Chemoselective reduction of functionalized 5-nitroisoxazoles: Synthesis of 5-amino- and 5-[hydroxy(tetrahydrofuran-2-yl)amino]isoxazoles

Article abstract of DOI:10.1055/s-0033-1340827

Reduction by using SnCl₂ of easily accessible 5-nitroisoxazoles substituted with an electron-withdrawing group (EWG) has been studied. Whereas the reaction in ethanol yielded 5-aminoisoxazoles, performing the reaction in tetrahydrofuran gave pr

Full text of DOI:10.1055/s-0033-1340827

PAPER
▌1107
paper
Chemoselective Reduction of Functionalized 5-Nitroisoxazoles: Synthesis of
5-Amino- and 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazoles
Chemoselective Reduction of Functionalized 5-Nitroisoxazoles
Elena B. Averina,*a,b Dmitry A. Vasilenko,a Yuri V. Samoilichenko,a Yuri K. Grishin,a Victor B. Rybakov,a
Tamara S. Kuznetsova,a,b Nikolay S. Zefirova,b
a
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russian Federation
b
IPhaC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russian Federation
Fax +7(495)9393969; E-mail: elaver@org.chem.msu.ru
Received: 06.12.2013; Accepted after revision: 24.01.2014
EWG
R
Abstract: Reduction by using SnCl2 of easily accessible 5-ni-
troisoxazoles substituted with an electron-withdrawing group
(EWG) has been studied. Whereas the reaction in ethanol yielded 5-
aminoisoxazoles, performing the reaction in tetrahydrofuran gave
previously unknown 5-[hydroxy(tetrahydrofuran-2-yl)amino]isox-
azoles. Both reduction procedures were optimized to afford the cor-
responding products in good to excellent yields. Some mechanistic
details concerning the inclusion of the tetrahydrofuranyl moiety
into the reaction product are discussed
N
EWG
R
NH2
R
O
[H]
TNM
Et3N
2
N
EWG
NO2
or
O
EWG
R
1
EWG = C(O)R1, CO2R2, NO2, P(O)(OEt)2
R = H, Alk
N
N
O
O
OH
Key words: reduction, chemoselectivity, isoxazoles, radical reac-
3
tion, tetrahydrofuran
Scheme 1 Synthesis of functionalized 5-nitroisoxazoles and reduc-
tion of the nitro group
The significant interest in isoxazole derivatives stems
from their versatility as synthetic building blocks and their
application in various fields such as agriculture, industry,
and medicine.1 In particular, aminoisoxazoles are known
to possess a wide range of physiological activities, for ex-
ample, cytotoxic (anticancer),2 biocidal,3 anti-inflamma-
tory and immune-suppressive4 activities. Amino-
substituted isoxazoles are also employed in the prepara-
tion of fused heterocyclic systems, such as isoxazolopyri-
dines, isoxazolopyrimidines, and isoxazolodiazepines,
which represent valuable scaffolds in pharmacological
agents.5 The majority of existing approaches to 3- and 5-
aminoisoxazoles include ring-closure reactions of organic
nitriles with hydroxylamine5,6 or halogenooximes.5,7
However, in a number of cases these methods are of low
regioselectivity and produce mixtures of 3- and 5-ami-
noisoxazoles. Moreover, the substituents that can be pres-
ent in such molecules are generally limited to alkyl and
aryl groups. Thus the development of new, effective re-
gioselective approaches to functionalized 5-aminoisoxa-
zoles remains a challenge.
Clearly, nitro-substituted heterocycles of type 1 are highly
reactive compounds that may be used as precursors for a
range of functionalized aminoisoxazoles and other valu-
able isoxazole derivatives. Continuing our research, we
have studied in detail functionalized 5-nitroisoxazoles in
reduction reactions and found that, depending on the
conditions applied, 5-aminoisoxazoles 2 or previously
unknown 5-[hydroxy(tetrahydrofuran-2-yl)amino]isoxa-
zoles 3 were formed (Scheme 1).
Herein we propose a simple method for the synthesis of
functionalized 5-aminoisoxazoles and 5-[hydroxy(tetra-
hydrofuran-2-yl)amino]isoxazoles from the reduction of
corresponding 5-nitroisoxazoles, which are easily avail-
able by heterocyclization of commercial electrophilic al-
kenes.
A brief study of known mild reducing agents, such as
Zn/NH4Cl,
Zn/AcOH,
Fe/CaCl2,
SnCl2/HCl,
SnCl2/EtOH, N2H4-H2O/NiRaney, HCO2NH4-Pd/C, and
Al/Hg by using 5-nitroisoxazole 1a as a model compound
revealed that 5-aminoisoxazole 2a was generated as the
sole product when zinc and acetic acid or tin(II) chloride
and ethanol were used. In the case of zinc and acetic acid,
the best yield of aminoisoxazole was achieved when the
reaction was carried out at 0 to –10°C for three hours.
When using the tin(II) chloride and ethanol system, com-
plete conversion of the starting nitro-compound into
amine could be achieved by the use of a five-fold excess
of the reducing agent, and keeping the reaction mixture at
room temperature for one hour. Under these conditions
we obtained a series of 5-aminoisoxazoles with an addi-
tional functional group in the 3-position (Table 1).
We have recently elaborated a novel preparative method
for the synthesis of a large variety of functionalized 5-ni-
troisoxazoles 1 by the reaction of tetranitromethane
(TNM) with electrophilic alkenes in the presence of trieth-
ylamine (Scheme 1).8
SYNTHESIS 2014, 46, 1107–1113
Advanced online publication: 19.02.2014
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DOI: 10.1055/s-0033-1340827; Art ID: SS-2013-Z0793-OP
© Georg Thieme Verlag Stuttgart · New York

