Generation and reactions of heteroaromatic arynes using hypervalent iodine compounds

Article abstract of DOI:10.3987/COM-14-S(K)34

The heterocyclic aryne precursors, (phenyl)[1-phenyl-6-(trimethylsilyl)benzotriazol-5-yl]iodonium triflate and [3-ethoxycarbonyl-6-(trimethylsilyl)indazol-5-yl](phenyl)iodonium triflate, were prepared from the cycloadducts of 4,5-bis(trimethylsilyl)benzyn

Full text of DOI:10.3987/COM-14-S(K)34

HETEROCYCLES, Vol. 90, No. 1, 2015
681
HETEROCYCLES, Vol. 90, No. 1, 2015, pp. 681 - 689. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 28th May, 2014, Accepted, 13th June, 2014, Published online, 18th June, 2014
DOI: 10.3987/COM-14-S(K)34
GENERATION AND REACTIONS OF HETEROAROMATIC ARYNES
USING HYPERVALENT IODINE COMPOUNDS
Keisuke Gondo, Juzo Oyamada, and Tsugio Kitamura*
Department of Chemistry and Applied Chemistry, Graduate School of Science and
Engineering, Saga University, Honjo-machi, Saga 840-8502, Japan; E-mail:
kitamura@cc.saga-u.ac.jp
Abstract
–
The
heterocyclic
aryne
precursors,
triflate and
(phenyl)[1-phenyl-6-(trimethylsilyl)benzotriazol-5-yl]iodonium
[3-ethoxycarbonyl-6-(trimethylsilyl)indazol-5-yl](phenyl)iodonium triflate, were
prepared from the cycloadducts of 4,5-bis(trimethylsilyl)benzyne generated from
(phenyl)[2,4,5-tris(trimethylsilyl)phenyl]iodonium triflate. These precursors
provide the corresponding arynes, 1-phenyl-5,6-didehydrobenzotriazole and
3-ethoxycarbonyl-5,6-didehydroindazole, to give the corresponding polycyclic
heteroaromatic compounds in good to high yields.
Heterocyclic aromatic compounds are important compounds which attract much attention as functional
materials as well as materials of pharmaceutical and agricultural chemicals. Arynes are suitable reactive
intermediates to construct annulated aromatic compounds using cycloaddition reactions.1 In recent years,
the applications of arynes to the synthesis of polycyclic aromatic compounds and the total synthesis of
natural products were reviewd.2 The significance of the aryne strategy is still noted in organic chemistry.
However, arynes bearing a heterocyclic skeleton were little reviewed until now, in spite of having
recognized the importance in chemistry. Very recently, it was reviewed about the use of heterocyclic
arynes in organic synthesis, stating that mild conditions are required for the generation of heterocyclic
arynes.3 We have so far studied on hypervalent iodine benzyne precursors which can generate benzynes
under mild conditions.4 Very recently, we developed an efficient synthesis of
(phenyl)[2,4,5-tris(trimethylsilyl)phenyl]iodonium triflate (2) from 1,2,4,5-tetrakis(trimethylsilyl)benzene
(1) using (diacetoxyiodo)benzene [PhI(OAc)2], and found that this iodonium triflate 2 was utilized as an
synthetic equivalent of 1,4-benzdiyne.5
Dedicated with respect to Prof. Dr. Isao Kuwajima on the occasion of his 77th birthday

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HETEROCYCLES, Vol. 90, No. 1, 2015
Thus, as shown in Scheme 1, we expected that the 1,4-benzdiyne strategy was applicable to synthesis of
heterocyclic aryne precursors using cycloaddition reactions of aryne 3 with phenylazide or ethyl
diazoacetate. In order to confirm the aryne strategy described in Scheme 1, we conducted the synthesis of
iodonium triflates having heterocyclic skeletons and the generation of the corresponding heterocyclic
arynes. Here we want to report the synthesis and reactions of aryne precursors bearing triazole and
indazole skeletons.
Scheme 1
At first, we examined the cycloaddition reaction of 4,5-bis(trimethylsilyl)benzyne (3) with phenylazide or
ethyl diazoacetate using 2,4,5-tris(trimethylsilyl)phenyliodonium triflate 2, as shown in Scheme 2. The
preparation of iodonium triflate 2 was conducted according to our method reported recently.5 When
iodonium triflate 2 was treated with a THF solution of Bu4NF in the presence of phenylazide in CH2Cl2 at
0 °C, the cycloadduct 4 was obtained in 76% yield. Similarly, the reaction of iodonium triflate 2 with
Bu4NF in the presence of ethyl diazoacetate gave the cycloadduct 5 in 94% yield. These results indicate
that 4,5-bis(trimethylsilyl)benzyne (3) was generated under mild conditions and efficiently trapped with
phenylazide or ethyl diazoacetate. The cycloaddition proceeded without any damage of two trimethylsilyl
groups. Then, the disilyl cycloadducts thus obtained were converted to the corresponding aryne
precursors.
Ph
N
N
Me3Si
Me3Si
PhN3
76%
N
Me3Si
Me3Si
SiMe3
Me3Si
Me3Si
Bu4NF
4
CO2Et
CH2Cl2
0 oC
I(Ph)OTf
Me3Si
C
N2CHCO2Et
94%
2
N
3
N
Me3Si
H
5
Scheme 2

