Annulation of five-membered cyclic enols with 3-aryl-2H-azirines: Catalytic versus non-catalytic cycloaddition

Article abstract of DOI:10.1016/j.tet.2017.06.037

A copper(I)-NHC-catalyzed annulation of 5-membered cyclic enols of furan, thiophene and indene family with 3-aryl-2H-azirines has been developed to provide a rapid access to furo[3,4-b]pyrrole, thieno[3,4-b]pyrrole, indeno[1,2-b]pyrrole derivatives. The reaction proceeds via a copper-initiated N–C² azirine bond cleavage with the retention of the C[dbnd]N double bond in the annulation product. The reaction of tetronic acids with 3-aryl-2H-azirines can also proceed under catalyst-free conditions, through a double addition of the enol to the azirine, but this route provides poor yields of the annulation products. This is the first example of the N–C² bond cleavage in 2-unsubstituted 2H-azirines in the absence of a transition metal catalyst.

Full text of DOI:10.1016/j.tet.2017.06.037

Accepted Manuscript
Annulation of five-membered cyclic enols with 3-aryl-2H-azirines: Catalytic versus
non-catalytic cycloaddition
Pavel A. Sakharov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Mikhail S. Novikov
PII:
S0040-4020(17)30670-1
10.1016/j.tet.2017.06.037
TET 28802
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 16 April 2017
Revised Date: 8 June 2017
Accepted Date: 19 June 2017
Please cite this article as: Sakharov PA, Rostovskii NV, Khlebnikov AF, Novikov MS, Annulation of five-
membered cyclic enols with 3-aryl-2H-azirines: Catalytic versus non-catalytic cycloaddition, Tetrahedron
(2017), doi: 10.1016/j.tet.2017.06.037.
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Annulation of five-membered cyclic enols
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Pavel A. Sakharov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Mikhail S. Novikov
St. Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg, 199034 Russia

1
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Tetrahedron
journal homepage: www.elsevier.com
Annulation of five-membered cyclic enols with 3-aryl-2H-azirines: catalytic versus
non-catalytic cycloaddition
Pavel A. Sakharov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Mikhail S. Novikov
St. Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg, 199034 Russia
Tel.: +7 812-428-9344; fax: +7 812-428-6939; e-mail address: E-mail: m.novikov@spbu.ru (M.S. Novikov).
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A copper(I)-NHC-catalyzed annulation of 5-membered cyclic enols of furan, thiophene and
indene family with 3-aryl-2H-azirines has been developed to provide a rapid access to furo[3,4-
b]pyrrole, thieno[3,4-b]pyrrole, indeno[1,2-b]pyrrole derivatives. The reaction proceeds via a
copper-initiated N−C2 azirine bond cleavage with the retention of the C=N double bond in the
annulation product. The reaction of tetronic acids with 3-aryl-2H-azirines can also proceed
under catalyst-free conditions, through a double addition of the enol to the azirine, but this route
provides poor yields of the annulation products. This is the first example of the N−C2 bond
cleavage in 2-unsubstituted 2H-azirines in the absence of a transition metal catalyst.
Available online
Keywords:
Azirines
Copper catalysis
Enols
2017 Elsevier Ltd. All rights reserved
.
Synthetic methods
1. Introduction
catalyst-free conditions to give 1,2-fused imidazole
derivatives.11 Several annulation reactions using N−С2 bond
cleavage of the azirine under metal catalysis are known.
Candito and Lautens reported the use of 3-aryl-2H-azirines as
C−C=N building blocks in the synthesis of indoles from
iodoarenes under Pd(II)-catalysis.12 3-Aryl-2H-azirines can
also produce the pyrrolo- and furo[3,4-b]pyrrole skeleton when
reacted with 3-diazopyrrolidine-2,4-diones and 3-diazofuran-
2,4-dione under Cu(acac)2 catalysis.13 It was recently reported
that the synthesis of 2,3-disubstituted indoles by annulation of
arynes with 2,3-disubstituted 2H-azirines proceeds via the
cleavage of the both carbon-nitrogen bonds.14
2H-Azirines serve as versatile building blocks for the
synthesis of 4−7-membered nitrogen heterocycles.1
A
promising area of azirine chemistry is the design of pyrrolo-
fused systems, which are of interest for medicinal chemistry2
and material science applications.3 The synthesis of such
compounds from an azirine precursor can be realized either via
an azirine ring opening−1,5-cyclization sequence4 or by
intermolecular annulation of cyclic compounds with azirines.
The second approach is based on the convergent scheme of
polycyclic backbone assembly and provides a route to
synthesize both 2,3- and 3,4-fused pyrrole derivatives. The
annulation reactions can occur through the ring-opening of any
bond of azirine depending on reaction conditions. UV-
irradiation causes a С−С azirine bond cleavage giving a nitrile
ylide, which can be employed as С−N−C building block for
annulation reactions. This approach was used for the
preparation of 3,4-fused pyrrole derivatives from thieno[2,3-
c]pyridine 1,1-dioxides,5 quinones,6 diazaphospholes,7
diazaarsoles7 and fullerene C60.8 The base-promoted reaction of
azirines with cyclic ketones proceeding via N=C3 azirine bond
cleavage was used for the synthesis of 2,3-fused pyrrole
derivatives.9 The same mode of azirine ring opening in NiCl2-
catalyzed annulation of dimedone with methyl 3-
phenylazirine-2-carboxylate to give a 4,5,6,7-tetrahydro-1H-
indole derivative was also reported.10 The ring-opening of the
azirine ring across the single N−С2 bond in annulation
reactions is characteristic of 3-aminoazirines. Thus, 3-
aminoazirines react with NH-lactam-like compounds under
Recently we described the stereoselective synthesis of
hexahydropyrrolo[3,4-b]pyrroles 3 from tetramic acids 1 and
2H-azirines
2
under Cu(I)-catalysis (Scheme 1).15 3-
Arylazirines 2 in the presence of the Cu(I)-NHC-complex
cycloadd to tetramic acids 1, which exist in enolic form, across
the C=C bond via N−C2 azirine bond cleavage. The reaction
enables the concise assembly of a 2,3-fused pyrrole backbone
with the retention of the C=N bond in the annulation product.
