Diastereoselective Diels-Alder Reaction of 2-Thienyl and 2-Furyl Substituted 3-Propenethioamides with Electron Deficient Dienophiles

Article abstract of DOI:10.1007/s00706-003-0089-y

The hetero-Diels-Alder reaction of N-aryl-3-(2-thienyl)-2- propenethioamides with N-phenylmaleimide and maleimide yielded a mixture of endo- and exo-2-arylimino-4-(2-thienyl)tetrahydrothiopyran[2,3-c]pyrroles. Cycloaddition to diethyl fumarate required acylation and furnished a mixture of diastereoisomeric 5-(N-acetylphenylamino)-2,3-bis-(ethoxycarbonyl)-4-(2-thienyl) -3,4-dihydro-2H-thiopyrans. Reactions of 3-(2-furyl)-2-propenethioamides with N-arylmaleimides furnished the correspondent 2-arylimino-4-(2-furyl) tetrahydrothiopyran[2,3-c]pyrroles. In the cycloadditions of the heterodienes with N-arylmaleimides the endo-cycloadducts were formed as the major products.

Full text of DOI:10.1007/s00706-003-0089-y

Monatshefte f €u r Chemie 135, 97–108 (2004)
DOI 10.1007/s00706-003-0089-y
Diastereoselective Diels-Alder Reaction
of 2-Thienyl and 2-Furyl Substituted
3-Propenethioamides with Electron
Deficient Dienophiles
ꢀ
Department of Organic Chemistry, Jagiellonian University, Pl-30060 Krak ꢀo w, Poland
Krystyna Bogdanowicz-Szwed and Artur Budzowski
Received June 12, 2003; accepted June 13, 2003
Published online October 6, 2003 # Springer-Verlag 2003
Summary. The hetero-Diels-Alder reaction of N-aryl-3-(2-thienyl)-2-propenethioamides with N-phe-
nylmaleimide and maleimide yielded a mixture of endo- and exo-2-arylimino-4-(2-thienyl)tetrahy-
drothiopyran[2,3-c]pyrroles. Cycloaddition to diethyl fumarate required acylation and furnished a
mixture of diastereoisomeric 5-(N-acetylphenylamino)-2,3-bis-(ethoxycarbonyl)-4-(2-thienyl)-3,4-
dihydro-2H-thiopyrans. Reactions of 3-(2-furyl)-2-propenethioamides with N-arylmaleimides fur-
nished the correspondent 2-arylimino-4-(2-furyl)tetrahydrothiopyran[2,3-c]pyrroles. In the cycloaddi-
tions of the heterodienes with N-arylmaleimides the endo-cycloadducts were formed as the major
products.
Keywords. ꢀ,ꢁ-Unsaturated thioamides; Hetero-Diels-Alder reaction; Thiopyrans.
Introduction
The hetero-Diels-Alder reactions have attracted considerable attention from both
synthetic utility and mechanistic point of view. Particularly, reactions employing
ꢀ
1
,ꢁ-unsaturated thiocarbonyl compounds, which can formally be treated as 1-thia-
,3-butadiene, with electron deficient dienophiles represent a straightforward and
useful route to sulphur-containing six-membered heterocycles. Its efficiency and
versatility combined with regio- and stereochemical control render the thia-Diels-
Alder reaction an attractive approach to 3,4-dihydro-2H-thiopyrans, which are
potential precursors of a wide range of sulphur heterocycles that exhibit interesting
biological properties [1–3].
Recently, we have described the hetero-Diels-Alder reaction of 2-furyl and 2-
thienyl substituted enaminothiones with electron deficient dienophiles, which led
to functionalized 3,4-dihydro-2H-thiopyrans [4–6]. In the present work we
ꢀ Corresponding author. E-mail: bogdanow@chemia.uj.edu.pl