1108
E. B. Averina et al.
PAPER
and also the addition to S–S (in disulfides),18 activated O–
H (alcohols),19 and N–H (amines) bonds.20 To the best of
our knowledge, the radical addition of tetrahydrofuran to
N=O bonds with the formation of tetrahydrofuranyl sub-
stituted hydroxylamine has not been described. However,
compounds including such a fragment could be of interest
due to their reactivity21 and potential pharmaceutical ap-
plications.22
Table 1 Synthesis of 5-Aminoisoxazolesa
EWG
R
EWG
R
[H]
N
N
[H]: SnCl2–EtOH (A)
or Zn-AcOH–i-PrOH (B)
NO2
NH2
O
O
1a–k
2a–k
Entry
Amine 2
R
EWG
Yield of 2
(%)b
Table 2 Synthesis of 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isox-
azolesa
1
2
2a
2b
H
H
С(O)Me
75 (A)
50 (B)
EWG
R
EWG
R
SnCl2–HCl
C(O)Et
79 (A)
49 (B)
N
THF–H2O
air
N
NO2
N
O
O
O
3
4
2c
-С(О)(СН2)3-
58 (A)
OH
1a–j,l,m
3a–j,l,m
2d
H
H
CO2Me
60 (A)
73 (B)
Entry Hydroxylamine 3
R
EWG
Yield of 3
(%)b
5
2e
СО2t-Bu
25 (A)
87 (B)
1
2
3a
3b
3c
3d
3e
3f
H
С(O)Me
80
77
68
78
80
6
7
2f
H
H
Et
CO2CH2Adc
CO2CH2Ph
CO2Et
75 (A)
72 (A)
75 (A)
65 (A)
90 (A)
50 (A)
H
C(O)Et
2g
2h
2i
3
-С(О)(СН2)3-
8
4
H
H
H
H
Et
CO2Me
9
(CH2)3Cl
CO2Et
5
СО2t-Bu
10
11
2j
H
H
P(O)(OEt)2
C(O)NH2
6
CO2CH2Adc 65
2k
7
3g
3h
3i
CO2CH2Ph
CO2Et
68
70
81
82
54
46
a Reaction conditions: Method A: 5-nitroisoxazole (0.6 mmol), SnCl2
(3.0 mmol for 1a–g, k and 6 mmol for 1h–j), 96% EtOH (2 mL), r.t.,
2 h (or 3 h for 1h–j); Method B: 5-nitroisoxazole (0.6 mmol), Zn (2.2
mmol), AcOH (4.2 mmol), iPrOH (6 mL), –10 to 0 °C, 3 h.
b Isolated yield. Reducing systems are given in parentheses.
c Ad = 1-adamantyl.
8
9
(CH2)3Cl
CO2Et
10
11
12
3j
H
H
H
P(O)(OEt)2
C(O)Ph
NO2
3l
3m
Reduction with the tin(II) chloride and ethanol system
was employed for the majority of compounds which were
obtained in high yields. In the case of the reduction of ni-
troisoxazoles 1h–j (Table 1, entries 8–10) larger excesses
of SnCl2 (7–10 equiv) and longer reaction time (3 h) were
needed for the reaction to reach completion. The structure
of 5-aminoisoxazoles was confirmed by X-ray crystal
structure analysis of a typical compound 2b.9
a Reaction conditions: 5-nitroisoxazole (0.3 mmol), SnCl2 (0.9 mmol
for 1a–g, l, m, and 1.5 mmol for 1h–j), H2O (5.5 mL), THF (5.5 mL),
concd. HCl (0.5 mL), 0 °C, 2 h (or 3 h for 1h–j).
b Isolated yield.
c Ad = 1-adamantyl.
The novel reaction of the radical addition of tetrahydrofu-
ran to the N=O bond prompted us to examine the reaction
with other 5-nitroisoxazoles. By optimizing the reaction
conditions for model compound 1a we found that highly
purified tetrahydrofuran did not react with nitroisoxa-
zoles. When AIBN or benzoyl peroxide were used as rad-
ical initiators in catalytic amounts, the desired product 3a
was obtained in approximately 50% yields (on the basis of
1H NMR spectra). In the course of our investigation we
found that the present reaction could be successfully car-
ried out when air was bubbled for several hours into tetra-
hydrofuran that had been previously distilled over sodium
hydroxide. This simple method of initiation of tetrahydro-
furanyl radicals was used for the synthesis of target isox-
azoles. In all cases, 5-[hydroxy(tetrahydrofuran-2-
By studying the influence of the reaction conditions, we
found that reduction of the model 5-nitroisoxazole 1a by
tin(II) chloride and hydrochloric acid in tetrahydrofuran
resulted in the formation of unexpected product 3a, which
was shown to be hydroxylaminoisoxazole containing a
tetrahydrofuran moiety covalently attached to the mole-
cule (Table 2, entry 1). Tetrahydrofuran radical addition
to different classes of organic compounds in the presence
of radical initiators is well-documented. The addition of
the tetrahydrofuran-2-yl radical to double C=C10 and tri-
ple C≡C11 bonds, and to C=O and C=N12 groups is known.
There are a few reports that describe the addition of tetra-
hydrofuran to activated C–X bonds in alkenes,13 al-
kynes,14 aryl compounds,15 fullerene,16 oxime ethers,17
Synthesis 2014, 46, 1107–1113
© Georg Thieme Verlag Stuttgart · New York

PAPER
Chemoselective Reduction of Functionalized 5-Nitroisoxazoles
1109
yl)amino]isoxazoles were obtained in good yields. The re-
sults of the reduction of a number of 5-nitroisoxazoles by
SnCl2–HCl in tetrahydrofuran are presented in Table 2.
To avoid partial decomposition of the isoxazole fragment,
the reduction was carried out at 0 °C for two hours. For 5-
nitroisoxazoles 1h–j (entries 8–10) the reaction time was
increased to three hours and greater amounts of SnCl2
were used (see the Experimental Section). The reaction
conditions detailed above were applied to a variety of 5-
nitroisoxazoles to provide 5-[hydroxy(tetrahydrofuran-2-
yl)amino]isoxazoles in good isolated yields (Table 2).
