J = 8.2 Hz, 1H),
5.07 (s, 1H), 3.94 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 149.8,
145.0, 126.3, 125.9, 125.8, 125.2, 122.0, 121.4, 107.9, 103.4, 55.8. IR
(CHCl3): 3277, 1598, 1268, 1090, 764 cm−1. HRMS (ESI-Q-TOF):
C11H11O2 [M + H]+ calcd, 175.0754; found, 175.0754.
Ethyl 2-(2-Acetylphenyl)acetate (7a).8 White solid, Rf = 0.3 (PE/
EA = 10:1), 80% yield (33.0 mg). mp 58−60 °C (literature reported:
57−59 °C). 1H NMR (300 MHz, CDCl3) δ 7.81 (dd, J = 7.6, 1.2 Hz,
1H), 7.46 (td, J = 7.4, 1.5 Hz, 1H), 7.39 (td, J = 7.5, 1.3 Hz, 1H), 7.25
(d, J = 8.6 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.94 (s, 2H), 2.60 (s,
3H), 1.27 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 201.2,
171.6, 137.2, 134.4, 132.6, 131.9, 129.9, 127.3, 60.7, 40.3, 28.8, 14.2.
Ethyl 2-(2-Benzoylphenyl)acetate (7b).8 Yellow oil, Rf = 0.3 (PE/
(5) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983, 12,
1211−1214.
(6) Choy, P. Y.; Chow, W. K.; So, C. M.; Lau, C. P.; Kwong, F. Y.
Chem.−Eur. J. 2010, 16, 9982−9985.
(7) Ikawa, T.; Nishiyama, T.; Nosaki, T.; Takagi, A.; Akai, S. Org.
Lett. 2011, 13, 1730−1733.
́
́ ́
s, S.; Csincsi, A. I.; Nagy, T. Z.; Boros, S.; Timari, G.;
(8) Kovac
Novak, Z. Org. Lett. 2012, 14, 2022−2025.
́
1
EA = 15:1), 56% yield (30.1 mg). H NMR (300 MHz, CDCl3) δ
(9) (a) Penney, C. L.; Perlin, A. S. Carbohydr. Res. 1981, 93, 241−
246. (b) Firth, W. C. J. Polym. Sci., Part B 1972, 10, 637−641.
(c) Parsons, J. S. J. Gas Chromatogr. 1967, 5, 254−256.
7.85−7.78 (m, 2H), 7.62−7.53 (m, 1H), 7.52−7.28 (m, 6H), 4.02 (q, J
= 7.1 Hz, 2H), 3.89 (s, 2H), 1.11 (t, J = 7.1 Hz, 3H). 13C NMR (75
F
DOI: 10.1021/acs.joc.5b00923
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(10) (a) Drummond, J. N.; Kirby, A. J. J. Chem. Soc. Perkin Trans. 2
1986, 579−583. (b) Zahler, W. D.; Huisgen, R. Chem. Ber. 1963, 96,
765−770. (c) Engelbrecht, A. Angew. Chem., Int. Ed. Engl. 1965, 4,
641−645. (d) Traube, W. Ber. Dtsch. Chem. Ges. 1913, 46, 2513−2524.
(11) Dong, J.; Krasnova, L.; Finn, M. G.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2014, 53, 9430−9448.
(12) (a) Suter, C. M. In The Organic Chemistry of Sulfur; Wiley: New
York, 1944; pp 453−572. (b) Lange, W. Reichspatent 532394, 27 Aug,
1931. (c) Lange, W.; Muller, E. Chem. Ber. 1930, 63, 2653−2657.
̈
(d) Steinkopf, W.; Jaeger, P. J. Prakt. Chem. 1930, 128, 63−88.
(e) Steinkopf, W. J. Prakt. Chem. 1927, 117, 1−82.
(13) In 2, -OSO2F could possibly interact with the ortho-TMS group
and deliver fluorine to silicon as its thermodynamically favored
destination, which would promote the desilylation of the precursor to
generate aryne. (a) Huang, T.; Shreeve, J. M. Inorg. Chem. 1986, 25,
496−498. (b) Wlassics, I.; Tortelli, V.; Carella, S.; Monzani, C.;
Marchionni, G. Molecules 2011, 16, 6512−6540.