HETEROCYCLES, Vol. 90, No. 1, 2015
683
The conversion of 1-phenyl-5,6-bis(trimethylsilyl)benzotriazole (4) to a didehydrobenzotriazole precursor
was conducted using a hypervalent iodine reagent. The results are given in Table 1. The reaction was
performed as follows. First, iodosylbenzene was treated with BF3•OEt2 in CH2Cl2 to activate it and then
reacted with bis(trimethylsilyl)benzotriazole 4. Although the reaction mixture was treated with aqueous
NaOTf to convert to the triflate salt, no desired product was obtained (Entry 1). Next, the similar reaction
was conducted in 1,2-dichloroethane at 40 °C. The desired iodonium triflate 6 was obtained in 8% yield
(Entry 2), but elevation of the reaction temperature did not improve the result (Entries 3 and 4). When the
solvent was replaced by acetonitrile, the yield of iodonium triflate 6 increased (Entry 5) to 51%. However,
the reaction with PhI(OAc)2 instead of PhIO resulted in lowering the yield (Entry 6).
Table 1. Synthesis of a Didehydrobenzotriazole Precursor
Substrate PhIO
Solvent
(mL)
Time
(h)
Temp
(°C)
Yield
(%)a
BF3•OEt2
(mmol)
3.0
1.2
1.2
1.2
12
1.2
Entry
(mmol)
(mmol)
1
2
3
4
5
6
0.5
0.2
0.2
0.2
2.0
0.5
0.6
DCM (4)
DCE (2)
DCE (2)
DCE (2)
MeCN (20)
MeCN (2)
2
5
5
5
4
4
0
0
8
4
6
51
15
0.24
0.24
0.24
2.4
40
60
80
40
40
0.6b
a Isolated yield. b PhI(OAc)2 was used instead of PhIO.
Generation of an aryne from iodonium triflate 6 was conducted by the reaction of 6 with Bu4NF. When
iodonium trifalte 6 was treated with 1.2 equivalents of Bu4NF in the presence of furan (5 equivalents) in
CH2Cl2 at 0 °C, the cycloadduct 8 with furan was obtained in 95% isolated yield. In the case of
tetraphenylcyclopentadienone as a trapping agent, the reaction of 6 with Bu4NF gave the cycloadduct 9 in
93% isolated yield, which was derived from the cycloaddition of aryne
7
with
teteraphenylcyclopentadienone followed by decarbonylation. In addition, the reaction of 6 with Bu4NF in
the presence of anthracene gave the cycloadduct 10 derived from the cycloaddition of 7 with anthracene,
in 79% yield.

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HETEROCYCLES, Vol. 90, No. 1, 2015
Scheme 3
In analogy with the synthesis of didehydrobenzotriazole precursor 6, the reaction of disilyl-substituted
indazole 5 was conducted using PhIO activated with BF3•OEt2 in MeCN and followed by treating with
aqueous NaOTf. The desired iodonium triflate 11 was obtained in 91% yield (Table 2, Entry 1). Moreover,
the reaction with PhI(OAc)2 activated with BF3•OEt2 also gave the iodonium triflate 11 in 72% yield
(Entry 2).
Table 2. Synthesis of a Didehydroindazole Precursor
EtO2C
EtO2C
.
I(Ph)OTf
SiMe3
SiMe3
SiMe3
1. PhIO/BF3 OEt2
C
C
N
N
2. aq. NaOTf
N
N
H
H
11
5
5
PhIO
(mmol) (mmol)
Solvent
(mL)
Time
(h)
Temp
(°C)
Yield
(%)a
BF3•OEt2
(mmol)
6
Entry
1
2
1
0.5
1.2
MeCN (10)
CH2Cl2 (5) 0.5
1
40
rt
91
72
0.6b
1.2
a Isolated yield. b PhI(OAc)2 was used instead of PhIO.

