Intramolecular [4+2] cycloaddition in n-allyl- and n-propargyl-α-furyl lactams

Article abstract of DOI:10.1007/s10593-018-2290-2

The size of nitrogen heterocycle in N-allyl- and N-propargyl-α-furyl lactams, as well as the nature of the unsaturated substituent linked to the nitrogen atom affected the possibility of thermal intramolecular [4+2] cycloaddition between multiple bond and the furan ring. N-Allyl-γ-(α-furyl)butyrolactam was shown to be unreactive at temperatures from 140 to 230°С. Substituted δ-valero- and ε-caprolactams underwent partial Diels–Alder cyclization, forming tautomeric mixtures that contained both the initial open-chain form and the cyclic form (diastereomeric 3a,6-epoxyisoindoles fused with an aza ring) in ratios between 19:81 and 55:45. N-Propargyl-α-furyl lactams did not participate in thermal IMDAF reaction regardless of the ring size and the temperature of the synthesis.

Full text of DOI:10.1007/s10593-018-2290-2

DOI 10.1007/s10593-018-2290-2
Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
Intramolecular [4+2] cycloaddition
in N-allyl- and N-propargyl-α-furyl lactams
Dmitry S. Poplevin1, Eugeniya V. Nikitina1, Vladimir P. Zaytsev1,
Alexey V. Varlamov1, Santosh G. Tilve2, Fedor I. Zubkov1*
1 RUDN University,
6 Miklukho-Maklaya St., Moscow 117198, Russia; е-mail: fzubkov@sci.pfu.edu.ru
2 Goa University,
Taleigao Plateau, Goa 403206, India; е-mail: stilve@unigoa.ac.in
Submitted August 28, 2017
Accepted after revision January 27, 2018
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(4), 451–457
The size of nitrogen heterocycle in N-allyl- and N-propargyl-α-furyl lactams, as well as the nature of the unsaturated substituent linked to
the nitrogen atom affected the possibility of thermal intramolecular [4+2] cycloaddition between multiple bond and the furan ring.
N-Allyl-γ-(α-furyl)butyrolactam was shown to be unreactive at temperatures from 140 to 230°С. Substituted δ-valero- and
ε-caprolactams underwent partial Diels–Alder cyclization, forming tautomeric mixtures that contained both the initial open-chain form
and the cyclic form (diastereomeric 3a,6-epoxyisoindoles fused with an aza ring) in ratios between 19:81 and 55:45. N-Propargyl-α-furyl
lactams did not participate in thermal IMDAF reaction regardless of the ring size and the temperature of the synthesis.
Keywords: epoxyisoindoles, furans, lactams, IMDAF reaction, intramolecular [4+2] cycloaddition.
Fused and substituted lactams are commonly found in
plants and form structural part of molecules that show
antibiotic, antitumor, anti-inflammatory, antifungal,
antimicrobial, antiaggregant, cytotoxic, and other types of
biological activity.1 For these reasons, chemists are
motivated to develop new, more effective routes for the
synthesis of natural compounds, their derivatives, and
pharmacophoric agents containing cyclic amide moieties,
in order to obtain drugs with superior efficacy.
In the current work, we studied intramolecular Diels–
Alder reaction of furans containing an unsaturated group
(known as IntraMolecular Diels–Alder of Furan or IMDAF
reaction) for the synthesis of new potentially biologically
active heterocycles combining two privileged scaffolds
(lactam and isoindole) in their structures. For our
experiments, we selected large-scale industrial products:
γ-butyrolactam, δ-valerolactam, and ε-caprolactam, which
are used in the synthesis of widely known active pharma-
ceutical ingredients.
described in literature sources, but the overwhelming
majority of examples covered by review articles2 involve
the cycloaddition of either furans activated with certain
electron-donating substituents to various dienophiles or, on
the contrary, the addition of dienophiles activated with
electron-withdrawing groups to furans.
Thus, besides the aforementioned practical task we were
also interested in gaining theoretical insights into the
possibilities for using such weak dienophiles as allyl and
propargyl substituents in IMDAF reaction with unactivated
furans. Transformations of this type are rarely described in
the literature.3
α-Methoxy-substituted γ-butyrolactam, δ-valerolactam,
and ε-caprolactam 1а–с were obtained according to the
described procedures4 by electrolysis of the appropriate
cyclic amides in MeOH in an electrochemical cell equipped
with graphite electrodes.4d We used tetraethylammonium
p-toluenesulfonate as the background electrolyte, because it
was stable under these conditions (Scheme 1).
It should be noted that the Diels–Alder reaction in the
series of furan derivatives, along with its tandem variants
(for example, a sequence of N-acylation / [4+2] cyclo-
addition in 2-aminofurans and furfuryl amines) are well
Methoxy derivatives 1 after the evaporation of solvents
were purified by silica gel column chromatography and
then used in reactions with furan or 2-methylfuran. The
best catalyst for electrophilic substitution among all of the
0009-3122/18/54(4)-0451©2018 Springer Science+Business Media, LLC
451

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
Scheme 1
tested options was HClO4. When other catalysts were used
(p-TsOH, HCl, and BF3·OEt2), the yields of the target
α-furyl lactams 2 were lower.5
Table 1. Reaction conditions and yields
of compounds 1a–c, 2a–d, 3a–f
Com-
n
R1
R2
Yield, %
Substituted furans 2 were isolated in moderate yields
after chromatographic purification as viscous colorless oils
pound
1а
1b
1c
1
2
3
1
2
2
3
1
2
2
3
2
2
–
–
–
70
78
73
45
51
57
61
72
62
75
55
75
71
1
(Table 1). Н NMR spectra of these compounds featured
–
proton signals of furan rings in the range of 5.86–7.37 ppm
–
–
with the spin-spin coupling constants J3,4 = 2.0–3.0,
Н
–
2a
2b
2c
J5,4 = 1.7–2.0 Hz, as well as the proton signal of СН proton
belonging to the aza ring manifested as a triplet or double
doublet at 3.92–4.78 ppm with the spin-spin coupling of
J = 5.1–7.6 Hz.
