Cascade of the Hinsberg / IMDAF reactions in the synthesis 2-arylsulfonyl-3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines in water

Article abstract of DOI:10.1016/j.tet.2021.132032

N-Furfuryl allylamines, readily accessible from corresponding furfurals or furfuryl amines, react with a broad range of arylsulfonyl chlorides with the formation of a 3a,6-epoxyisoindole core in one synthetic stage. Usually, in boiling water, the interaction sequence involves two consecutive steps: the Hinsberg reaction and the intramolecular Diels–Alder furanе (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key [4 + 2] cycloaddition step proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The method allows the ability to obtain N-sulfaryl-substituted 3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines, which are potentially useful substrates for further transformations and subsequent bioscreening, in particular antimicrobial activity.

Full text of DOI:10.1016/j.tet.2021.132032

Tetrahedron 85 (2021) 132032
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cascade of the Hinsberg / IMDAF reactions in the synthesis 2-
arylsulfonyl-3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines in
water
Maryana A. Nadirova a, Anastasia V. Khanova a, Fedor I. Zubkov a, Dmitriy F. Mertsalov a,
Irina A. Kolesnik b, Sergey K. Petkevich b, Vladimir I. Potkin b, Anton A. Shetnev c,
Sofia I. Presnukhina c, Anna A. Sinelshchikova d, Mikhail S. Grigoriev d,
,
*
Vladimir P. Zaytsev a
a Department of Organic Chemistry, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., 117198, Moscow, Russian
Federation
b Laboratory of Organoelement Compounds, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 13 Surganov St., 220072,
Minsk, Belarus
c Pharmaceutical Technology Transfer Center, Yaroslavl State Pedagogical University Named After K. D. Ushinsky, 108/1 Republican St., 150000, Yaroslavl,
Russian Federation
d Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky pr. 31, bld. 4, 119071, Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
N-Furfuryl allylamines, readily accessible from corresponding furfurals or furfuryl amines, react with a
broad range of arylsulfonyl chlorides with the formation of a 3a,6-epoxyisoindole core in one synthetic
stage. Usually, in boiling water, the interaction sequence involves two consecutive steps: the Hinsberg
reaction and the intramolecular DielseAlder furanе (IMDAF) reaction. The scope and limitations of the
proposed method were thoroughly investigated, and it was revealed that the key [4 þ 2] cycloaddition
step proceeds through an exo-transition state, giving rise to the exclusive formation of a single diaste-
reomer of the target heterocycle. The method allows the ability to obtain N-sulfaryl-substituted 3a,6-
epoxyisoindoles and 4a,7-epoxyisoquinolines, which are potentially useful substrates for further trans-
formations and subsequent bioscreening, in particular antimicrobial activity.
Received 23 December 2020
Received in revised form
12 February 2021
Accepted 15 February 2021
Available online 19 February 2021
Keywords:
Sulfonamides
IMDAF
© 2021 Elsevier Ltd. All rights reserved.
Isoindoles
Diels-alder reaction
Antimicrobial activity
1. Introduction
products containing sulfonamide fragments have a wide range of
physiological activity in that they possess antibacterial properties
Chemistry of sulfonamides, analogues of sulfamides with a sulfonyl
group connected to only one amine group, has been given consider-
able attention in the literature. One of the first examples of the syn-
thesis of sulfamide appeared in print in 1838 [1]. A large number of
publications that followed after this were based on various chemical
and physical properties, methods of synthesis, and application of sul-
fonamides [2a,b]. The electronic and structural properties of the sul-
fonamide moiety make it a bio isostere of such compounds as urea,
thiourea, carbamates, and sulfamides [3]. The steady attention paid to
sulfonamides can be explained by the fact that linear and cyclic
[2b,4a,b], cytotoxic [5] and diuretic activity [6a,b], are active against
seizures [7], and inhibit various enzymes (human leukocyte elastase
and cathepsin G, HIV-1 protease [8]). Sulfonamides are also used in
photography [9] as well as fungicidal [10a,b] and insecticidal mixtures
[11] as detergents. The most widely used sulfonylamides are de-
rivatives [12] of para-aminobenzenesulfamide or sulfanilic acid (Fig. 1).
On the other hand, isoindoles are well-known nitrogen-containing
heterocyclic [13aec] compounds (Fig. 1), a fragment of which is con-
tained in the molecules of phthalocyanine dyes [14], bioactive natural
alkaloids [15aed] (for example, isoborreverine alkaloid [15a]), and
some polymers [16aec]. Therefore, the main goal of this work is
todevelop a simple practical approach to heterocyclic systems con-
taining isoindole (specifically, 3a,6-epoxyisoindole) and sulfonylamide,
combining the above fragmentsinto one structure, in order to further
* Corresponding author.
E-mail address: vzaitsev@sci.pfu.edu.ru (V.P. Zaytsev).
https://doi.org/10.1016/j.tet.2021.132032
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
2. Results and discussion
Starting N-furfuryl allylamines 1 (Scheme 2) were obtained by
the direct alkylation of furfuryl amines with allyl halides in the
presence of DIEA or potash [21a] (1a¡e, path 1) or by reductive
amination reaction [13] (1f¡r, path 2). In the first stage, conden-
sation of the corresponding furfural with allylamine in benzene
with azeotropic distillation of water or in dichloromethane in the
presence of anhydrous magnesium sulphate led to the formation of
imines, which without isolation were taken into the second step,
reduction by sodium borohydride. Subsequent treatment and
fractional distillation of the crude reaction masses gave the starting
furfuryl allylamines 1 as yellowish mobile oils, yields of which are
presented below. In some cases, the obtained amines were used in
the next step without further purification. Furylpropylallyl- (1q)
Fig. 1. Representative biologically active compounds containing sulfonamide and
isoindole moieties.
and
b-furfuryl (1r) allylamines were synthesized analogously using
b
-furfural or furylpropylaldehyde as the starting materials. Furfur-
study their pharmacophoric properties. Sulfonyl substituted hydro-
genated isoindoles and isoquinolines possess a wide range of phar-
macological activity. For example, they are known to inhibit the
enzymatic activity of AKR1C3 (aldo-keto reductase family 1 member
C3) [17a], have activity as an matrix metalloproteinase inhibitor [17b,c]
and are potent modulators of glucocorticoid receptors [17d].
ylamines 1s and 1t were prepared by a CeC coupling reaction in
acceptable yields. Taking into account the availability and low cost
of the initial chemicals, in most cases we did not optimize the
alkylation and reductive amination conditions, therefore the yields
of amine derivatives 1 ranged between 18 and 65% (Scheme 2).
Considering the presence of a double bond in the target amines 1,
reduction with hydrogen on a catalyst, LAH, etc. may make them
difficult to obtain.
One of the common approaches to the synthesis of polycyclic
compounds (incl. isoindoles and isoquinolines) is the Intra-
molecular DielseAlder Furanе (IMDAF) reaction [18aee]. In 1977, a
group of chemists from Armenia was the first to describe the
cyclization of a sulfonamide containing both allyl- and furfuryl
moieties at a nitrogen atom (Scheme 1) [19]. Under heating, the
sulfonamide obtained from tosyl chloride and furfuryl allylamine
was transferred to a thermal Diels-Alder reaction product. Unfor-
tunately, the authors did not provide any spectral data or the in-
formation on the presence of stereoisomers. The first complete
description of N-sulfaryl-3a,6-epoxyisoindoles appeared only 20
years later [20]. McNelis and Starr carried out the allylation of
furfuryl sulfonylamides with allyl bromide in 1998. Subsequent
thermal cyclization at 80 ꢀC led to the formation of the desired
epoxyisoindoles [20a]. Refluxing solutions of N-allyl sulfonamides
in toluene produced 2-arylsulfonylepoxyisoindoles as well [20b].
The most recent and relevant article on this topic was published in
2016 [21aed]. The authors first proposed a “one-pot” approach
based on sequential N-acylation and the intramolecular [4 þ 2]
cycloaddition of the allyl substituent to a furan ring (Scheme 1).
In this research, we focused on investigating the influence of
various factors on the cyclization of Diels-Alder adducts as well as
on exploring the scope and limitations of the above-mentioned
reactions. Taking into account the promising biological activity of
sulfonamide and isoindole scaffolds, we planned to test target
compounds for antibacterial activity against sensitive strains of
gram-negative or gram-positive bacteria.
Literature [21] has shown that the intramolecular [4 þ 2]
cycloaddition of the allyl residue to the furan fragment in secondary
N-furfuryl allylamines (1) cannot be carried out either in boiling
benzene or during prolonged boiling in toluene [21a,b]. However,
boiling N-furfuryl allylamines (1a,b,d,f¡n) in water with various
arylsulfonyl chlorides in the presence of Na2CO3 gives the targeted
3a,6-epoxyisoindoles (2a¡ee,gg¡mm, 4a,b) (Schemes 3 and 4).
The choice of water as a solvent was determined by several factors:
simplicity of target compounds isolation, comparative stability of
aryl sulfonyl chlorides in aqueous solutions, and the concept of
“green chemistry” [22]. Unlike some work [21a], where it took
2e4 d at room temperature for the reaction to be completed, we
used the method of boiling in water for 3 h; 1H NMR analysis of the
reaction mixtures indicated that this time is sufficient for complete
formation of the required epoxyisoindoles 2. When the interaction
between aryl sulfonyl chlorides and allylamines 1fen was carried
out at 100 ꢀC in boiling water the exclusive formation of products 2
bearing an oxabicycloheptene ring was detected (Scheme 3). The
reaction of N-allylfurfurylamine 1f, which was used as a model
compound, with the simplest and most readily available tosyl
chloride, proceeded at r.t to afford tosyl amide 3b (Ar ¼ 4-MeC6H4,
R1 ¼ R2 ¼ H) in almost quantitative yield (91%). As established by
dynamic NMR experiments (ESI), compound 3b which possesses
diene and dienophile moieties remained almost intact at temper-
atures below 50 ꢀC. Thermal cyclization of the “not substituted”
compound 3b is described in detail in the work [20b]. Lowering the
temperature to 0ꢀС and below leads to freezing of the reaction
mixture.
The reaction products 2 are crystalline substances and can be
isolated in almost all cases by simple filtration after cooling of the
reaction mixtures to ambient temperature.
The reaction starts with the Hinsberg acylation, which leads to
N-sulfonamide formation. Corresponding intermediates 3 under-
went in situ the thermal [4 þ 2] cycloaddition step in boiling water,
giving the targeted epoxyisoindoles 2. Decipherment of the NMR
spectra showed that the resulting compounds contained charac-
teristic sets of proton signals of the epoxybicycloheptene fragment
(H-4, d, J ~5.5 Hz; H-5, dd, J ~1.6 Hz, 5.5 Hz; H-6, dd, J ~1.6 Hz,
4.5 Hz). On the other hand, J-coupling of the H-7 atom with the H-
7a atom (Н-7А, ddd, J ~3.4 Hz, J ~4.4 Hz, J ~11.7 Hz; Н-7В, dd, J
Scheme 1. Published general approaches to the synthesis of 2-arylsulfonyl-3a,6-
epoxyisoindoles using the IMDAF reaction.
2

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
Scheme 2. Reaction scope of the starting amines 1a¡t. Reaction conditions: (i) DIEA or K2CO3, dry THF; (ii) anhyd. MgSO4, DCM or PhH,
D
after NaBH4, MeOH; (iii) ArB(OH)2,
a
Pd(PPh3)4, THF, 1
М
KOH. Without purification.
~7.6 Hz, J ~11.7 Hz) shows that the cycloaddition step ends up
forming exo-adducts of the Diels-Alder reaction. This was also
confirmed by XRD analysis of compound 2w (Fig. 2).
Single-crystal XRD analysis fully supports the structure of 2w
and reveals that the compound crystallizes in a triclinic crystal
system P-1 space group with one molecule in the asymmetric unit.
The CeOeC angle of the epoxy fragment notably deviates from
120ꢀ and is equal to 95.8ꢀ, which is typical for epoxyisoindoles
[23a,b]. The pyrrolidine ring adopts a twist conformation, and the
tetrahydrofuran rings adopt an envelope conformation with the O
halogens (1j, 1k, 1l, 1n) in the furan ring, with corresponding
arylsulfonyl chlorides. On the other hand, the presence of ester
(CO2Et) or benzhydryl (CHPh2) groups in the C-5 position of the
furan ring in compounds 1d,p, or the location of two halogens (or a
CF3 group) in the aryl moiety of arylsulfonyl chlorides, interferes
with the [4 þ 2] cycloaddition stage. Thus, in addition to the 3a,6-
epoxyisoindoles 2, the formation of N-acylation products, N-aryl-
sulfonyl furfuryl allyl amines 3gg¡3 mm, has also been observed.
In the case of the trimethylsilyl group (amine 1o), only the non-
cyclic product 3ff was isolated (Scheme 3). Additional experi-
ments showed that prolonged heating for 6 h of the 2/3 isomeric
mixtures in toluene did not lead to the transformation of open
compounds 3 into cycloadducts 2. This can be explained by the
reversibility of the intramolecular DielseAlder reaction. Heating
the same mixtures (2/3gg¡mm) in toluene under MW irradiation
(120 ꢀC, 30 min, 1 atm) or in xylene at ~140 ꢀC resulted in rapid
destruction of sulfonamides 2 and 3. In cases of 3gg¡3 mm
preparation, the separation of “cyclic” and “non-cyclic” was needed.
Thus, to isolate each product in a pure state and to characterize
them, column chromatography was used (for yields, see part two of
Scheme 3). In cases when the cyclic and non-cyclic isomers were
formed it was interesting to study the equilibrium in course of the
reaction. Thus, as illustrated by the pair of the isomers 2jj/3jj, it has
been shown that heating each isomer individually in C6D6 during
50 h with monitoring the NMR spectra led each of the two
atom as the flap. The molecules are packed due to CeH/O and p-p
interactions (Table S5) forming 1D chains along the [001] direction
(Fig. S2).
The first task solved during this study was elucidating the effects
of aryl sulfonyl chlorides (ArSO2Cl) on the course of the acylation/
cycloaddition process. As follows from the analysis of the data
presented in Scheme 3, it is rather difficult to make unambiguous
conclusions about the influence of the N-sulfonamide substituent
in 3 on the course of the intramolecular [4 þ 2] cycloaddition. The
yields of epoxyisoindoles 2 presented in Scheme 3 varied from
medium to high.
Regarding substituents in the furan fragment (R1, R2), it can be
said that the effect is more definite. Only the desired arylsulfony-
lepoxyisoindoles 2n¡2ee are formed during the heating of furfuryl
allylamines bearing alkyl groups (1g, 1h, 1m), benzyl (1i), or
3

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
Scheme 3. Reaction scope of interaction amines 1d,f¡p with ArSO2Cl/Na2CO3/H2O,
D, 3 h. Reaction scope of interaction of amines 1d,f¡p with ArSO2Cl/Na2CO3/H2O,
D, 3 h.
experiments to almost the same ratio of the cyclic and non-cyclic
isomers (see SI). The composition of mixtures 2 % 3 was deter-
mined by the integral intensity ratio of 1H NMR signals due to the
protons of 5-methyl-2-furyl and at the double bond allyl moiety (H-
4,5 (Fur) and CH ¼ for isomers 3) or in the oxabicycloheptene
fragments (H-4,5 for isomers 2).
cyclic/linear products 4a/5a and 4b/5b; the same trend was
observed in another work [21a], while cases with the phenyl- and
p-chlorophenyl groups ended up giving pure “non-cyclic” products
(5c, 5d). Unlike the mechanism presented in the previous investi-
gation [24], it was not possible to fix the cyclization product even
after prolonged boiling in toluene. Heating the initial compounds in
xylene led to the destruction of sulfonamides 5c, 5d.
A similar situation occurred when there was a substituent (R3)
at the multiple bond of the allyl fragment (Scheme 4). Using a
methyl group or chlorine in that position gave rise to a mixture of
It should be noted that the length of the carbon chain between
the furan ring and the nitrogen atom or the b-location of the furan
4

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
Scheme 3. (continued).
ring in the starting amines were significant factors in the course of
the cycloaddition (Scheme 4). For instance, the presence of two
carbon atoms between furan and NH (1e) allowed the ability to
obtain the product of intramolecular thermal cyclization, epox-
yisoquinoline, mixed with the corresponding “non-cyclic” N-aryl-
sulfonylallylfurylethylamine (6/7). However, when there were three
carbon atoms in between (1q), the reaction culminated in the for-
mation of the N-tosyl derivative 8. The same behaviour could be
Another modification of the chemical structure of 2 was con-
nected to the reduction of the double bond. The double bond in the
oxabicycloheptene fragment of epoxyisoindoles 2i,u was
completely hydrogenated under continuous flow conditions [25],
with simultaneous reduction of the nitro-group (Scheme 5). The
optimum conditions for synthesis were as follows: H-Cube®, H2
(full mode), a disposable cartridge packed with 10% Pd/C, a 0.025 M
solution of isoindole 2 in DCM, 40 ꢀC, atmospheric pressure, and a
observed when
b
-furfuryl allylamine 1r was used as the starting
flow rate of 1 . Unstable intermediates, amino-
mL/minꢁ1
material, which provided the product of nucleophilic substitution
9.
benzenesulfamides, were introduced into the acylation reaction to
obtain stable N-acylsulfonamides 11a,b.
Based on the results, it can be concluded that the substituents in
the starting sulfonyl chlorides (with the exception of the presence
of two substituents at aryl moieties) do not affect the yields of the
target sulphonamides. On the other hand, some substituents in the
furan ring as well as at the double bond, and the length of the
hydrocarbon chain in amines, dramatically worsen the formation of
the [4 þ 2] Diels-Alder cycloaddition products. The second logical
piece in the present investigation relates to the expansion of the
chemical diversity of sulphonamides. To achieve this goal, some
adducts 2 were subjected to Suzuki coupling. Thus, refluxing the
epoxyisoindoles 2e,r with arylboronic acids in the presence of
Pd(PPh3)4 and potassium hydroxide under an argon atmosphere
ended in the formation of biphenylsulfonyl epoxyisoindoles 10a¡d
(Scheme 5).
The last step in this work was investigating the antibacterial
activity of the obtained sulfamides. Taking into account that a
number of sulfonamides are well-known antibacterial drugs, 42 of
the synthesized compounds were tested for antibacterial activity
against sensitive strains of gram-negative bacteria E. coli (C600) as
well as against gram-positive bacteria S. aureus (ATCC-25923) in
the concentration range of 2e256 mg/mL. Unfortunately, only three
cyclic compounds (2g, 2h, 10a) and three noncyclic furan-
containing compounds (3gg, 5a, 5c) showed bactiostatic activity
against E. coli in high concentrations (64e256 mg/mL). Most of the
compounds showed a non-toxic effect for the tested bacterial cells.
Antimicrobial activities were determined by the microbroth dilu-
tion method using the Clinical Laboratory Standards Institute’s
(CLSI) recommendations [26].
5

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
Scheme 4. Reaction scope of interaction of amines 1a,b,e,o¡r with ArSO2Cl/Na2CO3/H2O,
D, 3 h.
and revealed its broad capacity in the synthesis of isoindole-
containing heterocycles. In addition, the biological activity of the
isolated compounds was investigated. Finally, we believe that this
new, non-toxic for bacterial cells diastereomerical pure polycyclic
scaffolds may gain the attention of medicinal chemists as easily
accessible structures serving as a starting point for new biological
profiles.
2.1. Biological evaluation
2.1.1. In vitro antibacterial activity
All the synthesized compounds 2a¡gg, 3ff¡mm, 4a,5a¡d, 6b,
7b, 8a, 10a¡d, 11a,b were evaluated for their in vitro antimicrobial
activity against Staphylococcus aureus (ATCC 25923) as an example
of gram-positive bacteria, and Escherichia coli (ATCC 25922) as an
example of gram-negative bacteria. Cultures were grown overnight
at 37 ꢀC in lysogeny broth (LB) and diluted to obtain an opacity
equivalent to 0.5 on the McFarland scale. Screening vials were filled
with solutions of the test compounds in 0.5% DMSO as prepared
above, with three replications for each treatment. The active
pharmaceutical ingredient (API) pefloxacin (0.5e256 mg/mL) and
0.5% DMSO served as positive and negative controls, respectively.
All the vials were incubated at 35 2 ꢀC for 18 h. After incubation,
the antibacterial activity of the test compounds was determined by
measuring the absorption of the solution with a spectrophotometer
at 500 nm.
Fig. 2. Molecular structure of 2w. Displacement ellipsoids are shown at the 50%
probability level.
In conclusion, a short preparative IMDAF strategy which allows
obtaining 2-(arylsulfonyl)-3a,6-epoxyisoindoles starting from
readily available initial materials was proposed. The wide range of
scope and limitations of the method were thoroughly investigated
2.2. MIC measurement
The MICs (minimal inhibition concentrations) of the most active
6