HETEROCYCLES, Vol. 90, No. 1, 2015
685
When the iodonium triflate 11 was treated with Bu4NF in the presence of furan in CH2Cl2 at 0 °C, the
cycloadduct 13 with furan was obtained in 94% isolated yield. This reaction indicates that
3-ethoxycarbonyl-5,6-didehydroindazole (12) is generated almost quantitatively under the present
reaction conditions. The trapping reaction with tetraphenylcyclopentadienone gave the cycloadduct 14
with 12 in 97% isolated yield. In the case of anthracene as a trapping reagent, tripticene derivative 15 was
obtained in 52% isolated yield.
Scheme 4
In
summary,
we
have
demonstrated
that
two
new
heterocyclic
arynes,
1-phenyl-5,6-didehydrobenzotriazole (7) and 3-ethoxycarbonyl-5,6-didehydroindazole (12), can be
generated efficiently from the corresponding iodonium triflates 6 and 11. The cycloaddition of the
heterocyclic arynes 7 and 12 with furan, tetraphenylcyclopentadienone, or anthracene provides the
corresponding annulated heterocyclic compounds in good to high yields. These results suggest that the
heterocyclic aryne strategy is useful to construct the polycyclic heteroaromatic compounds.
EXPERIMENTAL
All solvents and starting materials were used during the research work as received without further
1
purification unless otherwise indicated. H and 13C NMR were recorded on a Agilent 400-MR NMR

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HETEROCYCLES, Vol. 90, No. 1, 2015
spectrometer (TMS as an internal standard). Melting points were measured with a Yanaco micro melting
point apparatus and are uncorrected. High resolution mass spectra were measured by the Analytical
Center, Institute for Materials Chemistry and Engineering, Kyushu University. Column chromatographic
separation was carried out using Silica Gel 60, spherical (Kanto Chemical Co.). Pre-coated plates (silica
gel 60 F254, MERCK) were used for TLC examination.
Preparation of 1-Phenyl-5,6-bis(trimethylsilyl)benzotriazole (4)
To a solution of (phenyl)[tris(trimethylsilyl)phenyl]iodonium triflate (2) (1 mmol) and phenylazide (5
mmol) in CH2Cl2 (5 mL) was added a THF solution of Bu4NF (1 mmol) at 0 °C and stirred for 20 min at
this temperature. The reaction mixture was poured into water and extracted with CH2Cl2 (10 mL × 3). The
combined organic extract was washed with brine, dried over anhydrous Na2SO4, and concentrated under
reduced pressure. The product was separated by column chromatography on silica gel (hexane/AcOEt) to
give 1-phenyl-5,6-bis(trimethylsilyl)benzotriazole (4) (0.258 g, 76%) as white crystals. Mp 116-117 °C;
1H NMR (400 MHz, CDCl3)  0.44 (s, 9H), 0.46 (s, 9H), 7.52 (t, J = 8 Hz, 1H), 7.64 (t, J = 8 Hz, 2H),
13
7.79 (d, J = 8 Hz, 2H), 8.10 (s, 1H), 8.51 (s, 1H); C NMR (100 MHz, CDCl3)  2.0, 2.1, 117.2, 122.6,
127.5, 128.5, 129.9, 131.7, 137.0, 141.4, 146.2, 146.5. HRMS (EI) calcd for C18H25N3Si2 (M+): 339.1587;
found: 339.1589.
Preparation of 3-Ethoxycarbonyl-5,6-bis(trimethylsilyl)indazole (5)
The similar reaction of 2 (2 mmol) and ethyl diazoacetate (10 mmol) in CH2Cl2 (10 mL) was carried out
using
a
THF solution of Bu4NF (2 mmol). Workup of the reaction mixture gave
3-ethoxycarbonyl-5,6-bis(trimethylsilyl)indazole (5) (0.628 g, 94%) as white crystals. Mp 198-200 °C; 1H
NMR (400 MHz, CDCl3)  0.456 (s, 9H), 0.459 (s, 9H), 1.53 (t, J = 7 Hz, 2H), 4.58 (q, J = 7 Hz, 3H),
13
8.30 (d, J = 7 Hz, 1H), 8.60 (s, 1H), 12.9 (s, 1H); C NMR (100 MHz, DMSO)  2.1, 2.2, 14.4, 61.0,
119.8, 121.4, 129.0, 136.0, 139.0, 141.4, 144.3, 163.4. HRMS (EI) calcd for C16H26N2O2Si2 (M+):
334.1533; found: 334.1533.
Preparation of (Phenyl)[1-phenyl-6-(trimethylsilyl)benzotriazol-5-yl]iodonium Triflate (6)
To a mixture of benzotriazole 4 (2 mmol) and PhIO (2.4 mmol) in MeCN (20 mL) was added BF3∙OEt2
(12 mmol) and the mixture was stirred at 40 °C for 4 h. The reaction mixture was poured into an aqueous
solution of NaOTf (20 mmol) and stirred vigorously. The product was extracted with CH2Cl2 (20 mL × 3).
The combined organic extract was dried over anhydrous Na2SO4 and concentrated under reduced pressure.
The
resulting
solid
was
filtered
and
washed
with
hexane
to
give
(phenyl)[1-phenyl-6-(trimethylsilyl)benzotriazol-5-yl]iodonium triflate (6) (0.315 g, 51%) as yellow
1
crystals. Mp 91-104 °C; H NMR (400 MHz, CDCl3)  0.50 (s, 9H), 7.46-7.89 (m, 10H), 8.04 (s, 1H),
13
9.01 (s, 1H); C NMR (100 MHz, CDCl3)  0.3, 114.6, 114.7, 120.1, 123.2, 129.7, 130.2, 132.1, 132.3,