Н
–
Me
Me
Н
–
–
2d
3a
3b
3c
The alkylation of α-furyl lactams 2 with allyl bromide or
propargyl bromide was performed according to the
standard procedure6 in DMSO in the presence of KOH at
room temperature. This synthesis provided N-alkyl
СH2CH=CH2
СH2CH=CH2
СH2CH=CH2
СH2CH=CH2
CH2C≡CH
CH2C≡CH
Н
Me
Me
Н
1
derivatives 3 (Scheme 1, Table 1). Н NMR spectra of
3d
3e
N-allyl-substituted compounds 3a–d additionally contained
proton signals of their unsaturated groups in the range of
2
Me
3f
4.6–5.8 ppm (spin-spin coupling constants J = 1.3–1.5,
3J = 10.3–11.2, and 16.9–17.1 Hz), while the spectra of
N-propargyl derivatives 3e,f contained a triplet at 2.1–
2.3 ppm (4J = 2.1–2.5 Hz). We tested the obtained
N-alkenylfurans 3 in a thermal intramolecular [4+2]
cycloaddition reaction.
Scheme 2
In order to optimize the conditions of the IMDAF
reaction, we selected 1-allyl-6-(furan-2-yl)piperidin-2-one
(3b) (Scheme 2), which was refluxed in о-xylene for 5 h
and produced a mixture of the starting compound 3b and
two cyclic isomers 4Ab/4Bb in 41:30:29 ratio according to
1H NMR spectra (Table 2). Longer refluxing of this
mixture for 8 h in о-xylene did not alter the ratio of
tautomers, but was accompanied by gradual accumulation
of unidentified polymeric products. Heating of piperidone
3b in MeCN under the conditions of microwave irradiation
(230°С, 10–11 bar, 30 min) shifted the equilibrium toward
In order to study the effect of reaction temperature on
the composition of products arising from intramolecular
[4+2] cycloaddition in N-allyl-6-(5-methylfuran-2-yl)-
piperidin-2-one 3с, we performed dynamic 1Н NMR
studies (see the Supplementary information file). It was
established that the IMDAF reaction proceeded at
significant rate at temperatures above 50°С. After the
reaction mixture was maintained in NMR ampoule for
5 min at 80°С, the content of compounds 3с/4Ac/4Bc in
CDCl2–CDCl2 solution was equal to 85:4:11. Heating of
the solution for 5 min at 140°С changed the ratio to
71:9:20. The equilibrium was completely established over
8 h at 140°С, reaching 55:13:32 ratio of the components
3с/4Ac/4Bc. This ratio of isomers was preserved upon
cooling of the sample to room temperature within NMR
spectrometer. It is interesting to note that the same exact
1
the cyclic forms 4Ab/4Bb. According to Н NMR spectra
acquired for CDCl3 solutions at room temperature, the
combined content of cyclic forms increased to 81%,
compared to 59% achieved in о-xylene. Thus, the
equilibrium composition of the reaction mixtures was
achieved more rapidly in a microwave reactor and all
subsequent experiments were performed under these
conditions.
The treatment of N-allyl derivatives 3c,d with
microwave irradiation under analogous conditions also led
to equilibrium mixtures of products 3с/4Aс/4Bс and
3d/4Ad/4Bd. At the same time, the position of tautomeric
equilibrium was not substantially affected by the presence
of a methyl group at position 5 of the furan ring, nor by
increasing the size of the nitrogen heterocycle.
452

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
Table 2. Tautomeric mixtures of compounds 3 and 4
products. The construction of similar fused ring systems by
using IMDAF reaction are quite seldom encountered in the
literature.8 Achieving a successful reaction always required
the presence of an additional heteroatom (S, O, or N) in the
pyrrolidine ring, which enhanced the conformational
mobility both of the starting molecules and the obtained
products.
in CDCl3 solutions at 22°С according to 1Н NMR spectra
Starting
n
1
R1
H
Conditions
Isomer ratio, %
compound
3a/4Aa/4Ba
100:0:0
100:0:0
o-xylene*
MW**
3a
It is known that triple bonds are generally less reactive
toward cycloaddition than double bonds. Successful
IMDAF reactions in the case of alkynylfurans, as a rule,
require the presence of electron-withdrawing substituents at
the triple bond,9 even though there are some exceptions.10
N-Propargyl-6-furylpiperidinones 3e,f under the condi-
tions of microwave irradiation at up to 250°С merely
underwent gradual resinification. According to the data of
1Н NMR spectroscopy, the obtained reaction mixtures did
not contain any of the intramolecular cycloaddition
products, compounds 4.
3b/4Ab/4Bb
41:30:29
2
Н
o-xylene*
3b
MW**
19:21:60
3с/4Aс/4Bс
55:13:32
85:4:11
55:13:32
3d/4Ad/4Bd
49:14:35
MW**
2
3
Me
Me
3c
C2D2Cl4***
C2D2Cl4*4
3d
MW**
* Refluxing in о-xylene, 5 h.
** Microwave irradiation in MeCN, 230°С, 10–11 bar, 30 min.
*** Heating in NMR ampoule with 1,1,2,2-tetrachloro-1,2-dideuterio-
ethane at 80°С for 5 min.
*4 Heating in NMR ampoule with 1,1,2,2-tetrachloro-1,2-dideuterioethane
at 140°С for 8 h.
Scheme 3
O
MW
N
N
O
ratio of isomeric forms 3с/4Ac/4Bc was detected when the
reaction was performed in a microwave reactor for 30 min
at 230°С (Table 2).
N
O
O
MeCN
140–250°C
CH2
3a
4Aa/4Ba
When the isomeric mixtures 3/4A/4B that were thus
obtained were separated by crystallization or silica gel
column chromatography, only the open-chain form 3 could
be isolated as an individual compound. The cyclic adducts
4A/4B could not be isolated as pure samples, as there was
always an impurity of the open-chain form 3. This allows
to assume that the retro Diels–Alder reaction occurred
during the chromatographic separation or upon moderate
heating of solutions containing the adducts 4A/4B, leading
to the formation of the thermodynamically more stable
starting material 3.
MW
O
N
O
O
O
CH
MeCN
140–250°C
R
R
3e R = H
f R = Me
4Ae/4Be R = H
4Af/4Bf
R = Me
Thus, we have shown in the current work that N-allyl-
α-furyl lactams featuring nitrogen heterocycles with size
larger than 5 atoms participate in IMDAF reactions with
the formation of tautomeric mixtures containing the
starting N-allyl derivatives along with Diels–Alder reaction
products. N-Propargyl-α-furyl lactams, regardless of the
size of the nitrogen heterocycle, as well as 5-membered
lactams do not undergo thermal intramolecular [4+2]
cycloaddition up to 250°С even under the conditions of
microwave irradiation.