(14) (a) Ishii, A.; Yasumoto, M. Central Glass Co., Ltd., PCT/
JP2009/067841, US 20110201825 A1, 2011. (b) Ishii, A.; Ishimaru,
T.; Yamazaki, T.; Yasumoto, M. Central Glass Co., Ltd., WO-2013-
002040, 2013. (c) The structure of 2h was determined by single-
crystal X-ray analysis: CCDC 1053309. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(15) (a) Andersen, S. P. S.; Blake, D. R.; Rowland, F. S.; Hurley, M.
D.; Wallington, T. J. Environ. Sci. Technol. 2009, 43, 1067−1070. (b)
Sulfuryl fluoride has low toxicity and has been successfully used for
controlling structure infesting pests for nearly 50 years under the trade
name Vikane gas fumigant. In china, SO2F2 is about $1/kg (CAS:
2699-79-8, MAUI (Hangzhou) Electronic Chemicals Co., Ltd.), which
is relatively cheaper than traditional sulfates (trifluoromethanesulfonic
anhydride, CAS: 358-23-6, $827/250g, from Alfa Aesar).
(16) Liang, Q.; Xing, P.; Huang, Z.; Dong, J.; Sharpless, K. B.; Li, X.;
Jiang, B. Org. Lett. 2015, 17, 1942−1945.
(17) For selected examples: (a) Gann, A. W.; Amoroso, J. W.; Einck,
V. J.; Rice, W. P.; Chambers, J. J.; Schnarr, N. A. Org. Lett. 2014, 16,
2003−2005. (b) Ikawa, T.; Takagi, A.; Goto, M.; Aoyama, Y.;
Ishikawa, Y.; Itoh, Y.; Fujii, S.; Tokiwa, H.; Akai, S. J. Org. Chem. 2013,
78, 2965−2983. (c) Zhang, F.; Moses, J. E. Org. Lett. 2009, 11, 1587−
1590. (d) Shi, F.; Waldo, J. P.; Chen, Y.; Larock, R. C. Org. Lett. 2008,
10, 2409−2412. (e) Reynolds, G. A. J. Org. Chem. 1964, 29, 3733−
3734.
(18) Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5340−
5341.
(19) (a) For an example of the activation of CsF with 18-c-6 and
MeCN, see: Nishikawa, T.; Shibuya, S.; Isobe, M. Synlett 1994, 482−
484. (b) For the complexation of CsF with 18-c-6, see: Takeda, Y.;
Kawarabayashi, A.; Endo, K.; Yahata, T.; Kudo, Y.; Katsuta, S. Anal. Sci.
1998, 14, 215−223.
1
(20) The regioselectivities were determined by H NMR spectra of
the crude reaction mixtures. For selected studies and reviews regarding
the aryne distortion model, see: (a) Medina, J. M.; Mackey, J. L.; Garg,
N. K.; Houk, K. N. J. Am. Chem. Soc. 2014, 136, 15798−15805.
(b) Cheong, P. H.-Y.; Paton, R. S.; Bronner, S. M.; Im, G-Y. J.; Garg,
N. K.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 1267−1269. (c) Im,
G.-Y. J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P. H.-Y.;
Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933−17944.
́ ́
(21) (a) Novak, Z.; Timari, G.; Kotschy, A. Tetrahedron 2003, 59,
7509−7513. (b) Nishide, K.; Miyamoto, T.; Kumar, K.; Ohsugi, S.;
Node, M. Tetrahedron Lett. 2002, 43, 8569−8573. (c) Shimizu, M.;
Mochida, K.; Hiyama, T. Angew. Chem., Int. Ed. 2008, 47, 9760−9764.
(d) Bentin, T.; Hamzavi, R.; Salomonsson, J.; Roy, H.; Ibba, M.;
Nielsen, P. E. J. Biol. Chem. 2004, 279, 19839−19845. (e) Xue, Q.; Xie,
J.; Li, H.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 49, 3700−3702.
(f) Liu, Q.-L.; Wen, D.-D.; Hang, C.-C.; Li, Q.-L.; Zhu, Y.-M. Helv.
Chim. Acta 2010, 93, 1350−1354. (g) Zhou, J.; He, J.; Wang, B.; Yang,
W.; Ren, H. J. Am. Chem. Soc. 2011, 133, 6868−6870.
G
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