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
spectrometer with an API-ES/APCI ionization mode. NMR spectra
were run in deuterated (>99%) solvents on Jeol JNM-ECA 600
(600.1 MHz for 1H, 150.9 MHz for 13C and 282.4 MHz for 19F), Bruker
Avance NEO 700 (700.2 MHz for 1H and 176.1 MHz for 13C) or
Bruker WH-400 (400 MHz for 1H and 100.6 MHz for 13C) spec-
trometer for 2e8% solutions in CDCl3, C6D6 or DMSO-d6 at
23e25 ꢀC. Residual signals of deuterated solvents were used as
internal standards (CDCl3: 7.26 ppm for 1Н nuclei, 77.2 ppm for 13
C
nuclei; C6D6: 7.16 ppm for 1Н nuclei; DMSO-d6: 2.50 ppm for 1Н
nuclei, 39.5 ppm for 13C nuclei). Microanalyses were performed for
C, H, N, and S with the elemental analysis system Eurovector EA
3000 (CHNS) and were within 0.4% of theoretical values.
2.3. General procedures
2.3.1. N-prop-2-en-1-amines (1); general procedures
Path 1.1. 2-Methylallyl chloride (77 mmol, 7.4 mL) (for 1a), 2-
chloroallyl chloride (77 mmol, 7.1 mL) (for 1b) and 2-bromoallyl
bromide (77 mmol, 7.5 mL) (for 1c) were added dropwise to fur-
furylamine (77 mmol, 6.8 mL) dissolved in dry THF (25 mL) in the
presence of diisopropylethylamine (80 mmol, 13.9 mL) over 1 h
with constant stirring. After approx. 2 h, the solutions were rinsed
with water (100 mL) and extracted with diethyl ether (3 ꢂ 50 mL),
and the organic layers were dried with anhydrous MgSO4. The
desiccator was filtered off, the solutions concentrated, and the
resulting dark brown oils were purified by fractional distillation.
Allylfurfurylamines 1a¡c were isolated as thin, light yellow oils.
The physicochemical characteristics of amine 1c have been
described earlier [21a].
Scheme 5. Some chemical modifications of 3a,6-epoxyisoindoles 2e,i,r,u. Reaction
Path 1.2. Allyl chloride (80 mmol, 6.5 mL) was added to ethyl 5-
(aminomethyl)furan-2-carboxylate (80 mmol) (for 1d) and fur-
ylethylamine (80 mmol) (for 1e) in dry THF (25 mL). The reaction
mixtures were stirred for 6 h (TLC control), then K2CO3 (360 mmol,
49.7 g) was added and the mixtures were heated at reflux for
another 48 h. The cooled solutions were washed with water
(100 mL), extracted with diethyl ether (3 ꢂ 50 mL), and the com-
bined organic layers were dried with anhydrous MgSO4. The
desiccator was filtered off, the solutions were concentrated, and the
dark brown residues were purified by acid-base treatment by
adding 1 equivalent of anhydrous oxalic acid in EtOAc (25 mL) and
filtration. The resulting salt was dissolved in 50 mL of NH3 aqueous
and extracted with diethyl ether (3 ꢂ 50 mL), and the combined
organic layers were dried with anhydrous MgSO4. The above pro-
cedure is repeated, allylamines 1d,e were isolated as light yellow
oils.
Path 2.1. Allylamine (27 mmol, 2.0 mL) was added to 27 mmol of
the corresponding furfural or 3-(2-methylfuryl)propanal (for 1 g) in
DCM (50 mL) in the presence of anhydrous MgSO4 (54 mmol). The
reaction mixtures were stirred (TLC control) at r.t, and after approx.
2 h, the MgSO4 was filtered off, rinsed with DCM (3 ꢂ 15 mL), and
the solutions were concentrated. The residues were dissolved in
methanol (15 mL) and sodium borohydride (20 mmol, 0.76 g) was
added portionwise over a 10 min period. The resulting mixtures
were vigorously stirred at r.t for 12 h, then poured into H2O (50 mL)
and extracted with DCM (3 ꢂ 50 mL). The organic layers were dried
with anhydrous MgSO4 and concentrated and purified by column
chromatography (SiO2, 23 ꢂ 1.6 cm, eluent: heptane) (for 1 h, l, q,
r). Allyl furfurylamines 1 h¡r were isolated as thin, light yellow oils
with corresponding yields,1iek, nep were used without additional
purification.
conditions: (i) ArB(OH)2, Pd(PPh3)4, THF, 1
TEA, DCM, r.t.
М KOH; (ii) H2, 10% Pd/C, DCM, r.t after Ac2O,
compounds were measured by using the twofold serial broth
dilution method. The test organisms were grown in suitable broth
for 18 h at 37 ꢀC. Twofold serial dilutions of solutions of the test
compounds were prepared at 256, 128, 64, 32, 16, 8, 4, and 2 mg/mL.
The tubes were then inoculated with the test bacteria; each 5 mL
received 0.1 mL of the above inoculums and were incubated at
37 ꢀC. The vials were subsequently observed for the presence or
absence of microbial growth.
2.2.1. Experimental section
2.2.1.1. General remarks. All reagents and solvents were purchased
from commercial suppliers (Acros Organics, Aldrich, Alfa Aesar, and
AstaTech) and used without further purification. No reactions
require absolute solvents (CH2Cl2, EtOH), argon was used as an inert
atmosphere in the Suzuki coupling. Distilled water was used for the
reaction. Thin layer chromatography, when necessary, was carried
out on aluminum backed silica plates Sorbfil. The plates were
visualized under UV light (254 nm) or in I2 vapor. Organic layers
were dried over anhydrous MgSO4 and concentrated in vacuo. In
rare cases, when the precipitate was not formed after 12 h standing
at room temperature, the solvent was removed in vacuo and the
residual was solidified by addition of hexane. Analytical samples for
the new compounds were obtained by recrystallization from EtOAc,
EtOH or EtOAc/hexane mixtures. Melting points for all crystalline
compounds were measured on a capillary point apparatus Stuart
SMP 10 or SMP 30 equipped with a digital thermometer and were
uncorrected. IR spectra were obtained in KBr pellets using an
Infralum FT-801 IR-Fourier spectrometer. GC-MS mass spectra were
taken on a Thermo Focus DSQ II GC-MS spectrometer (electron
ionization, 70 eV, ion source temperature 200 ꢀC, gas chromato-
graphic inlet with a Varian Factor-Four VF-5ms column). LC-MS
mass spectra were taken on Agilent 1100 series LC/MSD
Path 2.2. Allylamine (27 mmol, 2.0 mL) was added to 27 mmol of
the corresponding furfural in PhH (50 mL) in the presence of one
drop of AcOH. The reaction mixture was refluxed with the Dean-
Stark trap for 4 h. After separation of all amount of water
(0.49 mL), the resulting mixture was concentrated, the residue was
7

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
dissolved in methanol (15 mL), and 20 mmol (0.76 g) of sodium
borohydride was added portionwise. The resulting mixture was
vigorously stirred at r.t for 12 h, poured into water (100 mL), and
then extracted with DCM (3 ꢂ 50 mL). The organic layers were
dried with anhydrous MgSO4 and concentrated and purified by
fractional distillation. Allyl furfurylamines 1f, g, m were isolated as
thin, light yellow oils. The physicochemical characteristics of
compounds 1f, g have been published previously [20b,27].
Path 3. Corresponding boronic acid (9.4 mmol) was added to a
stirred solution of amine 1c (4.7 mmol, 1.02 g) dissolved in THF
(10 mL) in the presence of an 10% aqueous KOH (10 mL) and 0.05%
Pd(PPh3)4 under an argon atmosphere. The reaction mixture was
heated at 80 ꢀC for 6 h, cooled down to r.t, and extracted with ethyl
acetate (3 ꢂ 50 mL). The organic layers were dried with anhydrous
MgSO4 and concentrated and purified by column chromatography
(SiO2, 23 ꢂ 1.6 cm, eluent: hexane-ethyl acetate, gradient from 50:1
to 20:1). Allylamines 1s and 1t were isolated as yellow oils.
2.3.5. (3aRS,6SR,7aRS)-2-(Arylsulfonyl)octahydro-3a,6-
epoxyisoindoles (11); General procedure
A 0.025 M solution of nitroarylsulfonylepoxyisoindoles 2i and
2u in dichloromethane was passed through an H-Cube Pro™ flow-
through hydrogenation reactor (H2, 10% Pd/C, 40 ꢀC, P ¼ 1 atm, flow
rate 1 mL/min). The solvent was distilled off under reduced pres-
sure. The resulting powders were filtered off and without further
purification 0.7 mmol of the obtained product was dissolved in
20 mL of CH2Cl2 and 1.4 mmol (0.13 mL) of acetic anhydride was
added in the presence of 2 mmol of Et3N (0.28 mL). The mixture
was stirred at room temperature for 1 h, extracted with CH2Cl2
(3 ꢂ 10 mL), The organic layers were dried with anhydrous MgSO4
and concentrated. The obtained powders were filtered off and
recrystallized from EtOAc e hexane (1:2) system. Arylsulfonyle-
poxyisoindoles 11a, b were isolated as colourless crystals with
corresponding yields.
NMR spectra presented in Supplementary data were recorded
for these crystallized samples. In order to obtain a satisfactory
elemental analysis and correct melting points, all compounds were
dried under vacuum.
2.3.2. 2-(Arylsulfonyl)-1,2,3,6,7,7a-hexahydro-3a,6-
epoxyisoindoles (2 and 4), 2-[(4-methylphenyl)sulfonyl]-
1,3,4,7,8,8a-hexahydro-2H-4a,7-epoxyisoquinoline (7a) and N-
substituted N-arylsulfonamides (3, 5, 6, 8 and 9); general procedure
The corresponding arylsulfonyl chloride (43 mmol) was added
to the corresponding amine 1 (36 mmol) in water (50 mL) in the
presence of Na2CO3 (43 mmol). The resulting reaction mixture was
refluxed for 3 h, the formed powder was filtered off and rinsed with
hexane. When it was needed, the resulting reaction mixture
extracted with ethyl acetate (3 ꢂ 50 mL). The organic layers were
dried with anhydrous MgSO4. The solution was filtered and
concentrated. The resulting dark brown oils were triturated with
hexane and the obtained solid was recrystallized from a hexane-
EtOAc mixture or in rare cases from hexane with a dropwise add-
ing of EtOH. The formed crystals were filtered, washed with hexane
(3 ꢂ 5 mL) and dried in air to give the title arylsulfonyl-3a,6-
epoxyisoindoles (2, 4) as white powders. In cases when the sepa-
ration of “cyclic” and “non-cyclic” products was needed or only
“non-cyclic” products were formed, column chromatography was
used (SiO2, 23 ꢂ 1.6 cm, eluent: hexane-ethyl acetate, gradient from
20:1 to 5:1). The physicochemical characteristics of compounds 2a,
b, n have been published previously [28].
3. Compound identification and characterization
N-(Furan-2-ylmethyl)-2-methylprop-2-en-1-amine
Yield: 20%; light yellow oil; bp 77e76ꢀС/9 Torr; IR (KBr): 3339 (NH)
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
(1a).
d
(ppm) 7.36 (1H, t, J ¼ 1.0 Hz, H-
5 Fur), 6.31 (1H, dd, J ¼ 2.0 Hz, J ¼ 3.0 Hz, H-4 Fur), 6.17 (1H, dd,
J ¼ 1.0 Hz, J ¼ 3.0 Hz, H-3 Fur), 4.89e4.85 (2H, m, C]CH2), 3.76 (2H,
s, NCH2), 3.17 (2H, s, NCH2), 1.76 (3H, s, CH3), 1.49 (1H, br.s, NH); 13
C
NMR (150.9 MHz, CDCl3)
69.2, 27.3, 21.6. GCMS (EI, 70 eV): m/z (%) 151 (4) [
d
(ppm) 168.9, 141.2, 138.8, 87.2, 83.5, 73.9,
М
]þ, 122 (29), 95
(10), 81 (100), 53 (45), 39 (27). Anal. Calcd for C9H13NO: C, 71.49; H,
8.67; N, 9.26. Found: C, 71.53; H, 8.66; N, 9.35.
2-Chloro-N-(furan-2-ylmethyl)prop-2-en-1-amine
Yield: 18%; light yellow oil; bp 102e104ꢀС/22 Torr; IR (KBr): 3335
(NH) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
(1b).
d
(ppm) 7.38 (1H, d, J ¼ H-
5 Fur), 6.32 (1H, dd, J ¼ 1.7 Hz, J ¼ 3.3 Hz, H-4 Fur), 6.20 (1H, d,
J ¼ 3.3 Hz, H-3 Fur), 5.37e5.35 (2H, m, C]CH2), 3.77 (2H, s, CH2N),
3.42 (2H, s, CH2N), 1.78 (1H, s, NH); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 153.1, 141.9, 140.3, 113.6, 110.0, 107.2, 54.4, 44.1. GCMS (EI,
70 eV): m/z (%) 171 (1) for Cl35 þ, 142 (26), 82 (18), 81 (100), 53
[М]
(35), 39 (21). Anal. Calcd for C8H10ClNO: C, 55.99; H, 5.87; N, 8.16.
Found: C, 55.95; H, 5.78; N, 8.29.
2.3.3. N-allyl-N-(2-furylmethyl)-4-methylbenzenesulfonamide (3b)
Tosyl chloride (0.84 g 44 mmol) was added to the amine 1f
(0.50 g, 36 mmol) in water (50 mL) in the presence of Na2CO3
(0.47 g, 44 mmol). The resulting reaction mixture was stirred at
room temperature for 24 h, extracted with DCM (3 ꢂ 50 mL). The
organic layers were dried with anhydrous MgSO4. The solution was
filtered and concentrated. The resulting light-yellow oil 3b was
isolated without further purification in 91% (0.94 g) yield.
2-Bromo-N-(furan-2-ylmethyl)prop-2-en-1-amine (1c). Was
described. [21a] Yield: 66%; light yellow oil; bp 103e104ꢀС/8 Torr;
1H NMR (700.2 MHz, CDC13)
d
(ppm) 7.37 (1H, dd, J ¼ 0.9 Hz,
J ¼ 1.9 Hz, H-5 Furyl), 6.31 (1H, dd, J ¼ 1.9 Hz, J ¼ 3.1 Hz, H-4 Furyl),
6.19 (1H, dd, J ¼ 0.9 Hz, J ¼ 3.1 Hz, H-3 Furyl), 5.81 (1H, dd,
J ¼ 1.9 Hz, J ¼ 2.9 Hz, C]CH2), 5.59 (1H, d, J ¼ 1.9 Hz, C]CH2), 3.75
(2H, s, NCH2), 3.46 (2H, s, NCH2), 1.82 (1H, s, NH); 13C NMR
(176.1 MHz, CDCl3)
d (ppm) 153.1, 142.0, 132.8, 118.0, 110.1, 107.2,
56.3, 43.9. GCMS (EI, 70 eV): m/z (%) 215 (6) for Br79 þ, 188 (31),
[М]
136 (19), 95 (17), 81 (100), 68 (11), 53 (47), 39 (23).
2.3.4. (3aRS,6RS,7aRS)-2-(Biaryl-4-sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindoles (10); General procedure
Corresponding boronic acid (0.56 mmol) was added to a stirred
solution of epoxyisoindole 2e or 2r (0.28 mmol) dissolved in THF
(5 mL) in the presence of an 10% aqueous KOH (5 mL) and 0.05%
Pd(PPh3)4 under argon atmosphere. The reaction mixture was
heated at 80 ꢀC for 6 h, cooled down to r.t. and extracted with ethyl
acetate (3 ꢂ 10 mL). The organic layers were dried with anhydrous
MgSO4, concentrated and purified by column chromatography
(SiO2, 23 ꢂ 1.6 cm, eluent: hexane-ethyl acetate, gradient from 50:1
to 20:1). (Biaryl-4-ylsulfonyl)-3a,6-epoxyisoindoles 10aꢁd were
isolated as yellow solids.
Ethyl-5-[(allylamino)methyl]-2-furoate (1d). Yield: 54%; light
yellow oil; IR (KBr): 3335 (NH), 1725 (СО2Et) cmꢁ1 1H NMR
(600.2 MHz, CDC13)
(ppm) 7.09 (1H, d, J ¼ 3.3 Hz, H-3 Fur), 6.29
;
d
(1H, d, J ¼ 3.3 Hz, H-4 Fur), 5.89e5.82 (1H, m, CH]CH2), 5.18 (1H,
ddd, J ¼ 1.5 Hz, J ¼ 3.0 Hz, J ¼ 17.1 Hz, trans-CH]CH2), 5.10 (1H, ddd,
J ¼ 1.5 Hz, J ¼ 3.0 Hz, J ¼ 10.4 Hz, cis-CH]CH2), 4.33 (2H, quartet,
J ¼ 7.4 Hz, HeCH2 OEt), 3.82 (2H, s, NCH2), 3.24 (2H, dt, J ¼ 1.5 Hz,
J ¼ 6.1 Hz, NCH2), 1.59 (1H, s, NH), 1.34 (3H, t, J ¼ 7.4 Hz, HeCH3
OEt); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 158.5, 158.3, 143.7, 135.9,
118.4,116.3, 108.9, 60.5, 51.1, 45.1, 14.1. GCMS (EI, 70 eV): m/z (%) 209
(24) [
]þ,180 (37),167 (10),153 (100),136 (61),125 (73), 96 (37), 79
(22), 68 (19), 56 (44), 41 (62). Anal. Calcd for C11H15NO3: C, 63.14; H,
М
8