The assignment of NMR signals for mixtures of isomers
4 as belonging to the series A or B was based on the data
obtained from two-dimensional NMR experiments and
used analogies to related compounds.7 In particular, fused
epoxyisoindoles 4А showed a NOESY cross peak between
the closely positioned protons of СН groups, denoted with
blue color in Scheme 2. Such a cross peak was absent in
the series of isomers 4B. The proton signal of NCH group
was manifested as a double doublet at 3.72 (compound
4Bb), 3.91 (compound 4Bc), 4.57 (compound 4Bd) and
3.93 (compound 4Аb), 3.82 (compound 4Ac), and 4.54 ppm
Experimental
IR spectra were recorded for KBr pellets on an Infralum
FT-801 FTIR spectrometer. 1H NMR spectra were acquired
on a JEOL JNM-ECA600 instrument (600 MHz) in CDCl3,
using TMS as internal standard. 13C NMR spectra were
recorded on a Bruker Avance 600 instrument (151 MHz) in
CDCl3, using the solvent signal (δ 77.4 ppm) or DMSO-d6
multiplet (δ 40.0 ppm) as internal standards. The product
ratio in the mixtures was determined from 1Н NMR spectra
as the ratio of integrated intensities for the corresponding
3
(compound 4Ad) (spin-spin coupling constants J = 3.2–3.5,
3J = 11.0–11.5 Hz), while the proton signal of CH2CH=CH2
group in the same compounds was observed as a multiplet
in the range of 1.88–2.15 ppm.
5-Furylpyrrolidinone 3а did not undergo intramolecular
[4+2] cycloaddition neither when heated in о-xylene nor
under the conditions of microwave irradiation (230–250°С,
10–13 bar) (Scheme 3). Not even a trace of Diels–Alder
adducts 4Aa/4Ba could be detected in the reaction mixture
1
protons. Kinetic Н NMR experiments were performed in
1
by method of Н NMR spectroscopy. Apparently, this was
1,1,2,2-tetrachloro-1,2-dideuterioethane (C2D2Cl4), using
the residual solvent signal of C2DНCl4 as internal signal
(δ 5.89 ppm). Mass spectra were recorded on a Thermo
associated with the high conformational strain arising from
the fusion of four five-membered rings in the cycloaddition
453

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
Trace DSQ mass spectrometer (EI ionization, 70 eV,
H-3 Fur); 6.32 (1H, dd, J = 2.0, J = 3.0, H-4 Fur); 7.13
(1H, br. s, NH), 7.37 (1H, d, J = 2.0, H-5 Fur). 13C NMR
spectrum, δ, ppm: 26.9; 29.9; 51.7; 106.0; 110.3; 142.4;
154.7; 178.7. Mass spectrum, m/z (Irel, %): 151 [M]+ (7), 146
(12), 134 (17), 133 (20), 122 (11), 106 (24), 94 (100), 79 (23),
77 (27), 66 (26), 39 (67). Found, %: C 63.40; H 5.90;
N 9.20. C8H9NO2. Calculated, %: C 63.58; H 6.00; N 9.37.
source temperature 200°С, direct introduction of sample)
or a Thermo Focus DSQ II GC-MS instrument (EI
ionization, 70 eV, source temperature 200°С, carrier gas –
helium, RTX-5MS column). Elemental analysis was
performed on a Euro Vector EA 3000 CHNS-analyzer.
Melting points were determined on an SMP 30 apparatus in
open capillaries and were not corrected. TLC analysis was
performed on Sorbfil PTSKh-AF-A plates, visualization
with iodine vapor or KMnO4 solution. The reagents were
obtained from Acros Organics and Alfa Aesar and were
used without additional purification, while the solvents
were distilled prior to the syntheses.
6-(Furan-2-yl)piperidin-2-one (2b). Yield 3.81
g
(51%), pale-yellow needles, mp 85–86°С (EtOAc–hexane),
Rf 0.61 (EtOAc–hexane, 1:3). IR spectrum, ν, cm−1: 1581
(N–C=O), 3369 (N–H). 1H NMR spectrum, δ, ppm (J, Hz):
1.77–1.83 (1Н, m, 4-CH2); 1.83–1.95 (2H, m, 5-CH2); 2.06–
2.15 (1H, m, 4-СH2); 2.38–2.44 (2H, m, 3-CH2); 4.63 (1H,
t, J = 6.6, 6-CH); 6.22 (1H, d, J = 3.0, H-3 Fur); 6.27 (1H,
br. s, NH); 6.33 (1H, dd, J = 1.7, J = 3.0, H-4 Fur); 7.37
(1H, d, J = 1.7, H-5 Fur). 13C NMR spectrum, δ, ppm: 19.0;
27.4; 31.3; 50.8; 106.6; 110.4; 143.6; 154.3; 172.4. Mass
spectrum, m/z (Irel, %): 165 [M]+ (6), 160 (20), 148 (19),
147 (29), 136 (19), 120 (30), 108 (97), 93 (20), 91 (29), 80
(31), 53 (56), 49 (31). Found, %: C 65.61; H 6.80; N 8.31.
C9H11NO2. Calculated, %: C 65.44; H 6.71; N 8.48.
6-(5-Methylfuran-2-yl)piperidin-2-one (2с). Yield 4.80 g
(57%), yellow viscous oil, Rf 0.51 (EtOAc–hexane, 1:3).
IR spectrum, ν, cm−1: broad absorption band at 1599–1615
(N–C=O), 3415 (N–H). 1H NMR spectrum, δ, ppm (J, Hz):
1.76–1.79 (1Н, m, 5-CН2); 1.87–1.95 (2Н, m, 4-CН2); 2.02–
2.11 (1H, m, 5-CН2); 2.26 (3Н, s, СH3); 2.38–2.44 (2Н, m,
3-CН2); 4.56 (1Н, t, J = 6.7, 6-СН); 5.90 (1Н, br. d,
J = 3.0, H-4 Fur); 6.08 (1Н, d, J = 3.0, Н-3 Fur); 6.09 (1Н,
s, NH). 13C NMR spectrum, δ, ppm: 13.5; 19.0; 27.5; 31.4;
51.0; 106.1; 106.8; 151.9; 152.8; 172.1. Mass spectrum, m/z
(Irel, %): 179 [M]+ (15), 174 (31), 162 (25), 161 (21), 150 (19),
134 (25), 122 (81), 107 (22), 105 (36), 94 (38), 67 (45), 63
(22), 49 (19). Found, %: C 66.85; H 7.37; N 7.95.