9
8
K. Bogdanowicz-Szwed and A. Budzowski
extended our study to heterodiene cycloadditions of ꢀ,ꢁ-unsaturated thioamides
possessing heterocyclic substituents. To our knowledge Fishwick et al. [7–10] have
studied cycloadditions of N-alkylthiocinnamamides with N-phenylmaleimide,
cyclopentene and diethyl fumarate. They found that only N-acylated thiocinnam-
amides were reactive towards dienophiles. These authors reported also an in-
tramolecular heterodiene reaction of 2-allyloxy and 2-propynoxy substituted
N-alkylthiocinnamamides, which underwent cycloadditon after preliminary N-
acylation [11]. Thus, acylation of the N-alkylthioamide fragment of the heterodiene
was necessary to prevent from retro-cycloaddition or dimerization.
Results and Discussion
The aim of our study was to investigate the influence of heterocyclic substituents at
C-3 of ꢀ,ꢁ-unsaturated thioamides on yields as well as the regio- and diastereo-
selectivity of cycloadditions. We focused our attention on N-aryl substituted thio-
amides, which were supposed to be more reactive in cycloaddition reactions. In our
first approach we synthesized N-aryl-3-(2-thienyl)-2-propenethioamides 3a–3c,
which has not been published so far. They were prepared from commercially
available 3-(2-thienyl)-2-propenoic acid and arylamines via an acid chloride inter-
mediate [12]. Thioamides 3a–3c were prepared from amides 1a–1c using the
Lawesson reagent (LR) [13]. The appropriate 2-furyl-thioamides 4a–4c [12–14]
were synthesized in a similar way (Scheme 1). These compounds were stable and
did not dimerize like the N-alkylthiocinnamamides [8]. Compounds 3 and 4 con-
tain two conjugated diene systems, which are susceptible to competition in Diels-
Alder reaction with an active dienophile. The first 1,3-butadiene system consists of
the C¼C bond of thiophene or furane ring together with a conjugated vinyl frag-
ment. The second one is presented by the 1-thia-1,3-butadiene system.
Scheme 1

Diastereoselective Hetero-Diels-Alder Reaction
99
Scheme 2
In the following experiment the cycloaddition of 3a to N-phenylmaleimide (5)
was studied. The best results were obtained by heating the reagents for 36 h in
acetone solution and leaving the reaction mixture for one week at room tempera-
ture. The desired products 6a and 7a (Scheme 2) were obtained in good yield
(
diagnostic signals in the H NMR spectrum. Compounds 6a and 7a were separated
84%). The ratio of 6a:7a ¼ 14.7:1 was calculated on the basis of integration of
1
1
by column chromatography on silica gel. The H NMR spectra of both products
revealed the presence of two diastereotopic protons of a CH group, e.g. for 6a at
2
ꢂ ¼ 3.20 (J ¼ 16.2, 8.0 Hz) and 3.28 ppm (J ¼ 16.2, 3.4 Hz). However, the amine
proton could not be observed. Thus, both compounds exist in the phenylimine
tautomeric form. The structure, configuration, and conformation of 6a were estab-
1
1
1 13
lished by NMR studies employing H H COSY, H C COSY, and HMBC mea-
surements. For 6a the two vicinal protons attached to C-4 and C-4a resonated at
3
3
ꢂ ¼ 4.29 ( J ¼ 8.0, 6.1, 3.4 Hz) and at 3.81 ppm ( J ¼ 9.3, 6.1 Hz). The distinction
between endo- and exo-isomers was resolved by NOESY experiment. The NOESY
spectrum of 6a showed steric proximity of protons at H-4 and H-4a, as well as H-
4
a and H-7a indicating in both cases cis-relationship. Thus, 6a was the endo-
diastereoisomer [16, 17]. In a similar way we established the stereochemistry of
the exo-diastereoisomer 7a. Its NOESY spectrum revealed a correlation between
protons H-4a and H-7a, but did not show the correlation between H-4 and H-4a.
This indicated that the latter protons were in trans-relationship. Thus, the com-
pound 7a was the exo-diastereoisomer. The large coupling constants between H-4a
and H-7a suggested also that the thiopyran rings in both compounds exist in a boat
conformation.
Cycloaddition of 3b to 5 in acetonitrile afforded almost exclusively the endo-
diastereoisomer 6b in 17% yield (Scheme 2). The presence of the nitro group in 3b
decreased considerably the yield of product, however, the diastereoselectivity was
very high (d.e. ¼ 94%). All attempts of reactions of 3c and 5 led to complex
1
mixtures. The H NMR spectra of the reaction mixtures showed only traces of
the desired cycloadducts.
Reactions of 3a with maleimide (8) conducted in boiling acetone furnished a
mixture 9a:10a ¼ 8.9:1 (63%, Scheme 3). Poor solubility of the products in

