Easy Access to 2-Fluoro- And 2-Iodo-2 H -azirines via the Halex Reaction

Article abstract of DOI:10.1055/s-0039-1690200

A simple gram-scale method for the preparation of esters and dialkylamides of 2-(fluoro/iodo)-2 H -azirine-2-carboxylic acids via the halogen exchange (Halex) reaction of 2-bromo-substituted analogues is reported. The method operates with inexpensive and safe reagents, Bu ₄ NF and potassium iodide, providing high product yields. Alternatively, 2-fluoro-2 H -azirine-2-carboxylates can be prepared from 2-iodo- and 2-chloro-analogues. The latter compounds can be obtained in practically quantitative yield by treating the 2-iodo- and 2-bromo-2 H -azirine-2-carboxylic esters with Bu ₄ NCl.

Full text of DOI:10.1055/s-0039-1690200

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
Synthesis
A. V. Agafonova et al.
Paper
Easy Access to 2-Fluoro- and 2-Iodo-2H-azirines via the Halex
Reaction
Anastasiya V. Agafonova
Ilia A. Smetanin
CO Me
CO Me
2
2
Ph
Ph
DCM
98%
4
Bu NCl
Br
Cl
N
N
Nikolai V. Rostovskii
Alexander F. Khlebnikov
Mikhail S. Novikov*
0
0
0
0-0
0
0
2-6
1
0
0-
0
3
0
9
DCM
acetone
KI
Bu4NF
Bu4NBr
99%
Saint Petersburg State University, Institute of Chemistry,
/9 Universitetskaya nab., St. Petersburg, 199034, Russia
90%
DCM 69%
7
m.novikov@spbu.ru
CO2Me
CO2Me
Ph
DCM
Ph
Bu4NF
I
F
73%
N
N
Received: 18.07.2019
Accepted after revision: 19.08.2019
Published online: 05.09.2019
ing probes. Such reactions, in particular, include nucleo-
philic substitution reactions, which can use commercially
available isotopically labeled alkali metal fluorides and io-
dides as reagents.
DOI: 10.1055/s-0039-1690200; Art ID: ss-2019-c0403-op
Abstract A simple gram-scale method for the preparation of esters
and dialkylamides of 2-(fluoro/iodo)-2H-azirine-2-carboxylic acids via
the halogen exchange (Halex) reaction of 2-bromo-substituted ana-
logues is reported. The method operates with inexpensive and safe
One of the challenges of this chemistry is the introduc-
tion of halogen atoms into labile structures, which are easi-
ly destroyed by standard halogenating agents. It is particu-
larly true for 2H-azirines, the strain energy of the three-
membered ring of which makes them attractive building
blocks for the synthesis of four-, five-, and six-membered
reagents, Bu NF and potassium iodide, providing high product yields.
4
Alternatively, 2-fluoro-2H-azirine-2-carboxylates can be prepared from
2
-iodo- and 2-chloro-analogues. The latter compounds can be obtained
in practically quantitative yield by treating the 2-iodo- and 2-bromo-
H-azirine-2-carboxylic esters with Bu NCl.
8
heterocycles. Examples of the use of 2-bromoazirines for
2
4
the preparation of the azete and oxazoline derivatives, pro-
ceeding with the preservation of the halogen atom in the
Key words azirines, halogen exchange reaction, fluorine, iodine,
nucleophilic substitution
9
product have also been reported. 2-Fluoro- and 2-iodoazir-
ines are much less accessible compounds, and their chemis-
try is practically unexplored. Besides, 2-iodo-2H-azirines
are much more reactive in substitution reactions than
2-bromoazirines, and there are cases when less accessible
Fluorination and iodination are fundamental transfor-
mations in organic chemistry, and fluorinated and iodinat-
ed compounds are of extreme importance as building
1
2
10
blocks in organic synthesis. In particular, organic iodides
are considered among the best substrates for cross-coupling
iodides cannot be replaced by more accessible bromides.
The known methods for the synthesis of these com-
pounds are based on two strategies. In the framework of the
first strategy, the 2-haloazirine ring is formed through the
cyclization of halogenated open-chain precursor, for exam-
ple, through thermal cyclization of a 2-halovinylazide.
Some 2-iodo- and 2-fluorovinylazides can be obtained by
2
reactions, and the rapid development of modern coupling
methods have greatly increased the demand for iodinated
compounds as starting materials. Fluorinated compounds
3
have found a variety of applications especially as pharma-
4
ceuticals. It is well known that the introduction of a fluo-
11
rine atom into a certain position of a bioactive compound
may remarkably reduce its toxicity, or improve its efficien-
cy. Furthermore, both organic fluorides and iodides are
dehydrohalogenation of 1-azido-2,2-dihalo derivatives or
from -oxophosphonium ylides and N-iodosuccinimide in
the presence of azidotrimethylsilane (Scheme 1, reaction
12
used as imaging agents for positron emission tomography
1). The reaction of -carbonyl-substituted enamines with
5
(
PET) scanning. This method requires the use of a fluorine-
PhIF generated in situ from PhIO and Et N·3HF was used
2
3
1
8
6
containing agent enriched with the F nucleus or an io-
for the preparation of 2-fluoroazirines, containing a car-
123 124
131
13
dine-containing agent enriched with the I, I, or I nu-
cleus. These isotopes have half-life times from hundreds of
bonyl substituent at the С2 atom (reaction 4). Another
7
strategy for the synthesis of 2-fluoro- and 2-iodoazirine-2-
carbonyls is based on the metal-catalyzed ring contraction
minutes to several days, thus imposing strict requirements
for the speed and operational simplicity of reactions used
for the introduction of fluorine or iodine atoms into imag-
14,15
of 4-fluoro- and 4-iodoisoxazoles (reactions 2 and 3).
Unfortunately, the methods noted above require either po-
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synthesis
A. V. Agafonova et al.
Paper
tentially explosive compounds or expensive reagents. For
the preparation of starting materials such as 4-fluoro- and
the literature on the use of halide ions as nucleophiles in
such reactions.
4
-iodoisoxazoles, butyllithium is required. All of this calls
We began our study with the search for optimal condi-
tions for the preparation of fluoroazirine 2a via the halogen
exchange reaction of 2-bromoazirine 1a. The latter was
chosen because of its synthetic accessibility and high reac-
tivity in the substitution reactions.1
into question the scalability of such protocols and stimu-
lates the search for new methods for the preparation of
2-fluoro- and 2-iodoazirines.