C10H13NO2. Calculated, %: C 67.02; H 7.31; N 7.82.
7-(5-Methylfuran-2-yl)azepan-2-one (2d). Yield 5.32 g
(61%), yellow oil, Rf 0.49 (EtOAc–hexane, 1:3). IR spect-
rum, ν, cm−1: 1602 (N–C=O), 3410 (N–H). 1H NMR
spectrum, δ, ppm (J, Hz) (signal of the NH group is not
observed in the spectrum): 1.33–1.36 (1Н, m, 5-CН2); 1.64–
1.70 (2Н, m, 4,5-CН2); 1.94–1.98 (1H, m, 4-CН2); 2.19–
2.26 (7Н, m, 3,6-CН2, СН3); 3.92 (1Н, t, J = 6.8, 7-СН);
5.86 (1Н, d, J = 3.0, H-4 Fur); 5.92 (1Н, d, J = 3.0, Н-3 Fur).
13C NMR spectrum, δ, ppm: 13.6; 25.3; 27.1; 32.7; 35.8;
38.9; 106.0; 106.2; 150.7; 153.9; 176.0. Mass spectrum, m/z
(Irel, %): 193 [M]+ (12), 187 (2), 176 (11), 175 (100), 173
(4), 131 (6), 95 (5), 91 (6), 77 (5), 55 (4), 44 (11), 43 (30).
Found, %: C 68.43; H 7.90; N 7.27. C11H15NO2.
Calculated, %: C 68.31; H 7.72; N 7.39.
Synthesis of N-allyl- and propargyl-substituted lactams
3a–f (General method). The appropriate furyl-substituted
lactam 2 (0.006 mol) was added to a slurry of KOH
(1.42 g, 0.024 mol) in DMSO (12 ml), followed by the
addition of allyl or propargyl bromide (0.012 mol). The
reaction mixture was stirred at room temperature for 1.5 h.
The obtained solution was worked up by the addition of
water (120 ml), and the obtained emulsion was extracted
with dichloromethane (3×50 ml). The organic extracts were
combined, dried over MgSO4, and evaporated. The
Synthesis of α-methoxylactams 1а–с (General
method). Tetraethylammonium p-toluenesulfonate (3.0 g,
0.007 mol) was added as background electrolyte to a
solution of the commercially available lactam (0.2 mol) in
MeOH (150 ml). The solution was cooled to 10–20°С,
continuously stirred, and electrical current (1.5 A, 30 V)
was passed between the graphite electrodes. Four
electrodes with the diameter of 5 mm were used, with the
submerged area equal to 6.9·103 mm2. The design of the
electrochemical cell has been described in the literature.4d
The duration of electrolysis under these conditions was ~20 h.
Subsequently, MeOH was removed by evaporation at
reduced pressure, while the products were purified by silica
gel column chromatography (column length 20 cm, particle
size 0.035–0.07 mm, the eluent was hexane and 1:3 EtOAc–
hexane). The characteristics of the obtained compounds
1a–c were in agreement with published data.11
5-Methoxypyrrolidin-2-one (1а). Yield 16.1 g (70%),
light-yellow oil, Rf 0.46 (EtOAc–hexane, 1:4) (Rf 0.65
(EtOAc–hexane, 1:3)11a).
6-Methoxypiperidin-2-one (1b). Yield 20.1 g (78%),
colorless needles, mp 110–112°С (hexane–EtOAc) (mp 114–
115°С (EtOAc)11d).
7-Methoxyazepan-2-one (1с). Yield 20.9 g (73%), light-
yellow oil, Rf 0.39 (EtOAc–hexane, 1:4) (Rf 0.55 (EtOAc–
hexane, 1:3)11a).
Synthesis of α-furyl lactams 2a–d (General method). A
solution of the appropriate α-methoxy lactam 1a–c
(0.045 mol) in chloroform (60 ml) was stirred and treated
by the addition of furan or 2-methylfuran (0.55 mol) and
aqueous 30% HClO4 solution (40 ml). The reaction mixture
was stirred at room temperature for 5 h (control by TLC),
neutralized by aqueous 10% NH3 solution, the organic
layer was separated, and the aqueous phase was extracted
with chloroform (2×50 ml). The organic extracts were
combined and dried over MgSO4. The solids were removed
by filtration and the extracts were evaporated. The products
were purified by silica gel column chromatography
(column length 20 cm, particle size 0.035–0.07 mm, the
eluent was hexane and 1:3 EtOAc–hexane).
5-(Furan-2-yl)pyrrolidin-2-one (2a).12 Yield 3.10 g
(45%), yellow oil, Rf 0.65 (EtOAc–hexane, 1:3). IR spect-
rum, ν, cm−1: 1580 (N–C=O), 3370 (N–H). 1H NMR
spectrum, δ, ppm (J, Hz): 2.18–2.25 (1H, m, 4-CH2) and
2.34–2.40 (1H, m, 4-СH2); 2.43–2.52 (2H, m, 3-СH2); 4.78
(1H, dd, J = 5.1, J = 7.6, 5-CH); 6.22 (1H, br. d, J = 3.0,
454

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
obtained products were purified by silica gel chromato-
56 (19), 55 (44), 41 (54). Found, %: C 71.05; H 7.97;
N 6.14. C13H17NO2. Calculated, %: C 71.21; H 7.81;
N 6.39.
graphy (column length 30 cm, particle size 0.035–0.07 mm,
eluent hexane and 1:2 EtOAc–hexane).
1-Allyl-5-(furan-2-yl)pyrrolidin-2-one (3а). Yield 0.83 g
(72%), viscous pale-brown oil, Rf 0.45 (EtOAc–hexane,
1:2). IR spectrum, ν, cm−1: 1617 (N–C=O). 1H NMR
spectrum, δ, ppm (J, Hz): 2.17–2.23 (1Н, m, 4-CН2); 2.32–
2.38 (1Н, m, 4-CН2); 2.46 (1Н, ddd, J = 6.4, J = 9.8,
J = 16.8, 3-CН2); 2.63–2.69 (1Н, dddd, J = 1.0, J = 6.4,
J = 9.8, J = 16.8, 3-CН2); 3.24 (1Н, ddd, J = 1.0, J = 7.6,
J = 15.1, CН2CH=CH2); 4.25–4.28 (1Н, m, CН2CH=CH2);
4.68 (1Н, dd, J = 4.5, J = 8.6, 5-CН); 5.08 (1Н, dq, J = 17.1,
J = 1.5, CH=CH2); 5.13 (1Н, dq, J = 10.2, J = 1.5, CH=CH2);
5.60–5.67 (1H, m, CH=CH2); 6.24 (1H, d, J = 3.3, H-3
Fur); 6.34 (1H, dd, J = 3.3, J = 1.5, Н-4 Fur); 7.39 (1H, d,
J = 1.5, H-5 Fur). 13C NMR spectrum, δ, ppm: 24.6; 30.3;
43.4; 55.0; 108.3; 110.3; 117.9; 132.2; 142.8; 152.8; 174.6.