Taking into account of the ability of acyclic enols to expand
the azirine ring to the 1H-pyrrole system, via the breaking of
the N=C3 double bond under Cu(II)- or Cu(I)-catalysis,16 the
formation of adducts 3 seems to be rather unusual. Moreover,
the cyclic enol, 4-hydroxycoumarin, was recently reported to
produce spirofuranone-lactams via the two-atom azirine ring
expansion across N=C3 double bond in the presence of
Mn(OAc)2 as a catalyst.17 Thus, the synthesis of pyrrolo[3,4-
b]pyrroles 3 is the only example of (3+2)-cycloaddition of 2H-

2
Tetrahedron
ACCEPTED MANUSCRIPT
azirines to the double bond of the cyclic enols and the scope
compounds 1 in some cases produced along with annulation
of such an annulation reaction remains unclear. In this regard,
furo[3,4-b]pyrrole and indeno[1,2-b]pyrrole derivatives are of
special interest as synthetic targets, since these backbones
occur in biologically important compounds displaying
antitumor, neurokinin-1 receptor antagonist, neuronal nicotinic
acetylcholine receptor, human protein kinase CK2 inhibitor,
plant growth regulator and seed germination promoter
activities.18
products 3 noticeable amounts of aziridines 3′ (Scheme 1).15
Addition of catalytic amounts of IPrCuCl (5 mol%) to the
mixture of tetronic acid 4a and azirine 2a in MeOH at 100 °C
suppressed the formation of salt 12 completely. The reaction
was completed within several minutes under these conditions
giving the annulation product 8a in 97% yield (Scheme 3)
(Table 1, entry 1). It is notable that the reaction occurred even
at room temperature, although much slower (18 h), giving
furopyrrole 8a in a slightly lower yield (87%). Other tested
catalysts, such as CuCl, copper(I) phenylacetylide and
Previous work
1
Ar
Cu(OAc)2 gave unsatisfactory results according to H NMR
O
O
R2
O
R2
Ar
R2
spectra of the reaction mixtures. The efficient conditions above
provided high yields of furopyrroles 8 from 3-aryltetronic
acids and 3-arylazirines (entries 1, 2, 6, 7). 1,2-Dichloroethane
could also be used as a solvent and gave comparable yields of
furopyrroles 8 (entries 3, 5, 10−12). The annulation of tetronic
acids using 3-(4-nitrophenyl)-2H-azirine (2d) in methanol
failed, due to the instability of the azirine in this solvent, but by
carrying out of the reaction in 1,2-dichloroethane it was
possible to obtain furopyrroles 8d,h,m in 73−88% yield
(entries 4, 8, 13). The introduction of substituents at the 2-
position of the azirine ring caused a dramatic decrease in the
product yields (entries 9, 14, 15). The yields of thienopyrroles
9a,b (entries 17, 18) derived from thiotetronic acid 5 and
azirines 2a,d were significantly lower than those of the
corresponding furopyrroles (entries 5, 8). Generally, the nature
of the substituent in the aryl ring of tetronic acids had little
effect on the reaction outcome.
N
2
R1
N
Ar
+
NH
R1
N
R1
N
Cu(I)
N
OH
O
OH
3
1
3'
This work
Cu(I)-NHC-catalyst
Ar
High-efficiency
R
X
X
5
R
N
2
Ar
5
N
OH
OH
Ar
4 7
4 7
N
2
Low-efficiency
catalyst-free conditions
Scheme 1. Reaction of 5-membered cyclic enols with 3-
aryl-2H-azirines.
Herein, we report the Cu(I)-NHC-catalyzed cycloaddition
of 5-membered cyclic enols 4−7 with 3-arylazirines 2 as a very
efficient route to highly functionalized 2,3-fused pyrroles 8−11
with furo[3,4-b]pyrrole, thieno[3,4-b]pyrrole and indeno[1,2-
b]pyrrole backbones (Scheme 1). The results and mechanism
of the non-catalytic version of this reaction is also discussed.
2. Results and discussion
Scheme 3. Cu(I)-catalyzed reaction of enols 4a−d, 5 with
azirines 2a−f.
In our initial experiments the analogues of tetramic acids 1,
tetronic acids 4а−d, which exist in the enolic form in solution,
were used as the starting material for the synthesis of furo[3,4-
b]pyrrole derivatives 8 (Scheme 2). Compounds 4а−d were
synthesized in two steps from methyl bromoacetate and
arylacetic acids or malonic monomethyl ester according to a
known procedure.19 Treatment of tetronic acid 4а with azirine
2a at room temperature in methanol did not provide any
products. Two compounds, furopyrrole 8a and salt 12, were,
however, obtained in 15 and 82% yield, respectively, when a
1:1.6 mixture of 4а and 2a was heated in MeOH at 100 °C in a
sealed tube for 45 min (Scheme 2). Compounds 8a and 12
were formed from azirine 2a via independent pathways
involving cleavage of different azirine carbon−nitrogen bonds.
The analogous reaction in 1,2-dichloroethane (DCE) gave only
traces of furopyrrole 8a.
Tetronic acid 4d, containing an ester group as the R1
substituent, did not give the annulation product when treated
with azirine 2a and IPrCuCl in methanol (Table 1, entry 16):
no conversion of the enol was observed, while the azirine was
transformed into 2,5-di(p-tolyl)pyrazine 13. This result could
be explained by the excessive OH-acidity of compound 4d
which initiates the ring-opening of the azirine followed by
dimerization to the pyrazine derivative.20 To reduce the acidity
of the substrate the solvent was changed from methanol to
aprotic 1,2-dichloroethane. This replacement led to the
isolation of adduct 8p in 57% yield (Table 1, entry 16).
Scheme 2. Reaction of tetronic acid 4a with azirine 2a.
Next, we carried out the reaction of 2a with 4a under
catalytic conditions using IPrCuCl as a catalyst (Scheme 3).
This Cu(I)-NHC-complex was employed since it showed good
activity in the analogous reaction of tetramic acids 1, though
Figure 1. X-ray structure of compound 8a.

3
1
Сompounds 8a−p and 9a,b were characterized by H, 13C
additionally confirmed by X-ray crystallography (Figure 1).21
ACCEPTED MANUSCRIPT
NMR and HRMS data. The structure of furopyrrole 8a was
Table 1
Cu(I)-catalyzed reaction of enols 4a−d, 5 with azirines 2a−fa
Entry
Enol
4a
4a
4a
4a
4b
4b
4b
4b
4b
4c
4c
4c
4c
4c
4c
4d
5
X
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
R1
Azirine
R2
R3
H
R4
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
Solvent
MeOH
MeOH
DCE
Yield of 8, 9 %
97 (8a)
92 (8b)
87 (8c)
88 (8d)
90 (8e)
85 (8f)
1
Ph
2a
4-MeC6H4
Ph
2
Ph
2b
2c
H
3
Ph
4-MeOC6H4
4-O2NC6H4
4-MeC6H4
Ph
H
4
Ph
2d
2a
H
DCE
5
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
CO2Me
H
DCE
6
2b
2c
H
MeOH
MeOH
DCE
7
4-MeOC6H4
4-O2NC6H4
Ph
H
87 (8g)
73 (8h)
36 (8i)
8
2d
2e
H
9
Ph
H
MeOH
DCE
10
11
12
13
14
15
16
17
18
2a
4-MeC6H4
Ph
90 (8j)
2b
2c
H
DCE
84 (8k)
82 (8l)
4-MeOC6H4
4-O2NC6H4
Ph
H
DCE
2d
2e
H
DCE
80 (8m)
42 (8n)
2 (8o)
Ph
Me
H
DCE
2f
Ph
MeOH
DCE
2a
4-MeC6H4
4-MeC6H4
4-O2NC6H4
57 (8p)
28 (9a)
40 (9b)
4-MeOC6H4
4-MeOC6H4
2a
H
MeOH
DCE
5
S
2d
H
aReaction conditions: 0.067M soln of 4, 5 in MeOH or DCE, azirine 2 (1.6 equiv), IPrCuCl (0.05 equiv).
6 gave the addition products to the C=N bond of the azirines,
including 3-(4-nitrophenyl)azirine 2d.
Enol 622 was used as starting material for the synthesis of
indeno[1,2-b]pyrrole 10 (Scheme 4). The reaction of enol 6
with azirines 2a−c in the presence of IPrCuCl furnished
indenopyrroles 10a−c in 56−70% yield (Table 2). 1,2-
Dichloroethane was used as a solvent in the synthesis of
compound 10d from azirine 2d, which was unstable in
methanol (entry 4). In other cases methanol proved to be the
solvent of choice. Thus, the reaction of enol 6 with azirine 2a
in DCE afforded adduct 10a only in 23% yield.