EWG
R
EWG
R
N
N
O
N
NO2
O
O
II
1
EWG
R
air
N
O
O
N
O
O
I
O
III
EWG
R
It should be noted that 3,5-dinitroisoxazole 1m (Table 2,
entry 12) afforded only 5-hydroxylamine 3m, with the re-
tention of the nitro group in the 3-position both under
standard conditions and by using a large excess of SnCl2
(mol ratio SnCl2/1m, 10:1). The structure of 3m was un-
O
N
N
O
O
OH
3
ambiguously confirmed on the basis of X-ray crystal Scheme 2 Proposed mechanism for the formation of 5-[hydroxy(tet-
rahydrofuran-2-yl)amino]isoxazoles
structure analysis (Figure 1).
chemoselective reduction of 5-nitroisoxazoles by tin(II)
chloride, which affords either the adducts with tetrahydro-
furan or aminoisoxazoles, depending crucially on which
solvent was used.
1H (400.0 MHz), 13C (100.6 MHz) and 31P (161.9 MHz) NMR spec-
tra were recorded with an Agilent 400-MR NMR spectrometer at
r.t.; chemical shifts (δ) were measured with reference to the solvent
1
CDCl3 for Н (δ = 7.24 ppm) and 13C (δ = 77.13 ppm), and 85%
H3PO4 for 31P as external standard. Accurate mass measurements
(HRMS) were measured with a Bruker microOTOF II mass spec-
trometer using electrospray ionization (ESI) and a time-of-flight
(TOF) detector. X-ray diffraction analysis was carried out with
equipment diffractometer STADI VARI Pilatus-100K. Analytical
thin-layer chromatography was carried out with silica gel plates
(supported on aluminum); detection was achieved by irradiation un-
der a UV lamp (254 and 365 nm) and chemical staining (5% aque-
ous solution of KMnO4). Column chromatography was performed
on silica gel (230–400 mesh). Starting 5-nitroisoxazoles 1a–m were
Figure 1 X-ray crystal structure of 5-[hydroxy(tetrahydrofuran-2-
synthesized by our original procedures.8 Other starting materials
yl)amino]-3-nitroisoxazole (3m) (thermal ellipsoids are shown with
were commercially available. All reagents except commercial prod-
ucts of satisfactory quality were purified by literature procedures
prior to use.
50% probability level)23
Taking into account the experimental conditions and liter-
ature data10–20 we assumed that the reaction proceeds
through a radical mechanism (Scheme 2).
1-Adamantylmethyl 5-nitroisoxazole-3-carboxylate (1f)
Synthesized by our original procedure8 from 1-adamantylmethyl
acrylate (1.01 g, 4.59 mmol), TNM (2.25 g, 11.48 mmol), Et3N
(0.927 g, 9.18 mmol) in 1,4-dioxane (15 mL).
It is likely that radical species, formed as a result of in-
volving atmospheric oxygen in the reaction with tetrahy- Yield: 0.96 g (68%); pale-yellow crystals; mp 95–96 °C; Rf 0.59
(CHCl3).
drofuran under daylight, participate in the abstraction of a
1Н NMR (400 MHz, CDCl3): δ = 1.59 (br s, 3 H, 3CH2), 1.60 (br s,
3 H, 3CH2), 1.63–1.68 (m, 3 H, 3CH2), 1.71–1.77 (m, 3 H, 3CH2),
1.98–2.04 (m, 3 H, 3CH), 4.02 (s, 2 H, CH2O), 7.37 (s, 1 H, CH).
13С NMR (100 MHz, CDCl3): δ = 27.9 (3CH), 33.5 (C), 36.7
(3CH2), 39.1 (3CH2), 76.4 (CH2O), 102.3 (CH), 157.8 (C), 158.3
(C), 165.6 (CNO2).
labile α-hydrogen atom from tetrahydrofuran, giving tet-
rahydrofuran-2-yl radical I. 5-Nitrosoisoxazole II is gen-
erated in the reduction of 5-nitroisoxazole 1 by SnCl2.
This intermediate adds the radical I to produce intermedi-
ate III. Subsequent reaction of tetrahydrofuran with III
leads to product 3 and generates radical I. In this way, the
radical cycle mechanism may be completed.
HRMS (ESI): m/z [M + Na]+ calcd for C15H18N2O5Na+: 329.1108;
found: 329.1099.
In conclusion, we have developed a simple regioselective
method for the synthesis of functionalized 5-aminoisoxa-
zoles and the previously unknown 5-[hydroxy(tetrahydro-
furan-2-yl)amino]isoxazoles. Our strategy is based on
Synthesis of 5-Aminoisoxazoles; General Procedure
Method A: To a stirred solution of 5-nitroisoxazole (0.6 mmol) in
96% EtOH (2 mL), SnCl2 (580 mg, 3.0 mmol for 1a–g, k; and 1140
mg, 6 mmol for 1h–j) was added in one portion at r.t. The resulting
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1107–1113

1110
E. B. Averina et al.
PAPER
mixture was stirred for 2 h (or 3 h for 1h–j), then the solvent was
evaporated in vacuo and the residue was dissolved in CHCl3 (20
mL) and washed with sat. aq NaHCO3 (resulting in a solution at
pH 8). The aqueous phase was extracted with CHCl3 (3 × 10 mL)
and the combined organic layers were dried over MgSO4. The sol-
vent was evaporated in vacuo and the residue was purified by pre-
parative column chromatography on silica gel [petroleum ether–
EtOAc, 4:1 (for 2d–i), or CHCl3–MeOH, 20:1 (for 2a–c, j, k].
tert-Butyl 5-Aminoisoxazole-3-carboxylate (2e)
Yield: 28 mg (25%, A); 96 mg (87%, B); colorless crystals; mp
125–127 °C; Rf 0.29 (CHCl3–MeOH, 20:1).
IR (Nujol): 3440, 3050, 3010, 1720, 1650, 1605, 1380, 1245 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.61 (s, 9 H, 3 CH3), 4.62 (br s,
2 H, NH2), 5.51 (s, 1 H, CH).
13С NMR (100 MHz, CDCl3): δ = 28.0 (3 CH3), 80.7 (CH), 83.2 (C),
158.8 (C), 159.5 (C), 169.4 (C).
HRMS (ESI): m/z [M + H]+ calcd for C8H13N2O3 : 185.0926; found:
185.0921.