Mass spectrum, m/z (Irel,%): 191 [M]+ (2), 135 (4), 134 (8),
108 (32), 94 (46), 79 (84), 77 (51), 66 (30), 55 (25), 41
(100). Found, %: C 69.08; H 6.90; N 7.25. C11H13NO2.
Calculated, %: C 69.22; H 6.81; N 7.46.
1-Allyl-7-(5-methylfuran-2-yl)azepan-2-one
(3d).
Yield 0.76 g (55%), pale-brown oil, Rf 0.38 (EtOAc–
hexane, 1:2). IR spectrum, ν, cm−1: 1644 (N–C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.32–1.35 (1H, m, 5-CН2);
1.64–1.72 (1H, m, 5-CН2); 2.00–2.06 (1H, m, 4-CН2); 2.07–
2.19 (1H, m, 4-CН2); 2.24 (3H, s, СН3); 2.30–2.38 (2Н, m,
6-CН2); 2.40–2.50 (2Н, m, 3-CН2); 3.23 (1Н, dd, J = 7.6,
J = 15.4, CН2CH=CH2); 4.54 (1Н, t, J = 4.6, 7-СН); 4.68–
4.71 (1Н, m, CН2CH=CH2); 5.06–4.69 (1Н, dq, J = 16.3,
J = 1.3, CH=CH2); 5.16 (1Н, dq, J = 10.7, J = 1.3,
CH=CH2); 5.78–5.82 (1Н, m, CH=CH2); 5.85 (1Н, d, J = 3.0,
Н-3 Fur); 5.91 (1Н, br. d, J = 3.0, Н-4 Fur). 13C NMR
spectrum, δ, ppm: 17.9; 19.2; 23.8; 27.2; 36.7; 43.3; 59.1;
109.2; 116.4; 117.1; 141.6; 150.7; 153.9; 172.9. Mass
spectrum, m/z (Irel, %): 233 [M]+ (10), 190 (16), 162 (18),
150 (10), 136 (32), 122 (90), 121 (35), 109 (21), 95 (15),
93 (15), 91 (32), 79 (11), 70 (25), 69 (50), 55 (34), 41 (25).
Found, %: C 71.75; H 7.99; N 6.24. C14H19NO2.
Calculated, %: C 72.07; H 8.21; N 6.00.
6-(Furan-2-yl)-1-(prop-2-yn-1-yl)piperidin-2-one (3e).
Yield 0.91 g (75%), brown oil, Rf 0.44 (EtOAc–hexane,
1:2). IR spectrum, ν, cm−1: 1678 (N–C=O). 1H NMR
spectrum, δ, ppm (J, Hz): 1.73–1.77 (1Н, m, 4-CH2); 1.88–
1.92 (1Н, m, 4-CH2); 2.08–2.13 (2Н, m, 5-CH2); 2.18 (1Н,
t, J = 2.5, С≡СН); 2.43–2.55 (2Н, m, 3-CH2); 3.39 (1Н, dd,
J = 2.5, J = 17.4, NСН2); 4.91 (1H, t, J = 5.1, 6-CH); 4.94
(1Н, dd, J = 2.5, J = 17.4, NСН2); 6.22 (1H, br. d, J = 3.3,
H-3 Fur); 6.34 (1H, dd, J = 2.0, J = 3.3, H-4 Fur); 7.39
(1H, br. d, J = 2.0, H-5 Fur). 13C NMR spectrum, δ, ppm:
18.1; 28.6; 32.2; 33.9; 54.2; 71.7; 78.8; 108.0; 110.3; 142.5;
152.9; 170.1. Mass spectrum, m/z (Irel, %): 203 [M]+ (6), 202
(16), 175 (5), 174 (11), 160 (1), 133 (20), 122 (11), 106
(24), 94 (100), 77 (22), 66 (24), 55 (27), 39 (65). Found, %:
C 71.07; H 6.39; N 6.97. C12H13NO2. Calculated, %:
C 70.92; H 6.55; N 6.79.
6-(5-Methylfuran-2-yl)-1-(prop-2-yn-1-yl)piperidin-2-one
(3f). Yield 0.92 g (71%), brown oil, Rf 0.39 (EtOAc–
hexane, 1:2). IR spectrum, ν, cm−1: 1665 (N–C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.70–1.75 (1Н, m, 4-СН2);
1.91–1.94 (1Н, m, 4-СН2); 2.06–2.11 (1Н, m, 5-СН2); 2.20
(1Н, t, J = 2.5, С≡СН); 2.27 (3H, s, CH3); 2.40–2.56 (3H,
m, 3,5-СН2); 3.41 (1Н, dd, J = 2.5, J = 17.1, NСН2); 4.81
(1H, t, J = 5.1, 6-CH); 4.92 (1Н, dd, J = 2.5, J = 17.1,
NСН2); 5.91 (1H, dq, J = 3.0, J = 1.0, H-4 Fur); 6.09 (1H,
br. d, J = 3.0, H-3 Fur). 13C NMR spectrum, δ, ppm: 13.7;
18.2; 28.7; 32.2; 33.8; 54.3; 71.6; 79.0; 106.1; 108.8;
150.9; 152.3; 170.2. Mass spectrum, m/z (Irel, %): 217 [M]+
(9), 216 (27), 202 (7), 174 (28), 160 (12), 148 (22), 147
(43), 146 (32), 136 (19), 121 (23), 120 (94), 108 (100), 107
(55), 91 (41), 77 (38), 65 (29), 55 (60), 43 (76), 39 (84).
Found, %: C 72.02; H 6.83; N 6.28. C13H15NO2.
Calculated, %: C 71.87; H 6.96; N 6.45.