0,19
O
It was found that 1a reacted with tetrabutylammonium
N3
R1
I
COR2
NIS
Δ
R1
fluoride hydrate (TBAF·H O) in toluene at ambient tempera-
2
COR2
[Ref. 12]
O
(1)
TMSN3
PPh3
ture to afford the target fluoride 2a in good yield (Table 1,
entry 1). Screening of other sources of fluoride ion and sol-
vents (entries 2–6) showed that the highest yield of fluoride
R2
R1
Rh2(Piv)4
I
N
2
a from bromide 1a was achieved using TBAF·H O (1.3
2
Hal
O
or FeSO4·7H2O
equiv) in dichloromethane (DCM) at room temperature (en-
try 2). These conditions were used in further experiments
carried out to evaluate the substrate scope of the reaction.
R1
R2
Hal = I
[Ref. 14]
(
2)
N
Hal = F
[RhCl(C2H4)2]2
(3)
[Ref. 15]
O
R2
R1
Table 1 Optimization of Azirine 2a Synthesis
F
N
R1
R2
CO Me
CO Me
2
2
PhIO, Et3N·3HF
[Ref. 13]
Ph
reagent
Ph
(
4)
NH2
O
Br
F
N
solvent, rt
N
R2 = OAlk, Ar
1a
2a
Entry
Reagent (equiv)
TBAF·H O (1.3)
Solvent
Time (h) Yield of 2a (%)a
This work
COR
COR
Br
COR
Ar
Bu NF
Ar
KI
up to 99%
Ar
1
2
3
4
5
2
toluene
DCM
4
4
76
80
33
45
trace
0
4
(5)
F
I
TBAF·H O (1.3)
N
up to 86%
N
N
2
KF (1.5)
DMSO
DMSO
DMSO
toluene
12
12
48
12
Scheme 1 Synthesis of 2-halo-2H-azirine-2-carbonyl compounds
CsF (1.5)
One powerful method for the introduction of halogen
atoms into a cyclic molecule is the halogen exchange (Hal-
ex) reaction. A transition-metal-free version of this method
is widely used for the preparation of haloarenes and, to a
lesser extent, for the synthesis of haloheteroarenes, such as
fluorotriazoles and fluoropyridines. In this work, a new
method for the synthesis of 2-fluoro- and 2-iodoazirine-2-
carbonyls based on the halogen exchange reaction is devel-
oped (Scheme 1, reaction 5). This method uses easily avail-
able 2-bromo-2H-azirine-2-carboxylic acid derivatives as
starting materials and inexpensive and safe reagents for the
introduction of fluorine and iodine into the azirine ring.
Recently, we have shown that a bromine atom in 2-bro-
mo-2H-azirine-2-carboxylates can be easily substituted
CoF
2
(1.5)
6
FeF (1.5)
2
a
Yield of isolated product.
16
Bromoazirines 1a–n required for the experiments were
prepared from 5-(alkoxy/amino)isoxazoles 5a–n by bromi-
nation using N-bromosuccinimide (NBS) followed by FeSO4-
catalyzed isomerization of bromoisoxazoles 6a–n (Scheme
17
18
14a
2).
Isoxazoles 5 were synthesized from either 5-
14b
chloroisoxazoles 3 or isoxazol-5-ones 4.
The substitution reaction worked well with 2-bromo-3-
aryl-2H-azirine-2-carboxylic esters containing both elec-
tron-withdrawing (Scheme 3, compound 2e) and electron-
donating (Scheme 3, compound 2g) aryl group and afforded
the fluoroazirines in good to excellent yields. The reaction
was also insensitive to steric hindrance introduced by bulky
ortho-substituted aryl groups that could restrict the ap-
proach of the nucleophile (Scheme 3, compounds 2d,f,h).
This simple protocol could also be applied to 2-bromo-3-
aryl-2H-azirine-2-carboxamides, but the yields of the fluo-
1
0
19
with acyloxy-, alkoxy-, alkenyloxy-
and azolyl
substituents under mild conditions. These transformations
take place under the action of the corresponding O- and
N-nucleophiles via a cascade S 2′–S 2′ mechanism, which
imposes high requirements on both the nucleophilicity and
the nucleofugality of the reagent. Thus, aliphatic and aro-
matic carboxylic acids react with methyl 2-bromo-3-phe-
N
N
roazirine-2-carboxamides
were
significantly
lower
nyl-2H-azirine-2-carboxylate (1a) in the presence of Et N to
(Scheme 3, compounds 2k,l). To test the ability to scale-up
the synthesis of fluoroazirines 2, a gram-scale reaction of
3
afford 2-acyloxy derivatives in high yields, while with sub-
stantially more acidic trichloroacetic acid the reaction does
bromoazirine 1a (2.2 g, 8.66 mmol) with TBAF·H O (3.14 g,
2
10
not occur. As far as we know, there is no information in
11.26 mmol) was carried out to give fluoroazirine 2a in 80%
(1.34 g) yield.
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

C
Synthesis
A. V. Agafonova et al.
Paper
Cl
only 27%; after this the reaction stopped. Iodoazirines 7d,e
were obtained in 90% yield only when a 15-fold excess of KI
was used. This may be due to a significantly higher solubili-
ty of KBr, compared with KI in solutions containing ether
compounds, to which can be attributed compounds 1m,n
and 7d,e.