Method B: To a stirred solution of 5-nitroisoxazole (0.6 mmol) and
glacial AcOH (260 mg, 4.2 mmol) in i-PrOH (6 mL), Zn powder
(140 mg, 2.2 mmol) was added in one portion at –10 to 0 °C. The
resulting mixture was stirred at this temperature for 3 h, then fil-
tered and the solvent was evaporated in vacuo. The residue was dis-
solved in chloroform (10 mL) and washed with sat. aq NaHCO3
(resulting in a solution at pH 8). The aqueous phase was extracted
with CHCl3 (3 × 5 mL) and the combined organic layers were dried
over MgSO4. The solvent was evaporated in vacuo and the residue
was purified according to method A.
+
1-Adamantylmethyl 5-aminoisoxazole-3-carboxylate (2f)
Yield: 124 mg (75%, A); colorless crystals; mp 174–176 °C; Rf 0.41
(petroleum ether–EtOAc, 2:1).
IR (Nujol): 3440, 3300, 3010, 1715, 1645, 1610, 1375, 1240, 1025
cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.58 (br s, 3 H, 3 CH2), 1.59 (br s,
3 H, 3 CH2), 1.61–1.67 (m, 3 H, 3 CH2), 1.68–1.75 (m, 3 H, 3 CH2),
1.95–2.01 (m, 3 H, 3 CH), 3.92 (s, 2 H, CH2O), 4.62 (br s, 2 H,
NH2), 5.52 (s, 1 H, CH).
1-(5-Aminoisoxazol-3-yl)ethanone (2a)
Yield: 57 mg (75%, A); 38 mg (50%, B); colorless crystals; mp
133–135 °C; Rf 0.37 (CHCl3).
13С NMR (100 MHz, CDCl3): δ = 28.0 (3 CH), 33.4 (C), 36.8 (3
CH2), 39.2 (3 CH2), 75.0 (CH2O), 80.7 (CH), 157.5 (C), 160.6 (C),
169.5 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C15H20N2O3Na+: 299.1366;
found: 299.1355.
IR (Nujol): 3350, 3030, 1700, 1660, 1612 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 2.58 (s, 3 H, CH3), 4.58 (br s, 2 H,
NH2), 5.50 (s, 1 H CH).
13С NMR (100 MHz, CDCl3): δ = 26.9 (CH3), 78.3 (CH), 163.4 (C),
169.6 (C), 192.8 (C=O).
+
HRMS (ESI): m/z [M + H]+ calcd for C5H7N2O2 : 127.0508; found:
127.0494.
Benzyl 5-Aminoisoxazole-3-carboxylate (2g)
Yield: 94 mg (72%, A); pale-pink crystals; mp 112 °C; Rf 0.19 (pe-
troleum ether–EtOAc, 2:1).
1-(5-Aminoisoxazol-3-yl)propan-1-one (2b)
IR (Nujol): 3440, 3320, 3012, 1725, 1640, 1600, 1470, 1385, 1210,
1030 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 4.68 (br s, 2 H, NH2), 5.34 (s, 2 H,
CH2O), 5.51 (s, 1 H, CH), 7.31–7.37 (m, 3 H, Ph), 7.40–7.42 (m,
2 H, Ph).
13С NMR (100 MHz, CDCl3): δ = 67.4 (CH2O), 80.6 (CH), 128.52
(2 CH, Ph), 128.55 (CH, Ph), 128.61 (2 CH, Ph), 134.9 (C, Ph),
157.2 (C), 160.3 (C), 169.8 (C).
IR (Nujol): 3360, 3030, 1710, 1646, 1605 cm–1.
Yield: 66 mg (79%, A); 40 mg (49%, B); colorless crystals; mp
127–129 °C; Rf 0.24 (CHCl3).
3
1Н NMR (400 MHz, CDCl3): δ = 1.20 (t, J = 7.3 Hz, 3 H, CH3),
3.00 (q, 3J = 7.3 Hz, 2 H, CH2), 4.59 (br s, 2 H, NH2), 5.50 (s, 1 H,
CH).
13С NMR (100 MHz, CDCl3): δ = 7.5 (CH3), 32.8 (CH2), 78.5 (CH),
163.0 (C), 169.4 (C), 195.8 (C=O).
HRMS (ESI): m/z [M + H]+ calcd for C6H9N2O2 : 141.0664; found:
141.0655.
HRMS (ESI): m/z [M + Na]+ calcd for C11H10N2O3Na+: 241.0584;
found: 241.0590.
+
Ethyl 5-Amino-4-ethylisoxazole-3-carboxylate (2h)
Yield: 83 mg (75%, A); colorless crystal; mp 72–74 °C; Rf 0.28
(CHCl3).
3-Amino-5,6-dihydro-2,1-benzisoxazol-7(4H)-one (2c)
Yield: 53 mg (58%, A); colorless crystals; mp 95–97 °C; Rf 0.06
(petroleum ether–EtOAc, 5:1).
IR (Nujol): 3320, 3050, 1715, 1660, 1650, 1610 cm–1.
IR (Nujol): 3440, 3320, 3010, 1725, 1645, 1605, 1475, 1380, 1225
cm–1.
1Н NMR (400 MHz, CDCl3): δ = 2.10–2.16 (m, 2 H, CH2), 2.50–
2.55 (m, 2 H, CH2), 2.62–2.66 (m, 2 H, CH2), 4.62 (br s, 2 H, NH2).
13С NMR (100 MHz, CDCl3): δ = 18.2 (CH2), 23.7 (CH2), 40.3
(CH2), 95.2 (C), 157.8 (C), 165.6 (С), 192.8 (C=O).
3
1Н NMR (400 MHz, CDCl3): δ = 1.12 (t, J = 7.5 Hz, 3 H, CH3),
1.41 (t, 3J = 7.2 Hz, 3 H, CH3), 2.49 (q, 3J = 7.5 Hz, 2 H, CH2), 4.41
(q, 3J = 7.2 Hz, 2 H, CH2O), 4.51 (br s, 2 H, NH2).
13С NMR (100 MHz, CDCl3): δ = 14.0 (JC–H = 127 Hz, CH3), 14.1
+
HRMS (ESI): m/z [M + H]+ calcd for C7H9N2O2 : 153.0664; found:
153.0659.