1-Allyl-6-(furan-2-yl)piperidin-2-one (3b). Yield 0.76 g
(62%), pale-yellow needles, mp 102–102.5°С (hexane–
EtOAc), Rf 0.38 (EtOAc–hexane, 1:2). IR spectrum, ν, cm−1:
1
1610 (N–C=O). H NMR spectrum, δ, ppm (J, Hz): 1.70–
1.74 (1H, m, 4-CН2); 1.84–1.90 (1H, m, 4-CН2); 1.97–2.03
(1H, m, 5-CН2); 2.07–2.13 (1H, m, 5-CН2); 2.44 (1H, ddd,
J = 6.6, J = 10.3, J = 16.9, 3-CН2); 2.52 (1H, dt, J = 10.3,
J = 5.0, 3-CН2); 3.21 (1H, dddd, J = 0.8, J = 7.4, J = 15.3,
J = 8.3, CН2CH=CH2); 4.62 (1H, t, J = 5.0, 6-СH); 4.68–
4.73 (1H, m, CН2CH=CH2); 4.92 (1H, dq, J = 16.9,
J = 1.5, CH=CH2); 5.28 (1H, dq, J = 10.3, J = 1.5,
CH=CH2); 5.42 (1H, m, CH=CH2); 6.34 (1H, d, J = 3.1,
H-4 Fur); 6.38 (1H, dd, J = 1.7, J = 3.1, Н-3 Fur); 7.53
(1H, dd, J = 0.8, J = 1.7, H-5 Fur). 13C NMR spectrum,
δ, ppm: 17.8 (С-4); 32.0 (С-5); 35.1 (С-3); 47.5 (С-1 allyl);
54.2 (С-6); 107.5 (С-3 Fur); 110.2 (С-4 Fur); 117.1 (С-3
allyl); 132.8 (С-2 allyl); 142.2 (С-5 Fur); 153.7 (С-2 Fur),
170.0 (NCO). Mass spectrum, m/z (Irel, %): 205 [M]+ (3),
146 (2), 133 (4), 106 (7), 94 (24), 79 (11), 77 (16), 55 (25),
42 (29), 39 (100). Found, %: C 70.15; H 7.21; N 7.03.
C12H15NO2. Calculated, %: C 70.22; H 7.37; N 6.82.
1-Allyl-6-(5-methylfuran-2-yl)piperidin-2-one (3с). Yield
0.99 g (75%), pale-brown oil, Rf 0.42 (EtOAc–hexane, 1:2).
1
IR spectrum, ν, cm−1: 1622 (N–C=O). H NMR spectrum,
δ, ppm (J, Hz): 1.70–1.72 (1H, m, 4-CН2); 1.88–1.90 (1H,
m, 4-CН2); 1.97–2.00 (1H, m, 5-CН2); 2.07–2.09 (1H, m,
4-CН2); 2.26 (3H, s, CH3); 2.42 (1H, ddd, J = 6.4,
J = 10.1, J = 16.4, 3-CН2); 2.51 (1H, dt, J = 10.5, J = 5.1,
3-CН2); 3.21 (1H, dddd, J = 0.7, J = 7.5, J = 8.5, J = 15.2,
CН2CH=CH2); 4.54 (1H, t, J = 5.0, 6-СH); 4.68–4.71 (1H,
m, CН2CH=CH2); 5.06 (1H, dq, J = 16.6, J = 1.4,
CH=CH2); 5.12 (1H, dq, J = 10.4, J = 1.4, CH=CH2); 5.69–
5.75 (1H, m, CH=CH2); 5.90 (1H, d, J = 3.1, H-4 Fur);
6.02 (1H, d, J = 3.1, Н-3 Fur). 13C NMR spectrum, δ, ppm:
13.6; 23.8; 35.9; 39.9; 49.6; 51.0; 54.3; 96.0; 98.9; 106.1;
133.4; 151.7; 168.3. Mass spectrum, m/z (Irel, %): 219 [M]+
(12), 204 (1), 176 (6), 148 (8), 136 (19), 122 (32), 108
(100), 107 (40), 95 (14), 81 (19), 79 (25), 77 (22), 65 (13),
Intramolecular [4+2] cycloaddition in allyl derivatives
3b–d. A solution of N-allyl derivative 3b–d (2.4 mmol) in
MeCN (6 ml) was treated by microwave irradiation (230–
250°С, 10–13 bar) for 30 min in an Anton Paar® micro-
455

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
wave oven. The products were isolated by removing the
spectrum of isomer 4Bс, δ, ppm (J, Hz): 1.49–1.53 (1Н, m,
2-СH2); 1.64 (3Н, s, CH3); 1.69–1.74 (1Н, m, 2-СH2); 1.89–
1.96 (1Н, m, 7-CH2); 1.98–2.07 (4Н, m, 1,3,7-CH2, 6а-CН);
2.28–2.34 (1Н, m, 6-CН2); 2.41–2.54 (2Н, m, 1,3-CH2); 3.38
(1Н, dd, J = 8.6, J = 12.1, 6-СН2); 3.91 (1Н, dd, J = 3.3,
J = 11.2, 10b-CН); 6.26 (1Н, d, J = 5.6, 9-CН); 6.40 (1Н,
d, J = 5.6, 10-CН). 13C NMR spectrum of isomers 4Ас,
4Bс, δ, ppm (J, Hz): 13.6; 17.9; 19.3; 20.3; 20.9; 23.8;
26.1; 28.7; 30.3; 31.0; 32.1; 35.8; 39.9; 42.5; 44.4; 47.5;
47.8; 49.6; 50.8; 54.3; 59.1; 88.0; 88.3; 96.0; 98.9; 106.2;
106.3; 108.3; 117.0; 133.0; 133.3; 133.4; 140.4; 141.6;
151.7; 152.0; 168.4; 169.6; 170.2. Mass spectrum, m/z
(Irel, %): 219 [M]+ (12), 204 (19), 176 (6), 148 (8), 136
(19), 122 (32), 108 (100), 107 (40), 95 (14), 81 (19), 79
(25), 77 (22), 65 (13), 56 (19), 55 (44), 41 (54). Found, %:
C 71.53; H 8.13; N 6.64. C13H17NO2. Calculated, %: C 71.21;
H 7.81; N 6.39.
solvent at reduced pressure (Table 2). The composition and
spectral properties of products obtained as a result of
microwave irradiation are described below.