ROH, NaH
R1
O
or
HNR'2
R2
N
R2 = MeO,
i-BuO, BnO,
pyrrolidin-1-yl,
morpholin-4-yl
3
R1
O
20
N
O
5
a−n
CH2N2
R1
O
O
O
N
Et2O, 0 °C
R2
R2
KI
NBS, CHCl3,
rt, 3 h
R1
(2–15 equiv)
R1
4
Br
acetone, rt
I
N
N
30–120 h
O
R2
R2
Br
Br
FeSO ·7 H O
(60 mol %)
4
2
1a,b,e,j,m,n
7a−f
R1
O
Me
O2N
MeCN, rt, 5 h
R1
O
N
N
N
O
N
O
N
OMe
OMe
OMe
1a−n
6a−n
Ph
I
I
I
Scheme 2 Synthesis of bromoazirines 1a–n
7a (90%, from 1a)
7b: (92%, from 1b)
7c: (80%, from 1e)
O
O
R2
Br
Bu NF·H O
(1.3 equiv)
R2
O
4
2
MeO
MeO
O
O
R1
R1
O
O
N
OMe
OMe
I
Ph
Ph
F
N
DCM, rt, 4 h
N
O
I
I
N
1
a−l
2a−l
N
7d: (90% from 1m)
7e: (90% from 1n)
7f: (99%, from 1j)
O
Me
OMe
O
O
N
OMe
Scheme 4 Synthesis of iodoazirines 7 from bromoazirines 1
OMe
Ph
F
N
F
F
N
It was found that fluoroazirine 2a can be alternatively
synthesized from iodoazirine 7a or chloroazirine 8a under
the standard conditions (Scheme 5). The latter compound,
in turn, can be obtained in practically quantitative yield by
treating azirine 1a or 7a with tetrabutylammonium chlo-
ride in DCM. Unfortunately, the reverse transformation of
chloroazirine 8a into bromoazirine 1a using tetrabutylam-
monium bromide (3 equiv) could not be carried out. This
reaction does not occur at all. However, bromoazirine 1a
2
a: 80%
2b: 82%
2c: 81%
Me
O2N
O
N
O
O
OMe
OMe
OMe
F
F
F
Me
N
N
Br
2d: 86%
2e: 65%
2f: 75%
MeO
MeO
O
O
O
N
OMe
O
F
OMe
Ph
was obtained by treating iodoazirine 7a with Bu NBr (2
4
F
F
OMe
N
N
equiv) in DCM at room temperature in practically quantita-
tive yield (Scheme 5).
2
g: 81%
2h: 76%
2i: 83%
Taking into account the results of the calculations and
experimental data obtained for the halogen substitutions in
Ph
O
O
N
O
O
O
N
F
N
Ph
Ph
Ph
2-halo-2H-azirine-2-carboxylates with O- and N-nucleo-
F
F
10,19
N
N
philes,
we believe that the halogen exchange reactions
described above also proceed via a cascade S 2′–S 2′ mech-
2j: 95%
2k: 64%
2l: 40%
N
N
anism.
All the newly synthesized haloazirines 1, 2, and 7 were
characterized based of H, C NMR spectroscopic and
HRMS data.
Scheme 3 Synthesis of fluoroazirines 2 from bromoazirines 1
1
13
It was also shown that the treatment of bromoazirine 1a
with potassium iodide in acetone allowed the replacement
of the bromine with iodine in high yield (Scheme 4, com-
pound 7a). For the complete conversion of bromoazirines
In summary, we have developed a simple synthesis of
esters and dialkylamides of 2-(fluoro/iodo)-2H-azirine-2-
carboxylic acids from much more synthetically accessible
2-bromo-analogues by the halogen exchange (Halex) reac-
tion. The method operates with inexpensive and safe re-
agents, TBAF and potassium iodide, and provides high prod-
uct yields. For the synthesis of the 2-fluoro-substituted
azirine from the corresponding bromides, a small excess of
TBAF is sufficient. A threefold excess of KI in acetone is re-
quired to replace bromine with iodine in most 3-aryl-2-
1a,b,e,j, having no alkoxy groups in the aryl substituent,
three equivalents of potassium iodide were required. When
using tetrabutylammonium iodide (3 equiv) instead of po-
tassium iodide, no reaction was observed. Unexpectedly,
the conversion of alkoxy-substituted bromoazirines 1m,n
into iodoazirines 7d,e under the standard conditions was
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

D
Synthesis
A. V. Agafonova et al.
Paper
CO2Me
Br
CO2Me
Cl
3-(2-Bromophenyl)-5-methoxyisoxazole (5f)
Ph
Ph
Bu4NCl, DCM
Yield: 1.31 g (92%) (from isoxazole 3a); colorless oil.
N
98%
N
1
H NMR (400 MHz, CDCl ):  = 7.72–7.66 (m, 1 H), 7.66–7.60 (m, 1 H),
3
1a
8a
Bu4NF
DCM
Bu4NCl
DCM
7.44–7.36 (m, 1 H), 7.36–7.29 (m, 1 H), 5.67 (s, 1 H), 4.07 (s, 3 H).
13
C NMR (100 MHz, CDCl ):  = 173.6, 164.3, 133.6, 131.1, 130.0,
3
Bu4NBr
DCM
80%
98%
KI
acetone
Bu4NF
DCM
69%
130.9, 127.5, 122.1, 76.7, 58.8.
HRMS (ESI): m/z [M + Na]+ calcd for С10Н881BrNNaO2+: 277.9610;
99%
90%
found: 277.9606.
CO2Me
I
CO2Me
F
Ph
Bu4NF, DCM
3%
Ph
5-Isobutoxy-3-phenylisoxazole (5i)
7
N
N
Yield: 1.20 g (99%) (from isoxazole 3b); colorless solid; mp 76–77 °C.
7a
2a
1
H NMR (400 MHz, CDCl ):  = 7.82–7.74 (m, 2 H), 7.48–7.42 (m, 3 H),
3
Scheme 5 Halex reactions of methyl 2-halo-3-phenylazirine-2-carbox-
ylates
5
6
.52 (s, 1 H), 4.03 (d, J = 6.6 Hz, 2 H), 2.26–2.10 (m, 1 H), 1.07 (d, J =
.7 Hz, 6 H).
13
C NMR (100 MHz, CDCl ):  = 174.0, 164.1, 129.9, 129.7, 128.8,
3
1
26.4, 78.4, 75.6, 28.1, 18.8.
bromo-2H-azirine-2-carboxylates, with the exception of
those that contain alkoxy groups in the aryl substituent. In
the latter case, a 15-fold excess of the reagent enables high
yields of the iodoazirines to be achieved. Alternatively,
HRMS (ESI): m/z [M + Na] calcd for С13Н15NNaO2+: 240.0995; found:
+
240.0998.
Preparation of 3-(3,4-Dimethoxyphenyl)-5-methoxyisoxazole
5m)
2-fluoro-2H-azirine-2-carboxylates can be prepared from
(
2-iodo- and 2-chloro-analogues. The latter compounds, in
A solution of diazomethane (31.5 mmol) in Et O, prepared from N-ni-
troso-N-methylurea and KOH, was added dropwise at 0 °C to a stirred
suspension
2
turn, can be obtained in practically quantitative yield by
treating the 2-iodo- and 2-bromoazirines with Bu NCl.