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
7.23; N, 6.69. Found: C, 63.22; H, 7.20; N, 6.76.
N-[3-(5-Methyl-2-furyl)propyl]prop-2-en-1-amine
Yield: 42%; light yellow oil; IR (KBr): 3341 (NH) cmꢁ1
(600.2 MHz, CDC13) d (ppm) 5.94e5.83 (3H, m, H-3 Fur, H-4 Fur,
(1q).
N-(2-(Furan-2-yl)ethyl)prop-2-en-1-amine (1e). Yield: 38%;
;
1H NMR
light yellow not stable oil; IR (KBr): 3337 (NH) cmꢁ1
;
1H NMR
(600.2 MHz, CDC13)
d
(ppm) no peak NH, 7.33 (1H, dd, J ¼ 0.7 Hz,
CH]CH2), 5.17 (1H, ddd, J ¼ 1.5 Hz, J ¼ 3.3 Hz, J ¼ 16.9 Hz, trans-
CH]CH2), 5.09e5.07 (1H, m, cis-CH]CH2), 3.25 (2H, dt, J ¼ 1.5 Hz,
J ¼ 6.2 Hz, NCH2), 2.66 (2H, t, J ¼ 7.3 Hz, NCH2), 2.62 (2H, J ¼ 7.3 Hz,
CH2), 2.24 (3H, s, CH3), 1.82 (2H, quintet, J ¼ 7.3 Hz, CH2), 1.63 (1H, s,
J ¼ 1.8 Hz, H-5 Fur), 6.31 (1H, dd, J ¼ 1.8 Hz, J ¼ 3.1 Hz, H-4 Fur), 6.07
(1H, dd, J ¼ 0.7 Hz, J ¼ 3.1 Hz, H-3 Fur), 5.94e5.88 (1H, m, CH]CH2),
5.18 (1H, dq, J ¼ 1.7 Hz, J ¼ 17.2 Hz, trans-CH]CH2), 5.10 (1H, dq,
J ¼ 1.7 Hz, J ¼ 10.3 Hz, cis-CH]CH2), 3.29 (2H, dt, J ¼ 1.4 Hz,
J ¼ 6.0 Hz, NCH2), 2.92 (2H, dt, J ¼ 0.7 Hz, J ¼ 6.7 Hz, NCH2), 2.86 (2H,
NH); 13C NMR (100.6 MHz, CDCl3)
d (ppm) 154.0, 150.2, 137.0, 115.7,
105.8, 105.4, 52.4, 48.8, 28.6, 25.9, 13.5. GCMS (EI, 70 eV): m/z (%)
t, J ¼ 6.7 Hz, CH2); 13C NMR (176.1 MHz, CDCl3)
d
(ppm) 154.1, 141.2,
179 (10) [
М
]þ, 136 (13), 122 (36), 107 (33), 95 (50), 79 (22), 70 (100),
136.7, 116.0, 110.2, 105.8, 52.2, 47.5, 28.7. GCMS (EI, 70 eV): m/z (%)
56 (13), 41 (72). Anal. Calcd for C11H17NO: C, 73.70; H, 9.56; N, 7.81.
Found: C, 73.63; H, 9.71; N, 7.95.
151 (2) [М
]þ, 81 (14), 70 (100), 68 (16), 42 (18), 41 (86).
N-(2-Furylmethyl)prop-2-en-1-amine (1f). Was described.
N-(3-Furylmethyl)prop-2-en-1-amine (1r). Yield: 49%; light
yellow oil; IR (KBr): 3316 (NH) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
[20b] Yield: 60%; light yellow oil; bp 70e73ꢀС/14 Torr; 1H NMR
(700.2 MHz, CDC13)
d
(ppm) 7.33 (1H, br.s, H-5 Fur), 6.28 (1H, br.s,
d
(ppm) 7.37 (1H, t, J ¼ 1.7 Hz, H-5 Fur), 7.35 (1H, br.s, H-2 Fur), 6.39
H-Fur), 6.15 (1H, br.s, H-3 Fur), 5.84e5.90 (1H, m, CH]CH2), 5.16
(1H, d, J ¼ 17.2 Hz, trans-CH]CH2), 5.08 (1H, d, J ¼ 10.3 Hz, cis-CH]
CH2), 3.75 (2H, s, NCH2), 3.23 (2H, d, J ¼ 6.2 Hz, NCH2), 1.99 (1H, s,
(1H, d, J ¼ 1.7 Hz, H-3 Fur), 5.94e5.88 (1H, m, CH]CH2), 5.19 (1H,
ddd, J ¼ 1.7 Hz, J ¼ 3.3 Hz, J ¼ 17.3 Hz, trans-CH]CH2), 5.12e5.10
(1H, m, cis-CH]CH2), 3.64 (2H, s, NCH2), 3.27 (2H, dt, J ¼ 1.7 Hz,
J ¼ 7.4 Hz, NCH2), 1.37 (1H, s, NH); 13C NMR (150.9 MHz, CDCl3)
NH); 13C NMR (176.1 MHz, CDCl3)
d (ppm) 153.5, 141.7, 136.2, 116.2,
110.0, 106.9, 51.2, 45.1. GCMS (EI, 70 eV): m/z (%) 137 (12) [
(19), 108 (45), 81 (100), 68 (48), 56 (30), 53 (76), 41 (71).
М]
þ, 136
d (ppm) 143.0, 139.8, 136.4, 123.7, 116.1, 110.4, 51.6, 43.4. GCMS (EI,
70 eV): m/z (%) 137 (5) [М
]þ, 122 (6), 108 (8), 81 (100), 56 (57), 41
N-((5-Methyl-2-furyl)methyl)prop-2-en-1-amine (1g). Was
(22). Anal. Calcd for C8H11NO: C, 70.04; H, 8.08; N, 10.21. Found: C,
70.10; H, 8.01; N, 10.25.
described. [27] Yield: 50%; light yellow oil; bp 102ꢀС/28 Torr; 1H
NMR (700.2 MHz, CDC13)
d
(ppm) 6.04 (1H, d, J ¼ 3.1 Hz, H-Furyl),
N-(2-Furylmethyl)-2-phenylprop-2-en-1-amine (1s). Yield:
5.94e5.87 (2H, m, CH]CH2, H-Furyl), 5.19 (1H, dq, J ¼ 1.7 Hz,
J ¼ 17.2 Hz, trans-CH]CH2), 5.12 (1H, dq, J ¼ 1.7 Hz, J ¼ 10.3 Hz, cis-
CH]CH2), 3.72 (2H, s, NCH2), 3.27 (2H, dt, J ¼ 1.4 Hz, J ¼ 6.0 Hz,
NCH2), 2.27 (3H, s, CH3), 1.47 (1H, s, NH); 13C NMR (176.1 MHz,
20%; light yellow oil; IR (KBr): 3402 (NH) cmꢁ1 1H NMR
;
(600.2 MHz, CDC13) d (ppm) 7.44e7.28 (6H, m, H-Ph, H-5 Fur), 6.32
(1H, dd, J ¼ 2.3 Hz, J ¼ 3.0 Hz, H-4 Fur), 6.19 (1H, d, J ¼ 2.3 Hz, H-3
Fur), 5.44 (1H, br.s, C]CH2), 5.27 (1H, dd, J ¼ 1.5 Hz, J ¼ 3.0 Hz, C]
CDCl3)
d
(ppm) 151.6, 151.1, 136.2, 115.9, 107.5, 105.7, 51.1, 45.2, 13.2.
CH2), 3.81 (2H, s, NCH2), 3.68 (2H, br.s, NCH2), 1.79 (1H, s, NH); 13
C
GCMS (EI, 70 eV): m/z (%) 151 (41) [
94 (54), 68 (25), 53 (16), 43 (92), 41 (100).
М]
þ, 136 (13), 122 (43), 108 (18),
NMR (150.9 MHz, CDCl3)
(2C),127.7 (2C),126.2,113.7,110.1,107.1, 52.3, 45.2. GCMS (EI, 70 eV):
m/z (%) 213 (4) [
]þ, 184 (44), 110 (15), 91 (10), 81 (100), 77 (18), 53
d (ppm) 153.8, 145.9, 141.8, 139.7, 128.5
N-[(5-Ethyl-2-furyl)methyl]prop-2-en-1-amine (1h). Yield:
М
35%; light yellow oil; IR (KBr): 3341 (NH) cmꢁ1
;
1H NMR
(30). Anal. Calcd for C14H15NO: C, 78.84; H, 7.09; N, 6.57. Found: C,
(600.2 MHz, CDC13)
d
(ppm) 6.06 (1H, d, J ¼ 3.3 Hz, H-3 Fur),
78.93; H, 7.15; N, 6.59.
2-(4-Chlorophenyl)-N-(2-furylmethyl)prop-2-en-1-amine
(1t). Yield: 31%; light yellow oil; IR (KBr): 3399 (NH) cmꢁ1; 1H NMR
5.94e5.87 (2H, m, H-4 Fur, CH]CH2), 5.20e5.10 (2H, m, CH]CH2),
3.73 (2H, br.s, NCH2), 3.27 (2H, d, J ¼ 5.8 Hz, NCH2), 2.63 (2H, qt,
J ¼ 7.4 Hz, CH2CH3), 1.45 (1H, s, NH), 1.22 (3H, t, J ¼ 7.4 Hz, CH2CH3);
(600.2 MHz, CDC13)
d (ppm) 7.34e7.27 (5H, m, HeAr, H-5 Furyl),
13C NMR (150.9 MHz, CDCl3)
d
(ppm) 157.1, 151.7, 136.5, 116.1, 107.4,
6.30 (1H, dd, J ¼ 2.0 Hz, J ¼ 3.0 Hz, H-4 Furyl), 6.16 (1H, d, J ¼ 3.0 Hz,
H-3 Furyl), 5.39 (1H, m, C]CH2), 5.25 (1H, m, C]CH2), 3.77 (2H, s,
NCH2), 3.60 (2H, s, NCH2), 0.95 (1H, br.s, NH); 13C NMR (150.9 MHz,
104.1, 51.3, 45.4, 21.3, 12.0. GCMS (EI, 70 eV): m/z (%) 165 (12) [М
]þ,
136 (38), 109 (100), 94 (21), 81 (17), 68 (26), 53 (18), 41 (71). Anal.
Calcd for C10H15NO: C, 72.69; H, 9.15; N, 8.48. Found: C, 72.71; H,
9.18; N, 8.50.
CDC13)
d (ppm) 153.6, 144.8, 141.8, 138.1, 133.4, 128.5 (2C), 127.4
(2C), 114.2, 110.0, 107.1, 52.1, 45.1. MS (ESI): m/z 248 for Cl35
[
М
þH]þ.
N-[(4-Bromo-2-furyl)methyl]prop-2-en-1-amine (1l). Yield:
Anal. Calcd for C14H14ClNO: C, 67.88; H, 5.70; N, 5.65. Found: C,
67.99; H, 5.87; N, 5.90.
64%; colourless oil; IR (KBr): no peak NH, 801 (CBr) cmꢁ1; 1H NMR
(700.2 MHz, CDC13)
d
(ppm) 7.36 (1H, s, H-5 Fur), 6.25 (1H, s, H-3
(3aRS,6RS,7aRS)-2-(Phenylsulfonyl)-1,2,3,6,7,7a-hexahydro-
3a,6-epoxyisoindole (2a). Was described [28]. Yield 53%; beige
powder; mp 122e123ꢀС; IR (KBr): 1166 (ns SO2) and 1335 (nas SO2)
Fur), 5.91e5.85 (1H, m, CH]CH2), 5.20 (1H, dd, J ¼ 1.1 Hz,
J ¼ 17.2 Hz, trans-CH]CH2), 5.13 (1H, d, J ¼ 10.4 Hz, cis-CH]CH2),
3.76 (2H, s, NCH2), 3.25 (2H, d, J ¼ 6.2 Hz, NCH2),1.47 (1H, s, NH); 13
C
cmꢁ1 1H NMR (600.2 MHz, CDC13)
; d (ppm) 7.85e7.83 (2H, m, H-
NMR (176.1 MHz, CDCl3)
d
(ppm) 154.9, 140.1, 136.2, 116.5, 110.5,
Ph), 7.59 (1H, t, J ¼ 7.6 Hz, H-Ph), 7.53 (2H, t, J ¼ 7.6 Hz, H-Ph), 6.34
(1Н, dd, J ¼ 1.4 Hz, J ¼ 5.9 Hz, Н-5), 6.32 (1Н, d, J ¼ 5.9 Hz, Н-4), 4.94
(1Н, dd, J ¼ 1.4 Hz, J ¼ 4.4 Hz, Н-6), 3.96 (1Н, d, J ¼ 12.4 Hz, Н-3А),
3.92 (1Н, t, J ¼ 9.4 Hz, Н-1А), 3.55 (1Н, d, J ¼ 12.4 Hz, Н-3В), 2.72
(1Н, t, J ¼ 9.4 Hz, Н-1В), 2.10e2.05 (1Н, m, Н-7a), 1.64 (1Н, ddd,
J ¼ 3.4 Hz, J ¼ 4.4 Hz, J ¼ 11.7 Hz, Н-7А), 1.36 (1Н, dd, J ¼ 7.6 Hz,
99.8, 51.3, 45.2. GCMS (EI, 70 eV): m/z (%) 216 (6) for 81Br [
М
]þ, 214
(10) for Br79 ]þ, 188 (49), 172 (13), 161 (100), 159 (93), 131 (14),
[
М
108 (12), 68 (10), 51 (20), 41 (28). Anal. Calcd for C8H10BrNO: C,
44.47; H, 4.66; N, 6.48. Found: C, 44.60; H, 4.79; N, 6.65.
N-[(4,5-Dimethyl-2-furyl)methyl]prop-2-en-1-amine (1m).
Yield: 56%; light yellow oil; bp 110e113ꢀС/30 Torr; IR (KBr): 3073
J ¼ 11.7 Hz, Н-7В); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 137.2,136.9,
133.9, 132.7, 129.0 (2C), 127.3 (2C), 95.0, 80.1, 53.3, 49.2, 42.6, 30.2.
(NH) cmꢁ1
;
1H NMR (700.2 MHz, CDC13)
d
(ppm) 5.93 (1H, s, H-3
Fur), 5.93e5.87 (1H, m, CH]CH2), 5.18 (1H, dq, J ¼ 1.7 Hz,
J ¼ 17.2 Hz, trans-CH]CH2), 5.09 (1H, dq, J ¼ 1.7 Hz, J ¼ 10.4 Hz, cis-
CH]CH2), 3.67 (2H, s, NCH2), 3.25 (2H, dt, J ¼ 1.3 Hz, J ¼ 6.2 Hz,
NCH2), 2.17 (3H, s, CH3), 1.90 (3H, s, CH3), 1.41 (1H, s, NH); 13C NMR
GCMS (EI, 70 eV): 277 (1) [
(100), 106 (16), 107 (22), 108 (35), 136 (58). Anal. Calcd for
14H15NO3S: C, 60.63; H, 5.45; N, 5.05; S, 11.56. Found: C, 60.79; H,
М
]þ, 41 (21), 53 (30), 54 (10), 77 (39), 81
C
5.60; N, 5.15; S, 11.54.
(176.1 MHz, CDCl3)
51.4, 45.4,11.3, 9.8. GCMS (EI, 70 eV): m/z (%) 165 (28) [
136 (29),122 (14),109 (100), 68 (19), 43 (58), 39 (26). Anal. Calcd for
10H15NO: C, 72.69; H, 9.15; N, 8.48. Found: C, 72.77; H, 9.01; N,
8.23.
d
(ppm) 150.6, 146.5, 136.6, 116.0, 114.1, 110.2,
(3aRS,6RS,7aRS)-2-[(4-Methylphenyl)sulfonyl]-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2b). Was described [28]. Yield
64%; colourless needles; mp 119e120ꢀС; IR (KBr): 1167 (ns SO2) and
М
]þ,150 (10),
C
1330 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.71 (2Н,
d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.31 (2Н, d, J ¼ 8.3 Hz, Н-3 Ar, H-5 Ar),
9

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
6.33 (1Н, dd, J ¼ 1.4 Hz, J ¼ 5.2 Hz, Н-5), 6.31 (1Н, d, J ¼ 5.2 Hz, Н-4),
4.93 (1Н, dd, J ¼ 1.4 Hz, J ¼ 5.9 Hz, Н-6), 3.93 (1Н, d, J ¼ 12.1 Hz,
Н-3А), 3.87 (1H, t, J ¼ 9.3 Hz, H-1A), 3.51 (1H, d, J ¼ 12.1 Hz, He3B),
2.68 (1H, dd, J ¼ 9.3 Hz, J ¼ 10.3 Hz, He1B), 2.41 (3Н, s, CH3),
2.07e2.02 (1Н, m, Н-7a), 1.64 (1Н, ddd, J ¼ 2.8 Hz, J ¼ 4.9 Hz,
J ¼ 11.7 Hz, Н-7А), 1.34 (1Н, dd, J ¼ 7.6 Hz, J ¼ 11.7 Hz, Н-7В); 13C
NMR (150.9 MHz, CDCl3)
d
(ppm) 137.4. 135.8, 133.7, 132.4 (2C),
128.9 (2C), 127.7, 94.9, 80.2, 53.3, 49.3, 42.5, 30.3. GCMS (EI, 70 eV):
356 (1) for 81Br [ ]þ, 155 (18), 136 (42), 135 (17), 108 (29), 107 (21),
М
106 (18), 81 (100), 53 (33), 41 (28). Anal. Calcd for C14H14BrNO3S: C,
47.20; H, 3.96; N, 3.93; S, 9.00. Found: C, 47.30; H, 3.91; N, 3.96; S,
9.10.
(3aRS,6RS,7aRS)-2-((4-Iodophenyl)sulfonyl)-1,2,3,6,7,7a-hex-
ahydro-3a,6-epoxyisoindole (2f). Yield 61%; colourless needles;
mp 157e158ꢀС; IR (KBr): 1166 (ns SO2) and 1335 (nas SO2) cmꢁ1; 1H
NMR (150.9 MHz, CDCl3)
(2C), 127.4 (2C), 95.0, 80.2, 53.2, 49.2, 42.5, 30.1, 21.5. GCMS (EI,
70 eV): 291 (1) [
]þ, 207 (1), 155 (13), 136 (64), 108 (21), 91 (63), 81
d
(ppm) 143.4, 137.1, 133.9, 133.7, 129.7
М
(100), 65 (33), 53 (39), 41 (35). Anal. Calcd for C15H17NO3S: C, 61.83;
H, 5.88; N, 4.81; S, 11.00. Found: C, 61.99; H, 5.98; N, 4.98; S, 11.25.
N-Allyl-N-(2-furylmethyl)-4-methylbenzenesulfonamide
NMR (600.2 MHz, DMSO-d6)
d
(ppm) 8.01 (2H, d, J ¼ 8.6 Hz, HeAr),
7.58 (2H, d, J ¼ 8.6 Hz, HeAr), 6.42 (1H, d, J ¼ 5.8 Hz, H-4), 6.36 (1H,
dd, J ¼ 2.0 Hz, J ¼ 5.8 Hz, H-5), 4.90 (1H, dd, J ¼ 2.0 Hz, J ¼ 4.5 Hz, H-
6), 3.90 (1H, d, J ¼ 12.1 Hz, H-3A), 3.74 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.6 Hz,
H-1A), 3.41 (1H, d, J ¼ 12.1 Hz, He3B), 2.60 (1H, dd, J ¼ 9.6 Hz,
J ¼ 10.1 Hz, He1B), 1.99e1.95 (1H, m, H-7a), 1.57 (1H, ddd,
J ¼ 2.5 Hz, J ¼ 4.5 Hz, J ¼ 11.6 Hz, H-7A), 1.25 (1H, J ¼ 8.7 Hz,
(3b). Was described [20b]. Yield: 91%; dark yellow viscous oil; IR
(KBr): 1159 (ns SO2) and 1346 (nas SO2) cmꢁ1; 1H NMR (700.2 MHz,
CDC13)
d
(ppm) 7.67 (2H, d, J ¼ 7.9 Hz, H-2 Ar, H-6 Ar), 7.28e7.27
(3H, m, J ¼ 7.9 Hz, H-3 Ar, H-5 Ar, H-5 Fur), 6.27 (1H, dd, J ¼ 2.1 Hz,
J ¼ 3.2 Hz, H-4 Fur), 6.16 (1H, d, J ¼ 3.2 Hz, H-3 Fur), 5.68e5.62 (1H,
m, CH]CH2), 5.19e5.16 (2H, m, CH]CH2), 4.41 (2H, s, NCH2), 3.80
(2H, br. d, J ¼ 6.6 Hz, NCH2), 2.43 (3H, s, CH3); 13C NMR (176.1 MHz,
J ¼ 11.6 Hz, He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 138.3 (2C),
137.4, 136.5,133.8,128.7 (2C),100.2, 94.9, 80.2, 53.3, 49.3, 42.5, 30.3.
GCMS (EI, 70 eV): 403 (1) [М
]þ, 203 (20),150 (44),122 (35),113 (29),
CDCl3)
d
(ppm) 149.7, 143.2, 142.4, 137.2, 132.5, 129.5 (2C), 127.3
95 (100). Anal. Calcd for C14H14INO3S: C, 41.70; H, 3.50; N, 3.47; S,
(2C), 119.2, 110.3, 109.5, 49.6, 42.7, 21.5. GCMS (EI, 70 eV): m/z (%)
7.95. Found: C, 41.82; H, 3.62; N, 3.38; S, 7.90.
291 (4) [
41 (20).
М
]þ, 155 (13), 136 (100), 108 (13), 81 (14), 65 (16), 53 (19),
N-{4-[(3aRS,6RS,7aRS)-1,6,7,7a-Tetrahydro-3a,6-
epoxyisoindol-2-ylsulfonyl]phenyl} acetamide (2g). Yield 71%;
colourless needles; mp 127e128ꢀС; IR (KBr): 1168 (ns SO2) and
1330 (nas SO2), 1672 (NCO), 3432 (NH) cmꢁ1; 1H NMR (600.2 MHz,
(3aRS,6RS,7aRS)-2-((4-Fluorophenyl)sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2c). Yield 40%; colourless nee-
dles; mp 119e120ꢀС; IR (KBr): 1170 (ns SO2) and 1344 (nas SO2)
CDC13) d (ppm) 7.95 (1H, s, NH), 7.74e7.68 (4H, m, HeAr), 6.34 (1H,
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.85 (2H, dd, J ¼ 5.0 Hz,
dd, J ¼ 1.5 Hz, J ¼ 5.7 Hz, H-5), 6.32 (1H, d, J ¼ 5.7 Hz, H-4), 4.96 (1H,
dd, J ¼ 1.5 Hz, J ¼ 4.6 Hz, H-6), 3.91 (1H, d, J ¼ 12.1 Hz, H-3A), 3.86
(1H, dd, J ¼ 8.1 Hz, J ¼ 9.2 Hz, H-1A), 3.52 (1H, d, J ¼ 12.1 Hz, He3B),
2.69 (1H, dd, J ¼ 9.2 Hz, J ¼ 10.3 Hz, He1B), 2.19 (3H, s, CH3),
2.08e2.04 (1H, m, H-7a), 1.65 (1H, ddd, J ¼ 2.9 Hz, J ¼ 4.6 Hz,
J ¼ 8.7 Hz, H-3 Ar, H-5 Ar), 7.21e7.18 (2H, m, H-2 Ar, H-6 Ar), 6.35
(1H, dd, J ¼ 1.7 Hz, J ¼ 5.8 Hz, H-5), 6.33 (1H, d, J ¼ 5.8 Hz, H-4), 4.94
(1H, dd, J ¼ 1.7 Hz, J ¼ 4.5 Hz, H-6), 3.95 (1H, d, J ¼ 12.0 Hz, H-3A),
3.90 (1H, dd, J ¼ 8.3 Hz, J ¼ 9.1 Hz, H-1A), 3.52 (1H, d, J ¼ 12.0 Hz,
He3B), 2.68 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B), 2.12e2.07 (1H, m,
H-7a), 1.65 (1H, ddd, J ¼ 2.5 Hz, J ¼ 4.5 Hz, J ¼ 11.6 Hz, H-7A), 1.37
(1H, dd, J ¼ 7.4 Hz, 11.6 Hz, He7B). 13C NMR (150.9 MHz, CDCl3)
J ¼ 11.9 Hz, H-7A), 1.38 (1H, dd, J ¼ 7.8 Hz, J ¼ 11.9 Hz, He7B); 13
C
NMR (150.9 MHz, CDCl3)
d (ppm) 169.2 (CO), 142.4, 137.3, 133.8,
130.9, 128.5 (2C), 119.3 (2C), 95.0, 80.1, 53.3, 49.3, 42.5, 30.2, 24.5.
d
(ppm) 166.2 (d, J1 ¼ 254.3 Hz), 137.4, 133.8, 132.9, 130.1 (2C, d,
MS (ESI) m/z 335 [
М
þH]þ. Anal. Calcd for C16H18N2O4S: C, 57.47; H,
F
J3 ¼ 8.7 Hz), 116.3 (2C, d, J2 ¼ 23.1 Hz), 95.0, 80.2, 53.4, 49.3, 42.6,
5.43; N, 8.38; S, 9.59. Found: C, 57.55; H, 5.34; N, 8.35; S, 9.50.
(3aRS,6RS,7aRS)-2-((4-Nitrophenyl)sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2h). Yield 78%; colourless nee-
dles; mp 157e158ꢀС; IR (KBr): 1170 (ns SO2) and 1349 (nas SO2) 1355
F
F
30.3; 19F NMR (282.4 MHz, CDCl3)
296 [
S, 10.86. Found: C, 57.21; H, 4.85; N, 4.87; S, 10.92.
d
(ppm) ꢁ105.1. MS (ESI): m/z
М
þH]þ. Anal. Calcd for C14H14FNO3S: C, 56.94; H, 4.78; N, 4.74;
(3aRS,6RS,7aRS)-2-((4-Chlorophenyl)sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2d). Yield 38%; light brown
powder; mp 129e130ꢀС; IR (KBr): 1167 (ns SO2) and 1348 (nas SO2)
( d (ppm)
ns NO2), 1538 (nas NO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
8.38 (2H, dt, J ¼ 2.0 Hz, J ¼ 9.1 Hz, H-3 Ar, H-5 Ar), 8.01 (2H, dt,
J ¼ 2.0 Hz, J ¼ 9.1 Hz, H-2 Ar, H-6 Ar), 6.38 (1H, dd, J ¼ 1.5 Hz, 6.1 Hz,
H-5), 6.33 (1H, d, J ¼ 6.1 Hz, H-4), 4.94 (1H, dd, J ¼ 1.5 Hz, J ¼ 4.5 Hz,
H-6), 4.00 (1H, d, J ¼ 12.1 Hz, H-3A), 3.96 (1H, dd, J ¼ 8.1 Hz,
J ¼ 9.1 Hz, H-1A), 3.59 (1H, d, J ¼ 12.1 Hz, He3B), 2.72 (1H, dd,
J ¼ 9.1 Hz, J ¼ 10.1 Hz, He1B), 2.18e2.13 (1H, m, H-7a), 1.66 (1H,
ddd, J ¼ 2.5 Hz, J ¼ 4.5 Hz, J ¼ 11.9 Hz, H-7A), 1.41 (1H, dd, J ¼ 7.6 Hz,
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.78e7.76 (2Н, m, H-3
Ar, H-5 Ar), 7.51e7.49 (2Н, m, Н-2 Ar, H-6 Ar), 6.36 (1Н, dd,
J ¼ 1.7 Hz, J ¼ 5.8 Hz, Н-5), 6.33 (1Н, d, J ¼ 5.8 Hz, Н-4), 4.96 (1Н, dd,
J ¼ 1.7 Hz, J ¼ 4.5 Hz, Н-6), 3.96 (1Н, d, J ¼ 12.0 Hz, Н-3А), 3.90 (1H,
dd, J ¼ 8.5 Hz, J ¼ 9.0 Hz, H-1A), 3.53 (1Н, d, J ¼ 12.0 Hz, Н-3В), 2.69
(1Н, dd, J ¼ 9.0 Hz, J ¼ 9.9 Hz, Н-1В), 2.13e2.08 (1Н, m, Н-7a), 1.66
(1Н, ddd, J ¼ 2.5 Hz, J ¼ 4.5 Hz, J ¼ 11.8 Hz, Н-7А), 1.39 (1Н, dd,
J ¼ 11.9 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 150.0,
142.7, 137.6, 133.4, 128.5 (2C), 124.3 (2C), 94.7, 80.1, 53.5, 49.4, 42.4,
J ¼ 7.6 Hz, J ¼ 11.8 Hz, Н-7В); 13C NMR (150.9 MHz, CDCl3)
d
(ppm)
30.6. MS (ESI) m/z 323 [
52.17; H, 4.38; N, 8.69; S, 9.95. Found: C, 52.22; H, 4.45; N, 8.73; S,
М
þH]þ. Anal. Calcd for C14H14N2O5S: C,
139.2, 137.4, 135.3, 133.8, 129.4 (2C), 128.8 (2C), 94.9, 80.2, 53.4,
49.3, 42.5, 30.3. GCMS (EI, 70 eV): 311 (1) for Cl35
(35), 159 (90), 113 (29), 111 (88), 95 (75), 50 (49). Anal. Calcd for
14H14ClNO3S: C, 53.93; H, 4.53; N, 4.49; S,10.28. Found: C, 54.19; H,
[М
]þ, 286 (11), 161
9.91.
(3aRS,6RS,7aRS)-2-((3-Nitrophenyl)sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2i). Yield 25%; dark beige nee-
dles; mp 113e114ꢀС; IR (KBr): 1173 (ns SO2) and 1350 (nas SO2) 1347
C
4.68; N, 4.51; S, 10.41.
(3aRS,6RS,7aRS)-2-((4-Bromophenyl)sulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2e). Yield 66%; colourless nee-
dles; mp 170e171ꢀС; IR (KBr): 1168 (ns SO2) and 1349 (nas SO2)
( d (ppm)
ns NO2), 1542 (nas NO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
8.67 (1Н, m, H-2 Ar), 8.45 (1Н, dd, J ¼ 2.1 Hz, J ¼ 8.3 Hz, H-4 Ar),
8.16e8.15 (1Н, m, H-6 Ar), 7.76 (1H, t, J ¼ 8.3 Hz, H-5 Ar), 6.38 (1Н,
dd, J ¼ 1.7 Hz, J ¼ 5.8 Hz, H-5), 6.34 (1H, d, J ¼ 5.8 Hz, H-4), 4.94 (1Н,
dd, J ¼ 1.7 Hz, J ¼ 4.1 Hz, Н-6), 4.01 (1Н, d, J ¼ 12.0 Hz, Н-3А), 3.98
(1Н, dd, J ¼ 8.3 Hz, J ¼ 9.1 Hz, Н-1A), 3.58 (1H, d, J ¼ 12.0 Hz, He3B),
2.74 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B), 2.18e2.14 (1H, m, H-7a),
1.67 (1H, ddd, J ¼ 2.5 Hz, J ¼ 4.1 Hz, J ¼ 11.6 Hz, H-7A), 1.41 (1H, dd,
cmꢁ1 1H NMR (600.2 MHz, CDC13)
; d (ppm) 7.70e7.65 (4Н, m,
Н-Ar), 6.36 (1H, dd, J ¼ 1.7 Hz, J ¼ 5.8 Hz, H-5), 6.33 (1H, d,
J ¼ 5.8 Hz, H-4), 4.95 (1H, dd, J ¼ 1.7 Hz, J ¼ 4.5 Hz, H-6), 3.95 (1H, d,
J ¼ 12.2 Hz, H-3A), 3.90 (1H, dd, J ¼ 7.8 Hz, J ¼ 9.1 Hz, H-1A), 3.54
(1H, d, J ¼ 12.2 Hz, He3B), 2.69 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B),
2.13e2.08 (1H, m, H-7a), 1.66 (1H, ddd, J ¼ 2.5 Hz, J ¼ 4.5 Hz,
J ¼ 7.4 Hz, J ¼ 11.6 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
J ¼ 11.6 Hz, H-7A), 1.38 (1H, dd, J ¼ 7.8 Hz, J ¼ 11.6 Hz, He7B); 13
C
148.3, 139.2, 137.6, 133.4, 132.8, 130.5, 127.1, 122.4, 94.8, 80.1, 53.5,
10