(JC–H = 127 Hz, CH3), 14.9 (JC–H = 129 Hz, CH2), 61.6 (JC–H
148 Hz, CH2O), 96.4 (C), 155.1 (C), 161.0 (C), 166.7 (C).
=
Anal. Calcd for С8Н12N2O3: C, 52.17; H, 6.57; N, 15.21. Found: C,
52.20; H, 6.71; N, 15.28.
Methyl 5-Aminoisoxazole-3-carboxylate (2d)
Yield: 51 mg (60%, A); 62 mg (73%, B); colorless crystals; mp
137–139 °C; Rf 0.29 (petroleum ether–EtOAc, 5:1).
IR (Nujol): 3330, 3060, 1710, 1655, 1610, 1380, 1240, 1020 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 3.93 (s, 3 H, CH3), 4.63 (br s, 2 H,
NH2), 5.55 (s, 1 H, CH).
13С NMR (100 MHz, CDCl3 + CD3OD): δ = 52.4 (OCH3), 79.4
(CH), 156.8 (C), 161.1 (C), 171.1 (C).
HRMS (ESI): m/z [M + H]+ calcd for C5H7N2O3 : 143.0457; found:
Ethyl 5-Amino-4-(3-chloropropyl)isoxazole-3-carboxylate (2i)
Yield: 91 mg (65%, A); colorless crystals; mp 101–103 °C; Rf 0.33
(CHCl3).
IR (Nujol): 3460, 3410, 3330, 3010, 1705, 1655, 1610, 1480, 1375,
1240 cm–1.
3
1Н NMR (400 MHz, CDCl3): δ = 1.41 (t, J = 7.1 Hz, 3 H, CH3),
3
2.01–2.08 (m, 2 H, CH2), 2.68 (t, J = 6.7 Hz, 2 H, CH2), 3.58 (t,
+
3J = 6.0 Hz, 2 H, CH2), 4.41 (q, 3J = 7.1 Hz, 2 H, CH2), 4.69 (br s,
143.0452.
2 H, NH2).
Synthesis 2014, 46, 1107–1113
© Georg Thieme Verlag Stuttgart · New York

PAPER
Chemoselective Reduction of Functionalized 5-Nitroisoxazoles
1111
13С NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 18.2 (CH2), 31.8
(CH2), 44.6 (CH2Cl), 61.7 (CH2O), 92.4 (C), 155.1 (C), 160.9 (C),
168.0 (C).
Anal. Calcd for С9Н12N2O4: C, 50.94; H, 5.70; N, 13.20. Found: C,
50.80; H, 5.62; N, 12.96.
1-{5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazol-3-yl}pro-
Anal. Calcd for С9Н13ClN2O3: C, 46.46; H, 5.63; N, 12.04. Found:
C, 46.30; H, 5.69; N, 11.89.
pan-1-one (3b)
Yield: 52 mg (77%); yellow oil; Rf 0.43 (petroleum ether–EtOAc,
2:1).
Diethyl (5-Aminoisoxazol-3-yl)phosphonate (2j)
Yield: 120 mg (90%, A); colorless crystals; mp 90–92 °C; Rf 0.20
(CHCl3–MeOH, 20:1).
IR (Nujol): 3300, 3170, 3012, 1710, 1640, 1600, 1470, 1380, 1070
cm–1.
3
1Н NMR (400 MHz, CDCl3): δ = 1.20 (t, J = 7.3 Hz, 3 H, CH3),
IR (Nujol): 3350, 3000, 1650, 1590, 1252, 1045–1010 cm–1.
1.92–2.00 (m, 1 H, CH2), 2.11–2.32 (m, 3 H, 2CH2), 3.01 (q,
1Н NMR (400 MHz, CDCl3): δ = 1.36 (t, 3J = 7.1 Hz, 6 H, 2CH3),
3J = 7.3 Hz, 2 H, CH2), 3.87–3.92 (m, 1 H, CH2O), 4.08–4.13 (m,
3
4.17–4.27 (m, 4 H, 2CH2), 5.19 (br s, 2 H, NH2), 5.39 (d, JP–H
=
3
3
1 H, CH2O), 5.62 (dd, J = 4.0, J = 6.9 Hz, 1 H, CHO), 5.97 (s,
1.3 Hz, 1 H, CH).
1 H, CH), 6.92 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 16.1 (JC–P = 6 Hz, 2CH3), 63.5
(JC–P = 6 Hz, 2CH2), 82.1 (JC–P = 22 Hz, CH), 156.6 (JC–P = 210 Hz,
C), 169.9 (JC–P = 13 Hz, C).
31P NMR (162 MHz, CDCl3): δ = 5.46.
HRMS (ESI): m/z [M + H]+ calcd for C7H14N2O4Р+: 221.0691;
13С NMR (100 MHz, CDCl3): δ = 7.5 (CH3), 25.3 (CH2), 27.9
(CH2), 32.9 (CH2), 70.0 (CH2O), 84.7 (CH), 92.3 (CHO), 162.2 (C),
172.6 (C), 195.6 (C=O).
Anal. Calcd for С10Н14N2O4: C, 53.09; H, 6.24; N, 12.38. Found: C,
53.24; H, 6.18; N, 12.15.
found: 221.0694.
3-[Hydroxy(tetrahydrofuran-2-yl)amino]-5,6-dihydro-2,1-
benzisoxazol-7(4H)-one (3c)
Yield: 49 mg (68%); yellow crystals; mp 94–96 °C; Rf 0.13 (petro-
leum ether–EtOAc, 2:1).
Anal. Calcd for С7Н13N2O4Р: C, 38.19; H, 5.95; N, 12.72. Found:
C, 38.48; H, 5.75; N, 12.53.
5-Aminoisoxazole-3-carboxamide (2k)
Yield: 38 mg (50%, A); colorless crystals; mp 180 °C (dec.).
IR (Nujol): 3298, 3005, 1714, 1622, 1590, 1470, 1382, 1035 cm–1.
IR (Nujol): 3350, 3200, 3060, 1650, 1612 cm–1.
