Development of a Synthetic Method for Multifunctionalized Pyrroles Using Isocyanide Dichloride as a Key Intermediate

Article abstract of DOI:10.1021/acs.joc.8b00185

Multifunctionalized pyrrole derivatives were synthesized using a highly efficient method based on the Michael addition of carbanions generated in situ from isocyanide dichloride to α,β-unsaturated carbonyl compounds. The reactions proceeded smoothly to afford the pyrrole derivatives in good to high yields. A wide range of Michael acceptors, such as α,β-unsaturated carbonyl compounds and nitroolefin, were successfully applied to this reaction.

Full text of DOI:10.1021/acs.joc.8b00185

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Development of a Synthetic Method for Multifunctionalized
Pyrroles Using Isocyanide Dichloride as a Key Intermediate
Takahiro Soeta, Akihiro Matsumoto, and Yutaka Ukaji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00185 • Publication Date (Web): 30 Mar 2018
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Development of a Synthetic Method for Multifunctionalized Pyrroles Using
Isocyanide Dichloride as a Key Intermediate
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Takahiro Soeta*, Akihiro Matsumoto, Yutaka Ukaji*
Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa, 920-1192, Japan
soeta@se.kanazawa-u.ac.jp; ukaji@staff.kanazawa-u.ac.jp
R1
Cl
Cl
Ts
K2CO3
THF, rt
EWG
EWG
+
N
R1
NH
Ts
Abstract
Multifunctionalized pyrrole derivatives were synthesized using a highly efficient
method based on the Michael addition of carbanions generated in situ from isocyanide
dichloride to α,β-unsaturated carbonyl compounds. The reactions proceeded smoothly
to afford the pyrrole derivatives in good to high yields. A wide range of Michael
acceptors, such as α,β-unsaturated carbonyl compounds and nitroolefin, were
successfully applied to this reaction.
Multifunctionalized pyrroles are important building blocks in organic synthesis as well
as in pharmaceuticals, natural products, and functional materials.1,2 Many different
approaches to the synthesis of pyrrole derivatives have been reported, including
transition-metal-catalyzed synthetic methods.3 However, these methods have relied
mainly on precisely designed substrates that are not readily available.4,5 Thus, the direct
assembly of pyrroles from basic chemicals remains an important research objective.6
To accomplish this objective, isocyanide dihalides and α,β-unsaturated carbonyl
compounds were used for the synthesis of oligosubstituted pyrroles. Isocyanide
dihalides are readily formed by addition of chlorine or bromine to isocyanides.7 A
one-pot synthetic method was developed for formation of multifunctional
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dihydrooxazole and oxazole derivatives using isocyanide dichloride.8 To extend this
work to the synthesis of multifunctionalized heterocycles using versatile starting
materials, α,β-unsaturated carbonyl compounds such as ethyl acrylate were examined.
The atom-economic nature of the reaction makes cycloaddition to these substrates an
ideal route to oligosubstituted pyrroles without the need for transition metal catalysts.9
This report describes the highly efficient formation of multifunctional pyrrole
derivatives by reaction of isocyanide dichloride with α,β-unsaturated carbonyl
compounds, including an unexpected rearrangement reaction.
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Initially isocyanide dichloride 1a,10 which is easily prepared from the corresponding
4-toluenesulfonylmethylisocyanide (TsMIC) with SO2Cl2, was examined to determine
its ability to participate in 1,3-dipolar cycloaddition with an ethyl acrylate (2a) upon
treatment of diisopropylethylamine (DIPEA) to afford the 3,4-dihydropyrrole derivative
(Eq. 1).11,12,13 After several attempts, the results showed that the 3,4-dihydropyrrole
derivative was not obtained; instead, pyrrole 3aa14 was obtained in 30% yield along
with tosylpropionate 4 in 14% yield (Eq. 2). These unexpected results lead to the
development of the synthetic method for pyrrole derivatives.