The absence of endo-cyclic carbonyl group at the β-position
of the cyclic enol proved to be not crucial for the annulation
reaction to proceed. Thus, when enol 723 was reacted with
azirine 2a in the presence of IPrCuCl in ethanol at 100 °C it
gave adduct 11, although in moderate yield (Scheme 5).
Ar
O
O
CO2Me
CO2Me
OH
N
2a d
Ar
N
OH
IPrCuCl (5 mol%)
MeOH or DCE
100 C
Scheme 5. Cu(I)-catalyzed reaction of enol 7 with azirine
2a.
10a d
6
Scheme 4. Cu(I)-catalyzed reaction of enol 6 with azirines
2a−d.
The formation of the annulation products 8−11 could be
rationalized by the probable mechanism depicted in Scheme 6
for tetronic acids 4. In the absence of the catalyst (non-catalytic
route, colored blue) the protonation of azirine 2 by tetronic
acid 4 generates the azirinium cation 2-H+, which after addition
of the enolate of 4 across the C=N bond produces aziridine
intermediate A. When the reaction is carried out in methanol
the competitive reaction of cation 2-H+ with the solvent leads
to ketal 12. Nucleophilic attack of the enolate of 4 at the less
substituted position of aziridinium cation24 A-H+ breaks an
N−С bond to give intermediate B. According to DFT
calculations (B3LYP/6-31+G(d,p), PCM for MeOH) of the
formation of intermediate B (R = Ar = Ph), the activation free
energy and the reaction free energy are 31.0 and -12.3
kcal·mol-1 respectively. The three-membered ring opening in
cationic intermediate A-H+ could therefore occur irreversibly
Table 2 Cu(I)-catalyzed reaction of enol 6 with azirines
2a−d
Entry
Azirine
Ar
Solvent
Yield of
10, %
1
2
3
4
2a
2b
2c
2d
4-MeC6H4
Ph
MeOH
MeOH
MeOH
DCE
70 (10a)
59 (10b)
56 (10c)
60 (10d)
4-MeOC6H4
4-O2NC6H4
It is notable that, under IPrCuCl-catalyzed conditions,
neither tetronic/thiotetronic acids 4,5 nor the indene-based enol

4
Tetrahedron
ACCEPTED MANUSCRIPT
under the reaction conditions used (100 °C). A possible route
were used instead of the copper catalyst. For example, the
from intermediate B to bicycle 8 would involve the acid-
catalyzed elimination of tetronic acid 4 to give imine C
followed by cyclization. The last step proceeds similarly to the
reported cyclocondensation of ethyl 2-oxo-1-(2-oxo-2-
phenylethyl)cyclopentanecarboxylate with liquid ammonia
leading to the carbon analog of 8, ethyl 6a-hydroxy-2-phenyl-
4,5,6,6a-tetrahydrocyclopenta[b]pyrrole-3a(3H)-carboxylate.25
To the best of our knowledge, the above mentioned
transformation of azirines 2 to furopyrroles 8 is the first
example of N−C2 bond cleavage in 2-unsubstituted 3-aryl-2H-
azirines in the absence of transition metal compounds. This
type of ring opening under transition-metal-free conditions is
known only for 3-arylazirines with two substituents at the C2
atom, which provide a delocalization of the positive charge
during the N−C2 bond cleavage.26 The formation of furopyrrole
8a from 2-unsubstituted azirine 2a revealed the existence of an
alternative pathway for the N−C2 bond cleavage which does
not require the presence of donating substituents at the C2 atom
and proceeds via “NuH-addition−protonation−nucleophile-
assisted ring opening” sequence.
reaction of enol 4a with azirine 2a (1.6 equiv) in the presence
of Et3N (1.6 equiv) in DCE gave 4-(2-chloroethoxy)-3-
phenylfuran-2(5H)-one (15) as the sole product. Only a slight
decrease in the yield of furopyrrole 8a (from 97 to 77%) was
observed in the IPrCuCl-catalyzed reaction of 4a with 2a when
carried out in the presence of TEMPO (1.5 equiv) as a radical
trap. This result is an argument in favor of a non-radical
mechanism for the reaction.
N
Tol
Tol
IPrCuCl (5 mol%)
N
2a
MeOH, 100
C
Tol
N
13 (21%)
Tol
O
Ph
2a
N
O
IPrCuCl (5 mol%)
OMe
MeOH or DCE, 100
C
14
Tol
O
O
Ph
Ph
2a
N
O
O
Cl
Et3N, DCE, 100
C
O
OH
15 (93%)
Some additional experiments were carried out to provide an
insight into the catalytic mechanism of the reaction (Scheme
7). Azirine 2a was shown to be quite stable in MeOH at room
temperature, but decomposes in the presence of IPrCuCl giving
2,5-ditolylpyrazine (13) as the main product. The latter
reaction proceeds much more rapidly at 100 °C (5 min) to
4a
Scheme 7. Mechanistic studies.
Taking account of these facts a mechanism for the catalytic
version of the reaction was suggested (Scheme 6, catalytic
route, colored red). Azirine 2 coordinates with the copper
catalyst producing azirine complex D, which is further
transformed into the nitrene copper complex E through a
reversible N−C2 bond cleavage.13 Addition of intermediate E to
enol 4 is accompanied by a proton transfer from the enol to the
nitrogen atom of the nitrene complex. The formed iminium
complex F releases the Cu(I)-catalyst to give imine C, which
then further cyclizes into furopyrrole 8.
1
afford compound 13 in 21% yield. According to H NMR
spectroscopy, tetronic acid 4a, in the presence of IPrCuCl in
MeOH at room temperature, did not undergo any
transformations, and began to be consumed only when azirine
2a was added. It was also found that the O-methyl ether of 4a,
compound 14,27 was inactive in the reaction. The annulation
reaction also did not occur when such bases, as Et3N and NaH,
Scheme 6. Plausible reaction mechanism.
sequence, and provides the first example of N−C2 bond
cleavage in 2-unsubstituted 2H-azirines in the absence of a
transition metal catalyst.
3. Conclusions
In conclusion, we have developed a Cu(I)-NHC-catalyzed
annulation of 5-membered cyclic enols of furan, thiophene and
indene family with 3-aryl-2H-azirines to provide a rapid access
to furo[3,4-b]pyrrole, thieno[3,4-b]pyrrole and indeno[1,2-
b]pyrrole derivatives. The annulation proceeds via a N−C2
azirine bond cleavage with retention of the C=N double bond
in the product. Tetronic acids can react with 3-aryl-2H-azirines
under catalyst-free conditions at elevated temperatures to give
furo[3,4-b]pyrrole derivatives but in poor yields. According to
DFT calculations the non-catalytic reaction can occur by
double addition of the enol to the azirine via the “enol addition
to C=N bond/N-protonation/enolate-assisted ring opening”
4. Experimental section
4.1. General methods
Melting points were determined on a Stuart Melting Point
1
Apparatus SMP30. H (400 MHz) and 13C (100 MHz) NMR
spectra were recorded on a Bruker AVANCE 400 spectrometer
in solvent indicated below. Chemical shifts (δ) are reported in
ppm downfield from tetramethylsilane. Electrospray ionization
(ESI) mass spectra were measured on a Bruker MaXis and on

5
1
an Agilent 6538 UHD mass spectrometers. All solvents were
distilled and dried prior to use. 1,2-Dichloroethane was washed
with concentrated H2SO4, water, then distilled from P2O5 and
stored over anhydrous K2CO3. NHC complex IPrCuCl was
prepared by the reported procedure.28 Thin-layer
chromatography (TLC) was conducted on aluminum sheets
precoated with SiO2 ALUGRAM SIL G/UV254. 2H-Azirines
2a–c,29 2d,30 2e,31 2f26a and enols 4a–c,19a 4d,19b 5,32 7,23 1427
were prepared by the reported procedures.