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
49.4, 42.5, 30.6. MS (ESI) m/z 323 [
М
þH]þ. Anal. Calcd for
(3aRS,6RS,7aRS)-6-Methyl-2-(phenylsulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2n). Was described. [28] Yield
42%; colorless plates, mp 162e163ꢀС; IR (KBr): 1170 (ns SO2) and
C
14H14N2O5S: C, 52.17; H, 4.38; N, 8.69; S, 9.95. Found: C, 52.25; H,
4.49; N, 8.72; S, 9.99.
4-{[(3aRS,6RS,7aRS)-1,6,7,7a-Tetrahydro-3a,6-epoxyisoindol-
2-yl]sulfonyl}-2-benzonitrile (2j). Yield 72%; beige powder; mp
127e128ꢀС; IR (KBr): 1171 (ns SO2) and 1351 (nas SO2), 2228 (CN)
1335 (nas SO2). 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.83 (2H, dd,
J ¼ 1.1 Hz, J ¼ 8.1 Hz, H-Ph), 7.59 (1H, t, J ¼ 8.1 Hz, H-Ph), 7.52 (2H, t,
J ¼ 8.1 Hz, H-Ph), 6.30 (1Н, d, J ¼ 5.5 Hz) and 6.17 (1Н, d, J ¼ 5.5 Hz,
Н-4, H-5), 3.90 (1Н, d, J ¼ 12.1 Hz, H-3A), 3.90 (1Н, dd, J ¼ 8.1 Hz,
J ¼ 9.2 Hz, H-1A), 3.51 (1Н, d, J ¼ 12.1 Hz, He3B), 2.77 (1Н, dd,
J ¼ 9.2 Hz, J ¼ 9.9 Hz, He1B), 2.12e2.17 (1Н, m, H-7а), 1.51 (3Н, s,
СН3), 1.47(1Н, dd, J ¼ 7.3 Hz, J ¼ 11.7 Hz, H-7A), 1.35 (1Н, dd,
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.94 (2H, d, J ¼ 8.1 Hz,
H-3 Ar and H-5 Ar), 7.89 (2H, d, J ¼ 8.1 Hz, H-2 Ar and H-6 Ar), 6.36
(1H, dd, J ¼ 1.1 Hz, J ¼ 5.6 Hz, H-5), 6.32 (1H, d, J ¼ 5.6 Hz, H-4), 4.94
(1H, dd, J ¼ 1.1 Hz, J ¼ 4.3 Hz, H-6), 3.95 (1H, d, J ¼ 12.1 Hz, H-3A),
3.91 (1H, t, J ¼ 9.1 Hz, H-1A), 3.55 (1H, d, J ¼ 12.1 Hz, He3B), 2.70
(1H, t, J ¼ 9.1 Hz, He1B), 2.12e2.07 (1H, m, H-7a), 1.65 (1H, ddd,
J ¼ 2.5 Hz, J ¼ 4.3 Hz, J ¼ 11.9 Hz, H-7A), 1.38 (1H, dd, J ¼ 7.6 Hz,
J ¼ 2.9 Hz, J ¼ 11.7 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
140.4, 137.1, 134.5, 132.6, 129.0 (2C), 127.3 (2C), 94.7, 88.3, 53.3, 49.5,
46.0, 36.7, 18.9. GCMS (EI, 70 eV): 291 (2) [М
]þ, 150 (37), 122 (29),
J ¼ 11.9 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 167.8,
106 (13), 95 (100), 77 (50), 51 (18), 41 (24). Anal. Calcd for
С15H17NO3S: С, 61.83; Н, 5.88; N, 4.81; S, 11.01. Found: С, 62.00; Н,
5.71; N, 4.69; S, 10.91.
139.9, 137.5, 133.7, 128.2 (2C), 127.9, 127.7 (2C), 94.9, 80.2, 53.4, 49.4,
42.5, 30.4. MS (ESI) m/z 303 [
C, 59.59; H, 4.67; N, 9.27; S, 10.60. Found: C, 59.79; H, 4.78; N, 9.41;
М
þH]þ. Anal. Calcd for C15H14N2O3S:
(3aRS,6RS,7aRS)-6-Methyl-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2o). Yield 60%;
white powder; mp 108e109ꢀС; IR (KBr): 1168 (ns SO2) and 1338 (nas
S, 10.86.
(3aRS,6RS,7aRS)-2-(2-Naphthylsulfonyl)-1,2,3,6,7,7a-hexahy-
dro-3a,6-epoxyisoindole (2k). Yield 48%; white powder; mp
SO2) cmꢁ1 1H NMR (600.2 MHz, CDC13)
; d (ppm) 7.71 (2H, d,
153e154ꢀС; IR (KBr): 1167 (ns SO2) and 1337 (nas SO2) cmꢁ1
;
1H
J ¼ 8.1 Hz, HeAr), 7.31 (2H, d, J ¼ 8.1 Hz, HeAr), 6.31 (1H, d,
J ¼ 5.5 Hz, H-4), 6.17 (1H, d, J ¼ 5.5 Hz, H-5), 3.89e3.87 (2H, m, H-
1A, H-3A), 3.48 (1H, d, J ¼ 12.1 Hz, He3B), 2.75 (1H, dd, J ¼ 9.2 Hz,
J ¼ 10.3 Hz, He1B), 2.42 (3H, s, CH3), 2.16e2.11 (1H, m, H-7a), 1.52
(3H, s, CH3), 1.47 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.7 Hz, H-7A), 1.35 (1H, dd,
NMR (600.2 MHz, CDC13)
d
(ppm) 8.41 (1H, d, J ¼ 1.7 Hz, HeAr), 7.97
(2H, dd, J ¼ 3.3 Hz, J ¼ 8.3 Hz, HeAr), 7.91 (1H, d, J ¼ 8.3 Hz, HeAr),
7.84 (1H, dd, J ¼ 1.7 Hz, J ¼ 8.3 Hz, HeAr), 7.65e7.59 (2H, m, HeAr),
6.32e6.30 (2H, m, H-4, H-5), 4.90 (1H, d, J ¼ 4.1 Hz, H-6), 4.02 (1H,
d, J ¼ 12.1 Hz, H-3A), 3.97 (1H, dd, J ¼ 8.3 Hz, J ¼ 9.1 Hz, H-1A), 3.63
(1H, d, J ¼ 12.1 Hz, He3B), 2.77 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B),
2.10e2.05 (1H, m, H-7a),1.62 (1H, ddd, J ¼ 2.5 Hz, J ¼ 4.1 Hz,11.6 Hz,
H-7A), 1.34 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, He7B); 13C NMR
J ¼ 2.9 Hz, J ¼ 11.7 Hz, He7B). 13C NMR (176.1 MHz, CDCl3)
d (ppm)
143.3,140.3,134.6,133.9,129.6 (2C),127.3 (2C), 94.7, 88.3, 53.3, 49.4,
45.9, 36.5, 21.4, 18.9. GCMS (EI, 70 eV): 305 (1) [M]þ, 274 (32), 154
(10), 153 (100), 121 (20), 105 (14), 103 (13), 91 (18), 79 (16), 78 (10),
77 (30), 39 (8). Anal. Calcd for C16H19NO3S: C, 62.93; H, 6.27; N,
4.59; S, 10.50. Found: C, 62.75; H, 6.46; N, 4.31; S, 10.78.
(150.9 MHz, CDCl3)
129.2,128.7,128.6,127.9,127.4,122.8, 95.1, 80.1, 53.4, 49.3, 42.6, 30.2
. GCMS (EI, 70 eV): 327 (2) [M]þ, 136 (100), 128 (27), 127 (73), 126
d (ppm) 137.2, 134.9, 134.0, 133.9, 132.2, 129.3,
d
(3aRS,6RS,7aRS)-2-[(4-Fluorophenyl)sulfonyl]-6-methyl-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2p). Yield 63%;
white crystals; mp 134e135ꢀС; IR (KBr): 1170 (ns SO2) and 1340 (nas
(19), 108 (18), 107 (9), 81 (44), 77 (8), 53 (28), 41 (22), 39 (10). Anal.
Calcd. for C18H17NO3S: C, 66.04; H, 5.23; N, 4.28; S, 9.79. Found: C,
66.32; H, 5.48; N, 4.04; S, 9.67.
SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.86e8.83 (2H, m,
(3aRS,6RS,7aRS)-2-(2-Thienylsulfonyl)-1,2,3,6,7,7a-hexahy-
dro-3a,6-epoxyisoindole (2l). Yield 49%; white powder; mp
H-3 Ar, H-5 Ar), 7.21e7.18 (2H, m, H-2 Ar, H-6 Ar), 4.32 (1H, d,
J ¼ 5.4 Hz, H-4), 6.19 (1H, d, J ¼ 5.4 Hz, H-5), 3.91e3.88 (2H, m, H-
1A, H-3A), 3.49 (1H, d, J ¼ 11.6 Hz, He3B), 2.74 (1H, t, J ¼ 9.9 Hz,
He1B), 2.20e2.15 (1H, m, H-7a), 1.52 (3H, s, CH3), 1.49 (1H, dd,
J ¼ 7.4 Hz, J ¼ 11.6 Hz, H-7A), 1.35 (1H, dd, J ¼ 2.5 Hz, J ¼ 11.6 Hz,
137e138ꢀС; IR (KBr): 1160 (ns SO2) and 1340 (nas SO2) cmꢁ1 1H
;
NMR (600.2 MHz, CDC13)
d (ppm) 7.60e7.59 (2Н, m, Н-Thienyl),
7.13 (1Н, t, J ¼ 4.1 Hz, Н-4 Thienyl), 6.36 (1Н, dd, J ¼ 1.7 Hz, J ¼ 5.8 Hz,
Н-5), 6.33 (1Н, d, J ¼ 5.8 Hz, Н-4), 4.96 (1Н, dd, J ¼ 1.7 Hz, J ¼ 4.5 Hz,
Н-6), 3.95 (1Н, d, J ¼ 12.4 Hz, Н-3А), 3.89 (1Н, dd, J ¼ 8.3 Hz,
J ¼ 9.5 Hz, Н-1А), 3.61 (1Н, d, J ¼ 12.4 Hz, Н-3В), 2.78 (1Н, t,
J ¼ 9.5 Hz, Н-1В), 2.10e2.05 (1Н, m, Н-7a), 1.68 (1Н, ddd, J ¼ 2.5 Hz,
J ¼ 4.5 Hz, J ¼ 11.6 Hz, Н-7А), 1.38 (1Н, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz,
He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 165.1 (d,
J1 ¼ 254.3 Hz), 140.5, 134.4, 133.2, 130.1 (2C, d, J3 ¼ 10.1 Hz), 116.3
F
F
(2C, d, J2 ¼ 23.1 Hz), 94.7, 88.4, 53.4, 49.6, 46.0, 36.8, 19.0; 19F NMR
F
(282.4 MHz, CDCl3)
d
(ppm) ꢁ105.3. GCMS (EI, 70 eV): 309 (2) [M]þ,
150 (16), 149 (15), 122 (21), 121 (15), 106 (9), 96 (10), 95 (100), 75
(7), 67 (7), 43 (15), 41 (19). Anal. Calcd for C15H16FNO3S: C, 58.24; H,
5.21; N, 4.53; S, 10.36. Found: C, 58.36; H, 5.29; N, 4.70; S, 10.51.
(3aRS,6RS,7aRS)-2-((4-Chlorophenyl)sulfonyl)-6-methyl-
Н-7В); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 137.4, 136.6, 133.9,
132.1, 131.8, 127.5, 95.0, 80.2, 53.5, 49.5, 42.6, 30.3. MS (ESI) m/z 284
[
М
þH]þ. Anal. Calcd. for C12H13NO3S2: C, 50.87; H, 4.62; N, 4.94; S,
22.63. Found: C, 50.96; H, 4.55; N, 4.99; S, 22.55.
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2q). Yield 65%;
(3aRS,6RS,7aRS)-2-[(4-Nitro-2-thienyl)sulfonyl]-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2m). Yield 44%; dark brown
crystals; mp 165e166ꢀС; IR (KBr): 1169 (ns SO2) and 1340 (nas SO2)
white crystals; mp 129e130ꢀС; IR (KBr): 1169 (ns SO2) and 1344 (nas
SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.78e7.75 (2H, m,
H-3 Ar, H-5 Ar), 7.51e7.48 (2H, m, H-2 Ar, H-6 Ar), 6.32 (1H, d,
J ¼ 5.8 Hz, H-4), 6.19 (1H, d, J ¼ 5.8 Hz, H-5), 3.91e3.88 (2H, m, H-
1A, H-3A), 3.59 (1H, d, J ¼ 12.0 Hz, He3B), 2.74 (1H, dd, J ¼ 9.1 Hz,
J ¼ 9.9 Hz, He1B), 2.20e2.16 (1H, m, H-7a), 1.53 (3H, s, CH3), 1.49
(1H, dd, J ¼ 7.8 Hz, J ¼ 12.0 Hz, H-7A), 1.36 (1H, dd, J ¼ 2.9 Hz,
1361 (ns NO2), 1623 (nas NO2) cmꢁ1 1H NMR (600.2 MHz, CDC13)
;
d
(ppm) 7.80 (1Н, d, J ¼ 5.0 Hz, Н-5 Thienyl), 6.51 (1H, dd, J ¼ 1.7 Hz,
J ¼ 5.8 Hz, H-5), 6.46 (1H, d, J ¼ 5.8 Hz, H-4), 5.79 (1H, d, J ¼ 5.0 Hz,
H-3 Thienyl), 5.17 (1H, dd, J ¼ 1.7 Hz, J ¼ 4.1 Hz, H-6), 3.97 (1H, d,
J ¼ 12.0 Hz, H-3A), 3.80 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, H-1A), 3.78
(1H, d, J ¼ 12.0 Hz, He3B), 3.18 (1H, t, J ¼ 9.9 Hz, He1B), 2.41e2.37
(1H, m, H-7a), 1.93 (1H, ddd, J ¼ 2.5 Hz, J ¼ 4.1 Hz, J ¼ 11.6 Hz, H-7A),
1.59 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, He7B); 13C NMR (150.9 MHz,
J ¼ 12.0 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 140.5,
139.1, 135.6, 134.4, 129.4 (2C), 128.8 (2C), 94.6, 88.4, 53.4, 49.6, 46.0,
36.8, 19.0. GCMS (EI, 70 eV): 325 (2) for Cl35 [M]þ, 161 (28), 159 (88),
150 (20), 131 (25), 113 (27), 111 (84), 99 (16), 95 (70), 75 (100), 74
(30), 51 (26), 50 (49), 41 (20). Anal. Calcd for C15H16СlNO3S: 55.30;
H, 4.95; N, 4.30; S, 9.84. Found: 55.43; H, 4.87; N, 4.38; S, 9.85.
(3aRS,6RS,7aRS)-2-((4-Bromophenyl)sulfonyl)-6-methyl-
CDCl3)
d (ppm) 162.4, 138.0 (2C), 133.4, 133.3, 102.2, 95.2, 80.5, 56.2,
52.1, 42.8, 31.5. MS (ESI) m/z 329 [
C
М
þH]þ. Anal. Calcd for
12H12N2O5S2: C, 43.89; H, 3.68; N, 8.53; S, 19.53. Found: C, 43.98;
H, 3.61; N, 8.56; S, 19.51.
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2r). Yield 57%; beige
11