O
O
EtO
–
Ts
Cl
Cl
Ts
Ts
+
DIPEA
CH2Cl2
2a
(1)
(2)
N
Cl
N
EtO
CH2Cl2, rt, 2 d
N
1a
Cl
Nitrile ylide
O
Cl
Cl
Ts
EtO
Ts
O
DIPEA
CH2Cl2, rt, 2 d
+
+
N
EtO
EtO
O
NH
Ts
3aa; 30%
4; 14%
1a
2a
Bases other than DIPEA were evaluated for their ability to generate enolates during
Michael addition in CH2Cl2 (entries 2–7). The use of Et3N resulted in formation of the
desired 3aa in 53% yield along with side-product 4 in 22% yield (entry 2). Interestingly,
use of DBU as a base produced 4 in 72% yield without any of the desired 3aa (entry 3).
Formation of 4 could be suppressed when 1.0 equiv of 2a was used in the presence of
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Et3N (entry 4). A significant increase in yield of 3aa (to 92%) was observed when
K2CO3 was used as a base (entry 5). Other bases, such as Na2CO3, and Cs2CO3, were not
effective in this reaction (entries 6 and 7). The use of K2CO3, dichloroethane, THF, and
acetonitrile as solvents was also examined and the results indicated that THF was the
optimal solvent to produce 3aa in high yield (entries 8–10).
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Table 1. Optimized reaction conditions.
O
Cl
Cl
Ts
EtO
Ts
O
base (3.0 equiv)
solv., rt, 2 d
+
+
N
EtO
EtO
O
NH
Ts
2a (1.0 equiv)
3aa
4
1a
Entry
Base
Solvent
Yield of 3aa
Yield of 4
(%)
30
53
-
(%)
14
22
72
-
1a
2a
3a
4
DIPEA
Et3N
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DBU
Et3N
32
92
15
56
90
97
87
5
K2CO3
Na2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
-
6
-
7
-
8
dichloroethane
THF
-
9
-
10
MeCN
-
a 3.0 equiv of 2a used.
The reactivity of isocyanide dichloride 1a with various Michael acceptors was
examined in the presence of K2CO3 (Table 2); the results are shown in Table 2. For
these experiments, optimal amounts of isocyanide dichloride 1a (1.0 equiv) and Michael
acceptors 2a–i (1.0 equiv) were used in the presence of 3.0 equiv K2CO3. The results
demonstrate that these conditions allowed the reaction to proceed using a wide variety
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of Michael acceptors and that most reactions were complete within 2 days. Methyl
acrylate (2b) was also a suitable substrate for this reaction and afforded 3ab in 81%
yield (entry 2). Both the cis and trans isomers, such as fumarate 2c and malate 2d,
possessed similar reactivity (entries 3 and 4). Methyl crotonate (2e) and ethyl cinnamate
(2f) showed lower reactivity than the others, resulting in only 32% yield of 3ae and a
trace amount of 3af (entries 5 and 6). The other Michael acceptors, such as acrylonitrile
(2g), nitrostyrene (2h), and methyl vinyl ketone (2i), were also applicable to this
reaction, affording the products in good yields (entries 7–9).
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Table 2. Results of the synthesis of pyrroles using various Michael acceptors.
R2
K2CO3
(3.0 equiv)
Cl
Cl
Ts
R1
+
N
R1
R2
THF, rt, 2 d
NH
Ts
2 (1.0 equiv)
3
1a
Entrya
1
2
3; Yield (%)
EtO2C
EtO2C
NH
2a
Ts
3aa; 97%
2
3
MeO2C
MeO2C
NH
2b
Ts
3ab; 81%
MeO2C
CO2Me
MeO2C
CO2Me
2c
NH
Ts
3ac; 83%
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CO2Et
EtO2C
CO2Et
EtO2C
2d
9
NH
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Ts
3ad; 61%
MeO2C
Me
MeO2C
Me
2e
NH
Ts
3ae; 32%
EtO2C
Ph
MeO2C
Ph
2f
NH
Ts
3af; trace
7
8
NC
2g
NC
NH
Ts
3ag; 64%
O2N
Ph
O2N
Ph
2h
NH
Ts
3ah; 43%
O
O
9
NH
2i
Ts
3ai; 69%
a Reaction was conducted using 1.0 equiv of Michael acceptor 2 and 3.0 equiv K2CO3.