(50% EtOAc in hexane) 0.40. H NMR (CDCl3): 2.45 (s,
ACCEPTED MANUSCRIPT
3H), 3.50 (d, J = 17.8 Hz, 1H), 3.80 (d, J = 17.8 Hz, 1H), 4.42
(d, J = 9.7 Hz, 1H), 4.69 (d, J = 9.7 Hz, 1H), 5.93 (br s, 1H),
7.21 (d, J = 7.8 Hz, 2H), 7.36–7.48 (m, 5H), 7.64 (d, J = 7.9
Hz, 2H). 13C NMR (CDCl3): 21.6, 46.1, 58.5, 75.1, 105.7,
127.6, 128.1, 128.4, 128.7, 128.9, 129.5, 133.6, 143.4, 176.1,
178.3.
HRMS−ESI:
[M+Na]+
calcd
for
C19H17NNaO3+ 330.1101, found 330.1093. Crystal data
(CCDC-1532390): С19Н17NO3, M = 307.33, triclinic, space
group P-1, a = 9.4811(6), b = 9.9382(6), c = 10.4583(6) Å, α =
117.383(6), β = 91.730(5), γ = 116.298(6)°, V = 749.81(9) Å3,
Z = 2, T = 100 K, d = 1.361 mg mm−3, F(000) = 324, ꢀ = 0.748
mm−1, 11302 reflections measured, 2926 unique (Rint = 0.0682)
were used in all calculations. The final R1 was 0.0433 (2373
>2σ(I)) and wR2 was 0.1207 (all data).
4.2. Calculation details
All calculations were performed with the mPWB1K density
functional method by using the Gaussian 0933 suite of quantum
chemical programs. Geometry optimizations of 4-enolate,
compounds A-H+ and B, as well as the transition state, in
methanol were performed at the DFT B3LYP/6-31+G(d,p)
level using the PCM model. Stationary points on the
respective potential-energy surfaces were characterized at the
same level of theory by evaluating the corresponding Hessian
indices. Careful verification of the unique imaginary frequency
for the transition state was carried out to check whether the
frequency indeed pertains to the desired reaction coordinate.
4.4.2. rac-(3aS,6aR)-6a-Hydroxy-2,3a-diphenyl-3,3a,6,6a-
tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8b)
Compound 8b (92 mg, 92%) was prepared according to the
general procedure in MeOH from tetronic acid 4a (60 mg,
0.341 mmol) and azirine 2b (64 mg, 0.547 mmol). Colorless
solid, mp 138–140 °С (hexane–Et2O). Rf (50% EtOAc in
hexane) 0.38. 1H NMR (CDCl3): 3.57 and 3.82 (AB-q, J = 17.9
Hz, 2H), 4.42 (d, J = 9.8 Hz, 2H), 4.70 (d, J = 9.8 Hz, 2H),
5.71 (br s, 1H), 7.36–7.49 (m, 7H), 7.56–7.60 (m, 1H), 7.73–
7.75 (m, 2H). 13C NMR (CDCl3): 46.2, 58.5, 75.0, 105.8,
127.6, 128.2, 128.4, 128.8 (2C), 131.6, 132.7, 133.4, 176.3,
4.3. Preparation of methyl 3-hydroxy-1-oxo-1H-indene-2-
carboxylate (6)
Sodium salt of 3-hydroxy-1-oxo-1H-indene-2-carboxylic
acid methyl ester was prepared according to the reported
procedure from methyl acetate (50 mL), dimethyl phthalate
(21.3 g, 0.11 mol) and sodium (5.0 g, 0.21 mol).22 The above
salt was dissolved in water (500 mL) and carefully acidified
with conc. HCl (25 mL). The precipitate was filtered off and
dried in vacuo to afford 6 (9.0 g, 40%). Yellow solid, mp
128−130 °С. 1H NMR (CDCl3): enol : ketone = 5 : 1; [enol
form] 3.97 (s, 3H), 7.55−7.66 (m, 4H), 11.60 (br s, 1H); [keto
form] 3.81 (s, 3H), 4.18 (s, 1H), 7.90−7.93 (m, 2H), 8.06−8.09
(m, 2H). 13C NMR (CDCl3): [enol form] 52.0, 99.4, 121.1,
122.5, 132.7, 133.6, 133.8, 135.0, 168.6, 186.8, 189.0; [keto
form] 53.1, 60.3, 124.0, 136.1, 142.8, 164.4, 192.0.
178.3.
HRMS−ESI:
[M+Na]+
calcd
for
C18H15NNaO3+ 316.0944, found 316.0947.
4.4.3. rac-(3aS,6aR)-6a-Hydroxy-2-(4-methoxyphenyl)-3a-
phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8c)
Compound 8c (94 mg, 85%) was prepared according to the
general procedure in MeOH from tetronic acid 4a (60 mg,
0.341 mmol) and azirine 2c (80 mg, 0.544 mmol). The use of
DCE as a solvent gave compound 8c in 87% yield. Colorless
solid, mp 161–163 °С (hexane–Et2O). Rf (50% EtOAc in
hexane) 0.26. 1H NMR (CDCl3): 3.71 and 3.77 (AB-q, J = 17.6
Hz, 2H), 3.84 (s, 3H), 4.40 (d, J = 9.5 Hz, 1H), 4.63 (d, J = 9.5
Hz, 1H), 6.51 (s, 1H), 7.06 (d, J = 8.8 Hz, 2H), 7.32–7.43 (m,
5H), 7.96 (d, J = 8.8 Hz, 2H). 13C NMR (DMSO-d6): 44.7,
55.4, 58.9, 74.3, 105.4, 114.0, 125.2, 127.3, 127.8, 128.4,
130.0, 134.7, 162.1, 173.0, 179.0. HRMS−ESI: [M+Na]+ calcd
for C19H17NNaO4+ 346.1050, found 346.1050.
+
HRMS−ESI: [M+Na]+ calcd for C11H8NaO4 227.0315, found
227.0321.
4.4. General procedure for the preparation of compounds
8−11
Enol 4−7 (0.3 mmol), IPrCuCl (5 mol% calculated on enol),
azirine 2 (0.51 mmol) and methanol, ethanol or 1,2-
dichloroethane (DCE) (4.5 mL) were placed consequently to a
screw cap ampoule and heated at 100 °C for 3−15 min under
stirring until full consumption of the enol was detected (control
by TLC). The solvent was removed in vacuo and the residue
was purified by column chromatography on silica gel (eluent
petroleum ether–EtOAc, from 4 : 1 to 1 : 2) followed by
recrystallization from hexane–Et2O mixture to give adduct
8−11.