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
crystals; mp 154e155ꢀС; IR (KBr): 1168 (ns SO2) and 1339 (nas SO2)
1.58e1.55 (1H, m, H-7A), 1.52 (3H, s, CH3), 1.38 (1H, dd, J ¼ 2.5 Hz,
cmꢁ1
;
1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.70e7.65 (4H, m,
J ¼ 11.6 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 142.5,
HeAr), 6.32 (1H, d, J ¼ 5.8 Hz, H-4), 6.19 (1H, d, J ¼ 5.8 Hz, H-5),
3.91e3.88 (2H, m, H-1A, H-3A), 3.50 (1H, d, J ¼ 12.0 Hz, He3B), 2.75
(1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B), 2.21e2.16 (1H, m, H-7a), 1.53
(3H, s, CH3), 1.50 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, H-7A), 1.36 (1H, dd,
141.0, 135.6, 133.7, 132.8, 130.8, 125.4 (dd, J3 ¼ 8.7 Hz, J4 ¼ 4.3 Hz),
F
F
121.6 (d, J1 ¼ 274.6 Hz),114.2,113.8, 94.4, 88.5, 53.9, 49.9, 45.8, 37.6,
F
18.9. MS (ESI) m/z 385 [
53.12; H, 3.93; N, 7.29; S, 8.34. Found: C, 53.22; H, 3.86; N, 7.34; S,
М
þH]þ. Anal. Calcd for C17H15F3N2O3S: C,
J ¼ 2.9 Hz, J ¼ 11.6 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
8.47.
140.5, 136.2, 134.4, 132.3 (2C), 128.9 (2C), 127.6, 94.6, 88.4, 53.4,
49.6, 46.0, 36.8, 18.9. GCMS (EI, 70 eV): 371 (2) for Br81 [M]þ, 155
(11), 150 (49), 148 (14), 122 (30), 121 (19), 106 (15), 95 (100), 94 (12),
43 (18), 41 (22). Anal. Calcd for C15H16BrNO3S: C, 48.66; H, 4.36; N,
3.78; S, 8.66. Found: C, 48.64; H, 4.35; N, 3.74; S, 8.63.
(3aRS,6RS,7aRS)-6-Methyl-2-(2-thienylsulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2w). Yield 46%; colourless crys-
tals; mp 157e158ꢀС; IR (KBr): 1162 (ns SO2) and 1344 (nas SO2)
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.59 (2H, m, H-3 and H-
5 Thienyl), 7.13 (1H, m, H-4 Thienyl), 6.32 (1H, d, J ¼ 5.8 Hz, H-4),
6.19 (1H, d, J ¼ 5.8 Hz, H-5), 3.90e3.87 (2H, m, H-1A, H-3A), 3.58
(1H, d, J ¼ 12.4 Hz, He3B), 2.85 (1H, t, J ¼ 9.9 Hz, He1B), 2.17e2.12
(1H, m, H-7a), 1.53 (3H, s, CH3), 1.49 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz,
H-7A), 1.39 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.6 Hz, He7B); 13C NMR
(3aRS,6RS,7aRS)-2-((4-Iodophenyl)sulfonyl)-6-methyl-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2s). Yield 37%;
white crystals; mp 164e165ꢀС; IR (KBr): 1171 (ns SO2) and 1341 (nas
SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.89e7.87 (2H, m,
H-3 Ar, H-5 Ar), 7.55e7.53 (2H, m, H-2 Ar, H-6 Ar), 6.33 (1H, d,
J ¼ 5.8 Hz, H-4), 6.19 (1H, d, J ¼ 5.8 Hz, H-5), 3.90e3.88 (2H, m, H-
1A, H-3A), 3.50 (1H, d, J ¼ 12.0 Hz, He3B), 2.75 (1H, dd, J ¼ 9.3 Hz,
10.1 Hz, He1B), 2.21e2.16 (1H, m, H-7a), 1.54 (3H, s, CH3), 1.50 (1H,
dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, H-7A), 1.36 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.6 Hz,
(150.9 MHz, CDCl3) d (ppm) 140.5, 136.9, 134.5, 132.1, 131.7, 127.4,
94.7, 88.4, 53.6, 49.7, 46.0, 36.8, 19.0. GCMS (EI, 70 eV): m/z (%) 297
[M]þ (2), 150 (22), 149 (29), 147 (17), 134 (6), 122 (20), 106 (11), 95
(100), 79 (6), 67 (6), 39 (8). Anal. Calcd for C13H15NO3S2: C, 52.50; H,
5.08; N, 4.71; S, 21.56. Found: C, 52.63; H, 5.21; N, 4.91; S, 21.73.
((3aRS,6RS,7aRS)-6-Ethyl-2-[(4-methylphenyl)sulfonyl]-
He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 140.5, 138.3 (2C),
136.7, 134.4 (2C), 128.7, 100.1, 94.6, 88.4, 53.4, 49.6, 46.0, 36.8, 19.0.
GCMS (EI, 70 eV): 417 (2) [M]þ, 203 (18), 150 (36), 149 (33), 122 (32),
121 (21), 106 (15), 95 (100), 76 (24), 43 (20), 41 (28). Anal. Calcd for
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2x). Yield 73%; beige
powder; mp 130e132ꢀС; IR (KBr): 1169 (ns SO2) and 1345 (nas SO2)
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.72 (2H, d, J ¼ 8.3 Hz,
C
15H16INO3S: C, 43.18; H, 3.87; N, 3.36; S, 7.68. Found: C, 43.19; H,
H-2 Ar, H-6 Ar), 7.31 (2H, d, J ¼ 8.3 Hz, H-3 Ar, H-5 Ar), 6.32 (1H, d,
J ¼ 5.8 Hz, H-5), 6.24 (1H, d, J ¼ 5.8 Hz, H-4), 3.89e3.86 (2H, m, H-
1A, H-3A), 3.52 (1H, d, J ¼ 11.6 Hz, He3B), 2.74 (1H, t, J ¼ 9.9 Hz,
He1B), 2.42 (3H, s, CH3), 2.14e2.10 (1H, m, H-7a), 1.85 (2H, quartet,
J ¼ 7.4 Hz, CH2CH3), 1.41 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, H-7A), 1.36
(1H, dd, J ¼ 2.5 Hz, J ¼ 11.6 Hz, He7B), 0.94 (3H, t, J ¼ 7.4 Hz,
3.90; N, 3.41; S, 7.64.
N-(4-(((3aRS,6RS,7aRS)-6-Methyl-1,6,7,7a-tetrahydro-3a,6-
epoxyisoindol-2(3H)-yl)sulfonyl)phenyl)acetamide (2t). Yield
78%; colourless powder; mp 127e128ꢀС; IR (KBr): 1168 (ns SO2) and
1343 (nas SO2), 1671 (NCO), 3301 (NH) cmꢁ1; 1H NMR (600.2 MHz,
CDC13)
d
(ppm) 7.77e7.75 (3H, m, HeAr, NH), 7.68 (2H, d, J ¼ 8.8 Hz,
CH2CH3); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 143.3, 139.0, 134.7,
HeAr), 6.32 (1H, d, J ¼ 5.5 Hz, H-4), 6.18 (1H, d, J ¼ 5.5 Hz, H-5),
3.88e3.85 (2H, m, H-1A, H-3A), 3.59 (1H, d, J ¼ 12.1 Hz, He3B), 2.76
(1H, dd, J ¼ 9.5 Hz, J ¼ 9.9 Hz, He1B), 2.20 (3H, s, CH3CO), 2.17e2.12
(1H, m, H-7a), 1.53 (3H, s, CH3), 1.48 (1H, dd, J ¼ 7.5 Hz, J ¼ 11.7 Hz,
H-7A), 1.36 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.7 Hz, He7B); 13C NMR
134.1, 129.6 (2C), 127.4 (C), 94.6, 92.4, 53.3, 49.5, 45.5, 34.4, 25.7,
21.5, 8.9. MS (ESI) m/z 320 [
63.92; H, 6.63; N, 4.39; S, 10.04. Found: C, 64.13; H, 6.82; N, 4.55; S,
М
þH]þ. Anal. Calcd for C17H21NO3S: C,
10.12.
(3aRS,6SR,7aRS)-6-Bromo-2-(phenylsulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (2y). Yield 53%; light brown
crystals; mp 109e110ꢀС; IR (KBr): 1166 (ns SO2) and 1332 (nas SO2)
(150.9 MHz, CDCl3)
d (ppm) 169.1, 142.3, 140.5, 134.5 (2C), 131.3,
128.5 (2C),119.4, 94.7, 88.5, 53.4, 49.5, 46.0, 36.6, 24.6,19.0. MS (ESI)
m/z 349 [
М
þH]þ. Anal. Calcd for C17H20N2O4S: C, 58.60; H, 5.79; N,
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.83 (2H, d, J ¼ 8.3 Hz,
8.04; S, 9.20. Found: C, 58.75; H, 5.84; N, 8.09; S, 9.29.
HeAr), 7.63e7.53 (3H, m, HeAr), 6.39e6.37 (2H, m, H-5, H-4),
3.98e3.95 (2H, m, H-1A, H-3A), 3.54 (1H, d, J ¼ 12.4 Hz, He3B), 2.84
(1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B), 2.28e2.23 (1H, m, H-7a), 2.03
(1H, dd, J ¼ 7.4 Hz, J ¼ 12.0 Hz, H-7A), 1.99 (1H, dd, J ¼ 2.9 Hz,
(3aRS,6RS,7aRS)-6-Methyl-2-((3-nitrophenyl)sulfonyl)-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2u). Yield 32%; dark
brown crystals; mp 123e124ꢀС; IR (KBr): 1169 (ns SO2) and 1345
(
nas SO2), 1350 (ns NO2), 1543 (nas NO2) cmꢁ1; 1H NMR (600.2 MHz,
J ¼ 12.0 Hz, He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 141.0,
CDC13)
d
(ppm) 8.67 (1H, m, H-2 Ar), 8.45 (1H, dd, J ¼ 3.3 Hz, 7.9 Hz,
136.6, 135.0, 133.0, 129.2 (2C), 127.3 (2C), 94.2, 89.4, 53.0, 49.0, 46.5,
H-4 Ar), 8.16e8.15 (1H, m, HeAr), 7.75 (1H, t, J ¼ 7.9 Hz, HeAr), 6.33
(1H, d, J ¼ 5.4 Hz, H-4), 6.21 (1H, d, J ¼ 5.4 Hz, H-5), 3.98 (1H, dd,
J ¼ 8.3 Hz, J ¼ 9.1 Hz, H-1A), 3.95 (1H, d, J ¼ 12.4 Hz, H-3A), 3.55 (1H,
d, J ¼ 12.4 Hz, He3B), 2.81 (1H, dd, J ¼ 9.1 Hz, J ¼ 9.9 Hz, He1B),
2.27e2.22 (1H, m, H-7a), 1.53 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.6 Hz, H-7A),
1.51 (3H, s, CH3), 1.38 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.6 Hz, He7B); 13C
41.5. MS (ESI) m/z 358 for Br81
Calcd for C14H14BrNO3S: C, 47.20; H, 3.96; N, 3.93; S, 9.00. Found: C,
[М
þH]þ, 356 for Br79
[
М
þH]þ. Anal.
47.43; H, 3.80; N, 3.99; S, 9.12.
(3aRS,6SR,7aRS)-6-Bromo-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2z). Yield 63%; beige
crystals; mp 113e114ꢀС; IR (KBr): 1163 (ns SO2) and 1330 (nas SO2)
NMR (150.9 MHz, CDCl3)
d
(ppm) 148.3, 140.7, 139.4, 134.0, 132.8,
cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm) 7.70 (2H, d, J ¼ 8.3 Hz,
130.5, 127.1, 122.4, 94.5, 88.5, 53.7, 49.7, 45.9, 37.1, 18.9. MS (ESI) m/z
H-2 Ar, H-6 Ar), 7.33 (2H, d, J ¼ 8.3 Hz, H-3 Ar, H-5 Ar), 6.38e6.36
(2H, m, H-5, H-4), 3.96e3.92 (2H, m, H-1A, H-3A), 3.50 (1H, d,
J ¼ 12.4 Hz, He3B), 2.81 (1H, t, J ¼ 9.6 Hz, He1B), 2.43 (3H, s, CH3),
2.27e2.22 (1H, m, H-7a), 2.03 (1H, dd, J ¼ 7.2 Hz, J ¼ 12.1 Hz, H-7A),
1.98 (1H, dd, J ¼ 3.4 Hz, J ¼ 12.1 Hz, He7B); 13C NMR (150.9 MHz,
337 [
М
þH]þ. Anal. Calcd for C15H16N2O5S: C, 53.56; H, 4.79; N, 8.33;
S, 9.53. Found: C, 53.56; H, 4.81; N, 8.36; O, 23.81; S, 9.56.
4-{[(3aRS,6RS,7aRS)-6-Methyl-1,6,7,7a-tetrahydro-3a,6-
epoxyisoindol-2-yl]sulfonyl}-2-(trifluoromethyl)benzonitrile
(2v). Yield 39%; beige crystals; mp 103e104ꢀС; IR (KBr): 1171 (ns
CDCl3) d (ppm) 140.6, 136.2, 134.4, 132.4 (2C), 128.9 (2C), 127.7, 94.7,
SO2) and 1349 (nas SO2) 2256 (CN) cmꢁ1
CDC13)
;
1H NMR (600.2 MHz,
88.5, 53.4, 49.6, 46.0, 36.8, 19.0. GCMS (EI, 70 eV): m/z (%) 371 for
Br81 (1) [M]þ, 369 for Br79 (3) [M]þ, 216 (58), 215 (18), 214 (66), 213
(17), 188 (15), 186 (18), 161 (34), 159 (42), 134 (44), 133 (32), 131
(28), 107 (19), 106 (32), 91 (100), 79 (28), 65 (41), 55 (17), 51 (18), 41
(40), 39 (23). Anal. Calcd for C15H16BrNO3S: C, 48.66; H, 4.36; N,
3.78; S, 8.66. Found: C, 48.75; H, 4.43; N, 3.81; S, 8.71.
d
(ppm) 8.22 (1H, br.s, H-2 Ar), 8.13 (1H, dd, J ¼ 1.5 Hz,
J ¼ 7.9 Hz, H-5 Ar), 8.02 (1H, d, J ¼ 7.9 Hz, H-6 Ar), 6.33 (1H, d,
J ¼ 5.8 Hz, H-4), 6.24 (1H, d, J ¼ 5.8 Hz, H-5), 3.98 (1H, dd, J ¼ 8.4 Hz,
9.5 Hz, H-1A), 3.95 (1H, d, J ¼ 12.1 Hz, H-3A), 3.59 (1H, d, J ¼ 12.1 Hz,
He3B), 2.81 (1H, t, J ¼ 9.5 Hz, He1B), 2.30e2.25 (1H, m, H-7a),
12