1
00
K. Bogdanowicz-Szwed and A. Budzowski
Scheme 3
Scheme 4
common organic solvents excluded their separation by column chromatography.
Fractional crystallization of the mixture increased the ratio 9a:10a to 16.5:1. The
spectral features of obtained products were similar to those of 6a and 7a. The only
difference was the presence of a band at ꢃꢁ ¼ 3464 cmꢁ1 (N–H) in the IR spectrum
and the signal of a NH imide proton at ꢂ ¼ 11.54 ppm.
Reaction of 3a with diethyl fumarate (11) in boiling acetone solution proceeded
very slowly. Since prolonged heating did not influence the reaction, acetyl chloride
and pyridine were added to the reaction mixture. This resulted in the formation of
1
2a:13a ¼ 24:1 in 31% yield (Scheme 4). The structures were established on the
1
basis of the H NMR spectrum of the purified mixture of 12a and 13a.
The reaction of 3c with maleimide (8) in dry acetone furnished an unexpected
product 14c (31%) (Scheme 5). The H NMR spectrum of a crude reaction mixture
1
showed only traces of a simple [4 þ 2] cycloadduct. Analytical and spectral data of
1
4c as well as the molecular weight obtained from a MS spectrum indicated that 3c
reacted with 8 in a molar ratio 1:2. The mechanism of this reaction can be con-
sidered to involve an initial [4 þ 2] cycloaddition followed by a Michael reaction of
1
the formed thiopyran to 8. The structure of 14c was established by H H COSY,
1
1
13
H C COSY, and NOESY measurements. Unfortunately, the stereochemistry of
0
the protons at C-3 and C -3 could not be determined.
In the next experimental series we studied the reactions of 3-(2-furyl)-2-prope-
nethioamides 4a–4c [15] (Scheme 1) with N-phenylmaleimide (5) and N-(4-methyl-
phenyl)maleimide (15). Reactions of 4 with appropriate dienophiles were conducted

Diastereoselective Hetero-Diels-Alder Reaction
101
Scheme 5
Scheme 6
ꢂ
in acetonitrile at 60 C. The ratios of diastereoisomers were determined on the basis of
1
H NMR spectra of crude reaction mixtures. All reactions were stereoselective and
favoured formation of endo-cycloadducts. The reactions of the heterodiene with a p-
tolyl substituent at the amino group proceeded with higher diastereoselectivity. The
products were separated by column chromatography, however, only in two cases we
isolated exo-diastereoisomers 19b and 19c in 1% yield. The results of the reactions of
dienes 4a–4c with 5 and 15 are outlined in Scheme 6.
The structures, relative configurations, and conformations of the obtained
cycloadducts were deduced from chemical shift values and coupling constants of
1
protons at C-3, C-4, C-4a, and C-7a. The H NMR spectrum of 18a in CDCl
3
2
revealed two diastereotopic protons of the CH group at ꢂ ¼ 3.04 ( J ¼ 16.5,
2
3
2
3
J ¼ 9.3 Hz) and at 3.23 ppm ( J ¼ 16.5, J ¼ 2.6 Hz). However the IR spectrum
ꢁ
1
in KBr exhibited the presence of a band at ꢃꢁ ¼ 3483 cm of the NH group. This
indicated that in the solid state the enamine form is preferred, whereas in CDCl
solution the ketoimine form is predominant. The proton C(4)-H of 18a resonated at
3
3
3
ꢂ ¼ 3.98 ( J ¼ 9.3, 6.0, 2.6 Hz) and the proton C(4a)-H at 3.85 ppm ( J ¼ 9.5,