4.4.4. rac-(3aS,6aR)-6a-Hydroxy-2-(4-nitrophenyl)-3a-
phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8d)
Compound 8d (101 mg, 88%) was prepared according to
the general procedure in DCE from tetronic acid 4a (60 mg,
0.341 mmol) and azirine 2d (88 mg, 0.543 mmol). Colorless
solid, mp 160–162 °С (hexane–Et2O). Rf (50% EtOAc in
1
hexane) 0.41. H NMR (DMSO-d6): 3.84 and 3.96 (AB-q, J =
17.9 Hz, 2H), 4.50 (d, J = 9.7 Hz, 1H), 4.74 (d, J = 9.7 Hz,
1H), 6.78 (s, 1H), 7.19–7.44 (m, 5H), 8.22–8.40 (m, 4H). 13C
NMR (DMSO-d6): 45.1, 58.9, 74.3, 105.9, 123.8, 127.5, 127.8,
128.5, 129.5, 134.3, 138.2, 149.3, 172.6, 178.7. HRMS−ESI:
[M+H]+ calcd for C18H15N2O5+ 339.0975, found 339.0963.
4.4.1. rac-(3aS,6aR)-6a-Hydroxy-2-(4-methylphenyl)-3a-
phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8a)
Compound 8a (102 mg, 97%) was prepared according to
the general procedure in MeOH from tetronic acid 4a (60 mg,
0.341 mmol) and azirine 2a (71 mg, 0.542 mmol). The use of
DCE as a solvent at room temperature gave compound 8a in
87% yield. Colorless solid, mp 174–176 °С (hexane–Et2O). Rf
4.4.5. rac-(3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-2-(4-
methylphenyl)-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-
one (8e)
Compound 8e (74 mg, 75%) was prepared according to the
general procedure in MeOH from tetronic acid 4b (60 mg,

6
Tetrahedron
ACCEPTED MANUSCRIPT
0.291 mmol) and azirine 2a (61 mg, 0.466 mmol). The use of
9.3 Hz, 1H), 4.76 (d, J = 9.3 Hz, 1H), 5.33 (s, 1H), 6.66–6.72
DCE as a solvent gave compound 8e in 90% yield. Colorless
solid, mp 173–174 °С (hexane–Et2O). Rf (50% EtOAc in
hexane) 0.33. H NMR (CDCl3): 2.39 (s, 3H), 3.74 (s, 2H),
3.78 (s, 3H), 4.41 (d, J = 9.5 Hz, 1H), 4.65 (d, J = 9.5 Hz, 1H),
6.54 (s, 1H), 6.98 (d, J = 8.5 Hz, 2H), 7.33–7.34 (m, 4H), 7.91
(d, J = 7.8 Hz, 2H). 13C NMR (DMSO-d6): 21.1, 45.0, 55.1,
58.1, 74.3, 105.2, 113.8, 126.5, 128.1, 129.0, 129.3, 130.0,
141.9, 158.5, 173.6, 179.2. HRMS−ESI: [M+H]+ calcd for
C20H20NO4+ 338.1387, found 338.1376.
(m, 2H), 7.04–7.14 (m, 3H), 7.36–7.45 (m, 7H), 7.62 (br s,
1H), 7.89–7.95 (m, 2H). 13C NMR (DMSO-d6): 54.8, 60.9,
62.5, 74.0, 104.1, 113.0, 124.1, 127.1, 128.2, 128.6, 128.8,
130.3, 130.6, 131.6, 132.0, 135.4, 158.0, 175.4, 178.3.
1
HRMS−ESI: [M+H]+ calcd for C25H22NO4 400.1543, found
+
400.1537.
4.4.10. rac-(3aS,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-2-(4-
methylphenyl)-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-
one (8j)
4.4.6. rac-(3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-2-
phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8f)
Compound 8j (60 mg, 62%) was prepared according to the
general procedure in MeOH from tetronic acid 4c (60 mg,
0.286 mmol) and azirine 2a (60 mg, 0.458 mmol). The use of
DCE as a solvent gave compound 8j in 90% yield. Colorless
solid, mp 206–207 °С (hexane–Et2O). Rf (50% EtOAc in
Compound 8f (80 mg, 85%) was prepared according to the
general procedure in MeOH from tetronic acid 4b (60 mg,
0.291 mmol) and azirine 2b (55 mg, 0.470 mmol). Colorless
solid, mp 151–153 °С (hexane–Et2O). Rf (50% EtOAc in
1
hexane) 0.42. H NMR (DMSO-d6): 2.39 (s, 3H), 3.75 and
1
3.79 (AB-q, J = 17.8 Hz, 2H), 4.42 (d, J = 9.6 Hz, 1H), 4.66 (d,
J = 9.6 Hz, 1H), 6.64 (s, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.42 (d,
J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.90 (d, J = 8.0 Hz,
2H). 13C NMR (DMSO-d6): 21.1, 45.0, 58.4, 74.4, 105.5,
128.2, 128.4, 129.3, 129.77, 129.84, 132.3, 133.7, 142.0,
hexane) 0.30. H NMR (DMSO-d6): 3.73 and 3.75 (AB-q, J =
17.8 Hz, 2H), 3.77 (s, 3H), 4.40 (d, J = 9.6 Hz, 1H), 4.65 (d, J
= 9.6 Hz, 1H), 6.54 (s, 1H), 6.97 (d, J = 8.8 Hz, 2H), 7.32 (d, J
= 8.8 Hz, 2H), 7.50–7.60 (m, 3H), 7.99–8.01 (m, 2H). 13C
NMR (DMSO-d6): 45.0, 55.1, 58.1, 74.2, 105.3, 113.8, 126.4,
128.1, 128.7, 129.0, 131.9, 132.6, 158.5, 173.8, 179.1.
HRMS−ESI: [M+Na]+ calcd for C19H17NNaO4+ 346.1050,
found 346.1044.
+
173.4, 178.6. HRMS−ESI: [M+H]+ calcd for C19H1735ClNO3
342.0891, found 342.0901.
4.4.11. rac-(3aS,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-2-
phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8k)
4.4.7. rac-(3aS,6aR)-6a-Hydroxy-2,3a-bis(4-methoxyphenyl)-
3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one (8g)
Compound 8k (79 mg, 84%) was prepared according to the
general procedure in DCE from tetronic acid 4c (60 mg, 0.286
mmol) and azirine 2b (53 mg, 0.453 mmol). Colorless solid,
mp 188–190 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
0.41. 1H NMR (DMSO-d6): 3.80 and 3.84 (AB-q, J = 17.8 Hz,
2H), 4.45 (d, J = 9.7 Hz, 1H), 4.70 (d, J = 9.7 Hz, 1H), 6.70 (s,
1H), 7.44–7.55 (m, 6H), 7.58–7.61 (m, 1H), 8.01–8.03 (m,
2H). 13C NMR (DMSO-d6): 45.1, 58.5, 74.5, 105.6, 128.2,
128.4, 128.7, 129.8, 132.0, 132.3, 132.5, 133.6, 173.7, 178.6.
HRMS−ESI: [M+H]+ calcd for C18H1535ClNO3+ 328.0735,
found 328.0727.
Compound 8g (89 mg, 87%) was prepared according to the
general procedure in MeOH from tetronic acid 4b (60 mg,
0.291 mmol) and azirine 2c (69 mg, 0.469 mmol). Colorless
solid, mp 192–194 °С (hexane–Et2O). Rf (50% EtOAc in
hexane) 0.19. 1H NMR (DMSO-d6): 3.70 (s, 2H), 3.76 (s, 3H),
3.83 (s, 3H), 4.37 (d, J = 9.4 Hz, 1H), 4.61 (d, J = 9.4 Hz, 1H),
6.46 (br s, 1H), 6.90–7.10 (m, 4H), 7.25–7.37 (m, 2H), 7.88–
8.03 (m, 2H). 13C NMR (DMSO-d6): 44.9, 55.1, 55.4, 58.2,
74.3, 105.1, 113.8, 114.1, 125.2, 126.5, 129.0, 130.0, 158.5,
162.1, 173.0, 179.2. HRMS−ESI: [M+H]+ calcd for
C20H20NO5+ 354.1336, found 354.1337.