4
of
3-(3,4-dimethoxyphenyl)-5-methoxyisoxazolone
21b
(
4a) (10.5 mmol) in anhydrous Et O (50 mL). The resulting mixture
2
was stirred at ambient temperature for 2 h and then concentrated un-
der reduced pressure. The residue was purified by column chroma-
tography (silica gel; hexane/EtOAc, 3:1), followed by crystallization
Melting points were determined with a SMP30 melting point appara-
tus. H (400 MHz) and C (100 MHz) NMR spectra were recorded
1
13
with a Bruker AVANCE 400 spectrometer in CDCl . Chemical shifts ()
from Et O–hexane.
3
2
are reported in ppm downfield from tetramethylsilane. Electrospray
ionization (ESI), positive mode, mass spectra were measured with a
Bruker MaXis mass spectrometer using acetonitrile for dilution of
samples. Thin-layer chromatography (TLC) was conducted on alumi-
num sheets precoated with SiO2 ALUGRAM SIL G/UV254. Column
chromatography was performed on Macherey-Nagel silica gel 60 M
Yield: 1.88 g (76%); colorless solid; mp 69–71 °C.
1
H NMR (400 MHz, CDCl ):  = 7.42–7.34 (m, 1 H), 7.27–7.22 (m, 1 H),
3
6
3
.96–6.88 (m, 1 H), 5.50 (s, 1 H), 4.05 (s, 3 H), 3.95 (s, 3 H), 3.93 (s,
H).
13C NMR (100 MHz, CDCl
119.7, 111.0, 108.9, 75.1, 58.8, 56.0, 55.9.
):  = 174.3, 163.9, 150.6, 149.2, 122.3,
3
(
0.04–0.063 mm). All solvents were distilled and dried prior to use.
Toluene was distilled and stored over sodium metal. Dichloromethane
was washed with concentrated H SO and water, then distilled from
HRMS (ESI): m/z [M + Na]+ calcd for C12H13NNaO4+: 258.0737; found:
258.0739.
2
4
P O and stored over anhydrous K CO . Acetone was distilled from an-
2
5
2
3
hydrous CaCO3.
Bromoisoxazoles 6f and 6h; General Procedure
Bromoazirines 1a,b,e,g,k,l,n14 are known compounds and have full
characterization data. They were synthesized according to the report-
ed procedures that are illustrated in Scheme 2.
A solution of the isoxazole 5f or 5h (2 mmol) and N-bromosuccinim-
ide (392 mg, 2.2 mmol) in CHCl (25 mL) was stirred at ambient tem-
3
perature for 3 h. The reaction mixture was diluted with 10% Na S O
2
2
3
(
60 mL), and extracted with CH Cl (3 × 20 mL). The combined organic
2 2
Synthesis of Bromoazirines 1c,f,h–j,m
Isoxazoles 5f and 5i; General Procedure
extracts were dried over anhydrous Na SO , the solvent was removed
under reduced pressure, and the product was purified by silica gel
flash chromatography (hexane/EtOAc, 5:1), followed by crystalliza-
2 4
tion from Et O–hexane.
To a stirred suspension of NaH (60% in oil, 440 mg, 11 mmol, pre-
washed with hexane) in anhydrous THF (20 mL), alcohol (15 mmol)
was added at ambient temperature and the reaction mixture was
stirred for 0.5 h. 5-Chloro-3-arylisoxazole 3a (R = 2-BrC H ) or 3b
2
4-Bromo-3-(2-bromophenyl)-5-methoxyisoxazole (6f)
6
4
Yield: 466 mg (70%) (from isoxazole 5f); colorless solid; mp 108–
109 °C.
21a
(R = Ph) (5.6 mmol) was added and the mixture was heated at re-
flux for 1 h. The mixture was cooled to ambient temperature, the re-
action was quenched with water (20 mL) and the mixture was ex-
1
H NMR (400 MHz, CDCl ):  = 7.75–7.69 (m, 1 H), 7.48–7.34 (m, 3 H),
.26 (s, 3 H).
3
4
tracted with CH Cl2 (3 × 20 mL). The combined organic layers were
2
13
C NMR (100 MHz, CDCl ):  = 169.0, 164.5, 133.1, 131.5 (2C), 129.7,
dried over Na SO and concentrated under reduced pressure to give
3
2
4
1
27.3, 123.1, 68.9, 58.6.
pure compound 5f or 5i.
HRMS (ESI): m/z [M + Na] calcd for С10Н779Br81BrNNaO2+: 355.8716;
+
found: 355.8718.
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

E
Synthesis
A. V. Agafonova et al.
Paper
4-Bromo-3-(2,4-dimethoxyphenyl)-5-methoxyisoxazole (6h)
HRMS (ESI): m/z [M + Na]+ calcd for С12Н1279BrNNaO4+: 335.9842;
found: 335.9845.
Yield: 440 mg (70%) (from isoxazole 5h); colorless solid; mp 71–73 °C.
1
H NMR (400 MHz, CDCl ):  = 7.37–7.31 (m, 1 H), 6.62–6.55 (m, 2 H),
3
Bromoazirines 1i,j,m; General Procedure
4.21 (s, 3 H), 3.87 (s, 3 H), 3.85 (s, 3 H).
1
3
A solution of isoxazole 5i,j,m (2 mmol) and N-bromosuccinimide (392
C NMR (100 MHz, CDCl ):  = 168.6, 162.9, 162.7, 158.7, 131.7,
3
mg, 2.2 mmol) in CHCl (25 mL) was stirred at ambient temperature
3
1
10.0, 104.7, 98.9, 69.4, 58.3, 55.6, 55.4.
for 3 h. The reaction mixture was diluted with 10% Na S O (60 mL),
2
2
3
HRMS (ESI): m/z [M + H] calcd for С 2Н1379BrNO4+: 314.0022; found:
3
+
1
and extracted with CH Cl (3 × 20 mL). The combined organic extracts
2 2
14.0027.
were dried over anhydrous Na SO . The solvent was removed under
2
4
reduced pressure, and the obtained bromoisoxazole 6i,j,m was used
in the next step without further purification. A suspension of isoxaz-
Bromoazirines 1c,d,f,h; General Procedure
A suspension of isoxazole 6c,d,f,h (2 mmol) and FeSO ·7H O (239 mg,
ole 6i,j,m and FeSO ·7H O (239 mg, 1.2 mmol, 60 mol%) in MeCN (15
4 2
4
2
1
.2 mmol, 60 mol%) in MeCN (15 mL) was stirred at ambient tempera-
mL) was stirred at ambient temperature for 5 h, then the solvent was
removed under reduced pressure. In order to remove iron com-
pounds, the product was purified by silica gel flash chromatography
ture for 5 h, then the solvent was removed under reduced pressure. In
order to remove iron compounds, the product was purified by silica
gel flash chromatography (hexane/EtOAc, 10:1), followed by crystalli-
(hexane/EtOAc, 10:1), followed by crystallization from Et O–hexane.