1
02
K. Bogdanowicz-Szwed and A. Budzowski
6.0 Hz). It indicated that they are in a cis-relationship. The spectral features of
other endo-cycloadducts were similar to those of 18a. In the case of exo-cycload-
ducts 19b and 19c protons at C-4 and C-4a were in a trans-relationship.
In conclusion, an efficient diastereoselective synthesis of 2-thienyl and 2-furyl
substituted tetrahydrothiopyrano[2,3-c]pyrrole systems was developed. In spite of
the presence of two and three diene systems in the substrates, only the 1-thia-1,3-
butadiene fragment was reactive in the Diels-Alder reactions. Besides it was
proved, that an introduction of aryl groups into the thioamide fragment decreases
the electron releasing influence of the amino nitrogen and allows to obtain cycload-
ducts without preliminary acylation of heterodienes. Low yields of some products
were probably due to a retro Diels-Alder reaction. It is worth to note that cycload-
ditions of heterodienes 4 containing the 2-furyl substituent furnished almost exclu-
sively the endo-cycloadducts and required shorter times to complete reactions than
in the case of heterodienes 3.
Experimental
Mps were determined on a Boetius hot-stage apparatus and are uncorrected. IR spectra were run in KBr
pellets on a Bruker IFS 48 spectrometer. Mass spectra were obtained on a Finnigan Mat 95 (70 eV)
1
mass spectrometer. NMR spectra were recorded on a Bruker AMX 500 spectrometer ( H: 500.14 MHz,
1
3
C: 125.76 MHr) or Mercury-300 Varian in CDCl or DMSO-d using TMS as internal standard.
3
6
Microanalyses were performed on an Euro EA 3000 Elemental Analyzer, their results were in satis-
factory agreement with the calculated values. 2-Furyl-, 2-thienylacrylic acids, and the Lawesson
reagent were commercially available. Silica Gel 60, 0.063–0.2mm, was used for column chromato-
graphy. The appropriate arylamides 1a–1c and 2a–2c were synthesized according to Refs. [12, 14].
General Procedure for the Synthesis of 3-(2-Thienyl)-
and 3-(2-Furyl)-2-propene-N-arylamides
3
To a solution of 0.05 mol of the appropriate acid chloride in 30–50 cm of dry CH Cl , a solution of
2
2
3
3
0
.049mol of arylamine and 4.0 g of pyridine (0.05 mol) in 40–50 cm of dry CH Cl (300 cm in case of
2 2
1
b) was added dropwise over a period of 1 h and stirred for additional 2 h. The precipitated products 1b,
and 2b, 2c were collected by filtration, washed with H O, and recrystallized from toluene. In the case of
2
1
c and 2a the reaction mixtures were washed with H O and dried (MgSO ). After removing the solvent,
2 4
the crude products were purified by flash chromatography (CHCl ) and crystallized from toluene.
3
N-(4-Nitrophenyl)-3-(2-thienyl)-2-propeneamide (1b, C H N O S)
13 10 2 3
ꢂ
Pale yellow crystals; mp 216 C; yield 81%; IR (KBr): ꢃꢁ ¼ 3378 (N–H), 1688 (C¼O), 1619, 1610,
ꢁ
1
1
1
595, 1537cm ; H NMR (DMSO-d ): ꢂ ¼ 6.60 (d, J ¼ 15.4 Hz, CH vinyl), 7.17 (dd, J ¼ 5.0, 3.6 Hz,
6
CH), 7.52 (d, J ¼ 3.6 Hz, CH), 7.72 (d, J ¼ 5.0 Hz, CH), 7.84 (d, J ¼ 15.4Hz, CH vinyl), 7.92 (d,
1
3
J ¼ 9.2 Hz, 2CH arom), 8.25 (d, J ¼ 9.2 Hz, 2CH arom), 10.79 (s, NH) ppm; C NMR (DMSO-d ):
6
ꢂ ¼ 118.8, 119.8, 125.0, 128.5, 129.1, 132.0, 134.6, 139.4, 142.1, 145.4, 163.9 ppm; MS: m=z
þꢃ
(
%) ¼ 274.0 (15) [M] , 137.0 (100), 109.0 (21), 65.0 (8).
N-(4-Methoxyphenyl)-3-(2-thienyl)-2-propeneamide (1c, C H NO S)
1
4
13
2
ꢂ
Pale yellow crystals; mp 137 C; yield 80%; IR (KBr): ꢃꢁ ¼ 3329 (N–H), 3080, 3011, 2961, 2836 (C–
ꢁ
1
1
H), 1660 (C¼O), 1626, 1542, 1513 cm
;
H NMR (DMSO-d ): ꢂ ¼ 3.73 (s, OCH ), 6.56 (d,
6
3
J ¼ 15.4Hz, CH vinyl), 6.91 (d, J ¼ 9.1Hz, 2CH arom), 7.14 (dd, J ¼ 5.1, 3.5Hz, 2CH), 7.43 (d,