The α-substituted isocyanide dichloride 1b was also investigated. Reaction of 1b with
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2a in the presence of Cs2CO3 as a base gave the corresponding imino chloride 3b’a in
76% yield. Iminochloride 3b’a was converted easily to 2-aminopyrrole 3ba through an
addition-elimination reaction (Eq. 3). Furthermore, reaction of 1b with dimethyl
fumarate (2c) proceeded to afford the tetrasubstituted pyrrole 3bc in moderate yield (Eq.
4).
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2a
(1.0 equiv)
Cs2CO3
(3.0 equiv)
Et2NH (1.0 equiv)
K2CO3 (3.0 equiv)
Ph
Ts
Ph
N
EtO2C
Ph
EtO2C
Cl
Cl
Ts
(3)
NH
N
THF, rt, 2 d
THF, rt, 2d
Et2N
Cl
1b
3ba: 50%
3b’a: 76%
CO2Me
Ph
K2CO3
(3.0 equiv)
Ph
N
MeO2C
Ts
Cl
Cl
MeO2C
+
(4)
THF, rt, 2 d
CO2Me
NH
Cl
1b
2c
(1.0 equiv)
3bc: 37%
To determine the reaction mechanism, a series of controlled experiments were
conducted. To confirm the generation of nitrile ylide from the isocyanide dichloride 1a
1
under basic conditions, H NMR and 13C NMR spectra were obtained in CDCl3.
Treatment of isocyanide dichloride 1a with 3.0 equiv K2CO3 did not induce a chemical
shift of the methylene hydrogen atom (at 4.71 ppm). The same behavior was observed
13
with C NMR, in which the signal for the imino carbon (at 145.6 ppm) did not shift.
Thus, the nitrile ylide was not generated from isocyanide dichloride 1a. In addition, the
Michael addition of the tosylate group proceeded to afford the tosylpropionate 4 (Table
1, entries 1–3). Based on these results, the mechanism for this reaction is proposed in
Scheme 1. The carbanion generated from 1a under basic conditions attacks the
β-position of 2a to afford the enolate A, which undergoes nucleophilic
addition-elimination to an imino dichloride to afford intermediate B. Then, the tosylate
group is removed from B under basic conditions and the remaining tosylate attacks the
imino chloride moiety to afford D. Finally, isomerization proceeds to give 3aa. In
reaction of 1b with 2c (Eq. 4), aromatization proceeds more quickly than addition of
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tosylate to imino chloride intermediate.
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Scheme 1. Proposed reaction mechanism
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O
O
Cl
Cl
Ts
K2CO3
+
N
EtO
EtO
NH
Ts
1a
2a
3aa
K2CO3
O
–
Cl
Cl
Ts
O
N
EtO
N
EtO
Ts
D
O–
H
O
O
EtO
base
Ts
Ts–
EtO
EtO
Cl
Cl
Ts
N
N
N
Cl
Cl
C
A
B
In conclusion, an efficient method for the synthesis of multifunctionalized pyrrole
derivatives utilizing isocyanide dichloride was developed. The key to the success of the
reaction was the Michael addition of a carbanion generated from isocyanide dichloride
to the α,β-unsaturated carbonyl compound, followed by nucleophilic
addition-elimination to the iminodichloride. The reactions proceeded smoothly to afford
the pyrrole derivatives in good to high yields. A wide range of Michael acceptors were
applied successfully to this reaction.
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Experimental Section
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1
General: H NMR spectra were recorded on a 400 MHz NMR spectrometer. Chemical
shifts δ are reported in ppm using TMS as an internal standard. Data are reported as
follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constant (J) and integration. 13C NMR spectra were recorded on
100 MHz NMR spectrometer. The chemical shifts were determined in the δ-scale
relative to CDCl3 (δ = 77.0 ppm). The wave numbers of maximum absorption peaks of
IR spectroscopy are presented in cm−1. HRMS (DART and ESI) was measured with and
TOF mass spectrometers. All melting points were measured using a micro melting point
apparatus. Dehydrated solvents were purchased for the reactions and used without
further desiccation. Compound 1a was prepared according to the literature.10
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General procedure
(Phenyl(tosyl)methyl)carbonimidic dichloride (1b)
To a solution of 1-((isocyano(phenyl)methyl)sulfonyl)-4-methylbenzene (0.30 mmol) in
CHCl3 (1.0 mL), SO2Cl2 (3.0 mmol) in CHCl3 (3.0 mL) was added dropwise at –45 ℃.