4.4.12. rac-(3aS,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-2-(4-
methoxyphenyl)-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-
one (8l)
4.4.8. rac-(3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-2-(4-
nitrophenyl)-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one
(8h)
Compound 8l (84 mg, 82%) was prepared according to the
general procedure in DCE from tetronic acid 4c (60 mg, 0.286
mmol) and azirine 2c (67 mg, 0.456 mmol). Colorless solid,
mp 203–205 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
0.27. 1H NMR (DMSO-d6): 3.75 and 3.76 (AB-q, J = 18.4 Hz,
2H), 3.84 (s, 3H), 4.41 (d, J = 9.6 Hz, 1H), 4.65 (d, J = 9.6 Hz,
1H), 6.59 (s, 1H), 7.07 (d, J = 9.6 Hz, 2H), 7.42 (d, J = 9.5 Hz,
2H), 7.48 (d, J = 9.5 Hz, 2H), 7.96 (d, J = 9.6 Hz, 2H). 13C
NMR (DMSO-d6): 45.0, 55.4, 58.6, 74.5, 105.4, 114.1, 125.1,
128.4, 129.8, 130.1, 132.3, 133.8, 162.2, 172.9, 178.7.
HRMS−ESI: [M+H]+ calcd for C19H1735ClNO4+ 358.0841,
found 358.0834.
Compound 8h (78 mg, 73%) was prepared according to the
general procedure in DCE from tetronic acid 4b (60 mg, 0.291
mmol) and azirine 2d (75 mg, 0.463 mmol). Pale yellow
1
semisolid. Rf (50% EtOAc in hexane) 0.33. H NMR (DMSO-
d6): 3.78 (s, 3H), 3.80 and 3.87 (AB-q, J = 18.0 Hz, 2H), 4.46
(d, J = 9.7 Hz, 1H), 4.70 (d, J = 9.7 Hz, 1H), 6.71 (s, 1H), 6.98
(d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 8.26 (d, J = 8.6
Hz, 2H), 8.35 (d, J = 8.6 Hz, 2H). 13C NMR (DMSO-d6): 45.2,
55.1, 58.2, 74.2, 105.6, 113.9, 123.8, 126.1, 129.0, 129.5,
138.2, 149.3, 158.6, 172.6, 178.8. HRMS−ESI: [M+H]+ calcd
for C19H17N2O6+ 369.1081, found 369.1084.
4.4.9. rac-(3R,3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-
2,3-diphenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one
(8i)
4.4.13. rac-(3aS,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-2-(4-
nitrophenyl)-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one
(8m)
Compound 8i (42 mg, 36%) was prepared according to the
general procedure in MeOH from tetronic acid 4b (60 mg,
0.291 mmol) and azirine 2e (90 mg, 0.466 mmol). Colorless
solid, mp 182–184 °С (hexane–Et2O). Rf (50% EtOAc in
Compound 8m (85 mg, 80%) was prepared according to
the general procedure in DCE from tetronic acid 4c (60 mg,
0.286 mmol) and azirine 2d (74 mg, 0.457 mmol). Colorless
solid, mp 170–172 °С (hexane–Et2O). Rf (50% EtOAc in
1
hexane) 0.45. H NMR (DMSO-d6): 3.64 (s, 3H), 4.50 (d, J =
1
hexane) 0.45. H NMR (DMSO-d6): 3.83 and 3.94 (AB-q, J =

7
18.0 Hz, 2H), 4.48 (d, J = 9.8 Hz, 1H), 4.72 (d, J = 9.8 Hz,
1H), 6.86 (br s, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4
106.0, 113.7, 127.6, 128.0, 129.1, 129.2, 130.2, 141.7, 158.4,
ACCEPTED MANUSCRIPT
Hz, 2H), 8.25 (d, J = 8.4 Hz, 2H), 8.36 (d, J = 8.4 Hz, 2H). 13
173.4, 209.2. HRMS−ESI: [M+H]+ calcd for C20H20NO3S+
C
354.1158, found 354.1140.
NMR (DMSO-d6): 45.3, 58.5, 74.4, 105.9, 123.8, 128.4, 129.5,
129.8, 132.4, 133.4, 138.0, 149.3, 172.4, 178.3. HRMS−ESI:
[M+H]+ calcd for C18H1435ClN2O5+ 373.0586, found 373.0570.
4.4.18. rac-(3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-2-(4-
nitrophenyl)-3,3a,6,6a-tetrahydro-4H-thieno[3,4-b]pyrrol-4-
one (9b)
4.4.14. rac-(3R,3aS,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-
2,3-diphenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-4-one
(8n)
Compound 9b (42 mg, 40%) was prepared according to the
general procedure in DCE from thiotetronic acid 5 (60 mg,
0.270 mmol) and azirine 2d (70 mg, 0.432 mmol). Pale yellow
solid, mp 170–172 °С (hexane–Et2O). Rf (50% EtOAc in
hexane) 0.32. 1H NMR (DMSO-d6): 3.77 (s, 3H), 3.79 (s, 2H),
3.88 and 4.05 (AB-q, J = 11.8 Hz, 2H), 6.65 (s, 1H), 6.97 (d, J
= 8.8 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 8.23 (d, J = 8.9 Hz,
2H), 8.35 (d, J = 8.9 Hz, 2H). 13C NMR (DMSO-d6): 39.6,
44.7, 55.1, 66.1, 106.3, 113.8, 123.8, 127.3, 129.1, 129.3,
138.4, 149.2, 158.5, 172.6, 208.7. HRMS−ESI: [M+Na]+ calcd
for C19H16N2NaO5S+ 407.0672, found 407.0656.
Compound 8n (43 mg, 37%) was prepared according to the
general procedure in MeOH from tetronic acid 4c (60 mg,
0.286 mmol) and azirine 2e (88 mg, 0.456 mmol). The use of
DCE as a solvent gave compound 8n in 42% yield. Colorless
solid, mp 183–184 °С (hexane–Et2O). Rf (25% EtOAc in
hexane) 0.49. 1H NMR (CDCl3): 4.44 (d, J = 9.3 Hz, 1H), 4.85
(d, J = 9.3 Hz, 1H), 5.30 (s, 1H), 5.91 (br s, 1H), 7.09–7.15 (m,
7H), 7.34–7.38 (m, 4H), 7.45–7.49 (m, 1H), 7.84 (d, J = 7.6
Hz, 2H). 13C NMR (CDCl3): 61.3, 64.3, 74.0, 104.7, 128.0
(2C), 128.78, 128.83, 129.4, 129.5, 129.8, 131.0, 131.3, 132.5,
134.0, 134.6, 177.5, 178.8. HRMS−ESI: [M+H]+ calcd for
C24H1935ClNO3+ 404.1048, found 404.1057.