2
zation from Et O–hexane.
2
Isobutyl 2-Bromo-3-phenyl-2H-azirine-2-carboxylate (1i)
Methyl 2-Bromo-3-[4-(tert-butyl)phenyl]-2H-azirine-2-carboxyl-
Yield: 539 mg (91%) (from isoxazole 5i); colorless oil.
ate (1c)
1
H NMR (400 MHz, CDCl ):  = 8.02–7.93 (m, 2 H), 7.79–7.71 (m, 1 H),
.69–7.60 (m, 2 H), 4.08–3.94 (m, 2 H), 2.06–1.88 (m, 1 H), 0.95–0.86
3
Yield: 608 mg (98%) (from isoxazole 6c22); colorless solid; mp 85–
7
86 °C.
(m, 6 H).
1
H NMR (400 MHz, CDCl ):  = 7.94–7.88 (m, 2 H), 7.70–7.64 (m, 2 H),
13
3
C NMR (100 MHz, CDCl ):  = 166.7, 164.6, 135.0, 130.8, 129.6,
3
19.8, 73.2, 44.2, 27.6, 18.8.
3.82 (s, 3 H), 1.40 (s, 9 H).
1
13
C NMR (100 MHz, CDCl ):  = 167.4, 163.8, 159.5, 130.9, 126.8,
HRMS (ESI): m/z [M + Na]+ calcd for С13Н1479BrNNaO +: 318.0100;
found: 318.0093.
3
2
116.7, 54.1, 43.9, 35.6, 31.0.
HRMS (ESI): m/z [M + Na]+ calcd for С14Н1679BrNNaO2+: 332.0257;
found: 332.0259.
Benzyl 2-Bromo-3-phenyl-2H-azirine-2-carboxylate (1j)
Yield: 594 mg (90%) (from isoxazole 5j14a); colorless solid; mp 60–
61 °C.
Methyl 2-Bromo-3-(2,4-dimethylphenyl)-2H-azirine-2-carboxyl-
ate (1d)
1
H NMR (400 MHz, CDCl ):  = 7.98–7.92 (m, 2 H), 7.78–7.72 (m, 1 H),
.67–7.61 (m, 2 H), 7.39–7.30 (m, 5 H), 5.28 (s, 2 H).
3
Yield: 485 mg (86%) (from isoxazole 6d23); colorless solid; mp 60–
7
61 °C.
13
C NMR (100 MHz, CDCl ):  = 166.6, 164.4, 135.1, 134.9, 130.9,
3
1
H NMR (400 MHz, CDCl ):  = 7.75–7.68 (m, 1 H), 7.28–7.22 (m, 2 H),
3
129.6, 128.5, 128.4, 127.9, 119.6, 68.7, 43.9.
HRMS (ESI): m/z [M + Na]+ calcd for С16Н1279BrNNaO2+: 351.9944;
found: 351.9949.
3.83 (s, 3 H), 2.67 (s, 3 H), 2.46 (s, 3 H).
13
C NMR (100 MHz, CDCl ):  = 167.6, 162.9, 146.3, 142.6, 132.5,
3
132.3, 127.6, 115.8, 54.1, 43.5, 21.9, 19.7.
HRMS (ESI): m/z [M + Na]+ calcd for С12Н1279BrNNaO2+: 303.9944;
Methyl 2-Bromo-3-(3,4-dimethoxyphenyl)-2H-azirine-2-carbox-
found: 303.9948.
ylate (1m)
Yield: 597 mg (95%) (from isoxazole 5m); colorless solid; mp 102–
103 °C.
Methyl 2-Bromo-3-(2-bromophenyl)-2H-azirine-2-carboxylate
(
1f)
1
H NMR (400 MHz, CDCl ):  = 7.61–7.49 (m, 1 H), 7.49–7.39 (m, 1 H),
.13–7.03 (m, 1 H), 4.01 (s, 3 H), 3.98 (s, 3 H), 3.82 (s, 3 H).
3
Yield: 619 mg (93%) (from isoxazole 6f); colorless solid; mp 83–84 °C.
1
7
13
H NMR (400 MHz, CDCl ):  = 8.07–8.00 (m, 1 H), 7.86–7.79 (m, 1 H),
.65–7.55 (m, 2 H), 3.84 (s, 3 H).
3
C NMR (100 MHz, CDCl ):  = 167.4, 163.3, 154.9, 150.0, 126.3,
3
11.9, 111.7, 111.4, 56.3, 56.2, 54.1, 44.6.
7
1
1
3
C NMR (100 MHz, CDCl ):  = 167.0, 164.9, 136.0, 134.4, 133.6,
HRMS (ESI): m/z [M + Na]+ calcd for С12Н1279BrNNaO +: 335.9842;
found: 335.9835.
3
4
1
28.2, 126.3, 120.8, 54.2, 45.0.
HRMS (ESI): m/z [M + Na] calcd for С10Н779Br81BrNNaO2+: 355.8716;
+
found: 355.8734.
2-Fluoro-2H-azirines 2a–l; General Procedure
A solution of 2-bromo-2H-azirines 1a–l (1 mmol) and TBAF·H O (363
2
Methyl 2-Bromo-3-(2,4-dimethoxyphenyl)-2H-azirine-2-carbox-
ylate (1h)
mg, 1.3 mmol) in DCM (5 mL) was stirred at ambient temperature for
4 h. The solvent was removed under reduced pressure and the residue
was purified by column chromatography on silica gel (hexane–EtOAc
mixture) to give fluoroazirines 2a–l.
Yield: 616 mg (98%) (from isoxazole 6h); colorless solid; mp 85–86 °C.
1
H NMR (400 MHz, CDCl ):  = 7.72–7.66 (m, 1 H), 6.71–6.65 (m, 1 H),
3
6
.59–6.56 (m, 1 H), 3.99 (s, 3 H), 3.93 (s, 3 H), 3.80 (s, 3 H).
Methyl 2-Fluoro-3-phenyl-2H-azirine-2-carboxylate (2a)13
13
C NMR (100 MHz, CDCl ):  = 167.9, 167.2, 162.8, 159.6, 134.7,
3
Yield: 155 mg (80%) (from azirine 1a); colorless solid; mp 58–59 °C.