The reaction mixture was stirred for 10 min at –45 ℃, then allowed to warm to room
temperature. After removing the solvents, 1b was obtained and was used without further
purification.8
To a suspension of the 1a (0.30 mmol) and K2CO3 (0.9 mmol) in THF (3.0 mL),
Michael acceptor 2 (0.30 mmol) was added at room temperature, then the whole was
stirred at room temperature for 2 days. To the reaction mixture, water (2.0 mL) was
added and separated. The aqueous layer was extracted with CHCl3 (5 mL x 3) and the
combined organic layers were washed with brine, and dried over Na2SO4. Concentration
and the subsequent purification by silica gel flash column chromatography gave the
corresponding pyrrole derivatives 3.
Ethyl 2-tosyl-1H-pyrrole-3-carboxylate (3aa)14
Silica gel column chromatography (hexane/ethyl acetate = 3/1) gave 3aa (86 mg, 97%
yield) as a white solid of mp = 94–96 °C (hexane/ethyl acetate). 1H NMR (CDCl3): 1.25
(t, J = 6.8 Hz, 3H), 2.40 (s, 3H), 4.22 (t, J = 6.8 Hz, 2H), 6.74 (d, J = 2.8 Hz, 1H), 6.92
(d, J = 2.8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H). 9.83 (brs, 1H).
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13C NMR (CDCl3): 14.2, 21.7, 60.6, 114.5, 118.7, 120.6, 128.1, 129.4, 130.3, 137.6,
144.5, 161.8. IR (KBr): 3240, 1710, 1470, 1310, 1210, 1160, 1040 cm–1. HRMS–DART
(m/z): Calcd for C14H16NO4S [M+H]+: 294.0800. Found: 294.0809.
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Methyl 2-tosyl-1H-pyrrole-3-carboxylate (3ab)
Silica gel column chromatography (hexane/ ethyl acetate = 3/1) gave 3ab (68 mg, 81%
1
yield) as a white solid of mp = 137–139 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.34 (s, 3H), 3.68 (s, 3H), 6.67 (t, J = 2.8 Hz, 1H), 6.85 (d, J = 2.8 Ha, 1H), 7.24 (d, J =
13
8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 9.93 (brs, 1H). C NMR (CDCl3): 21.7, 51.6,
114.5, 118.2, 120.8, 128.2, 129.4, 130.4, 137.5, 144.6, 162.3. IR (KBr): 3230, 1700,
1470, 1310, 1210, 1150, 1030 cm–1. HRMS–DART (m/z): Calcd for C13H14NO4S
[M+H]+: 280.0644. Found: 280.0651.
Dimethyl 2-tosyl-1H-pyrrole-3,4-dicarboxylate (3ac)
Silica gel column chromatography (hexane/ ethyl acetate = 2/1) gave 3ac (84 mg, 83%
yield) as a white solid of mp = 87–90 °C (hexane/ethyl acetate). 1H NMR (CDCl3): 2.36
(s, 3H), 3.72 (s, 3H), 3.87 (s, 3H), 7.26 (d, J = 8.4 Hz, 2H), 7.39 (s, 1H), 7.81 (d, J = 8.4
Hz, 2H), 9.80 (brs, 1H). 13C NMR (CDCl3): 21.6, 51.8, 51.9, 116.6, 121.7, 126.9, 127.6,
128.6, 129.9, 137.4, 145.0, 162.3, 164.2. IR (KBr): 3150, 1710, 1590, 1450, 1380, 1290,
1220, 1150, 1080, 1070 cm–1. HRMS–DART (m/z): Calcd for C15H16NO6S [M+H]+:
338.0698. Found: 338.0699.
Diethyl 2-tosyl-1H-pyrrole-3,4-dicarboxylate (3ad)
Silica gel column chromatography (hexane/ ethyl acetate = 2/1) gave 3ad (67 mg, 61%
1
yield) as a white solid of mp = 154–157 °C (hexane/ethyl acetate). H NMR (CDCl3):
1.20 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 6.8 Hz, 3H), 2.31 (s, 3H), 4.17 (q, J = 7.2 Hz, 2H),
4.35 (t, J = 6.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.38 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H),
10.5 (brs, 1H). 13C NMR (CDCl3): 13.9, 14.1, 21.6, 60.7, 62.1, 116.8, 122.2, 126.9,
127.6, 128.1, 129.9, 137.6, 144.9, 162.3, 163.9. IR (KBr): 3130, 1720, 1590, 1510,
1440, 1380, 1280, 1210, 1160 cm–1. HRMS–DART (m/z): Calcd for C17H20NO6S
[M+H]+: 366.1011. Found: 366.1005.