HETEROCYCLES, Vol. 90, No. 1, 2015
687
133.0, 133.2, 133.7, 135.8, 145.2, 147.9. HRMS (FAB) calcd for C21H21IN3Si (M+–OTf): 470.0544;
found 470.0549.
Trapping Reactions of a 5,6-Didehydrobenzotriazole (7)
To a solution of iodonium triflate 6 (0.2 mmol) and a dienophile (1 mmol) in CH2Cl2 (1 mL) was slowly
added a THF solution of Bu4NF (0.24 mmol). The mixture was stirred at 0 °C for 20 min. The reaction
mixture was poured into water and extracted with CH2Cl2 (10 mL × 3). The combined organic extract was
washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The product
was separated by column chromatography on silica gel (hexane/AcOEt).
5,9-Epoxy-5,9-dihydro-1-phenyl-1H-naphtho[2,3-d]triazole (8)
1
The product was obtained as white crystals, mp 119-121 °C; yield 0.050 g (95%); H NMR (400 MHz,
CDCl3)  5.77 (s, 1H), 5.85 (s, 1H), 7.00 (d, J = 3 Hz, 1H), 7.07 (d, J = 3 Hz, 1H), 7.52-7.54 (m, 2H),
13
7.61 (t, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H), 7.84 (s, 1H); C NMR (100 MHz, CDCl3)  81.8, 81.9,
103.0, 111.3, 123.2, 128.9, 129.8, 131.4, 136.8, 141.6, 142.9, 144.7, 145.0, 149.2. HRMS (EI) calcd for
C16H11N3O (M+): 261.0902; found: 261.0907.
1,5,6,7,8-Pentaphenyl-1H-naphtho[2,3-d]triazole (9)
The product was obtained as yellow crystals, mp 232-233 °C; yield 0.102 g (93%). The spectra were in
accord with the reported ones.5b
5,10[1’,2’]-Benzeno-1-phenyl-1H-anthra[2,3-d]triazole (10)
The product was obtained as yellow crystals, mp 197-199 °C; yield 0.059 g (79%). The spectra were in
accord with the reported ones.5b
Preparation of [3-Ethoxycarbonyl-6-(trimethylsilyl)indazol-5-yl](phenyl)iodonium Triflate (11)
To a mixture of indazole 5 (1 mmol) and PhIO (1.2 mmol) in MeCN (10 mL) was added BF3∙OEt2 (6
mmol) and the mixture was stirred at 40 °C for 1 h. The reaction mixture was poured into an aqueous
solution of NaOTf (10 mmol) and stirred vigorously. The product was extracted with CH2Cl2 (10 mL × 3).
The combined organic extract was dried over anhydrous Na2SO4 and concentrated under reduced pressure.
The
resulting
solid
was
filtered
and
washed
with
hexane
to
give
[3-ethoxycarbonyl-6-(trimethylsilyl)indazol-5-yl](phenyl)iodonium triflate (11) (0.559 g, 91%) as white
crystals. Mp 218-220 °C; 1H NMR (400 MHz, CD3CN)  0.43 (s, 9H), 1.42 (t, J = 7 Hz, 3H), 4.47 (q, J =
7 Hz, 2H), 7.50 (t, J = 8 Hz, 2H), 7.64 (t, J = 8 Hz, 1H), 7.79 (d, J = 8 Hz, 2H), 8.10 (s, 1H), 9.12 (s, 1H),
13
12.4 (s, 1H); C NMR (100 MHz, CD3CN)  0.6, 14.9, 62.6, 114.4, 115.1, 123.6, 126.2, 133.6, 133.7,
134.1, 136.1, 138.3, 143.0, 143.9, 162.9. HRMS (FAB) calcd for C19H22IN2O2Si (M+–OTf): 465.0495;
found: 465.0495.
Trapping Reactions of a Didehydroindazole (12)