4.4.19. Methyl rac-(3aS,8bS)-8b-hydroxy-2-(4-methylphenyl)-
4-oxo-4,8b-dihydroindeno[1,2-b]pyrrole-3a(3H)-carboxylate
(10a)
Compound 10a (69 mg, 70%) was prepared according to the
general procedure in MeOH from enol 6 (60 mg, 0.294 mmol)
and azirine 2a (62 mg, 0.473 mmol). Beige solid, mp 193–195
4.4.15. rac-(3aR,6aR)-3a-(4-Chlorophenyl)-6a-hydroxy-3,3-
dimethyl-2-phenyl-3,3a,6,6a-tetrahydro-4H-furo[3,4-b]pyrrol-
4-one (8o)
1
°С (hexane–Et2O). Rf (50% EtOAc in hexane) 0.27. H NMR
Compound 8o (2 mg, 2%) was prepared according to the
general procedure in MeOH from tetronic acid 4c (60 mg,
0.286 mmol) and azirine 2f (66 mg, 0.455 mmol). Colorless
solid. Rf (50% EtOAc in hexane) 0.45. 1H NMR (CDCl3): 1.11
(s, 3H), 1.52 (s, 3H), 4.21 (d, J = 9.2 Hz, 1H), 4.53 (d, J = 9.2
Hz, 1H), 5.85 (br s, 1H), 7.34–7.38 (m, 2H), 7.45–7.55 (m,
3H), 7.63–7.65 (m, 2H), 7.99–8.01 (m, 2H). 13C NMR
(CDCl3): 21.1, 25.8, 56.9, 60.0, 72.4, 102.5, 128.2, 128.5,
128.6, 130.4, 131.0, 131.3, 132.6, 134.4, 174.6, 186.8.
HRMS−ESI: [M+H]+ calcd for C20H1935ClNO3+ 356.1048,
found 356.1054.
(CDCl3): 2.40 (s, 3H), 3.42 (d, J = 18.6 Hz, 1H), 3.79 (s, 3H),
4.10 (d, J = 18.6 Hz, 1H), 5.87 (br s, 1H), 7.20 (d, J = 8.0 Hz,
2H), 7.55−7.59 (m, 3H), 7.79−7.83 (m, 2H), 8.21−8.25 (m,
1H). 13C NMR (CDCl3): 21.6, 41.8, 53.1, 68.2, 110.7, 124.1,
125.7, 128.3, 129.1, 129.3, 130.3, 135.4, 136.3, 142.8, 154.1,
169.3, 172.6, 199.9. HRMS-ESI: [M+H]+ calcd for
C20H18NO4+ 336.1230, found 336.1239.
4.4.20. Methyl rac-(3aS,8bS)-8b-hydroxy-4-oxo-2-phenyl-4,8b-
dihydroindeno[1,2-b]pyrrole-3a(3H)-carboxylate (10b)
Compound 10b (56 mg, 59%) was prepared according to
the general procedure in MeOH from enol 6 (60 mg, 0.294
mmol) and azirine 2b (55 mg, 0.470 mmol). Colorless solid,
mp 171–173 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
4.4.16. Methyl rac-(3aR,6aR)-6a-hydroxy-2-(4-methylphenyl)-
4-oxo-6,6a-dihydro-3H-furo[3,4-b]pyrrole-3a(4H)-
carboxylate (8p)
1
0.27. H NMR (CDCl3): 3.40 (d, J = 18.7 Hz, 1H), 3.79 (s,
Compound 8p (63 mg, 57%) was prepared according to the
general procedure in DCE from tetronic acid 4d (60 mg, 0.380
mmol) and azirine 2a (80 mg, 0.611 mmol). Colorless solid,
mp 205–207 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
3H), 4.06 (d, J = 18.7 Hz, 1H), 6.55 (br s, 1H), 7.37–7.40 (m,
2H), 7.46−7.47 (m, 1H), 7.55–7.61 (m, 3H), 7.79–7.83 (m,
2H), 8.28–8.30 (m, 1H). 13C NMR (CDCl3): 41.6, 53.1, 68.2,
110.7, 124.0, 125.8, 128.2, 128.7, 130.4, 131.5, 132.2, 135.4,
136.3, 154.0, 169.1, 172.6, 199.8. HRMS−ESI: [M+Na]+ calcd
for C19H15NNaO4+ 344.0893, found 344.0898.
1
0.52. H NMR (CDCl3−DMSO-d6 mixture): 2.35 (s, 3H), 3.40
(d, J = 17.7 Hz, 1H), 3.77 (s, 3H), 3.91 (d, J = 17.7 Hz, 1H),
4.48 and 4.60 (AB-q, J = 9.3 Hz, 2H), 6.81 (s, 1H), 7.20 (d, J =
8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H). 13C NMR
(CDCl3−DMSO-d6 mixture) 20.6, 40.8, 52.2, 60.6, 74.7, 107.3,
127.4, 128.5, 128.7, 141.7, 165.2, 172.6, 173.5. HRMS−ESI:
[M+H]+ calcd for C15H16NO5+ 290.1023, found 290.1011.
4.4.21. Methyl rac-(3aS,8bS)-8b-hydroxy-2-(4-
methoxyphenyl)-4-oxo-4,8b-dihydroindeno[1,2-b]pyrrole-
3a(3H)-carboxylate (10c)
Compound 10c (58 mg, 56%) was prepared according to
the general procedure in MeOH from enol 6 (60 mg, 0.294
mmol) and azirine 2c (69 mg, 0.469 mmol). Colorless solid,
mp 195–197 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
4.4.17. rac-(3aS,6aR)-6a-Hydroxy-3a-(4-methoxyphenyl)-2-(4-
methylphenyl)-3,3a,6,6a-tetrahydro-4H-thieno[3,4-b]pyrrol-4-
one (9a)
1
0.18. H NMR (DMSO-d6): 3.40 (d, J = 18.5 Hz, 1H), 3.61 (s,
Compound 9a (27 mg, 28%) was prepared according to the
general procedure in MeOH from thiotetronic acid 5 (60 mg,
0.270 mmol) and azirine 2a (57 mg, 0.435 mmol). Pale yellow
3H), 3.79 (s, 3H), 3.98 (d, J = 18.5 Hz, 1H), 6.96−6.99 (m,
2H), 7.29 (s, 1H), 7.58–7.62 (m, 1H), 7.71–7.73 (m, 1H),
7.83−7.87 (m, 3H), 7.98–8.00 (m, 1H). 13C NMR (DMSO-d6):
41.3, 52.5, 55.3, 68.1, 110.6, 113.9, 123.5, 125.1, 125.6, 129.9,
130.1, 134.5, 136.2, 155.1, 161.9, 168.9, 169.3, 200.1.
HRMS−ESI: [M+Na]+ calcd for C20H17NNaO5+ 347.0999,
found 347.0983.
1
semisolid. Rf (50% EtOAc in hexane) 0.47. H NMR (DMSO-
d6): 2.38 (s, 3H), 3.65 and 3.70 (AB-q, J = 17.2 Hz, 2H), 3.77
(s, 3H), 3.81 and 3.98 (AB-q, J = 11.7 Hz, 2H), 6.43 (s, 1H),
6.95 (d, J = 8.8 Hz, 2H), 7.31–7.37 (m, 4H), 7.87 (d, J = 8.1
Hz, 2H). 13C NMR (DMSO-d6): 21.0, 39.8, 44.4, 55.1, 66.0,

8
Tetrahedron
9.06 (s, 2H). 13C NMR (CDCl3): 21.4, 126.6, 129.8, 133.6,
ACCEPTED MANUSCRIPT
139.8, 140.9, 150.4.