Methyl 4-methyl-2-tosyl-1H-pyrrole-3-carboxylate (3ae)
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Silica gel column chromatography (hexane/ ethyl acetate = 3/1) gave 3ae (29 mg, 32%
yield) as an amorphous. 1H NMR (CDCl3): 2.14 (s, 3H), 2.34 (s, 3H), 3.61 (s, 3H), 6.68
(d, J = 2.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 9.75 (brs, 1H).
13C NMR (CDCl3): 12.0, 21.6, 51.2, 116.7, 120.2, 125.5, 127.9, 129.3, 130.2, 138.1,
144.2, 163.2. IR (KBr): 3150, 1710, 1590, 1450, 1380, 1290, 1220, 1150, 1080, 1070
cm–1. HRMS–DART (m/z): Calcd for C14H16NO4S [M+H]+: 294.0800. Found:
294.0803.
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2-Tosyl-1H-pyrrole-3-carbonitrile (3ag)
Silica gel column chromatography (hexane/ ethyl acetate = 3/1) gave 3ag (47 mg, 64%
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yield) as a white solid of mp = 165–168 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.41 (s, 3H), 6.57 (t, J = 2.8 Hz, 1H), 6.92 (m, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.94 (d, J
= 8.4 Hz, 2H), 9.90 (brs, 1H). 13C NMR (CDCl3): 21.7, 97.5, 113.2, 115.6, 122.5, 127.5,
130.3, 134.5, 137.0, 145.6. IR (KBr): 3270, 2230, 1750, 1640, 1590, 1470, 1380, 1310,
1230, 1150, 1090, 1040 cm–1. HRMS–DART (m/z): Calcd for C12H11N2O2S [M+H]+:
247.0541. Found: 247.0538.
3-Nitro-4-phenyl-2-tosyl-1H-pyrrole (3ah)
Silica gel column chromatography (hexane/ ethyl acetate = 4/1) gave 3ah (45 mg, 43%
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yield) as a white solid of mp = 165–167 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.37 (s, 3H), 6.87 (d, J = 3.2 Hz, 1H), 7.19 (s, 1H), 7.22–7.30 (m, 6H), 7.91 (d, J = 8.0
Hz, 2H), 10.3 (brs, 1H). 13C NMR (CDCl3): 21.7, 119.8, 124.7, 127.6, 128.2, 128.3,
128.9, 129.1, 129.8, 130.5, 136.0, 145.6. IR (KBr): 3260, 1650, 1510, 1450, 1370, 1350,
1320, 1230, 1170, 1140, 1080 cm–1. HRMS–DART (m/z): Calcd for C17H15N2O4S
[M+H]+: 343.0753. Found: 343.0751.
1-(2-Tosyl-1H-pyrrol-3-yl)ethan-1-one (3ai)
Silica gel column chromatography (ethyl acetate = 2/1) gave 3ai (54 mg, 69% yield) as
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a white solid of mp = 143–145 °C (hexane/ ethyl acetate). H NMR (CDCl3): 2.31 (s,
3H), 2.31 (s, 3H), 6.56 (t, J = 2.8 Hz, 1H), 6.89 (t, J = 2.8 Hz, 1H), 7.20 (d, J = 8.4 Hz,
2H), 7.90 (d, J = 8.4 Hz, 2H), 10.5 (brs, 1H). 13C NMR (CDCl3): 21.6, 28.3, 113.7,
121.2, 126.2, 128.4, 129.2, 137.3, 144.4, 192.3. IR (KBr): 3150, 1660, 1600, 1470,
1410, 1370, 1320, 1320, 1220, 1180, 1150, 1090 cm–1. HRMS–DART (m/z): Calcd for
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C13H14NO3S [M+H]+: 264.0694. Found: 264.0699.