1-Allyl-6-(furan-2-yl)piperidin-2-one (3b),
(6aRS,8RS,10aRS,10bRS)-1,2,3,6,6a,7,8,10b-octahydro-
4H-8,10a-epoxypyrido[2,1-a]isoindol-4-one (4Ab) and
(6aRS,8RS,10aRS,10bSR)-1,2,3,6,6a,7,8,10b-octahydro-
4H-8,10a-epoxypyrido[2,1-a]isoindol-4-one (4Bb) (a mixture
of compounds; in CDCl3 solution the ratio of 3b/4Ab/4Bb
1
was equal to 19:21:60 according to Н NMR data). All
spectral data are given for the isomeric mixture. Yellow oil.
IR spectrum, ν, cm−1: 1654 (N–C=O). The characteristics of
piperidine 3b are given above. 1H NMR spectrum of
isomer 4Ab, δ, ppm (J, Hz): 1.61 (1Н, dd, J = 6.2, J = 11.6,
7-CH2); 1.68–1.85 (3H, m, 1,2,7-CH2); 1.95–2.05 (3Н, m,
1,2,3-CH2); 2.15–2.46 (2Н, m, 3-CH2, 6а-CН); 3.28 (1Н,
dd, J = 8.1, J = 12.3, 6-СН2); 3.78 (1Н, dd, J = 9.4,
J = 12.3, 6-СН2); 3.93 (1Н, dd, J = 3.3, J = 11.0, 10b-CН);
5.05 (1Н, dd, J = 1.5, J = 6.2, 8-CН); 6.31 (1Н, d, J = 5.9,
10-CН); 6.41 (1Н, dd, J = 1.5, J = 5.9, 9-CН). 13C NMR
spectrum of isomer 4Ab, δ, ppm (the assignment of
specific carbon signals was based on a set of two-
dimensional NMR experiments COSY, HSQC, HMBC,
NOESY): 20.9 (С-2); 23.8 (С-1); 31.0 (С-3); 33.4 (С-7);
39.0 (С-6a); 50.6 (С-6); 58.7 (С-10b); 79.7 (С-8); 96.2
1-Allyl-7-(5-methylfuran-2-yl)azepan-2-one
(3d),
(3RS,4aRS,11aRS,11bRS)-3-methyl-3,4,4a,5,9,10,11,11a-
octahydro-3,11b-epoxyazepino[2,1-a]isoindol-7(8H)-one
(4Ad)
and
(3RS,4aRS,11aSR,11bRS)-3-methyl-
3,4,4a,5,9,10,11,11a-octahydro-3,11b-epoxyazepino[2,1-a]-
isoindol-7(8H)-one (4Bd) (a mixture of compounds; in
CDCl3 solution the ratio of 3d/4Ad/4Bd was equal to
49:14:35 according to 1H NMR data). (All spectral data are
given for the isomeric mixture). Beige oil. Rf 0.38 (EtOAc–
hexane, 1:2). IR spectrum, ν, cm−1: 1629 (N–C=O). The
1
(С-10a); 132.7 (С-10); 138.3 (С-9); 169.5 (С-4). H NMR
1
spectrum of isomer 4Bb, δ, ppm (J, Hz): 1.36 (1Н, dd,
J = 6.2, J = 11.6, 7-CH2); 1.68–1.85 (3H, m, 1,2,7-CH2);
1.95–2.05 (3Н, m, 1,2,3-CH2); 2.15–2.46 (2Н, m, 3-CH2,
6а-CН); 3.18 (1Н, dd, J = 8.1, J = 12.3, 6-СН2); 3.72 (1Н,
dd, J = 3.3, J = 11.0, 10b-CН); 4.47 (1Н, dd, J = 9.4,
J = 12.3, 6-СН2); 4.98 (1Н, dd, J = 1.5, J = 6.2, 8-CН);
6.12 (1Н, d, J = 5.9, 10-CН); 6.36 (1Н, dd, J = 1.5,
J = 5.9, 9-CН). 13C NMR spectrum of isomer 4Bb, δ, ppm:
20.2 (С-2); 26.1 (С-1); 30.2 (С-3); 32.0 (С-7); 41.0 (С-6a);
49.4 (С-6); 58.9 (С-10b); 80.1 (С-8); 99.2 (С-10a); 132.8
(С-10); 137.1 (С-9); 168.2 (С-4). Mass spectrum, m/z
(Irel, %): 205 [M]+ (15), 203 (3), 146 (2), 133 (4), 106 (7),
94 (24), 79 (11), 77 (16), 55 (25), 42 (29), 39 (100). Found,
%: C 70.37; H 7.61; N 6.43. C12H15NO2. Calculated, %: C
70.22; H 7.37; N 6.82.
characteristics of azepine 3d are given above. H NMR
spectrum of isomer 4Ad, δ, ppm (J, Hz): 1.25 (1Н, dd,
J = 7.2, J = 11.1, 4-СH2); 1.31–1.36 (1H, m, 4-СH2); 1.64–
1.72 (2Н, m, 10-СH2); 1.88–1.98 (3Н, m, 9,11-СН2, 4а-СН);
1.99–2.08 (1Н, m, 9-СH2); 2.16 (1Н, m, 11-СH2); 2.24
(3Н, s, СН3); 2.31–2.53 (3H, m, 5,8-СH2); 3.22 (1Н, dd,
J = 7.1, J = 15.1, 5-СН2); 4.54 (1Н, dd, J = 3.2, J = 11.5,
11а-СН); 5.85 (1Н, d, J = 5.7, 2-СН); 5.91 (1Н, d, J = 5.7,
1
1-СН). H NMR spectrum of isomer 4Bd, δ, ppm (J, Hz):
1.21 (1Н, dd, J = 7.3, J = 11.1, 4-СH2); 1.31–1.36 (1H, m,
4-СH2); 1.64–1.72 (2Н, m, 10-СH2); 1.88–1.98 (3Н, m,
9,11,-СH2, 4а-CН); 1.99–2.08 (1Н, m, 9-СH2); 2.16 (1Н,
m, 11-СH2); 2.26 (3Н, s, СН3); 2.31–2.53 (4Н, m, 5,8-СН2);
4.57 (1Н, dd, J = 3.2, J = 11.5, 11а-CН); 5.85 (1Н, d, J = 5.7,
2-CН); 5.90 (1Н, d, J = 5.7, 1-CН). 13C NMR spectrum of
isomers 4Ad, 4Bd, δ, ppm: 13.7 (2C); 17.9; 19.2; 20.3;
20.9; 23.8, 24.5 (2C); 25.6; 28.7; 31.0; 32.1; 32.7; 36.7;
38.9; 41.9; 43.3; 47.5; 50.9; 54.3 (2C); 55.2; 59.1; 106.0;
106.1; 106.2 (2C); 108.3; 109.2; 116.4; 117.1; 133.0;
134.4; 141.6; 150.7; 151.7; 152.0; 153.9; 170.3; 172.9
(2C). Mass spectrum, m/z (Irel, %): 233 [M]+ (10), 190 (16),
162 (18), 150 (10), 136 (32), 122 (90), 121 (35), 109 (21),
95 (15), 93 (15), 91 (32), 79 (11), 70 (25), 69 (50), 55 (34),
41 (25). Found, %: C 72.35; H 7.94; N 6.34. C14H19NO2.