1Н NMR (400 MHz, CD3OD): δ = 5.37 (s, 1 H, CH). The signals of
2 NH2-groups are aligned with the signals of solvent.
13С NMR (100 MHz, CD3OD): δ = 76.6 (CH), 159.3 (C), 163.1 (C),
1Н NMR (400 MHz, CDCl3): δ = 1.93–2.00 (m, 1 H, CH2), 2.05–
2.22 (m, 4 H, 2CH2), 2.25–2.33 (m, 1 H, CH2), 2.61–2.64 (m, 2 H,
CH2), 2.75–2.90 (m, 2 H, CH2), 3.88–3.94 (m, 1 H, CH2O), 4.09–
4.14 (m, 1 H, CH2O), 5.59 (dd, J = 4.1, J = 7.0 Hz, 1 H, CHO),
7.06 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 19.7 (CH2), 23.5 (CH2), 25.4
(CH2), 28.0 (CH2), 40.3 (CH2), 69.9 (CH2O), 92.3 (CHO), 102.7
(C), 157.9 (C), 167.3 (C), 192.8 (C=O).
3
3
172.1 (C).
+
HRMS (ESI): m/z [M + H]+ calcd for C4H6N3O2 : 128.0460; found:
128.0455.
Anal. Calcd for С11Н14N2O4: C, 55.46; H, 5.92; N, 11.76. Found: C,
55.48; H, 6.02; N, 11.63.
Synthesis of 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxa-
zoles; General Procedure
THF was distilled over NaOH, then air was bubbled through the dis-
tillate for 10 h prior its use in the reaction. To a stirred solution of
5-nitroisoxazole (0.3 mmol) in a mixture of H2O–THF (1:1, 11 mL),
SnCl2 (170 mg, 0.9 mmol for 1a–g, l, m; and 285 mg, 1.5 mmol for
1h–j) was added in one portion, then concd. HCl (0.5 mL) was add-
ed dropwise at 0 °C. The resulting mixture was stirred for 2 h (or 3 h
for compounds 1h–j), then THF was evaporated in vacuo and sat.
aq NaHCO3 was added to the residue until pH 8 was reached. The
aqueous phase was extracted with CHCl3 (3 × 7 mL) and the com-
bined organic layers were dried over MgSO4. The solvent was evap-
orated in vacuo and the residue was purified by preparative column
chromatography on silica gel [petroleum ether–EtOAc, 2:1, or
CHCl3–MeOH, 20:1 for 3j].
Methyl 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazole-3-
carboxylate (3d)
Yield: 53 mg (78%); yellow oil; Rf 0.21 (petroleum ether–EtOAc,
2:1).
IR (Nujol): 3280, 3010, 1728, 1610, 1475, 1382, 1115, 1060 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.93–2.01 (m, 1 H, CH2), 2.11–
2.32 (m, 3 H, 2CH2), 3.88–3.93 (m, 1 H, СH2О), 3.96 (s, 3 H, CH3),
3
3
4.08–4.13 (m, 1 H, CH2O), 5.63 (dd, J = 4.0, J = 7.0 Hz, 1 H,
CHO), 6.04 (s, 1 H, CH), 6.74 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 25.3 (JC–H = 132 Hz, CH2), 27.9
(JC–H = 132 Hz, CH2), 52.8 (JC–H = 148 Hz, CH3), 70.0 (JC–
H = 148 Hz, CH2O), 86.9 (JC–H = 191 Hz, CH), 92.2 (JC–H = 163 Hz,
CHN), 156.7 (С), 160.5 (C), 172.8 (C).
HRMS (ESI): m/z [M + H]+ calcd for C9H13N2O4: 213.0870; found:
213.0864.
1-{5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazol-3-yl}eth-
anone (3a)
Yield: 51 mg (80%); yellow oil; Rf 0.37 (petroleum ether–EtOAc,
2:1).
Anal. Calcd for С9Н12N2O5: C, 47.37; H, 5.30; N, 12.28. Found: C,
47.11; H, 5.22; N, 12.38.
IR (Nujol): 3300, 3170, 3010, 1710, 1640, 1600, 1470, 1380, 1060
cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.87–1.97 (m, 1 H, CH2), 2.05–
tert-Butyl 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazole-3-
carboxylate (3e)
2.28 (m, 3 H, 2CH2), 2.55 (s, 3 H, CH3), 3.83–3.88 (m, 1 H, CH2O),
3
3
Yield: 65 mg (80%); yellow oil; Rf 0.40 (petroleum ether–EtOAc,
2:1).
IR (Nujol): 3300, 3010, 1732, 1640, 1600, 1475, 1380, 1040 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.59 (s, 9 H, 3CH3), 1.90–1.97 (m,
4.03–4.09 (m, 1 H, CH2O), 5.58 (dd, J = 4.1, J = 6.9 Hz, 1 H,
CHO), 5.93 (s, 1 H, CH), 6.78 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 25.3 (CH2), 27.0 (CH3), 27.9
(CH2), 69.9 (CH2O), 84.5 (CH), 92.2 (CHO), 162.6 (C), 172.9 (C),
192.5 (C=O).
HRMS (ESI): m/z [M + H]+ calcd for C9H13N2O4: 213.0870; found:
213.0864.
1 H, CH2), 2.09–2.30 (m, 3 H, 2CH2), 3.86–3.91 (m, 1 H, CH2O),
3
3
4.06–4.11 (m, 1 H, CH2O), 5.59 (dd, J = 4.0, J = 7.0 Hz, 1 H,
CHO), 5.96 (s, 1 H, CH), 6.72 (br s, 1 H, OH).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1107–1113

1112
E. B. Averina et al.
PAPER
13С NMR (100 MHz, CDCl3): δ = 25.3 (CH2), 27.9 (CH2), 28.0
(3CH3), 69.9 (CH2O), 83.5 (C), 87.0 (CH), 92.4 (CHO), 158.1 (C),
159.1 (C), 172.6 (C).
IR (Nujol): 3310, 3015, 1735, 1612, 1565, 1480, 1370, 1200, 1075
cm–1.
3
1Н NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.1 Hz, 3 H, CH3),
Anal. Calcd for С12Н18N2O5: C, 53.33; H, 6.71; N, 10.36. Found: C,
53.39; H, 6.64; N, 9.98.