106.4, 101.4, 98.7, 56.1, 55.9, 53.9, 43.7.
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

F
Synthesis
A. V. Agafonova et al.
Paper
1
HRMS (ESI): m/z [M + Na]+ calcd for C10H779BrFNNaO2+: 293.9536;
H NMR (400 MHz, CDCl ):  = 8.02–7.94 (m, 2 H), 7.77–7.71 (m, 1 H),
3
7.68–7.61 (m, 2 H), 3.88 (s, 3 H).
found: 293.9529.
13
C NMR (100 MHz, CDCl ):  = 167.0 (d, J = 43.4 Hz), 166.0 (d, J =
3
11.5 Hz), 135.0, 130.7, 129.6, 120.2, 78.1 (d, J = 264.6 Hz), 53.3.
Methyl 2-Fluoro-3-(4-methoxyphenyl)-2H-azirine-2-carboxylate
HRMS (ESI): m/z [M + Na] calcd for C H FNNaO2+: 216.0431; found:
+
(2g)
10
8
Yield: 181 mg (81%) (from azirine 1g); colorless solid; mp 53–54 °C.
2
16.0428.
1
H NMR (400 MHz, CDCl ):  = 7.95–7.87 (m, 2 H), 7.15–7.08 (m, 2 H),
3
Methyl 2-Fluoro-3-(p-tolyl)-2H-azirine-2-carboxylate (2b)13
3.94 (s, 3 H), 3.86 (s, 3 H).
13
Yield: 170 mg (82%) (from azirine 1b); colorless solid; mp 44–45 °C.
C NMR (100 MHz, CDCl ):  = 167.4 (d, J = 44.7 Hz), 165.0, 164.3 (d,
3
1
J = 10.9 Hz), 133.0, 115.2, 112.3, 78.2 (d, J = 262.7 Hz), 55.7, 53.2.
H NMR (400 MHz, CDCl ):  = 7.89–7.83 (m, 2 H), 7.47–7.40 (m, 2 H),
.86 (s, 3 H), 2.50 (s, 3 H).
3
HRMS (ESI): m/z [M + Na] calcd for C11H10FNNaO3+: 246.0537; found:
+
3
13
246.0539.
C NMR (100 MHz, CDCl ):  = 167.2 (d, J = 43.9 Hz), 165.4 (d,
3
J = 11.5 Hz), 146.4, 130.8, 130.3, 117.3, 78.1 (d, J = 263.0 Hz), 53.3,
2.0.
HRMS (ESI): m/z [M + Na] calcd for C11H10FNNaO2+: 230.0588; found:
30.0579.
2
Methyl 3-(2,4-Dimethoxyphenyl)-2-fluoro-2H-azirine-2-carboxyl-
ate (2h)
+
Yield: 192 mg (76%) (from azirine 1h); colorless solid; mp 120–
2
1
21 °C.
1H NMR (400 MHz, CDCl
7.09–7.03 (m, 1 H), 4.00 (s, 3 H), 3.98 (s, 3 H), 3.87 (s, 3 H).
Methyl 3-[4-(tert-Butyl)phenyl]-2-fluoro-2H-azirine-2-carboxyl-
ate (2c)
3
):  = 7.57–7.51 (m, 1 H), 7.49–7.43 (m, 1 H),
13
Yield: 202 mg (81%) (from azirine 1c); colorless oil.
C NMR (100 MHz, CDCl ):  = 167.3 (d, J = 44.5 Hz), 164.4 (d,
3
1
J = 11.3 Hz), 154.8, 149.9, 126.1, 112.3, 111.8, 111.3, 78.4 (d,
J = 263.0 Hz), 56.3, 56.2, 53.3.
H NMR (400 MHz, CDCl ):  = 7.95–7.87 (m, 2 H), 7.69–7.64 (m, 2 H),
.87 (s, 3 H), 1.40 (s, 9 H).
3
3
+
+: 276.0643; found:
13
HRMS (ESI): m/z [M + Na] calcd for C12
H
12FNNaO
4
C NMR (100 MHz, CDCl ):  = 167.3 (d, J = 43.9 Hz), 165.4 (d,
3
276.0651.
J = 10.9 Hz), 159.4, 130.7, 126.7, 117.4, 78.1 (d, J = 262.9 Hz), 53.9,
5.6, 31.0.
HRMS (ESI): m/z [M + Na] calcd for C14H16FNNaO2+: 272.1057; found:
72.1057.
3
+
Isobutyl 2-Fluoro-3-phenyl-2H-azirine-2-carboxylate (2i)
Yield: 195 mg (83%) (from azirine 1i); colorless oil.
2
1
H NMR (400 MHz, CDCl ):  = 8.01–7.94 (m, 2 H), 7.77–7.70 (m, 1 H),
3
Methyl 3-(2,4-Dimethylphenyl)-2-fluoro-2H-azirine-2-carboxyl-
ate (2d)
7.68–7.62 (m, 2 H), 4.11–4.01 (m, 2 H), 2.06–1.93 (m, 1 H), 0.95–0.90
(m, 6 H).
13
Yield: 190 mg (86%) (from azirine 1d); colorless solid; mp 64–65 °C.
C NMR (100 MHz, CDCl ):  = 166.6 (d, J = 43.2 Hz), 166.2 (d,
3
1
J = 11.5 Hz), 134.9, 130.7, 129.6, 120.4, 78.1 (d, J = 264.5 Hz), 72.4,
7.6, 18.8.
HRMS (ESI): m/z [M + Na] calcd for C13
58.0907.
H NMR (400 MHz, CDCl ):  = 7.76–7.69 (m, 1 H), 7.27–7.20 (m, 2 H),
.87 (s, 3 H), 2.65 (s, 3 H), 2.45 (s, 3 H).
3
2
3
+
H14FNNaO
+: 258.0901; found:
2
13
C NMR (100 MHz, CDCl ):  = 167.5 (d, J = 44.4 Hz), 164.3 (d,
3
2
J = 11.0 Hz), 146.1, 142.1, 132.21, 132.15, 127.5, 116.2, 77.2 (d,
J = 261.9 Hz), 53.2, 21.9, 19.6.
HRMS (ESI): m/z [M + Na]+ calcd for C12H12FNNaO2+: 244.2168; found:
Benzyl 2-Fluoro-3-phenyl-2H-azirine-2-carboxylate (2j)
Yield: 256 mg (95%) (from azirine 1j); colorless solid; mp 52–53 °C.
244.2169.