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Ethyl 5-chloro-2-phenyl-2-tosyl-3,4-dihydro-2H-pyrrole-4-carboxylate (3b’a)
Silica gel column chromatography (hexane/ethyl acetate = 4/1) gave 3b’a (308 mg,
76% yield, 1.0 mmol scale) as a white solid of mp = 77–79 °C (hexane/ethyl acetate).
1H NMR (CDCl3): 0.80 (t, J = 7.2 Hz, 3H), 2.27 (s, 3H), 3.14 (dd, J = 2.0, 17.6 Hz, 1H),
3.53–3.64 (m, 2H), 3.73 (m, 1H), 4.40 (dd, J = 2.0, 17.6 Hz, 1H), 7.01 (d, J = 8.0 Hz,
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2H), 7.09–7.19 (m, 5H), 7.43 (d, J = 8.0 Hz, 2H). C NMR (CDCl3): 13.4, 21.6, 47.3,
47.9, 61.3, 102.5, 127.6, 128.5, 128.9, 129.2, 130.3, 131.2, 132.6, 145.0, 169.6, 170.5.
IR (KBr): 2990, 1730, 1630, 1600, 1510, 1490, 1450, 1370, 1340, 1300, 1200, 1150,
1100, 1090 cm–1. HRMS–DART (m/z): Calcd for C20H21NO4SCl [M+H]+: 406.0871
. Found: 406.0879.
Ethyl 2-(diethylamino)-5-phenyl-1H-pyrrole-3-carboxylate (3ba)
To a solution of 3b’a (0.3 mmol) in THF (3.0 mL), diethylamine (0.3 mmol) was added
dropwise and the whole was stirred at room temperature for 2 days. Water (2.0 mL) was
added to the reaction mixture and aqueous layer was extracted with CHCl3 (5 mL x 3).
Combined organic layers were washed with brine and dried over Na2SO4. Concentration
and the residue was purified by silica gel column chromatography (hexane/diethyl ether
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= 2/1) gave 3ba (43 mg, 50% yield) as an amorphous. H NMR (CDCl3): 1.04 (t, J =
7.2 Hz, 6H), 1.19 (t, J = 7.2 Hz, 3H), 3.02 (q, J = 7.2 Hz, 4H), 4.14 (q, J = 7.2 Hz, 2H),
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5.87 (d, J = 2.8 Hz, 1H), 7.21–7.51 (m, 5H), 7.96 (brs, 1H). C NMR (CDCl3): 12.4,
14.3, 46.6, 59.1, 95.3, 111.2, 127.3, 127.5, 128.0, 128.7, 131.1, 132.4, 140.2, 165.1. IR
(KBr): 3300, 2980, 1680, 1590, 1530, 1490, 1450, 1380, 1270, 1240, 1150, 1100 cm–1.
HRMS–DART (m/z): Calcd for C17H23N2O2 [M+H]+: 287.1760. Found: 287.1768.
Dimethyl 2-chloro-5-phenyl-1H-pyrrole-3,4-dicarboxylate (3bc)
Silica gel column chromatography (hexane/ethyl acetate = 5/1) gave 3bc (33 mg, 37%
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yield) as a white solid of mp = 104–107 °C (hexane/ethyl acetate). H NMR (CDCl3):
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3.70 (s, 3H), 3.76 (s, 3H), 7.19–7.37 (m, 5H), 9.11 (brs, 1h). C NMR (CDCl3): 51.8,
52.2, 112.5, 114.2, 120.3, 127.5, 128.7, 129.8, 132.5, 163.3, 165.6. IR (KBr): 3190,
2950, 1690, 1510, 1490, 1460, 1410, 1340, 1290, 1220, 1130, 1080 cm–1. HRMS–
DART (m/z): Calcd for C14H13NO4Cl [M+H]+: 294.0533. Found: 294.0536.
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ACKNOWLEDGEMENTS
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This work was supported by a Grant-in-Aid for Young Scientists (B) (15K17820), a
Grant-in-Aid for Scientific Research (B) (24350022) from the Japan Society for the
Promotion of Science, Kanazawa University CHOZEN Project, and Kanazawa
University SAKIGAKE.Project.
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Supporting Information
Copies of 1H NMR and 13C NMR spectra of products. This material is available free of
charge via the Internet at http://pubs.acs.org.
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