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
(3aRS,6SR,7aRS)-6-Iodo-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2aa). Yield 21%;
beige crystals; mp 135e136ꢀС; IR (KBr): 1169 (ns SO2) and 1357 (nas
d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.35 (2H, d, J ¼ 7.8 Hz, HeAr), 7.27e7.13
(5H, m, HeAr), 6.28 (1H, d, J ¼ 5.5 Hz, H-5), 6.21 (1H, d, J ¼ 5.5 Hz,
H-4), 3.86 (1H, d, J ¼ 12.4 Hz, H-3A), 3.83 (1H, dd, J ¼ 7.8 Hz,
J ¼ 9.2 Hz, H-1A), 3.57 (1H, d, J ¼ 12.4 Hz, He3B), 3.15 (1H, d,
J ¼ 14.2 Hz, CH2), 3.11 (1H, d, J ¼ 14.2 Hz, CH2), 2.68 (1H, dd,
J ¼ 9.2 Hz, J ¼ 10.1 Hz, He1B), 2.46 (3H, s, CH3), 2.12e2.08 (1H, m, H-
7a), 1.40 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.7 Hz, H-7A), 1.36 (1H, dd,
SO2) cmꢁ1 1H NMR (600.2 MHz, CDC13)
; d (ppm) 7.71 (2H, d,
J ¼ 8.1 Hz, H-2 Ar, H-6 Ar), 7.34 (2H, d, J ¼ 8.1 Hz, H-3 Ar, H-5 Ar),
6.46 (1H, d, J ¼ 5.5 Hz, H-5), 6.21 (1H, d, J ¼ 5.5 Hz, H-4), 3.98 (1H, d,
J ¼ 12.3 Hz, H-3A), 3.94 (1H, dd, J ¼ 7.9 Hz, J ¼ 9.3 Hz, H-1A), 3.53
(1H, d, J ¼ 12.3 Hz, He3B), 2.81 (1H, dd, J ¼ 9.3 Hz, J ¼ 9.9 Hz, He1B),
2.45 (3H, s, CH3), 2.22e2.18 (1H, m, H-7a), 2.10e2.04 (2H, m, H-7A,
J ¼ 7.4 Hz, J ¼ 11.7 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
143.3, 139.0, 136.7, 134.3, 133.9, 129.7 (2C), 129.6 (2C), 128.2 (2C),
127.5, 126.5 (2C), 94.5, 91.3, 53.4, 49.5, 45.4, 39.3, 34.6, 21.5. GCMS
(EI, 70 eV): m/z (%) 381 (2) [M]þ, 226 (22), 171 (18), 155 (12), 128
(26), 105 (38), 91 (100), 77 (12), 65 (37), 55 (13), 41 (21). Anal. Calcd
for C22H23NO3S: C, 69.27; H, 6.08; N, 3.67; S, 8.40. Found: C, 69.23;
H, 6.15; N, 3.70; S, 8.41.
He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 144.0, 143.8, 134.5,
133.6, 129.8 (2C), 127.4 (2C), 94.7, 63.5, 52.9, 48.7, 46.2, 44.9, 21.5.
MS (ESI) m/z 418 [
М
þH]þ. Anal. Calcd for C15H16INO3S: C, 43.18; H,
3.87; N, 3.36; S, 7.68. Found: C, 43.14; H, 3.87; N, 3.35; S, 7.63.
(3aSR,6RS,7aRS)-5-Bromo-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2bb). Yield 70%;
colourless needles; mp 161e162ꢀС; IR (KBr): 810 (CeBr), 1168 (ns
N-Allyl-4-methyl-N-{[5-(trimethylsilyl)-2-furyl]methyl}ben-
zenesulfonamide (3ff). Yield 63%; brown oil; IR (KBr): 1165 (ns
SO2) and 1336 (nas SO2) cmꢁ1; 1H NMR (700.2 MHz, CDC13)
d
(ppm)
SO2) and 1341 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm)
7.70 (2H, d, J ¼ 8.0 Hz, H-2 Ar, H-6 Ar), 7.31 (2H, d, J ¼ 8.0 Hz, H-3 Ar,
H-5 Ar), 6.35 (1H, s, H-4), 4.75 (1H, d, J ¼ 4.5 Hz, H-6), 3.89 (1H, d,
J ¼ 12.5 Hz, H-3A), 3.88 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.3 Hz, H-1A), 3.50
(1H, d, J ¼ 12.5 Hz, He3B), 2.68 (1H, t, J ¼ 9.3 Hz, He1B), 2.42 (3H, s,
CH3), 2.24e2.20 (1H, m, H-7a), 1.66 (1H, ddd, J ¼ 3.0 Hz, J ¼ 4.5 Hz,
7.65 (2H, d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.24 (2H, d, J ¼ 8.3 Hz, H-3 Ar,
H-5 Ar), 6.47 (1H, d, J ¼ 2.9 Hz, H Furyl), 6.13 (1H, d, J ¼ 2.9 Hz, H
Furyl), 5.71e5.64 (1H, m, CH), 5.19e5.16 (2H, m, CH2), 4.44 (2H, s,
NCH2), 3.79 (2H, d, J ¼ 6.2 Hz, NCH2), 2.41 (3H, s, CH3), 0.18 (9H, s,
Si(CH3)3); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 160.5, 153.9, 142.9,
J ¼ 12.1 Hz, H-7A), 1.52 (1H, dd, J ¼ 7.6 Hz, J ¼ 12.1 Hz, He7B); 13
C
137.3, 132.7, 129.5 (2C), 127.2 (2C), 120.2, 119.0, 109.5, 49.7, 42.8,
NMR (176.1 MHz, CDCl3)
d
(ppm) 143.6, 133.5, 132.7, 129.7 (2C),
21.5, ꢁ1.8 (3C). MS (ESI) m/z 364
[
М
þH]þ. Anal. Calcd for
127.4 (2C), 127.2, 97.1, 85.0, 52.7, 48.9, 43.9, 29.6, 21.5. GCMS (EI,
70 eV): m/z (%) 371 for Br81 (4) [M]þ, 214 (100), 188 (55), 186 (36),
161 (94), 159 (94), 155 (19), 134 (16), 131 (16), 91 (11), 65 (27), 51
(23), 41 (32). Anal. Calcd for C15H16BrNO3S: C, 48.66; H, 4.36; N,
3.78; S, 8.66. Found: C, 48.59; H, 4.25; N, 3.87; S, 8.39.
C18H25NO3SSi: C, 59.47; H, 6.93; N, 3.85; S, 8.82; Si, 7.73. Found: C,
59.61; H, 7.12; N, 3.94; S, 8.99; Si, 7.86.
Ethyl(3aRS,6RS,7aRS)-2-{[4-cyano-3-(trifluoromethyl)
phenyl]sulfonyl}-2,3,7,7a-tetrahydro-3a,6-epoxyisoindole-
6(1H)-carboxylate (2gg). Yield 15%; light brown powder; mp
162e163ꢀС; IR (KBr): 1175 (ns SO2) and 1352 (nas SO2), 2233 (CN),
(3aRS,6RS,7aRS)-5,6-Dimethyl-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2cc). Yield 62%;
light brown needles; mp 139e140ꢀС; IR (KBr): 1165 (ns SO2) and
1733 (CO2Et) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 8.21 (1H,
br. s, H-2 Ar), 8.13 (1H, dd, J ¼ 2.0 Hz, J ¼ 8.1 Hz, H-5 Ar), 8.03 (1H, d,
J ¼ 8.1 Hz, H-6 Ar), 6.52 (1H, d, J ¼ 5.6 Hz, H-5), 6.46 (1H, d,
J ¼ 5.6 Hz, H-4), 4.33e4.28 (2H, m, OCH2), 4.05e4.02 (2H, m, H-1A,
H-3A), 3.79 (1H, d, J ¼ 12.6 Hz, He3B), 2.88 (1H, t, J ¼ 9.6 Hz, He1B),
2.34e2.30 (1H, m, H-7a), 1.82 (2H, m, H-7A, He7B), 1.32 (3H, t,
1338 (nas SO2) cmꢁ1; 1H NMR (700.2 MHz, CDC13)
d (ppm) 7.69 (2H,
d, J ¼ 8.0 Hz, H-2 Ar, H-6 Ar), 7.28 (2H, d, J ¼ 8.0 Hz, H-3 Ar, H-5 Ar),
5.84 (1H, br.d, J ¼ 1.7 Hz, H-4), 3.84 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.3 Hz, H-
1A), 3.78 (1H, d, J ¼ 12.1 Hz, H-3A), 3.44 (1H, d, J ¼ 12.7 Hz, He3B),
2.74 (1H, dd, J ¼ 9.3 Hz, J ¼ 10.0 Hz, He1B), 2.40 (3H, s, CH3),
2.14e2.10 (1H, m, H-7a), 1.70 (3H, d, J ¼ 1.7 Hz, CH3), 1.41 (3H, s,
CH3), 1.37 (1H, dd, J ¼ 7.6 Hz, J ¼ 11.9 Hz, H-7A), 1.27 (1H, dd,
J ¼ 7.1 Hz, CH3); 13C NMR (150.9 MHz, DMSO-d6)
d (ppm) 168.4,
141.5 (2C), 136.9, 136.2, 134.7, 132.0, 125.0 (d, J4 ¼ 4.3 Hz), 120.1
F
(quartet, J1 ¼ 270.8 Hz), 114.6, 112.6, 95.2, 87.9, 61.0, 52.9, 48.8,
F
J ¼ 2.8 Hz, J ¼ 11.8 Hz, He7B). 13C NMR (176.1 MHz, CDCl3)
d
(ppm)
43.3, 35.2, 13.9. MS (ESI) m/z 443 [
C19H17F3N2O5S: C, 51.58; H, 3.87; N, 6.33; S, 7.25. Found: C, 51.65; H,
М
þH]þ. Anal. Calcd for
149.2, 143.2, 134.0, 129.6 (2C), 127.7, 127.3 (2C), 102.9, 93.9, 89.4,
53.3, 49.3, 47.5, 35.9, 21.4, 17.3, 11.8. GCMS (EI, 70 eV): m/z (%) 319
(35) [M]þ, 164 (100), 148 (11), 135 (49), 120 (24), 109 (64), 65 (13),
43 (29). Anal. Calcd for C17H21NO3S: C, 63.92; H, 6.63; N, 4.39; S,
10.04. Found: C, 64.02; H, 6.36; N, 4.56; S, 9.87.
3.99; N, 6.53; S, 7.53.
Ethyl-5-(((N-allyl-4-cyano-3-(trifluoromethyl)phenyl)sulfo-
namido)methyl)furan-2-carboxylate (3gg). Yield 32%; beige
crystals; mp 94e95ꢀС; IR (KBr): 1165 (ns SO2) and 1344 (nas SO2),
(3aSR,6SR,7aRS)-5,6-Dibromo-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2dd). Yield 60%;
light brown crystals; mp 179e180ꢀС; IR (KBr): 1159 (ns SO2) and
2236 (CN), 1730 (CO2Et) cmꢁ1 1H NMR (600.2 MHz, DMSO-d6)
;
d
(ppm) 8.38 (1H, d, J ¼ 8.1 Hz, H-6 Ar), 8.32 (1H, dd, J ¼ 1.5 Hz,
J ¼ 8.1 Hz, H-5 Ar), 8.05 (1H, br.s, H-2 Ar), 7.10 (1H, d, J ¼ 3.3 Hz, H-
Furyl), 6.56 (1H, d, J ¼ 3.3 Hz, H-Furyl), 5.76e5.69 (1H, m, CH]CH2),
5.28e5.19 (2H, m, CH]CH2), 4.54 (2H, s, NCH2), 4.23 (2H, quartet,
J ¼ 7.1 Hz, OCH2CH3), 3.99 (2H, d, J ¼ 6.1 Hz, NCH2), 1.27 (3H, t,
1339 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.70 (2H,
d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.34 (2H, d, J ¼ 8.3 Hz, H-3 Ar, H-5 Ar),
6.46 (1H, s, H-4), 3.95 (1H, dd, J ¼ 7.9 Hz, J ¼ 9.6 Hz, H-1A), 3.92 (1H,
d, J ¼ 12.7 Hz, H-3A), 3.50 (1H, d, J ¼ 12.7 Hz, He3B), 2.83 (1H, t,
J ¼ 9.6 Hz, He1B), 2.45 (3H, s, CH3), 2.39e2.35 (1H, m, H-7a), 2.10
(1H, dd, J ¼ 7.3 Hz, J ¼ 12.3 Hz, H-7A), 1.98 (1H, dd, J ¼ 2.9 Hz,
J ¼ 7.1 Hz, OCH2CH3); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 157.8,
152.8, 144.9, 144.7, 135.7, 133.6 (quartet, J2 ¼ 33.7 Hz), 131.4, 130.7,
F
124.9 (dd, J3 ¼ 9.4 Hz, J4 ¼ 4.8 Hz), 121.6 (quartet, J1 ¼ 274.6 Hz),
F
F
F
J ¼ 12.3 Hz, He7B). 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 143.9,
120.6, 117.8, 114.2, 113.5, 111.7, 61.1, 50.7, 42.8, 14.2. MS (ESI) m/z 443
134.2,133.8,133.5,129.9 (2C),127.4 (2C),102.9, 95.5, 52.5, 48.9, 47.6,
40.8, 21.5. GCMS (EI, 70 eV): m/z (%) 447 for Br79 (1) [M]þ, 262 (54),
261 (18), 234 (12), 207 (32), 179 (26), 134 (29), 106 (51), 91 (100), 79
(83), 65 (62), 52 (83), 41 (58). Anal. Calcd for C15H15 Br2NO3S: C,
40.11; H, 3.37; N, 3.12; S, 7.14. Found: C, 40.15; H, 3.35; N, 3.18; S,
7.10.
[
М
þH]þ. Anal. Calcd for C19H17F3N2O5S: C, 51.58; H, 3.87; N, 6.33; S,
7.25. Found: C, 51.68; H, 3.86; N, 6.51; S, 7.45.
Ethyl (3aRS,6RS,7aRS)-2-[(4-methylphenyl)sulfonyl]-2,3,7,7a-
tetrahydro-3a,6-epoxyisoindole-6(1H)-carboxylate (2hh) and
ethyl
furoate (3hh). Ratio 2hh/3hh ¼ 21/79. Yield 46%; brown oil. 2hh:
1H NMR (600.2 MHz, CDCl3)
5-((allyl[(4-methylphenyl)sulfonyl]amino)methyl)-2-
(3aRS,6SR,7aRS)-6-Benzyl-2-[(4-methylphenyl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2ee). Yield 68%;
dark orange crystals; mp 131e132ꢀС; IR (KBr): 1167 (ns SO2) and
d
(ppm) 7.71 (2H, d, J ¼ 8.6 Hz, HeAr),
7.32 (2H, d, J ¼ 8.6 Hz, HeAr), 6.44e6.42 (2H, m, H-4, H-5),
4.30e4.26 (2H, m, CH2CH3), 3.96e3.92 (2H, m, H-1A, H-3A), 3.58
(1H, d, J ¼ 12.6 Hz, He3B), 2.79 (1H, dd, J ¼ 9.6 Hz, J ¼ 10.1 Hz,
1340 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d (ppm) 7.33 (2H,
13

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
He1B), 2.42 (3H, s, CH3), 2.20e2.15 (1H, m, H-7a), 1.78 (1H, dd,
J ¼ 3.3 Hz, J ¼ 11.9 Hz, H-7A), 1.71 (1H, dd, J ¼ 7.6 Hz, J ¼ 11.9 Hz,
He7B), 1.30 (3H, t, J ¼ 7.1 Hz, CH2CH3); 3hh: 1H NMR (600.2 MHz,
d
(ppm) ꢁ130.6, ꢁ134.5. MS (ESI) m/z 328 [
М
þH]þ. Anal. Calcd for
C
15H15F2NO3S: C, 55.04; H, 4.62; N, 4.28; S, 9.79. Found: C, 55.36; H,
4.72; N, 4.40; S, 9.90.
CDCl3)
d
(ppm) 7.68 (2H, d, J ¼ 8.6 Hz, HeAr), 7.27 (2H, d, J ¼ 8.6 Hz,
(3aRS,6RS,7aRS)-2-[(3-Chloro-4-fluorophenyl)sulfonyl]-6-
methyl-1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2kk). Yield
48%; colourless powder; mp 126e127ꢀС; IR (KBr): 1159 (ns SO2) and
HeAr), 7.04 (1H, d, J ¼ 3.3 Hz, H-4 Furyl), 6.29 (d, J ¼ 3.3 Hz, H-3
Furyl), 5.67e5.60 (1H, m, CH]CH2), 5.20e5.16 (2H, m, CH]CH2),
4.42 (2H, s, NCH2), 4.33 (2H, quartet, J ¼ 7.1 Hz, CH2CH3), 3.84 (2H, d,
J ¼ 6.6 Hz, NCH2), 2.41 (3H, s, CH3), 1.36 (t, J ¼ 7.1 Hz, CH2CH3).
((3aRS,6RS,7aRS)-6-(Diphenylmethyl)-2-[(4-methylphenyl)
sulfonyl]-1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2ii). Yield
10%; beige needles; mp 150e151ꢀС; IR (KBr): 1162 (ns SO2) and
1350 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 7.92 (1H,
dd, J ¼ 2.3 Hz, J ¼ 6.8 Hz, H-2 Ar), 7.73 (1H, ddd, J ¼ 2.3 Hz,
J ¼ 6.8 Hz, J ¼ 8.6 Hz, H-6 Ar), 7.29 (1H, t, J ¼ 8.6 Hz, H-5 Ar), 6.34
(1H, d, J ¼ 5.6 Hz, H-5), 6.21 (1H, d, J ¼ 5.6 Hz, H-4), 3.92e3.89 (2H,
m, H-1A, H-3A), 3.51 (1H, d, J ¼ 12.1 Hz, He3B), 2.77 (1H, dd,
J ¼ 9.1 Hz, J ¼ 10.1 Hz, He1B), 2.24e2.19 (1H, m, H-7a), 1.54 (3H, s,
CH3), 1.52 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.9 Hz, H-7A), 1.39 (1H, dd,
1341 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 7.75 (2H,
d, J ¼ 8.1 Hz, HeAr), 7.39e7.17 (12H, m, HeAr), 6.25 (1H, d,
J ¼ 5.8 Hz, H-5), 6.24 (1H, d, J ¼ 5.8 Hz, H-4), 4.36 (1H, s, CHAr2),
3.90 (1H, d, J ¼ 12.1 Hz, H-3A), 3.77 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.3 Hz, H-
1A), 3.66 (1H, d, J ¼ 12.1 Hz, He3B), 2.55 (1H, dd, J ¼ 9.3 Hz,
J ¼ 10.1 Hz, He1B), 2.49 (3H, s, CH3), 2.12e2.08 (1H, m, H-7a), 1.44
(1H, dd, J ¼ 2.8 Hz, J ¼ 11.9 Hz, H-7A), 1.35 (1H, dd, J ¼ 7.4 Hz,
J ¼ 2.8 Hz, J ¼ 11.9 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
160.7 (d, J1 ¼ 257.2 Hz), 140.8, 134.5, 134.4, 130.3, 127.9 (d,
F
J3 ¼ 8.7 Hz), 122.5 (d, J2 ¼ 18.8 Hz), 117.5 (d, J2 ¼ 21.7 Hz), 94.7,
F
F
F
88.6, 53.6, 49.8, 46.1, 37.0, 19.1; 19F NMR (282.4 MHz, CDCl3)
d
(ppm) ꢁ107.5. MS (ESI) m/z 344 for Cl35
[
М
þH]þ. Anal. Calcd for
11.9 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 143.3, 141.2,
C
15H15ClFNO3S: C, 52.40; H, 4.40; N, 4.07; S, 9.33. Found: C, 52.56;
140.9, 139.6, 134.0, 133.2, 129.6 (2C), 129.4 (2C), 129.3 (2C), 128.1
(4C), 127.6 (2C), 126.5 (2C), 94.6, 93.6, 54.0, 53.2, 49.7, 45.1, 34.3,
H, 4.49; N, 4.24; S, 9.39.
N-Allyl-3-chloro-4-fluoro-N-[(5-methylfuran-2-yl)methyl]
benzenesulfonamide (3kk). Yield 25%; yellow oil; IR (KBr): 1161
21.6. MS (ESI) m/z 458 [
М
þH]þ. Anal. Calcd for C28H27NO3S: C,
73.50; H, 5.95; N, 3.06; S, 7.01. Found: C, 73.59; H, 5.85; N, 3.16; S,
( ;
ns SO2) and 1349 (nas SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
7.13.
d
(ppm) 7.83 (1H, dd, J ¼ 2.0 Hz, J ¼ 6.6 Hz, H-2 Ar), 7.68 (1H, ddd,
N-Allyl-N-{[5-(diphenylmethyl)-2-furyl]methyl}-4-
methylbenzenesulfonamide amide (3ii). Yield 33%; yellow oil, IR
(KBr): 1165 (ns SO2) and 1344 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz,
J ¼ 2.0 Hz, J ¼ 6.6 Hz, J ¼ 8.6 Hz, H-6 Ar), 7.21 (1H, t, J ¼ 8.6 Hz, H-5
Ar), 6.1 (1H, d, J ¼ 3.0 Hz, H-Furyl), 5.83 (1H, d, J ¼ 3.0 Hz, H-Furyl),
5.76e5.70 (1H, m, CH]CH2), 5.27e5.23 (2H, m, CH]CH2), 4.39
(2H, s, NCH2), 3.81 (2H, d, J ¼ 6.6 Hz, NCH2), 2.12 (3H, s, CH3); 13C
CDCl3)
d (ppm) 7.68e7.62 (3H, m, HeAr), 7.35e7.23 (5H, m, HeAr),
7.14 (2H, d, J ¼ 7.6 Hz, HeAr), 7.07e7.06 (4H, m, HeAr), 6.09 (1H, d,
J ¼ 3.0 Hz, H-Furyl), 5.78 (1H, d, J ¼ 3.0 Hz, H-Furyl), 5.65e5.59 (1H,
m, CH]CH2), 5.25 (1H, s, CHAr2), 5.11e5.02 (2H, m, CH]CH2), 4.38
(2H, s, NCH2), 3.72 (2H, d, J ¼ 6.6 Hz, NCH2), 2.70 (3H, s, CH3); 13C
NMR (150.9 MHz, CDCl3)
d
(ppm) 162.1 (d, J1 ¼ 289.0 Hz), 152.5,
F
147.0, 137.6 (d, J4 ¼ 4.3 Hz), 132.3, 130.3, 127.8 (d, J3 ¼ 7.2 Hz), 121.9
F
F
(d, J2 ¼ 18.8 Hz), 119.6, 116.8 (d, J2 ¼ 21.7 Hz), 111.0, 106.1, 49.5,
F
F
42.7, 13.4; 19F NMR (282.4 MHz, CDCl3)
d
(ppm) ꢁ108.5. MS (ESI) m/
NMR (150.9 MHz, CDCl3)
d
(ppm) 156.7, 149.0, 142.9, 141.6, 137.3,
z 344 for Cl35
[М
þH]þ. Anal. Calcd for C15H15ClFNO3S: C, 52.40; H,
132.6, 129.6 (2C), 129.4 (2C), 128.6 (2C), 128.4 (2C), 127.8 (2C), 127.3
(2C), 126.7 (2C), 119.1, 110.2, 109.0, 50.8, 49.3, 42.7, 37.9, 21.5. MS
(ESI) m/z 458 [
4.40; N, 4.07; S, 9.33. Found: C, 52.62; H, 4.53; N, 4.18; S, 9.25.
(3aRS,6RS,7aRS)-2-[(3,4-Dichlorophenyl)sulfonyl]-6-methyl-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2ll). Yield 51%;
beige powder; mp 134e135ꢀС; IR (KBr): 1158 (ns SO2) and 1347 (nas
М
þH]þ. Anal. Calcd for C28H27NO3S: C, 73.50; H, 5.95;
N, 3.06; S, 7.01. Found: C, 73.65; H, 5.99; N, 3.12; S, 7.17.
(3aRS,6RS,7aRS)-2-[(3,4-Difluorophenyl)sulfonyl]-6-methyl-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (2jj). Yield 60%; col-
ourless light powder; mp 125e126ꢀС; IR (KBr): 1168 (ns SO2) and
SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
; d (ppm) 7.92 (1H, d,
J ¼ 2.0 Hz, H-2 Ar), 7.66 (1H, dd, J ¼ 2.0 Hz, J ¼ 8.6 Hz, H-6 Ar), 7.60
(1H, d, J ¼ 8.6 Hz, H-5 Ar), 6.34 (1H, d, J ¼ 5.6 Hz, H-5), 6.21 (1H, d,
J ¼ 5.6 Hz, H-4), 3.93e3.89 (2H, m, H-1A, H-3A), 3.52 (1H, d,
J ¼ 12.1 Hz, He3B), 2.78 (1H, dd, J ¼ 9.6 Hz, J ¼ 10.1 Hz, He1B),
2.24e2.19 (1H, m, H-7a), 1.55 (3H, s, CH3), 1.52 (1H, dd, J ¼ 7.4 Hz,
1344 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 7.67e7.58
(2H, m, H-2 Ar, H-5 Ar), 7.32e7.28 (1H, m, H-6 Ar), 6.31 (1H, d,
J ¼ 5.6 Hz, H-5), 6.18 (1H, d, J ¼ 5.6 Hz, H-4), 3.89e3.86 (2H, m, H-
1A, H-3A), 3.47 (1H, d, J ¼ 12.1 Hz, He3B), 2.74 (1H, t, J ¼ 9.6 Hz,
He1B), 2.21e2.16 (1H, m, H-7a), 1.51 (3H, s, CH3), 1.49 (1H, dd,
J ¼ 7.6 Hz, J ¼ 11.6 Hz, H-7A), 1.36 (1H, dd, J ¼ 3.0 Hz, J ¼ 11.6 Hz,
J ¼ 11.9 Hz, H-7A), 1.39 (1H, dd, J ¼ 3.0 Hz, J ¼ 11.9 Hz, He7B); 13
C
NMR (150.9 MHz, CDCl3)
d (ppm) 140.7, 137.5, 137.1, 134.3, 133.7,
131.2, 129.3, 126.4, 94.6, 88.5, 53.5, 49.6, 46.0, 36.9, 19.00. MS (ESI)
He7B); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 153.2 (dd,
m/z 360 for Cl35
[М
þH]þ. Anal. Calcd for C15H15Cl2NO3S: C, 50.01; H,
J1 ¼ 257.2 Hz, J2 ¼ 13.8 Hz),150.2 (dd, J1 ¼ 254.3 Hz, J2 ¼ 13.8 Hz),
4.20; N, 3.89; S, 8.90. Found: C, 50.19; H, 4.29; N, 3.95; S, 8.98.
N-Allyl-3,4-dichloro-N-((5-methylfuran-2-yl)methyl) benze-
nesulfonamide (3ll). Yield 24%; yellow oil; IR (KBr): 1171 (ns SO2)
F
F
F
F
140.7, 134.3, 134.0, 124.4 (dd, J3 ¼ 7.2 Hz, J4 ¼ 4.3 Hz), 118.2 (d,
F
F
J2 ¼ 18.9 Hz), 117.2 (d, J2 ¼ 21.7 Hz), 94.6, 88.5, 53.5, 49.6, 46.0,
F
F
36.9, 19.0; 19F NMR (282.4 MHz, CDCl3)
d
(ppm) ꢁ129.7, ꢁ133.6. MS
and 1346 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 7.84
(ESI) m/z 328 [
М
þH]þ. Anal. Calcd for C15H15F2NO3S: C, 55.04; H,
(1H, d, J ¼ 2.0 Hz, H-2 Ar), 7.60 (1H, dd, J ¼ 2.0 Hz, J ¼ 8.6 Hz, H-6
Ar), 7.53 (1H, d, J ¼ 8.6 Hz, H-5 Ar), 6.06 (1H, d, J ¼ 3.0 Hz, H-Furyl),
5.83 (1H, d, J ¼ 3.0 Hz, H-Furyl), 5.76e5.70 (1H, m, CH]CH2),
5.27e5.24 (2H, m, CH]CH2), 4.38 (2H, s, NCH2), 3.81 (2H, d,
J ¼ 6.6 Hz, NCH2), 2.10 (3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
4.62; N, 4.28; S, 9.79. Found: C, 55.33; H, 4.70; N, 4.36; S, 9.86.
N-Allyl-3,4-difluoro-N-[(5-methylfuran-2-yl)methyl] benze-
nesulfonamide (3jj). Yield 20%; yellow oil; IR (KBr): 1156 (ns SO2)
and 1352 (nas SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
; d (ppm)
7.63e7.60 (2H, m, H-2 Ar, H-5 Ar), 7.26e7.22 (1H, m, H-6 Ar), 6.05
(1H, d, J ¼ 3.0 Hz, H-Furyl), 5.83 (1H, d, J ¼ 3.0 Hz, H-Furyl),
5.75e5.68 (1H, m, CH]CH2), 5.26e6.22 (2H, m, CH]CH2), 4.38
(2H, s, NCH2), 3.80 (2H, d, J ¼ 6.1 Hz, NCH2), 2.13 (3H, s, CH3); 13C
d (ppm) 152.5, 146.9, 140.3, 136.9, 133.2, 132.3, 130.6, 129.3, 126.4,
119.6, 111.1, 106.1, 49.6, 42.7, 13.3. MS (ESI) m/z 360 for Cl35
[
М
þH]þ.
Anal. Calcd for C15H15Cl2NO3S: C, 50.01; H, 4.20; N, 3.89; S, 8.90.
Found: C, 50.23; H, 4.31; N, 3.98; S, 8.99.
NMR (150.9 MHz, CDCl3)
d
(ppm) 152.9 (dd, J1 ¼ 254.7 Hz,
(3aRS,6RS,7aRS)-2-{[4-Chloro-3-(trifluoromethyl)phenyl]
sulfonyl}-6-methyl-1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole
(2mm). Yield 40%; beige powder; mp 103e104ꢀС; IR (KBr): 1169 (ns
F
J2 ¼ 13.8 Hz), 152.5, 150.0 (dd, J1 ¼ 254.7 Hz, J2 ¼ 13.8 Hz), 147.1,
F
F
F
137.4 (dd, J3 ¼ 8.7 Hz, J4 ¼ 4.3 Hz), 132.4, 124.5 (dd, J3 ¼ 8.7 Hz,
F
F
F
J4 ¼ 4.3 Hz), 119.6, 117.7 (d, J2 ¼ 18.8 Hz), 117.4 (d, J2 ¼ 20.2 Hz),
SO2) and 1344 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDC13)
d
(ppm)
F
F
F
111.0, 106.2, 49.6, 42.8, 13.4; 19F NMR (282.4 MHz, CDCl3)
8.14 (1H, d, J ¼ 2.0 Hz, H-2 Ar), 7.93 (1H, dd, J ¼ 2.0 Hz, J ¼ 8.6 Hz, H-
14