1
H NMR (400 MHz, CDCl ):  = 7.99–7.93 (m, 2 H), 7.77–7.71 (m, 1 H),
3
Methyl 2-Fluoro-3-(4-nitrophenyl)-2H-azirine-2-carboxylate (2e)
7.67–7.61 (m, 2 H), 7.41–7.35 (m, 5 H), 5.32 (s, 2 H).
13
Yield: 155 mg (65%) (from azirine 1e); colorless solid; mp 115–116 °C.
C NMR (100 MHz, CDCl ):  = 166.6 (d, J = 43.2 Hz), 166.1 (d,
3
1
J = 11.2 Hz), 135.0, 134.8, 130.8, 129.6, 128.7, 128.6, 128.3, 120.9, 78.2
d, J = 265.1 Hz), 68.1.
HRMS (ESI): m/z [M + Na] calcd for C16
92.0733.
H NMR (400 MHz, CDCl ):  = 8.53–8.48 (m, 2 H), 8.22–8.16 (m, 2 H),
.91 (s, 3 H).
3
(
3
+
H12FNNaO
+: 292.0744; found:
2
13
C NMR (100 MHz, CDCl ):  = 166.3 (d, J = 10.8 Hz), 166.1 (d,
3
2
J = 43.3 Hz), 151.4, 131.6, 125.8, 124.7, 77.8 (d, J = 268.8 Hz), 53.6.
HRMS (ESI): m/z [M + Na] calcd for C H FN NaO4+: 261.0282; found:
2
+
10
7
2
(2-Fluoro-3-phenyl-2H-azirin-2-yl)(pyrrolidin-1-yl)methanone
61.0289.
(2k)
Yield: 149 mg (64%) (from azirine 1k); colorless solid; mp 67–68 °C.
1H NMR (400 MHz, CDCl
):  = 8.05–7.98 (m, 2 H), 7.72–7.66 (m, 1 H),
.63–7.58 (m, 2 H), 4.11–4.01 (m, 1 H), 3.94–3.84 (m, 1 H), 3.63–3.56
Methyl 3-(2-Bromophenyl)-2-fluoro-2H-azirine-2-carboxylate
2f)
(
3
7
Yield: 204 mg (75%) (from azirine 1f); colorless solid; mp 45–46 °C.
(m, 2 H), 2.12–1.87 (m, 4 H).
1
H NMR (400 MHz, CDCl ):  = 8.13–8.06 (m, 1 H), 7.84–7.77 (m, 1 H),
3
13
C NMR (100 MHz, CDCl ):  = 169.7 (d, J = 12.9 Hz), 163.3 (d,
7.63–7.55 (m, 2 H), 3.89 (s, 3 H).
3
J = 39.3 Hz), 134.5, 130.7, 129.3, 121.3, 82.3 (d, J = 274.9 Hz), 47.1 (d,
J = 9.2 Hz), 47.0, 26.3 (d, J = 3.2 Hz), 23.7.
13
C NMR (100 MHz, CDCl ):  = 166.74 (d, J = 12.2 Hz), 166.73 (d,
3
J = 43.2 Hz), 136.0, 134.1, 132.8, 128.2, 126.5, 121.3, 78.2 (d,
J = 266.5 Hz), 53.4.
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

G
Synthesis
A. V. Agafonova et al.
Paper
HRMS (ESI): m/z [M + H]+ calcd for C13H14FN O : 233.1085; found:
+
Methyl 3-(3,4-Dimethoxyphenyl)-2-iodo-2H-azirine-2-carboxyl-
2
233.1086.
ate (7d)
Yield: 325 mg (90%) [from azirine 1m, KI (2.5 g, 15 mmol), 120 h];
(2-Fluoro-3-phenyl-2H-azirin-2-yl)(morpholino)methanone (2l)
colorless solid; mp 93–94 °C.
1
Yield: 99 mg (40%) (from azirine 1l); colorless solid; mp 53–54 °C.
H NMR (400 MHz, CDCl ):  = 7.58–7.49 (m, 1 H), 7.46–7.40 (m, 1 H),
3
1
7.12–7.03 (m, 1 H), 4.01 (s, 3 H), 3.99 (s, 3 H), 3.81 (s, 3 H).
H NMR (400 MHz, CDCl ):  = 8.11–8.02 (m, 2 H), 7.77–7.69 (m, 1 H),
.68–7.60 (m, 2 H), 4.14–4.01 (m, 2 H), 3.90–3.65 (m, 6 H).
3
13
7
C NMR (100 MHz, CDCl ):  = 166.6, 164.2, 154.9, 150.1, 126.2,
3
1
3
112.1, 111.8, 111.4, 56.3, 56.2, 54.3, 14.9.
C NMR (100 MHz, CDCl ):  = 171.0 (d, J = 13.0 Hz), 163.1 (d,
3
HRMS (ESI): m/z [M + Na] calcd for C12H12INNaO4+: 383.9703; found:
+
J = 39.3 Hz), 134.9, 130.8, 129.5, 121.1, 82.2 (d, J = 274.2 Hz), 67.1,
6.4, 46.5, 42.9.
6
383.9686.
HRMS (ESI): m/z [M + Na]+ calcd for C13H13FN NaO2+: 271.0853;
2
found: 271.0855.
Methyl 3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-2-iodo-2H-azir-
ine-2-carboxylate (7e)
Gram-Scale Synthesis of Fluoroazirine 2a from Bromoazirine 1a
Yield: 323 mg (90%) [from azirine 1n, KI (2.5 g, 15 mmol), 120 h]; col-
orless solid; mp 109–110 °C (dec.).
A solution of azirine 1a (2.2 g, 8.66 mmol) and Bu NF·H O (3.14 g,
4
2
1
11.26 mmol) in DCM (40 mL) was stirred at ambient temperature for
h. The solvent was removed under reduced pressure and the residue
H NMR (400 MHz, CDCl ):  = 7.54–7.42 (m, 2 H), 7.15–7.05 (m, 1 H),
3
4
4.42–4.33 (m, 4 H), 3.80 (s, 3 H).
was purified by column chromatography on silica gel (hexane/EtOAc
mixture) to give methyl 2-fluoro-3-phenyl-2H-azirine-2-carboxylate
13
C NMR (100 MHz, CDCl ):  = 166.5, 164.1, 149.7, 144.4, 125.1,
3
119.9, 118.8, 112.7, 64.8, 64.0, 54.3, 14.6.
2a (1.34 g, 80%).