1.87–1.97 (m, 2 H, CH2), 2.00–2.17 (m, 4 H, 2CH2), 2.82–2.86 (m,
2 H, CH2), 3.57 (t, 3J = 6.5 Hz, 2 H, CH2), 3.87–3.92 (m, 1 H,
CH2O), 4.05–4.10 (m, 1 H, CH2O), 4.42 (q, 3J = 7.1 Hz, 2 H,
CH2O), 5.46–5.49 (m, 1 H, CHO), 6.91 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 19.4 (CH2), 25.2
(CH2), 28.4 (CH2), 33.0 (CH2), 44.7 (CH2Cl), 62.0 (CH2O), 69.5
(CH2O), 93.3 (CHO), 105.8 (C), 155.6 (C), 160.4 (C), 168.4 (C).
1-Adamantylmethyl 5-[Hydroxy(tetrahydrofuran-2-yl)ami-
no]isoxazole-3-carboxylate (3f)
Yield: 70 mg (65%); colorless crystals; mp 144–145 °C; Rf 0.25
(petroleum ether–EtOAc, 2:1).
IR (Nujol): 3300, 3010, 1725, 1645, 1610, 1475, 1370, 1060 cm–1.
Anal. Calcd for С13Н19ClN2O5: C, 48.98; H, 6.01; N, 8.79. Found:
C, 48.89; H, 6.12; N, 8.78.
1Н NMR (400 MHz, CDCl3): δ = 1.54 (br s, 3 H, 3CH2), 1.55 (br s,
3 H, 3CH2), 1.58–1.65 (m, 3 H, 3CH2), 1.66–1.74 (m, 3 H, 3CH2),
1.82–1.92 (m, 1 H, CH2), 1.93–1.98 (m, 3 H, 3CH), 2.05–2.27 (m,
3 H, 2CH2), 3.80–3.86 (m, 1 H, CH2O), 3.92 (s, 2 H, CH2O), 4.02–
Diethyl {5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazol-3-
yl}phosphonate (3j)
Yield: 75 mg (82%); yellow oil; Rf 0.36 (CHCl3–MeOH, 20:1).
3
3
4.07 (m, 1 H, CH2O), 5.57 (dd, J = 4.0, J = 7.0 Hz, 1 H, CHO),
5.95 (s, 1 H, CH), 7.35 (br s, 1 H, OH).
IR (Nujol): 3290, 3010, 1640, 1610, 1470, 1380, 1250, 1020 cm–1.
13С NMR (100 MHz, CDCl3): δ = 25.3 (CH2), 27.85 (CH2), 27.9
(3CH), 33.4 (C), 36.8 (3CH2), 39.1 (3CH2), 69.9 (CH2O), 75.2
(CH2O), 86.6 (CH), 92.2 (CHO), 156.8 (C), 160.2 (C), 173.0 (C).
HRMS (ESI): m/z [M + Na]+ calcd for C19H26N2O5Na+: 385.1734;
found: 385.1728.
3
4
1Н NMR (400 MHz, CDCl3): δ = 1.35 (dt, J = 7.1 Hz, JP–H
=
0.5 Hz, 3 H, CH3), 1.37 (dt, 3J = 7.1 Hz, 4JP–H = 0.5 Hz, 3 H, CH3),
1.86–1.96 (m, 1 H, CH2), 2.12–2.19 (m, 2 H, CH2), 2.29–2.36 (m,
1 H, CH2), 3.84–3.89 (m, 1 H, CH2O), 4.07–4.12 (m, 1 H, CH2O),
4.16–4.27 (m, 4 H, 2CH2), 5.65 (dd, 3J = 4.0, 3J = 7.1 Hz, 1 H,
CHO), 5.76 (d, 3JH–P = 1.2 Hz, 1 H, CH), 8.80 (br s, 1 H, OH).
Anal. Calcd for С19Н26N2O5: C, 62.97; H, 7.23; N, 7.73. Found: C,
62.75; H, 7.36; N, 7.56.
13С NMR (100 MHz, CDCl3): δ = 16.1 (JC–P = 6 Hz, 2CH3), 25.4
(CH2), 28.1 (CH2), 63.9 (d, JC–P = 6 Hz, СН2), 64.1 (d, JC–P = 6 Hz,
СН2), 69.9 (CH2O), 87.7 (JC–P = 22 Hz, CH), 91.8 (CHO), 155.7
(JC–P = 211 Hz, C), 173.2 (JC–P = 13 Hz, C).
Benzyl 5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazole-3-
carboxylate (3g)
Yield: 62 mg (68%); pale-brown oil; Rf 0.15 (petroleum ether–
EtOAc, 3:1).
31P NMR (162 MHz, CDCl3): δ = 5.55.
Anal. Calcd for С11Н19N2O6Р: C, 43.14; H, 6.25; N, 9.15. Found: C,
43.28; H, 6.29; N, 9.21.
IR (Nujol): 3300, 3280, 3070, 3020, 1715, 1645, 1612, 1585, 1470,
1180, 1070 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.88–1.99 (m, 1 H, CH2), 2.00–
2.29 (m, 3 H, 2CH2), 3.82–3.91 (m, 1 H, CH2O), 4.03–4.10 (m, 1 H,
CH2O), 5.38 (s, 2 H, CH2O), 5.57–5.61 (m, 1 H, CHO), 6.02 (s, 1 H,
CH), 6.71 (br s, 1 H, OH), 7.31–7.49 (m, 5 H, Ph).
{5-[Hydroxy(tetrahydrofuran-2-yl)amino]isoxazol-3-yl}(phe-
nyl)methanone (3l)
Yield: 45 mg (54%); yellow oil; Rf 0.38 (petroleum ether–EtOAc,
3:1).
13С NMR (100 MHz, CDCl3): δ = 25.3 (CH2), 27.9 (CH2), 67.5
(CH2O), 69.9 (CH2O), 86.9 (CH), 92.2 (CHO), 128.50 (2CH, Ph),
128.56 (CH, Ph), 128.61 (2CH, Ph), 134.9 (C, Ph), 156.7 (C), 159.8
(C), 172.9 (C).
IR (Nujol): 3350, 3010, 2990, 1695, 1645, 1600, 1580, 1528, 1350,
1045 cm–1.