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HETEROCYCLES, Vol. 90, No. 1, 2015
To a solution of iodonium triflate 11 (0.2 mmol) and a dienophile (1 mmol) in CH2Cl2 (1 mL) was slowly
added a THF solution of Bu4NF (0.24 mmol). The mixture was stirred at 0 °C for 20 min. The reaction
mixture was poured into water and extracted with CH2Cl2 (10 mL × 3). The combined organic extract was
washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The product
was separated by column chromatography on silica gel (hexane/AcOEt). In the trapping reaction with
anthracene, iodonium triflate 11 (0.1 mmol) was used.
Ethyl 5,8-Epoxy-5,8-dihydro-1H-benzo[f]indazole-3-carboxylate (13)
1
The product was obtained as white crystals, mp 173-174 °C; yield 0.048 g (94%); H NMR (400 MHz,
CDCl3)  1.47 (t, J = 7 Hz, 3H), 4.54 (q, J = 7 Hz, 2H), 5.77 (s, 1H), 5.80 (s, 1H), 6.97-7.04 (m, 2H), 7.58
(s, 1H), 7.92 (s, 1H); 13C NMR (100 MHz, CDCl3)  14.4, 61.1, 81.88, 81.91, 104.4, 112.5, 120.2, 140.5,
141.6, 142.6, 143.0, 147.8, 163.0 (one carbon overlapped). HRMS (EI) calcd for C14H12N2O3 (M+):
256.0848; found: 256.0850.
Ethyl 5,6,7,8-Tetraphenyl-1H-benzo[f]indazole-3-carboxylate (14)
1
The product was obtained as white crystals, mp 330-332 °C; yield 0.106 g (97%); H NMR (400 MHz,
CDCl3)  1.27 (t, J = 7 Hz, 3H), 4.39 (q, J = 7 Hz, 2H), 6.88 (m, 10H), 7.24-7.28 (m, 10H), 7.76 (s, 1H),
8.57 (s, 1H), 10.4 (s, 1H); 13C NMR (100 MHz, CDCl3)  13.9, 61.1, 106.0, 120.7, 122.2, 125.36, 125.41,
126.6, 127.6, 127.7, 129.7, 131.1, 131.3, 131.3, 131.4, 132.3, 137.1, 137.5, 137.7, 139.3, 139.5, 139.6,
139.8, 140.4, 162,6 (5 carbons overlapped). HRMS (FAB) calcd for C38H28N2O2 (M+): 544.2151; found:
544.2149.
Ethyl 5,10[1’,2’]-Benzeno-1H-naphtho[2,3-f]indazole-3-carboxylate (15)
The product was obtained as yellow crystals, mp 195-197 °C; yield 0.038 g (52%); 1H NMR (400 MHz,
CDCl3)  1.46 (t, J = 7 Hz, 3H), 4.51 (q, J = 7 Hz, 2H), 5.47 (s, 1H), 5.53 (s, 1H), 7.00-7.02 (m, 4H),
7.38-7.43 (m, 4H), 7.58 (s, 1H), 8.12 (s, 1H); 13C NMR (100 MHz, CDCl3)  14.4, 53.8, 54.2, 61.0, 105.9,
115.8, 120.3, 123.7, 123.7, 125.5, 125.7, 136.2, 139.8, 140.7, 144.2, 144.8, 144.9, 162.9. HRMS (EI)
calcd for C24H18N2O2 (M+): 366.1368; found: 366.1366.
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