Diastereoselective Hetero-Diels-Alder Reaction
103
J ¼ 3.5 Hz, CH), 7.60 (d, J ¼ 9.1 Hz, 2CH arom), 7.65 (d, J ¼ 5.1 Hz, CH), 7.71 (d, J ¼ 15.4 Hz, CH
1
3
vinyl), 10.07 (s, NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 55.1, 113.9, 120.5, 121.0, 128.2, 128.4, 131.0,
6
þꢃ
1
1
32.4, 132.6, 139.8, 155.3, 162.7 ppm; MS: m=z (%) ¼ 259.0 (100) [M] , 137.0 (27), 123.1 (21),
09.0 (10), 92.1 (13), 91.0 (22), 63.0 (15).
General Procedure for the Reactions of 1 and 2 with the Lawesson Reagent
A suspension of 20 mmol of appropriate N-arylamide (1 or 2) and 4.85 g of the Lawesson reagent
3
12 mmol) in 150 cm of dry toluene was stirred at 70 C for 30 h. Then the reaction mixture was
ꢂ
(
3
concentrated to 30–60cm . The crude product was collected by filtration, purified by flash chromato-
graphy (CHCl ), and recrystallized from toluene.
3
N-Phenyl-3-(2-thienyl)-2-propenethioamide (3a, C H NS )
11
1
3
2
ꢂ
Orange crystals; mp 128 C; yield 56%; IR (KBr): ꢃꢁ ¼ 3450 (N–H), 3256–3205, 3130–3017 (C–H),
ꢁ
1
1
1
3
7
625, 1603, 1552cm ; H NMR (DMSO-d ): ꢂ ¼ 7.11 (d, J ¼ 15.0Hz, CH vinyl), 7.15 (dd, J ¼ 5.0,
6
.6 Hz, CH), 7.24 (t, J ¼ 7.4 Hz, CH arom), 7.41 (dd, J ꢄ 7.8 Hz, 2CH arom), 7.50 (d, J ¼ 3.6 Hz, CH),
.67 (d, J ¼ 5.0Hz, CH), 7.93 (d, J ¼ 7.8 Hz, 2CH arom), 8.01 (d, J ¼ 15.0Hz, CH vinyl), 11.58 (s,
1
3
NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 123.0, 125.8, 127.6, 128.4, 128.6, 131.7, 135.0, 139.5, 140.0,
6
þꢃ
1
91.3ppm; MS: m=z (%) ¼ 245.0 (81) [M] , 244.0 (61), 212.0 (28), 153.0 (100), 109.0 (15), 92.1
(
36), 91.1 (55), 77.1 (13), 69.0 (11).
N-(4-Nitrophenyl)-3-(2-thienyl)-2-propenethioamide (3b, C H N O S )
13 10 2 2 2
3
A suspension of 3.01 g of 3b (11 mmol) and 2.67g of the Lawesson reagent (6.6mmol) in 200 cm of
dry THF was gently refluxed in an oil bath for 24 h. Then the reaction mixture was concentrated to
3
0cm and 40cm of toluene were added. The crude product was collected by filtration, and recrys-
3
3
tallized from toluene:THF ¼ 1:1.
ꢂ
Orange plates, mp 236–238 C; yield 54%; IR (KBr): ꢃꢁ ¼ 3208 (N–H), 3012, 2923, 2853 (C–H),
ꢁ
1
1
1
614, 1593, 1541, 1515 cm ; H NMR (DMSO-d ): ꢂ ¼ 7.14 (d, J ¼ 14.9Hz, CH vinyl), 7.18 (dd,
6
J ¼ 5.0, 3.6 Hz, CH), 7.58 (d, J ¼ 3.6 Hz, CH), 7.74 (d, J ¼ 5.0Hz, CH), 8.05 (d, J ¼ 15.4Hz, CH
1
3
vinyl), 8.30 (d, J ¼ 9.3 Hz, 2CH arom), 8.34 (d, J ¼ 9.3 Hz, 2CH arom), 12.02 (s, NH) ppm; C NMR
(
DMSO-d ): ꢂ ¼ 122.5, 124.3, 127.5, 128.7, 129.3, 132.5, 136.2, 139.9, 143.7, 145.3, 192.8ppm; MS:
6
þꢃ
m=z (%) ¼ 290.0 (71) [M] , 257.0 (23), 243.0 (9), 222.0 (41), 211.0 (9), 171.1 (11), 153.0 (100), 149.0
(
33), 137.0 (50).
N-(4-Methoxyphenyl)-3-(2-thienyl)-2-propenethioamide (3c, C H NOS )
1
4
13
2
ꢂ
Orange crystals; mp 158 C; yield 68%; IR (KBr): ꢃꢁ ¼ 3189 (N–H), 3004, 2947–2905, 2830 (C–H),
ꢁ
1
1
1
625, 1533, 1506cm ; H NMR (DMSO-d ): ꢂ ¼ 3.78 (s, OCH ), 6.97 (d, J ¼ 9.0 Hz, 2CH arom),
6
3
7
.07 (d, J ¼ 15.0Hz, CH vinyl), 7.15 (dd, J ¼ 5.0, 3.5Hz, CH), 7.48 (d, J ¼ 3.5Hz, CH), 7.66 (d,
J ¼ 5.0 Hz, CH), 7.84 (d, J ¼ 9.0 Hz, 2CH arom), 7.98 (d, J ¼ 15.0 Hz, CH vinyl), 11.49 (s, NH) ppm;
1
3
C NMR (DMSO-d ): ꢂ ¼ 55.2, 113.5, 124.5, 127.6, 128.4, 128.5, 131.4, 132.6, 134.6, 140.1, 157.0,
6
þꢃ
1
90.3ppm; MS: m=z (%) ¼ 275.1 (65) [M] , 274.1 (16), 242.1 (46), 153.0 (100), 140.0 (27).
N-Phenyl-3-(2-furyl)-2-propenethioamide (4a)
ꢂ
ꢂ
Orange crystals; mp 101 C (Ref. [15] 101–102 C); 42%; IR (KBr): ꢃꢁ ¼ 3227 (N–H), 3130, 3070 (C–
ꢁ
1
1
H), 1631, 1600, 1548 cm ; H NMR (DMSO-d ): ꢂ ¼ 6.64 (dd, J ¼ 3.3, 1.8 Hz, CH), 6.93 (d,
6
J ¼ 3.3 Hz, CH), 7.15 (d, J ¼ 15.1Hz, CH vinyl), 7.24 (t, J ¼ 7.2 Hz, CH arom), 7.41 (dd, J ꢄ 7.8 Hz,