1Н NMR (400 MHz, CDCl3): δ = 1.90–2.00 (m, 1 H, CH2), 2.08–
2.33 (m, 3 H, 2CH2), 3.87–3.92 (m, 1 H, CH2O), 4.08–4.13 (m, 1 H,
+
3
3
HRMS (ESI): m/z [M + H]+ calcd for C15H17N2O5 : 305.1132;
CH2O), 5.64 (dd, J = 4.1, J = 7.0 Hz, 1 H, CHO), 5.95 (s, 1 H,
CH), 6.12 (br s, 1 H, OH), 7.47–7.50 (m, 2 H, Ph), 7.59–7.63 (m,
1 H, Ph), 8.23–8.25 (m, 2 H, Ph).
found: 305.1138.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16N2O5Na+: 327.0951;
found: 327.0955.
13С NMR (100 MHz, CDCl3): δ = 25.3 (CH2), 27.9 (CH3), 27.9
(CH2), 70.0 (CH2O), 87.0 (CH), 92.3 (CHO), 128.5 (2CH, Ph),
130.6 (2CH, Ph), 134.0 (CH, Ph), 135.6 (C, Ph), 162.4 (C), 172.1
(C), 186.1 (C=O).
HRMS (ESI): m/z [M + H]+ calcd for C14H15N2O4: 275.1026; found:
275.1024.
Ethyl 4-Ethyl-5-[hydroxy(tetrahydrofuran-2-yl)amino]isoxa-
zole-3-carboxylate (3h)
Yield: 57 mg (70%); colorless crystals; mp 74–76 °C; Rf 0.40 (pe-
troleum ether–EtOAc, 2:1).
IR (Nujol): 3280, 3008, 1720, 1610, 1480, 1382, 1110, 1070 cm–1.
3
1Н NMR (400 MHz, CDCl3): δ = 1.17 (t, J = 7.5 Hz, 3 H, CH3),
5-[Hydroxy(tetrahydrofuran-2-yl)amino]-3-nitroisoxazole
(3m)
Yield: 30 mg (46%); yellow crystals; mp 108–110 °C; Rf 0.31 (pe-
troleum ether–EtOAc, 2:1).
1.42 (t, 3J = 7.1 Hz, 3 H, CH3), 1.88–1.98 (m, 1 H, CH2), 1.99–2.07
(m, 1 H, CH2), 2.09–2.16 (m, 2 H, CH2), 2.69 (q, 3J = 7.5 Hz, 2 H,
CH2), 3.89–3.95 (m, 1 H, CH2O), 4.06–4.11 (m, 1 H, CH2O), 4.44
3
(q, J = 7.1 Hz, 2 H, CH2), 5.40–5.43 (m, 1 H, CHO), 6.38 (br s,
IR (Nujol): 3280, 3005, 1645, 1610, 1510, 1340, 1045 cm–1.
1 H, OH).
1Н NMR (400 MHz, CDCl3): δ = 1.95–2.06 (m, 1 H, CH2), 2.12–
2.33 (m, 3 H, 2CH2), 3.91–3.96 (m, 1 H, CH2O), 4.10–4.15 (m, 1 H,
CH2O), 5.67 (dd, J = 4.1, 6.9 Hz, 1 Н, CHO), 6.18 (s, 1 H, CH),
6.49 (br s, 1 H, OH).
13С NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 15.0 (CH3), 15.4
(CH2), 25.2 (CH2), 28.4 (CH2), 61.8 (CH2O), 69.4 (CH2O), 93.7
(CHO), 110.3 (C), 155.6 (C), 160.4 (C), 167.5 (C).
Anal. Calcd for С12Н18N2O5: C, 53.33; H, 6.71; N, 10.36. Found: C,
53.34; H, 6.91; N, 10.28.
13С NMR (100 MHz, CDCl3): δ = 25.2 (CH2), 28.0 (CH2), 70.2
(CH2O), 81.5 (CH), 91.8 (CHO), 167.5 (br s, CNO2), 174.0 (C).
Anal. Calcd for С7Н9N3O5: C, 39.07; H, 4.22; N, 19.53. Found: C,
39.33; H, 4.33; N, 19.54.
Ethyl 4-(3-Chloropropyl)-5-[hydroxy(tetrahydrofuran-2-
yl)amino]isoxazole-3-carboxylate (3i)
Yield: 77 mg (81%); yellow oil; Rf 0.40 (petroleum ether–EtOAc,
2:1).
Synthesis 2014, 46, 1107–1113
© Georg Thieme Verlag Stuttgart · New York

PAPER
Chemoselective Reduction of Functionalized 5-Nitroisoxazoles
1113
Tetrahedron Lett. 2012, 53, 1472; The regiochemistry
reported in ref. 8a was revised in ref. 8b.
Acknowledgment
We thank the Russian Foundation for Basic Research (Projects 11-
03-01040-а, 14-03-00469-а) and the Presidium of RAS (Program N
8) for financial support of this work. The research work was carried
out with a STADI VARI Pilatus-100K diffractometer and an Agi-
lent 400-MR NMR spectrometer, purchased under the program of
MSU development.
(9) The X-ray crystal structures of 2b have been assigned the
number CCDC-820549 and described in our previous
manuscript, see ref. 8b.
(10) (a) Matthews, D. P.; McCarthy, J. R. J. Org. Chem. 1990,
55, 2973. (b) Chen, J.; Zhang, Y.-F.; Zheng, X.; Vij, A.;
Wingate, D.; Meng, D.; White, K.; Kirchmeier, R. L.;
Shreeve, J. M. Inorg. Chem. 1996, 35, 1590. (c) Bravo, A.;
Bjørsvik, H.-R.; Fontana, F.; Liguori, L.; Minisci, F. J. Org.
Chem. 1997, 62, 3849. (d) Hirano, K.; Sakaguchi, S.; Ishii,
Y. Tetrahedron Lett. 2002, 43, 3617.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
(11) Shiosaki, M.; Unno, M.; Hanamoto, T. J. Org. Chem. 2010,
75, 8326.
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(23) Crystallographic data for compound 3m (CCDC-865299)
can be obtained free of charge from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: +44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk; Web site:
www.ccdc.cam.ac.uk/conts/retrieving.html.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1107–1113