HRMS (ESI): m/z [M + Na] calcd for C12H10INNaO4+: 381.9547; found:
+
381.9547.
2-Iodo-2H-azirines 7a–f; General Procedure
A solution of 2-bromo-2H-azirines 1a,b,e,j,m,n (1 mmol) and KI (332
mg, 2 mmol) in acetone (5 mL) was stirred at ambient temperature for
the time indicated below. The solvent was removed under reduced
pressure and the residue was purified by column chromatography on
Benzyl 2-Iodo-3-phenyl-2H-azirine-2-carboxylate (7f)
Yield: 373 mg (99%) (from azirine 1j, 48 h); colorless oil.
1
H NMR (400 MHz, CDCl ):  = 8.00–7.90 (m, 2 H), 7.80–7.72 (m, 1 H),
3
silica gel (hexane/EtOAc mixture) and crystallization from Et O–hex-
7.70–7.61 (m, 2 H), 7.41–7.29 (m, 5 H), 5.25 (s, 2 H).
2
ane to give iodoazirines 7a–f.
13
C NMR (100 MHz, CDCl ):  = 165.8, 165.3, 135.0 (2C), 130.9, 129.7,
3
1
28.5, 128.4, 127.9, 120.1, 69.0, 13.8.
Methyl 2-Iodo-3-phenyl-2H-azirine-2-carboxylate (7a)14a
HRMS (ESI): m/z [M + Na] calcd for C16H12INNaO2+: 399.9805; found:
+
Yield: 271 mg (90%) (from azirine 1a, 30 h); colorless solid; mp 87–
399.9800.
14a
8
8 °C (lit. 87–88 °C).
Synthesis of Bromoazirine 1a from 2-Iodoazirine 7a
Methyl 2-Iodo-3-(p-tolyl)-2H-azirine-2-carboxylate (7b)
A solution of iodoazirine 7a (301 mg, 1 mmol) and Bu NBr (645 mg,
4
Yield: 290 mg (92%) (from azirine 1b, 48 h); colorless solid; mp 81–
2.0 mmol) in DCM (5 mL) was stirred at ambient temperature for 15
82 °C.
h. The solvent was removed under reduced pressure and the residue
was purified by column chromatography on silica gel (hexane/EtOAc,
4:1) to give bromoazirine 1a (252 mg, 99%).
1
H NMR (400 MHz, CDCl ):  = 7.89–7.81 (m, 2 H), 7.50–7.43 (m, 2 H),
3
3.80 (s, 3 H), 2.51 (s, 3 H).
13
C NMR (100 MHz, CDCl ):  = 166.5, 164.8, 146.5, 130.9, 130.5,
3
Synthesis of Chloroazirine 8a from Bromoazirine 1a
117.2, 54.3, 22.1, 14.0.
HRMS (ESI): m/z [M + Na] calcd for C11H10INNaO2+: 337.9648; found:
+
A solution of bromoazirine 1a (254 mg, 1 mmol) and Bu
NCl (417 mg,
4
1.5 mmol) in DCM (5 mL) was stirred at ambient temperature for 12
337.9643.
h. The solvent was removed under reduced pressure and the residue
was purified by column chromatography on silica gel (hexane/EtOAc,
Methyl 2-Iodo-3-(4-nitrophenyl)-2H-azirine-2-carboxylate (7c)
Yield: 277 mg (80%) (from azirine 1e, 40 h); colorless solid; mp 131–
4:1) to give chloroazirine 8a (205 mg, 98%).
1
33 °C.
Synthesis of Chloroazirine 8a from 2-Iodoazirine 7a
1
H NMR (400 MHz, CDCl ):  = 8.58–8.42 (m, 2 H), 8.26–8.10 (m, 2 H),
3
A solution of iodoazirine 7a (301 mg, 1 mmol) and Bu NCl (249 mg,
4
3.84 (s, 3 H).
1.5 mmol) in DCM (5 mL) was stirred at ambient temperature for 6 h.
13
C NMR (100 MHz, CDCl ):  = 165.7, 165.3, 151.3, 131.6, 125.8,
The solvent was removed under reduced pressure and the residue was
purified by column chromatography on silica gel (hexane/EtOAc, 4:1)
to give chloroazirine 8a (205 mg, 98%).
3
124.8, 54.6, 12.2.
HRMS (ESI): m/z [M + Na] calcd for C H IN NaO +: 368.9343; found:
+
10
7
2
4
368.9348.
Funding Information
We gratefully acknowledge the financial support of the Russian Sci-
ence Foundation (Grant No. 17-13-01078).
R
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S
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(17-13-0
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8)
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2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

H
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A. V. Agafonova et al.
Paper
Acknowledgment
(9) Smetanin, I. A.; Novikov, M. S.; Rostovskii, N. V.; Khlebnikov, A.
F.; Starova, G. L.; Yufit, D. S. Tetrahedron 2015, 71, 4616.
10) Rostovskii, N. V.; Smetanin, I. A.; Agafonova, A. V.; Sakharov, P.
A.; Ruvinskaya, J. O.; Khlebnikov, A. F.; Novikov, M. S. Org.
Biomol. Chem. 2018, 16, 3248.
11) (a) Alonso-Cruz, C. R.; Kennedy, A. R.; Rodríguez, M. S.; Suárez,
E. J. Org. Chem. 2008, 73, 4116. (b) Alonso-Cruz, C. R.; Kennedy,
A. R.; Rodríguez, M. S.; Suárez, E. Tetrahedron Lett. 2007, 48,
This research used resources of the ‘Magnetic Resonance Research
Centre’, the ‘Chemical Analysis and Materials Research Centre’, and
the ‘Chemistry Educational Centre’ of the Research Park of St. Peters-
burg State University.
(
(
Supporting Information
7207.
(
(
(
12) Pinho e Melo, T. M. V. D.; Lopes, C. S. J.; Cardoso, A. L.; Rocha
Supporting information for this article is available online at
Gonsalves, A. M. d'A. Tetrahedron 2001, 57, 6203.
13) Zhang, Y.; Zhao, X.; Zhuang, C.; Wang, S.; Zhang-Negrerie, D.;
Du, Y. Adv. Synth. Catal. 2018, 360, 2107.
14) (a) Rostovskii, N. V.; Agafonova, A. V.; Smetanin, I. A.; Novikov,
M. S.; Ruvinskaya, J. O.; Starova, G. L. Khlebnikov A. F. Synthesis
https://doi.org/10.1055/s-0039-1690200.
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©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H