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
5 Ar), 7.68 (1H, d, J ¼ 8.6 Hz, H-6 Ar), 6.34 (1H, d, J ¼ 5.8 Hz, H-4),
6.22 (1H, d, J ¼ 5.8 Hz, H-5), 3.95e3.91 (2H, m, H-1A, H-3A), 3.54
(1H, d, J ¼ 12.1 Hz, He3B), 2.79 (1H, t, J ¼ 9.6 Hz, He1B), 2.26e2.22
(1H, m, H-7a), 1.55e1.52 (4H, m, H-7A, CH3), 1.39 (1H, dd, J ¼ 2.5 Hz,
methylbenzenesulfonamide (5b). Yield 32%; beige powder; mp
50e51ꢀС; IR (KBr): 1159 (ns SO2) and 1337 (nas SO2) cmꢁ1; 1H NMR
(600.2 MHz, CDCl3)
d
(ppm) 7.68 (2H, d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar),
7.28e7.25 (3H, m, H-3 Ar, H-5 Ar, H-5 Furyl), 6.26 (1H, dd, J ¼ 2.1 Hz,
J ¼ 3.3 Hz, H-4 Furyl), 6.16 (1H, d, J ¼ 3.3 Hz, H-3 Furyl), 5.42e5.37
(2H, m, C]CH2), 4.45 (2H, s, NCH2), 3.96 (2H, s, NCH2), 2.43 (3H, s,
J ¼ 11.6 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 140.8,
137.0, 136.8, 134.1, 132.4, 131.5, 129.4 (d, J2 ¼ 31.8 Hz), 126.4 (dd,
C,F
J3 ¼ 10.1 Hz, J4 ¼ 5.8 Hz), 122.0 (quartet, J1 ¼ 274.6 Hz), 94.5,
CH3); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 143.6,137.6, 134.2,133.0,
129.7 (2C),127.4 (2C), 96.7, 80.9, 72.0, 62.1, 47.3, 41.2, 21.6. GCMS (EI,
70 eV): 325 (1) for Cl35 ]þ, 172 (14), 170 (46), 142 (40), 107 (14), 91
(60), 81 (100), 65 (30), 53 (49), 39 (21). Anal. Calcd for
15H16ClNO3S: C, 55.30; H, 4.95; N, 4.30; S, 9.84. Found: C, 55.33; H,
C,F
C,F
C,F
88.5, 53.6, 49.7, 46.0, 37.2, 18.9. MS (ESI) m/z 395 [
Calcd for C16H15ClF3NO3S: C, 48.80; H, 3.84; N, 3.56; S, 8.14. Found:
М
þH]þ. Anal.
[М
C, 48.84; H, 3.85; N, 3.53; S, 8.13.
N-Allyl-4-chloro-N-[(5-methylfuran-2-yl)methyl[-3-(tri-
fluoromethyl)benzenesulfon amide (3mm). Yield 20%; colourless
C
4.98; N, 4.35; S, 9.80.
oil; IR (KBr): 1169 (ns SO2) and 1349 (nas SO2) cmꢁ1
;
1H NMR
N-(2-Furylmethyl)-4-methyl-N-(2-phenylprop-2-en-1-yl)
(600.2 MHz, CDCl3)
d (ppm) 8.11 (1H, br.s, H-2 Ar), 8.06 (1H, dd,
benzenesulfonamide (5c). Yield 81%; beige powder; mp 50e51ꢀС;
J ¼ 1.5 Hz, J ¼ 8.1 Hz, H-6 Ar), 7.93 (1H, d, J ¼ 8.1 Hz, H-5 Ar), 6.08
(1H, d, J ¼ 3.0 Hz, H-Furyl), 5.80e5.72 (2H, m, H-Furyl, CH]CH2),
5.32e5.28 (2H, m, CH]CH2), 4.42 (2H, s, NCH2), 3.89 (2H, d,
J ¼ 6.1 Hz, NCH2), 2.01 (3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
IR (KBr): 1163 (ns SO2) and 1335 (nas SO2) cmꢁ1 1H NMR
;
(600.2 MHz, CDCl3)
d
(ppm) 7.60 (2H, d, J ¼ 8.6 Hz, HeAr), 7.39e7.19
(8H, m, HeAr, H-5 Furyl), 6.22 (1H, dd, J ¼ 2.0 Hz, J ¼ 3.0 Hz, H-4
Furyl), 6.06 (1H, d, J ¼ 3.0 Hz, H-3 Furyl), 5.49 (1H, s, C]CH2), 5.29
(1H, s, C]CH2), 4.36 (2H, s, NCH2), 4.25 (2H, s, NCH2), 2.42 (3H, s,
d
(ppm) 152.6, 150.2, 145.4, 135.0, 131.8, 130.7, 125.4 (dd,
J3 ¼ 9.4 Hz, J4 ¼ 5.1 Hz), 121.6 (quartet, J1 ¼ 274.6 Hz), 120.1, 114.2,
CH3); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 149.6, 142.3, 142.2,
F
F
F
113.1, 111.4, 106.2, 50.1, 42.9, 13.1; 19F NMR (282.4 MHz, CDCl3)
d
138.4, 136.8, 133.4, 129.3 (2C), 128.3 (2C), 127.9, 127.4 (2C), 126.5
(ppm) ꢁ62.0. MS (ESI) m/z 395 for Cl35
[
М
þH]þ. Anal. Calcd for
(2C), 116.3, 110.2, 109.6, 50.7, 42.6, 21.5. MS (ESI) m/z 368 [
Anal. Calcd for C21H21NO3S: C, 68.64; H, 5.76; N, 3.81; S, 8.72.
М
þH]þ.
C
16H15ClF3NO3S: C, 48.80; H, 3.84; N, 3.56; S, 8.14. Found: C, 48.91;
H, 3.95; N, 3.70; S, 8.31.
Found: C, 68.80; H, 5.92; N, 3.95; S, 8.89.
(3aRS,6RS,7aRS)-7a-Methyl-2-(phenylsulfonyl)-1,2,3,6,7,7a-
hexahydro-3a,6-epoxyisoindole (4a). Yield 22%; beige powder;
mp 119e120ꢀС; IR (KBr): 1164 (ns SO2) and 1336 (nas SO2) cmꢁ1; 1H
N-[2-(4-Chlorophenyl)prop-2-en-1-yl]-N-(2-furylmethyl)-4-
methylbenzenesulfonamide (5d). Yield 81%; beige powder; mp
50e51ꢀС; IR (KBr): 1163 (ns SO2) and 1335 (nas SO2) cmꢁ1; 1H NMR
NMR (600.2 MHz, CDCl3)
d
(ppm) 7.85e7.84 (2H, m, HeAr),
(600.2 MHz, CDCl3)
d
(ppm) 7.59 (2H, d, J ¼ 8.6 Hz, H-3 and H-5
7.60e7.50 (3H, m, HeAr), 6.40 (1H, dd, J ¼ 1.5 Hz, J ¼ 5.7 Hz, H-5),
6.31 (1H, J ¼ 5.7 Hz, H-4), 4.88 (1H, dd, J ¼ 1.5 Hz, J ¼ 4.7 Hz, H-6),
3.90 (1H, d, J ¼ 11.7 Hz, H-3A), 3.61e5.55 (2H, m, H-1A, He3B), 3.01
(1H, d, J ¼ 8.3 Hz, He1B), 2.01 (1H, dd, J ¼ 4.7 Hz, J ¼ 11.7 Hz, H-7A),
1.00 (1H, d, J ¼ 11.7 Hz, He7B), 0.90 (3H, s, CH3); 13C NMR
C6H4Cl), 7.31e7.26 (4H, m, HeAr), 7.22 (2H, d, J ¼ 8.1 Hz, H-3 and H-
4 HeAr), 7.18e7.17 (1H, m, H-5 Furyl), 6.21 (1H, dd, J ¼ 1.5 Hz,
J ¼ 3.0 Hz, H-4 Furyl), 6.04 (1H, d, J ¼ 3.0 Hz, H-3 Furyl), 5.46 (1H,
br.s, C]CH2), 5.28 (1H, br.s, C]CH2), 4.32 (2H, s, NCH2), 4.20 (2H, s,
NCH2), 2.42 (3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
(150.9 MHz, CDCl3)
d
(ppm) 137.2, 137.0, 132.6, 132.2, 128.9 (2C),
149.5, 143.2, 142.2, 141.4, 136.8, 136.7, 133.8, 129.4 (2C), 128.5 (2C),
127.2 (2C), 96.1, 80.0, 59.8, 48.3, 48.0, 38.0, 22.0. GCMS (EI, 70 eV):
127.8 (2C),127.3 (2C),117.1,110.2, 109.7, 50.8, 42.6, 21.5. MS (ESI) m/z
291 (1) [
М
]þ, 139 (13), 96 (100), 91 (81), 81 (63), 65 (65), 53 (51), 39
402 for Cl35
[
М
þH]þ. Anal. Calcd for C21H20ClNO3S: C, 62.76; H,
(60). Anal. Calcd for C15H17NO3S: C, 61.83; H, 5.88; N, 4.81; S, 11.00.
Found: C, 61.87; H, 5.90; N, 4.86; S, 11.01.
5.02; N, 3.49; S, 7.98. Found: C, 62.98; H, 5.31; N, 3.72; S, 7.76.
(4aRS,7RS,8aRS)-2-(Phenylsulfonyl)-1,3,4,7,8,8a-hexahydro-
2H-4a,7-epoxyisoquinoline (6a). Yield 13%; white powder; mp
N-(2-Methylprop-2-en-1-yl)-N-(2-furylmethyl)-benzene-
sulfonamide (5a). Yield 46%; yellow oil; IR (KBr): 1168 (ns SO2) and
157e158ꢀС; IR (KBr): 1162 (ns SO2) and 1342 (nas SO2) cmꢁ1 1H
;
1341 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d
(ppm) 7.75e7.74
NMR (700.2 MHz, CDC13)
d
(ppm) 7.77 (2H, d, J ¼ 7.4 Hz, H-2 and H-
(2H, m, HeAr), 7.53e7.51 (1H, m, HeAr), 7.45e7.43 (2H, m, HeAr),
7.15 (1H, dd, J ¼ 1.0 Hz, J ¼ 2.0 Hz, H-5 Furyl), 6.20 (1H, dd,
J ¼ 2.0 Hz, J ¼ 3.0 Hz, H-4 Furyl), 6.06 (1H, d, J ¼ 3.0 Hz, H-3 Furyl),
4.96 (1H, s, C]CH2), 4.91 (1H, s, C]CH2), 4.38 (2H, s, NCH2), 3.74
6 Ph), 7.59 (1H, t, J ¼ 7.4 Hz, H-4 Ph), 7.53 (2H, t, J ¼ 7.4 Hz, H-3 and
H-5 Ph), 6.40 (1H, dd, J ¼ 1.7 Hz, J ¼ 5.6 Hz, H-6), 6.00 (1H, d,
J ¼ 5.6 Hz, H-5), 4.86 (1H, J ¼ 1.7 Hz, J ¼ 4.9 Hz, H-7), 3.97 (1H, ddd,
J ¼ 2.2 Hz, J ¼ 6.2 Hz, J ¼ 11.6 Hz, H-1A), 3.82e3.79 (1H, m, H-3A),
2.47e2.37 (2H, m, He1B, He3B), 2.26e2.24 (1H, m, H-4A), 2.08 (1H,
t, J ¼ 11.6 Hz, He4B), 1.92e1.88 (1H, m, H-8a), 1.46 (1H, dd,
J ¼ 7.5 Hz, J ¼ 11.8 Hz, H-8A), 1.28 (1H, ddd, J ¼ 2.6 Hz, J ¼ 4.9 Hz,
(2H, s, NCH2),1.70 (3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
d (ppm)
149.6, 142.4, 140.3, 139.9, 132.3, 128.8 (2C), 127.3 (2C), 115.0, 110.3,
109.8, 53.2, 42.4, 19.8. MS (ESI) m/z 292 [
М
þH]þ. Anal. Calcd for
C
15H17NO3S: C, 61.83; H, 5.88; N, 4.81; S, 11.00. Found: C, 61.73; H,
J ¼ 11.8 Hz, He8B). 13C NMR (176.1 MHz, CDCl3)
d (ppm) 137.9,136.7,
5.97; N, 4.65; S, 11.23.
136.5, 132.7, 129.1 (2C), 127.5 (2C), 83.8, 78.6, 51.0, 43.1, 34.6, 31.9,
28.2. GCMS (EI, 70 eV): m/z (%) 291 (2) [M]þ, 210 (100), 141 (41), 81
(10), 77 (34), 68 (37), 51 (23), 44 (41). Anal. Calcd for C15H17NO3S: C,
61.83; H, 5.88; N, 4.81; S, 11.01. Found: C, 62.02; H, 6.10; N, 4.66; S,
10.91.
(3aSR,6RS,7aSR)-7a-Chloro-2-tosyl-1,2,3,6,7,7a-hexahydro-
3a,6-epoxyisoindole (4b). Yield 30%; brown powder; mp
120e121ꢀС; IR (KBr): 1166 (ns SO2) and 1339 (nas SO2) cmꢁ1 1H
;
NMR (600.2 MHz, CDCl3)
d
(ppm) 7.72 (2H, d, J ¼ 8.6 Hz, H-2 Ar, H-6
Ar), 7.31 (2H, d, J ¼ 8.6 Hz, H-3 Ar, H-5 Ar), 6.52 (1H, dd, J ¼ 2.0 Hz,
J ¼ 5.8 Hz, H-5), 6.39 (1H, d, J ¼ 5.8 Hz, H-4), 5.00 (1H, dd, J ¼ 2.0 Hz,
J ¼ 4.5 Hz, H-6), 4.04e3.99 (2H, m, H-1A, H-3A), 3.70 (1H, d,
J ¼ 12.1 Hz, He3B), 3.41 (1H, d, J ¼ 11.1 Hz, He1B), 2.48 (1H, dd,
J ¼ 4.5 Hz, J ¼ 12.6 Hz, H-7A), 2.41 (3H, s, CH3), 1.60 (1H, d,
N-Allyl-N-[2-(2-furyl)ethyl]benzenesulfonamide (7a). Yield
66%; yellow oil; IR (KBr): 1156 (ns SO2) and 1341 (nas SO2) cmꢁ1; 1H
NMR (700.2 MHz, CDC13)
d (ppm) 7.83e7.82 (2H, m, H-2 and H-6
Ph), 7.58 (1H, t, J ¼ 7.6 Hz, H-4 Ph), 7.52 (2H, t, J ¼ 7.6 Hz, H-3 and H-
5 Ph), 7.30 (1H, d, J ¼ 1.8 Hz, H-5 Furyl), 6.28 (1H, dd, J ¼ 1.8 Hz,
J ¼ 3.0 Hz, H-4 Furyl), 6.02 (1H, d, J ¼ 3.0 Hz, H-3 Furyl), 5.63e5.58
(1H, m, CH]CH2), 5.17e5.14 (2H, m, CH]CH2), 3.78 (2H, d,
J ¼ 5.0 Hz, NCH2), 3.44e3.39 (2H, m, NCH2), 2.91e2.85 (2H, m, CH2).
J ¼ 12.6 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 143.6,
137.6, 134.1, 132.8, 129.6 (2C),127.3 (2C), 96.6, 80.8, 71.9, 62.0, 47.2,
41.1, 21.5. MS (ESI) m/z 326 for Cl35
[
М
þH]þ. Anal. Calcd for
C
15H16ClNO3S: C, 55.30; H, 4.95; N, 4.30; S, 9.84. Found: C, 55.37; H,
13C NMR (176.1 MHz, CDCl3)
d (ppm) 152.2,141.3, 140.0,132.8,132.5,
4.99; N, 4.33; S, 9.83.
N-(2-Chloroprop-2-en-1-yl)-N-(2-furylmethyl)-4-
129.1 (2C), 127.1 (2C), 119.1, 110.3, 106.5, 51.0, 45.8, 27.9. GCMS (EI,
70 eV): m/z (%) 291 (2) [M]þ, 210 (100), 141 (29), 77 (18), 68 (16), 41
15