4.4.22. Methyl rac-(3aS,8bS)-8b-hydroxy-2-(4-nitrophenyl)-4-
oxo-4,8b-dihydroindeno[1,2-b]pyrrole-3a(3H)-carboxylate
(10d)
4.7. 4-(2-Chloroethoxy)-3-phenylfuran-2(5H)-one (15).
Enol 4a (46 mg, 0.26 mmol), Et3N (42 mg, 0.42 mmol),
azirine 2a (55 mg, 0.42 mmol), and DCE (4 mL) were placed
consequently to a screw cap ampoule and heated at 100 °C for
24 h under stirring. The solvent was removed in vacuo and the
residue was purified by column chromatography on silica gel
(eluent petroleum ether−EtOAc, 1 : 1) to give 14 (58 mg,
Compound 10d (65 mg, 60%) was prepared according to
the general procedure in DCE from enol 6 (60 mg, 0.294
mmol) and azirine 2d (76 mg, 0.469 mmol). Colorless solid,
mp 191–193 °С (hexane–Et2O). Rf (50% EtOAc in hexane)
1
0.29. H NMR (DMSO-d6): 3.55 (d, J = 18.8 Hz, 1H), 3.63 (s,
3H), 4.06 (d, J = 18.8 Hz, 1H), 7.52 (s, 1H), 7.61−7.65 (m,
1H), 7.74–7.76 (m, 1H), 7.86–7.90 (m, 1H), 8.01–8.03 (m,
1H), 8.13–8.15 (m, 2H), 8.26–8.28 (m, 2H). 13C NMR
(DMSO-d6): 41.5, 52.6, 68.0, 110.7, 123.6 (2C), 125.7, 129.5,
130.4, 134.8, 136.3, 138.3, 149.1, 154.3, 168.7, 169.0, 199.5.
HRMS−ESI: [M+Na]+ calcd for C19H14N2NaO6+ 389.0744,
found 389.0729.
1
93%). Colorless solid, mp 121–122 °С (CHCl3). H NMR
(CDCl3): 3.79 (t, J = 5.3 Hz, 2H), 4.33 (t, J = 5.3 Hz, 2H), 4.85
(s, 2H), 7.31–7.35 (m, 1H), 7.40–7.44 (m, 2H), 7.81–7.85 (m,
2H). 13C NMR (CDCl3): 41.7, 64.9, 70.7, 103.7, 127.9, 128.0,
128.3, 128.9, 171.2, 172.3. HRMS-ESI: [M+Na]+ calcd for
C12H1135ClNaO3 261.0289, found 261.0295.
4.8. Catalytic reaction of enol 4a with azirine 2a in the
presence of TEMPO
4.4.23. Ethyl rac-(3aR,11bR)-11b-hydroxy-2-(4-methylphenyl)-
6-oxo-6,11b-dihydro-3H-pyrrolo[2',3':3,4]pyrrolo[2,1-
b]quinazoline-3a(4H)-carboxylate (11)
Enol 4a (20 mg, 0.1 mmol), IPrCuCl (2.8 mg, 0.006 mmol),
azirine 2a (24 mg, 0.18 mmol), 2,2,6,6-tetramethylpiperidin-1-
yl)oxyl (TEMPO) (27 mg, 0.17 mmol) and DCE (1.7 mL) were
placed consequently to a screw cap ampoule and heated at 100
°C for 12 min under stirring. The solvent was removed in
vacuo. Dibromomethane was added as an internal standard,
Compound 11 (36 mg, 40%) was prepared according to the
general procedure in EtOH from enol 7 (60 mg, 0.221 mmol)
and azirine 2a (46 mg, 0.350 mmol). Colorless solid, mp 125–
1
128 °С (hexane–Et2O). Rf (50% EtOAc in hexane) 0.22. H
NMR (CDCl3): 1.24 (t, J = 7.1 Hz, 3H), 2.40 (s, 3H), 3.35 (d, J
= 17.8 Hz, 1H), 3.80 (d, J = 13.0 Hz, 1H), 4.24–4.29 (m, 3H),
5.05 (d, J = 13.0 Hz, 1H), 5.09 (br s, 1H), 7.22 (d, J = 8.1 Hz,
2H), 7.49–7.53 (m, 1H), 7.74–7.78 (m, 1H), 7.81 (d, J = 8.1
Hz, 2H), 7.88 (d, J = 8.1 Hz, 1H), 8.30–8.33 (m, 1H). 13C
NMR (CDCl3): 14.1, 21.6, 45.1, 53.4, 55.8, 62.3, 110.5, 121.3,
126.4, 127.1, 127.9, 128.7, 129.4, 129.5, 134.3, 143.1, 149.3,
156.0, 160.4, 169.6, 176.1. HRMS-ESI: [M+Na]+ calcd for
C23H21N3NaO4+ 426.1424, found 426.1435.
1
and H NMR analysis was performed to determine a NMR
yield. The yield of 8a is 77%.
Acknowledgements
We gratefully acknowledge the financial support of the
Russian Foundation for Basic Research (grant no. 16-03-
00596, 16-33-60130) and Saint Petersburg State University
(grant no. 12.38.217.2015). This research used resources of
‘Magnetic Resonance Research Centre’, ‘Chemical Analysis
and Materials Research Centre’, ‘Centre for X-ray Diffraction
Studies’, ‘Computing Centre’, and ‘Chemistry Educational
Centre’ of Research Park of Saint Petersburg State University.
4.5. Reaction of enol 4a with azirine 2a under catalyst-free
conditions
Enol 4a (60 mg, 0.34 mmol), azirine 2a (71 mg, 0.55
mmol), and MeOH (5 mL) were placed consequently to a
screw cap ampoule and heated at 100 °C for 45 min under
stirring. The solvent was removed in vacuo and the residue was
treated with ethyl acetate and 12 was filtered off (104 mg,
82%). Filtrate was concentrated in vacuo and purified by
column chromatography on silica gel (eluent petroleum ether–
EtOAc, from 4 : 1 to 1 : 2) to give 8a (16 mg, 15%). 2,2-
Supplementary data
1H, 13C NMR spectra of all new compounds and Cartesian
coordinates of optimized structures can be found online.
Supplementary data related to this article can be found online
at http://dx.doi.org/10.1016/j.tet.…. These data include MOL
files and InChiKeys of the most important compounds
described in this article.
Dimethoxy-2-(4-methylphenyl)ethan-1-aminium
5-oxo-4-
phenyl-2,5-dihydrofuran-3-olate (12). Colorless solid, mp
1
137−139 °C (EtOAc). H NMR (CDCl3−DMSO-d6 mixture):
2.28 (s, 3H), 3.01 (s, 2H), 3.11 (s, 6H), 4.33 (s, 2H), 6.90–7.09
(m, 4H), 7.13 (d, J = 7.8 Hz, 2H), 7.20 (t, J = 7.6 Hz, 2H), 7.29
(d, J = 7.9 Hz, 2H), 8.03 (d, J = 7.7 Hz, 2H). 13C NMR
(CDCl3−DMSO-d6 mixture): 20.3, 43.5, 48.2, 67.7, 92.2,
100.3, 123.3, 124.7, 126.3, 126.9, 128.5, 133.1, 133.5, 137.7,
176.2, 183.5. HRMS−ESI: cation [M–MeOH]+ calcd for
C10H14NO+ 164.1070, found 164.1067; anion [M]- calcd for
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