Calculated, %: C 72.07; H 8.21; N 6.00.
6-(5-Methylfuran-2-yl)piperidin-2-one (3с),
(6aRS,8RS,10aRS,10bRS)-8-methyl-1,2,3,6,6a,7,8,10b-octa-
hydro-4H-8,10a-epoxypyrido[2,1-a]isoindol-4-one (4Ac) and
(6aRS,8RS,10aRS,10bSR)-8-methyl-1,2,3,6,6a,7,8,10b-octa-
hydro-4H-8,10a-epoxypyrido[2,1-a]isoindol-4-one (4Bc)
(a mixture of compounds; in CDCl3 solution the ratio of
1
3с/4Aс/4Bс was equal to 55:13:32 according to H NMR
data). (All spectral data are given for this isomeric
mixture.) Yellow oil, Rf 0.42 (EtOAc–hexane, 1:2). IR spect-
rum, ν, cm−1: 1661 (N–C=O). The characteristics of piperidine
3с are given above. 1H NMR spectrum of isomer 4Aс, δ, ppm
(J, Hz): 1.49–1.53 (1Н, m, 2-СH2); 1.64 (3Н, s, CH3); 1.69–
1.74 (1Н, m, 2-СH2); 1.89–1.96 (1Н, m, 7-CH2); 1.98–2.07
(4Н, m, 1,3,7-CH2, 6а-CН); 2.28–2.34 (1Н, m, 6-СН2); 2.41–
2.54 (2Н, m, 1,3-CH2); 3.23 (1Н, dd, J = 7.6, J = 15.1,
6-СН2); 3.82 (1Н, dd, J = 3.5, J = 11.1, 10b-CН); 6.30 (1Н,
Determination of cyclization reaction kinetics for
compound 3с. An ampoule containing 5% solution of
compound 3с in C2D2Cl4 was heated while placed inside
NMR spectrometer. After every temperature increase by
10°С (2–3 min), the sample was thermostated and
maintained for 5 min, then 1Н NMR spectrum was
acquired. The spectra were acquired within the temperature
1
d, J = 5.6, 9-CН), 6.36 (1Н, d, J = 5.6, 10-СН). H NMR
456

Chemistry of Heterocyclic Compounds 2018, 54(4), 451–457
Khrustalev, V. N.; Novikov, R. A; Borisov, R. S.;
range from 30 to 140°С. When the temperature reached
140°С, the sample was maintained at that temperature,
Varlamov, A. V. Chem. Heterocycl. Compd. 2012, 48, 785.
[Khim. Geterotsikl. Soedin. 2012, 844.] (h) Claeys, D. D.;
Stevens, C. V.; Roman, B. I.; Van De Caveye, P.; Waroquier, M.;
Van Speybroeck, V. Org. Biomol. Chem. 2010, 8, 3644.
(i) Claeys, D. D.; Moonen, K.; Roman, B. I.; Nemykin, V. N.;
Zhdankin, V. V.; Waroquier, M.; Van Speybroeck, V.;
Stevens, C. V. J. Org. Chem. 2008, 73, 7921. (j) Varlamov, A. V.;
Boltukhina, E. V.; Zubkov, F. I.; Nikitina, E. V.; Turchin, K. F. J.
Heterocycl. Chem. 2006, 43, 1479. (k) Namboothiri, I. N. N.;
Ganesh, M.; Mobin, S. M.; Cojocaru, M. J. Org. Chem. 2005,
70, 2235. (l) Varlamov, A. V.; Boltukhina, E. V.; Zubkov, F. I.;
Nikitina, E. V.; Turchin, K. F. J. Heterocycl. Chem. 2006, 43, 1479.
4. (a) Nyberg, K.; Servin, R. Acta Chem. Scand. 1976, B30, 640.
(b) Warning, K.; Mitzlaff, M. Tetrahedron Lett. 1979, 20,
1563. (c) Shono, T.; Matsumura, Y.; Tsubata, K.; Sugihara, Y.;
Yamane, S.; Kanazawa, T.; Aoki, T. J. Am. Chem. Soc. 1982,
104, 6697. (d) Shono, T.; Matsumura, Y.; Tsubata, K. Org.
Synth. Coll. Vol. 1990, 7, 307.
1
while Н NMR spectra were acquired every 30 min for a
total of 12 h. There were no visible changes in the obtained
spectra after 8 h.
A Supplementary information file containing 1Н and 13
С
NMR spectra of the synthesized compounds, two-
dimensional COSY, HMBC, HSQC, NOESY spectra for
the mixtures of isomers 3b/4Ab/4Bb and dynamic
1Н NMR spectra for the isomeric mixture of 3с/4Aс/4Bс at
different temperatures is available at the journal website at
http://link.springer.com/journal/10593.
Synthesis of the starting compounds 2 and 3 was
supported by the Russian Foundation for Basic Research
(grant No. 17-53-45016). The synthesis and NMR
spectroscopy of adducts 4 were performed with financial
support from the RUDN University program ''5-100''.
5. (a) Edwards, O. E.; Greaves, A. M.; Sy, W. W. Can. J. Chem.
1988, 66, 1163. (b) Ben-Ishai, D.; Sataty, I.; Bernstein, Z.
Tetrahedron 1976, 32, 1571. (c) Shono, T.; Matsumura, Y.;
Tsubata, K.; Takata, J. Chem. Lett. 1981, 1121.
6. Vasse, J.; Levacher, V.; Bourguignon, J.; Dupas, G.
Tetrahedron 2003, 59, 4911.
7. Zubkov, F. I.; Golubev, V. D.; Zaytsev, V. P.;
Bakhanovich, O. V.; Nikitina, E. V.; Khrustalev, V. N.;
Aysin, R. R.; Timofeeva, T. V.; Novikov, R. A.; Varlamov, A. V.
Chem. Heterocycl. Compd. 2016, 52, 225. [Khim. Geterotsikl.
Soedin. 2016, 52, 225.]
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