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
(16). Anal. Calcd for C15H17NO3S: C, 61.83; H, 5.88; N, 4.81; S, 11.01.
Found: C, 61.89; H, 5.90; N, 5.12; S, 11.17.
J ¼ 11.9 Hz, He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 145.5,
139.3, 137.2, 135.4, 134.0, 129.0 (2C), 128.4, 127.9 (2C), 127.7 (2C),
(4aRS,7RS,8aRS)-2-[(4-Methylphenyl)sulfonyl]-1,3,4,7,8,8a-
hexahydro-2H-4a,7-epoxyisoquinoline (6b). Yield 15%; colourless
needles; mp 123e124ꢀС; IR (KBr): 1161 (ns SO2) and 1334 (nas SO2)
127.3 (2C), 95.1, 80.2, 53.3, 49.3, 42.6, 30.2. MS (ESI) m/z 354
[
М
þH]þ. Anal. Calcd for C20H19NO3S: C, 67.97; H, 5.42; N, 3.96; S,
9.07. Found: C, 67.99; H, 5.41; N, 3.93; S, 9.06.
cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d
(ppm) 7.62 (2H, d, J ¼ 8.3 Hz,
(3aRS,6RS,7aRS)-2-[(2′-Methylbiphenyl-4-yl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (10b). Yield 40%;
white powder; mp 105e106ꢀС; IR (KBr): 1166 (ns SO2) and 1337 (nas
H-2 Ar, H-6 Ar), 7.30 (2H, d, J ¼ 8.3 Hz, H-3 Ar, H-5 Ar), 6.38 (1H, dd,
J ¼ 1.7 Hz, J ¼ 5.8 Hz, H-6), 5.98 (1H, d, J ¼ 5.8 Hz, H-5), 4.84 (1H, dd,
J ¼ 1.7 Hz, J ¼ 5.0 Hz, H-7), 3.94e3.90 (1H, m, H-1A), 3.77e3.74 (1H,
m, H-3A), 2.42 (3H, s, CH3), 2.40e2.37 (1H, m, He1B), 2.24e2.22
(1H, m, He3B), 2.02 (1H, t, J ¼ 11.5 Hz, H-4A), 1.90e1.85 (1H, m, H-
8a), 1.44 (1H, dd, J ¼ 7.6 Hz, J ¼ 11.5 Hz, He4B), 1.27e1.24 (2H, m, H-
SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
; d (ppm) 7.88 (2H, d,
J ¼ 8.1 Hz, HeAr), 7.48 (2H, d, J ¼ 8.1 Hz, HeAr), 7.32e7.22 (4H, m,
HeAr), 6.37e6.35 (2H, m, H-4, H-5), 4.98 (1H, d, J ¼ 4.3 Hz, H-6),
4.02 (1H, d, J ¼ 12.1 Hz, H-3A), 3.97 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.4 Hz, H-
1A), 3.62 (1H, d, J ¼ 12.1 Hz, He3B), 2.81 (1H, t, J ¼ 9.4 Hz, He1B),
2.26 (3H, s, CH3), 2.15e2.10 (1H, m, H-7a), 1.70 (1H, ddd, J ¼ 3.0 Hz,
J ¼ 4.3 Hz, J ¼ 11.9 Hz, H-7A), 1.40 (1H, dd, J ¼ 7.4 Hz, J ¼ 11.9 Hz,
8A and He8B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 143.5, 137.8,
136.7, 133.4, 129.6 (2C), 127.5 (2C), 83.8, 78.5, 51.0, 43.1, 34.6, 31.8,
28.1, 21.4. MS (ESI) m/z 306 [
62.93; H, 6.27; N, 4.59; S, 10.50. Found: C, 63.12; H, 6.41; N, 4.69; S,
М
þH]þ. Anal. Calcd for C16H19NO3S: C,
He7B). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 146.6, 140.1, 137.3,
10.62.
135.4, 135.2, 134.1, 132.4, 130.6, 129.9, 129.5, 128.9, 128.1, 127.2,
126.0, 95.2, 80.2, 53.3, 29.3, 42.7, 30.2, 20.3. GCMS (EI, 70 eV): 367
[M]þ(1), 168 (10), 167 (14), 165 (45), 152 (28), 136 (46), 115 (11), 108
(19), 107 (13), 81 (100), 80 (15), 79 (10), 53 (48), 41 (37). Anal. Calcd
for C21H21NO3S: C, 68.64; H, 5.76; N, 3.81; S, 8.72. Found: C, 68.65;
H, 5.73; N, 3.80; S, 8.72.
N-Allyl-N-(2-(furan-2-yl)ethyl)-4-
methylbenzenesulfonamide (7b). Yield 29%; colourless oil; IR
(KBr): 1158 (ns SO2) and 1330 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz,
CDCl3)
d
(ppm) 7.71 (2H, d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.31e7.30 (3H,
m, H-3 Ar, H-5 Ar, H-5 Furyl), 6.28 (1H, dd, J ¼ 2.1 Hz, J ¼ 3.3 Hz, H-4
Furyl), 6.03 (1H, dd, J ¼ 0.8 Hz, J ¼ 3.3 Hz, H-3 Furyl), 5.64e5.58 (1H,
m, CH]CH2), 5.18e5.14 (2H, m, CH]CH2), 3.76 (2H, d, J ¼ 6.2 Hz,
NCH2), 3.41e3.39 (2H, m, NCH2), 2.89 (2H, dd, J ¼ 7.0 Hz, J ¼ 8.3 Hz,
(3aRS,6RS,7aRS)-2-(Biphenyl-4-sulfonyl)-6-methyl-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (10c). Yield 32%;
yellow crystals; mp 140e141ꢀС; IR (KBr): 1169 (ns SO2) and 1343
CH2), 2.43 (3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 152.5,
( ; d (ppm) 7.90 (2H, d,
nas SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
143.4, 141.4, 137.1, 133.1, 129.8 (2С), 127.3 (2С), 119.1, 110.4, 106.6,
J ¼ 7.8 Hz, HeAr), 7.73 (2H, d, J ¼ 7.8 Hz, HeAr), 7.60 (2H, d,
J ¼ 7.8 Hz, HeAr), 7.50e7.41 (3H, m, HeAr), 6.34 (1H, d, J ¼ 5.8 Hz,
H-4), 6.19 (1H, d, J ¼ 5.8 Hz, H-5), 3.96e3.93 (2H, m, H-1A, H-3A),
3.56 (1H, d, J ¼ 12.0 Hz, He3B), 2.82 (1H, dd, J ¼ 9.5 Hz, J ¼ 9.9 Hz,
He1B), 2.21e2.16 (1H, m, H-7a), 1.53 (3H, s, CH3), 1.50 (1H, dd,
J ¼ 7.4 Hz, J ¼ 11.6 Hz, He7B), 1.36 (1H, dd, J ¼ 2.9 Hz, J ¼ 11.6 Hz, H-
51.2, 45.9, 28.1, 21.6. MS (ESI) m/z 306 [
М
þH]þ. Anal. Calcd for
C
16H19NO3S: C, 62.93; H, 6.27; N, 4.59; S, 10.50. Found: C, 62.90; H,
6.22; N, 4.61; S, 10.53.
N-Allyl-4-methyl-N-(3-(5-methylfuran-2-yl)propyl)benzene-
sulfonamide (8). Yield 87%; bright yellow oil; IR (KBr): 1159 (ns
SO2) and 1343 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d
(ppm)
7A). 13C NMR (150.9 MHz, CDCl3)
d (ppm) 145.5, 140.4, 139.3, 135.7,
7.69 (2H, d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.30 (2H, d, J ¼ 8.3 Hz, H-3 Ar,
H-5 Ar), 5.86e5.83 (2H, m, H-3 Furyl, H-4 Furyl), 5.66e5.60 (1H, m,
CH]CH2), 5.17e5.11 (2H, m, CH]CH2), 3.80 (2H, d, J ¼ 6.2 Hz,
NCH2), 3.17e3.14 (2H, m, NCH2), 2.56 (2H, t, J ¼ 7.5 Hz, CH2), 2.43
134.6, 129.0 (2C), 128.4, 127.9 (2C), 127.7 (2C), 127.3 (2C), 94.8, 88.4,
53.4, 49.5, 46.1, 36.7, 19.0. MS (ESI) m/z 368 [
М
þH]þ. Anal. Calcd for
C
21H21NO3S: C, 68.64; H, 5.76; N, 3.81; S, 8.72. Found: C, 68.66; H,
5.78; N, 3.83; S, 8.75.
(3H, s, CH3), 2.24 (3H, s, CH3), 1.85 (2H, quintet, J ¼ 7.5 Hz, CH2); 13
C
(3aRS,6RS,7aRS)-2-[(4′-Methylbiphenyl-4-yl)sulfonyl]-
1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole (10d). Yield 42%;
yellow crystals; mp 161e162ꢀС; IR (KBr): 1162 (ns SO2) and 1341
NMR (150.9 MHz, CDCl3)
d (ppm) 153.0, 150.3, 143.1, 137.0, 133.1,
129.6 (2C), 127.1 (2C), 118.8, 105.8, 99.9, 50.7, 46.7, 26.7, 25.1, 21.5,
13.5. MS (ESI) m/z 334 [
64.84; H, 6.95; N, 4.20; S, 9.61. Found C, 64.98; H, 7.25; N, 4.43; S,
М
þH]þ. Anal. Calcd for C18H23NO3S: C,
( ; d (ppm) 7.89 (2H, d,
nas SO2) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
J ¼ 8.6 Hz, HeAr), 7.72 (2H, d, J ¼ 8.6 Hz, HeAr), 7.52 (2H, d,
J ¼ 8.1 Hz, HeAr), 7.29 (2H, d, J ¼ 8.1 Hz, HeAr), 6.36e6.34 (2H, m,
H-4 and H-5), 4.96 (1H, dd, J ¼ 1.1 Hz, J ¼ 4.4 Hz, H-6), 3.99 (1H, d,
J ¼ 12.1 Hz, H-3A), 3.95 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.1 Hz, H-1A), 3.59
(1H, d, J ¼ 12.1 Hz, He3B), 2.76 (1H, dd, J ¼ 9.1 Hz, J ¼ 10.1 Hz,
He1B), 2.42 (3H, s, CH3), 2.13e2.08 (1H, m, H-7a), 1.68 (1H, ddd,
J ¼ 2.5 Hz, J ¼ 4.4 Hz, J ¼ 11.9 Hz, H-7A), 1.38 (1H, dd, J ¼ 7.6 Hz,
9.87.
N-Allyl-N-(furan-3-ylmethyl)-4-methylbenzenesulfon-
amide (9). Yield 80%; light brown oil; IR (KBr): 1155 (ns SO2) and
1331 (nas SO2) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 7.72 (2H,
d, J ¼ 8.3 Hz, H-2 Ar, H-6 Ar), 7.34 (1H, t, J ¼ 1.7 Hz, H-5 Furyl), 7.31
(2H, d, J ¼ 8.3 Hz, H-3 Ar, H-5 Ar), 7.24 (1H, s, H-2 Furyl), 6.22 (1H, d,
J ¼ 1.7 Hz, H-4 Furyl), 5.59e5.53 (1H, m, CH]CH2), 5.15e5.09 (2H,
m, CH]CH2), 4.22 (2H, s, NCH2), 3.79 (2H, d, J ¼ 6.6 Hz, NCH2), 2.44
J ¼ 11.9 Hz, He7B); 13C NMR (150.9 MHz, CDCl3)
d (ppm) 145.5,
138.4, 137.3, 136.4, 135.1, 134.1, 129.7 (2C), 127.9 (2C), 127.4 (2C),
(3H, s, CH3); 13C NMR (150.9 MHz, CDCl3)
d
(ppm) 143.5, 143.3,
127.1 (2C), 95.1, 80.2, 53.3, 49.3, 42.7, 30.2, 21.2. MS (ESI) m/z 368
141.2, 137.5, 132.6, 129.7 (2C), 127.2 (2C), 120.1, 119.1, 110.7, 49.0,
[
М
þH]þ. Anal. Calcd for C21H21NO3S: C, 68.64; H, 5.76; N, 3.81; S,
40.9, 21.5. MS (ESI) m/z 292 [
61.83; H, 5.88; N, 4.81; S, 11.00. Found C, 61.56; H, 6.02; N, 4.99; S,
М
þH]þ. Anal. Calcd for C15H17NO3S: C,
8.72. Found: C, 68.78; H, 5.86; N, 3.94; S, 8.75.
N-{3-[(3aRS,6SR,7aRS)-Octahydro-3a,6-epoxyisoindol-2-
ylsulfonyl]phenyl}acetamide (11a). Yield 25%; white powder; mp
159e161ꢀС; IR (KBr): 1156 (ns SO2) and 1344 (nas SO2), 1665 (NCO),
11.12.
(3aRS,6RS,7aRS)-2-(Biphenyl-4-ylsulfonyl)-1,2,3,6,7,7a-hex-
ahydro-3a,6-epoxyisoindole (10a). Yield 47%; bright yellow crys-
tals; mp 125e127ꢀС; IR (KBr): 1161 (ns SO2) and 1344 (nas SO2)
3300 (NH) cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d (ppm) 8.33 (1H, s,
H-2 Ar), 8.06 (1H, d, J ¼ 8.1 Hz, H-6 Ar), 7.83 (1H, s, NH), 7.51e7.45
(2H, m, H-4 Ar, H-5 Ar), 4.51 (1H, t, J ¼ 5.1 Hz, H-6), 3.68 (1H, dd,
J ¼ 8.6 Hz, J ¼ 9.4 Hz, H-1A), 3.62e3.58 (2H, m, H-3A, He3B), 2.72
(1H, t, J ¼ 9.4 Hz, He1B), 2.28e2.22 (1H, m, H-7a), 2.19 (3H, s,
CH3CO), 1.80e1.47 (6H, m, H-4 CH2, H-5 CH2, H-7A, He7B). 13C NMR
cmꢁ1; 1H NMR (600.2 MHz, CDCl3)
d
(ppm) 7.90 (2H, d, J ¼ 8.6 Hz,
HeAr), 7.74 (2H, d, J ¼ 8.6 Hz, HeAr), 7.62e7.41 (5H, m, HeAr),
6.37e6.32 (2H, m, H-4, H-5), 4.96 (1H, dd, J ¼ 1.0 Hz, J ¼ 4.5 Hz, H-
6), 4.00 (1H, d, J ¼ 12.1 Hz, H-3A), 3.95 (1H, dd, J ¼ 8.1 Hz, J ¼ 9.4 Hz,
H-1A), 3.60 (1H, d, J ¼ 12.1 Hz, He3B), 2.77 (1H, dd, J ¼ 9.4 Hz,
J ¼ 10.1 Hz, He1B), 2.13e2.09 (1H, m, H-7a), 1.68 (1H, ddd,
J ¼ 3.0 Hz, J ¼ 4.5 Hz, J ¼ 11.9 Hz, H-7A), 1.38 (1H, dd, J ¼ 7.6 Hz,
(150.9 MHz, CDCl3)
d (ppm) 169.2, 139.3, 136.7, 129.9, 123.9, 122.2,
118.0, 92.5, 78.3, 54.3, 50.4, 46.4, 36.9, 30.1, 29.6, 24.4. MS (ESI) m/z
337 [
М
þH]þ. Anal. Calcd for C16H20N2O4S: C, 57.13; H, 5.99; N, 8.33;
16

M.A. Nadirova, A.V. Khanova, F.I. Zubkov et al.
Tetrahedron 85 (2021) 132032
[10] (a) Z.H. Chohan, U. Shaikh, A. Rauf, C.T. Supuran, J. Enzym. Inhib. Ch. 21 (2006)
741e748;
S, 9.53. Found: C, 57.15; H, 5.95; N, 8.32; S, 9.55.
N-(3-{[(3aRS,6SR,7aRS)-6-Methyl-octahydro-3a,6-
(b) Z.H. Chohan, M.H. Youssoufi, A. Jarrahpour, T.B. Hadda, Eur. J. Med. Chem.
45 (2010) 1189e1199.
epoxyisoindol-2-yl]sulfonyl}phenyl)acetamide (11b). Yield 24%;
white powder; mp 149e151ꢀС; IR (KBr): 1162 (ns SO2) and 1347 (nas
[11] V.N. Beesley, V. PeteRS, J. Econ. Entomol. 64 (1971) 897e899.
[12] D.K. Luci, J.B. Jameson II, A. Yasgar, G. Diaz, N. Joshi, A. Kantz, K. Markham,
S. Perry, N. Kuhn, J. Yeung, E.H. Kerns, L. Schultz, M. Holinstat, J.L. Nadler,
D.A. Taylor-Fishwick, A. Jadhav, A. Simeonov, Th R. Holman, D.J. Maloney,
J. Med. Chem. 57 (2014) 495e506.
[13] (Regarding the isoindole-containing heterocycles synthesis see:). (a)
M.A. Nadirova, Y.-O.V. Laba, V.P. Zaytsev, J.S. Sokolova, K.M. Pokazeev,
V.A. Anokhina, V.N. Khrustalev, Y.I. Horak, R.Z. Lytvyn, M. Siczek,
V. Kinzhybalo, Y.V. Zubavichuse, M.L. Kuznetsov, M.D. Obushak, F.I. Zubkov,
Synthesis 52 (2020) 2196e2223;
SO2), 1697 (NCO), 3323 (NH) cmꢁ1 1H NMR (600.2 MHz, CDCl3)
;
d
(ppm) 8.36 (1H, s, H-2 Ar), 8.11 (1H, d, J ¼ 7.6 Hz, H-6 Ar), 7.81 (1H,
s, NH), 7.51e7.45 (2H, m, H-4 Ar, H-5 Ar), 3.69 (1H, t, J ¼ 9.4 Hz, H-
1A), 3.59 (1H, d, J ¼ 11.6 Hz, H-3A), 3.53 (1H, d, J ¼ 11.6 Hz, He3B),
2.78 (1H, dd, J ¼ 9.4 Hz, J ¼ 10.1 Hz, He1B), 2.32e2.27 (1H, m, H-7a),
2.20 (3H, s, CH3CO),1.86e1.82 (1H, m, H-4A),1.79 (1H, dd, J ¼ 7.6 Hz,
J ¼ 12.1 Hz, He7B), 1.68e1.51 (3H, m, He4B, H-5 CH2), 1.38 (3H, s,
CH3), 1.33 (1H, dt, J ¼ 3.1 Hz, J ¼ 12.1 Hz, H-7A). 13C NMR
(b) V.P. Zaytsev, D.F. Mertsalov, L.V. Chervyakova, G. Krishna, F.I. Zubkov,
P.V. Dorovatovskii, V.N. Khrustalev, V.V. Zarubaev, Tetrahedron Lett. 60 (2019)
151204e151208;
(150.9 MHz, CDCl3)
d (ppm) 169.2, 139.3, 137.0, 129.9, 123.9, 122.5,
(c) K.A. Alekseeva, E.A. Kvyatkovskaya, E.V. Nikitina, V.P. Zaytsev,
S.M. Eroshkina, K.S. Shikhaliev, H.H. Truong, V.N. Khrustalev, F.I. Zubkov,
Synlett 31 (2020) 255e260.
118.0, 92.3, 86.2, 54.6, 50.8, 47.9, 42.7, 36.1, 31.3, 24.4, 21.0. MS (ESI)
m/z 351 [
М
þH]þ. Anal. Calcd for C17H22N2O4S: C, 58.27; H, 6.33; N,
7.99; S, 9.15. Found: C, 58.25; H, 6.35; N, 7.93; S, 9.19.
[14] V.M. Martínez-Díaz, G. de la Torrea, T. Torres, Chem. Commun. 46 (2010)
7090e7108.
[15] (Regarding the isoindole-containing bioactive natural alkaloids see:). (a)
F. Tillequin, M. Koch, J. Nat. Prod. 42 (1979) 92e95;
Declaration of competing interest
(b) L.S. Fernandez, M.S. Buchanan, A.R. Carroll, Y.J. Feng, R.J. Quinn, V.M. Avery,
Org. Lett. 11 (2009) 329e332;
(c) R. Vallakati, J.A. May, J. Am. Chem. Soc. 134 (2012) 6936e6939;
(d) Yixizhuoma, N. Ishikawa, M.S. Abdelfattah, M. Ishibashi, J. Antibiot. 70
(2017) 601e606.
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
[16] (Regarding the isoindole-containing polymers see:). (a) Y. Ding, A.S.J. Hay,
Polym. Sci. A Polym. Chem. 37 (1999) 3293e3299;
Acknowledgments
(b) J.P. Blinco, K.E. Fairfull-Smith, A.S. Micallef, S.E. Bottle, Polym. Chem. 1
(2010) 1009e1012;
The authors are grateful to the Russian Foundation for Basic
Research (RFBR) (award no. 19-53-04002, Бел_мол_a) and the
(c) Y. Wu, Y. Jing, X. Guo, S. Zhang, M. Zhang, L. Huoa, J. Hou, Polym. Chem. 4
(2013) 536e541.
[17] (a) M. Koppitz, et al., International Patent WO2018/114677 A2, 2018;
(b) M. Schudok, et al., International Patent WO2005/30728 A1, 2005;
(c) M. Schudok, et al., U.S. Patent US2005/80127 A1, 2005;
(d) R.D. Clark, et al., International Patent WO2005/70893 A2, 2005.
[18] (For some reviews concerning the IMDAF reaction, see:). (a) G. Brieger,
J.N. Bennett, Chem. Rev. 80 (1980) 63e97;
Belarusian Republican Foundation for Fundamental Research
(BRFFR) (award no. X19PM-003) for financial support of this
research. Antibacterial activity was investigated with the support of
the ‘‘RUDN University Program 5e100”. We thank Dr. Dmitriy
Zakusilo at the Saint-Petersburg State Forestry University for
providing this work with reagent for the synthesis of the starting
materials. We thank Mr. Fakhrutdinov A.N., the researcher from the
Department of Structural Studies of N. D. Zelinsky Institute of
Organic Chemistry.
(b) C.O. Kappe, S.S. Murphree, A. Padwa, Tetrahedron 53 (1997)
14179e14233;
(c) P. Vogel, J. Cossy, J. Plumet, O. Arjona, Tetrahedron 55 (1999)
13521e13642;
(d) F.I. Zubkov, E.V. Nikitina, A.V. Varlamov, Russ. Chem. Rev. 74 (2005)
639e669;
(e) A. Padwa, A.C. Flick, Adv. Heterocycl. Chem. 110 (2013) 1e41.
[19] R.S. Mkrtchyan, G.O. Torosyan, T.R. Melikyan, K. Ts Tagmazyan, A.T. Babayan,
Arm. Khim. Zh. (1977) 573e577.
Appendix A. Supplementary data
[20] (a) B.J. McNelis, J.T. Starr, H. Dang, J. Heterocycl. Chem. 35 (1998) 1509e1513;
(b) N. Choony, A. Dadabhoy, P.G. Sammes, J. Chem. Soc., Perkin Trans. 1 (1998)
2017e2021.
[21] (a) A. Demircan, M.K. Kandemir, M. Colak, M. Karaarslan, Synthesis 48 (2016)
2873e2880;
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132032.
(b) M. Karaarslan, F. Cansu, J. Iran. Chem. Soc. 16 (2019) 2055e2063;
(c) C. Alasalvar, A. Demircan, B. Kosar, A.I. Pekacar, O. Büyükgüngor, J. Mol.
Struct. 1123 (2016) 213e224;
(d) A. Demircan, B. Kosar, H. Arslan, O. Büyükgüngor, Acta Crystallogr. E 67
(2011) o994eo995.
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