1
04
K. Bogdanowicz-Szwed and A. Budzowski
3
2
1
1
CH arom), 7.67 (d, J ¼ 15.1 Hz, CH vinyl), 7.83 (d, J ¼ 1.8Hz, CH), 7.93 (d, J ¼ 7.8Hz, 2CH arom),
1
3
1.61 (bs, NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 112.7, 115.2, 123.0, 125.8, 126.0, 128.3, 128.9, 139.5,
6
þꢃ
45.1, 151.1, 191.3 ppm; MS: m=z (%) ¼ 229.0 (100) [M] , 201.0 (18), 200.0 (11), 196.1 (12), 175.0
(48), 137.0 (51), 109.0 (27), 77.0 (14), 65.0 (17).
N-(4-Methylphenyl)-3-(2-furyl)-2-propenethioamide (4b)
ꢂ
1
1
ꢂ
Orange crystals; mp 144 C (Ref. [15] 142–143 C); yield 74%; IR (KBr): ꢃꢁ ¼ 3224 (N–H), 3192, 3045
ꢁ
(
C–H), 1635, 1539 cm ; H NMR (DMSO-d ): ꢂ ¼ 2.31 (s, CH ), 6.64 (dd, J ¼ 3.4, 1.8 Hz, CH), 6.92
6
3
(
d, J ¼ 3.4Hz, CH), 7.13 (d, J ¼ 15.1Hz, CH vinyl), 7.21 (d, J ¼ 8.2 Hz, 2CH arom), 7.65 (d,
1
3
J ¼ 15.1Hz, CH vinyl), 7.79–7.83 (m, 3CH), 11.54 (s, NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 20.5,
6
1
12.6, 115.0, 122.9, 126.0, 128.7, 135.1, 137.0, 145.0, 151.1, 190.8 ppm; MS: m=z (%) ¼ 243.0 (100)
þꢃ
[
M] , 215.0 (11), 210.1 (13), 189.0 (37), 137.0 (49), 109.0 (16), 65.0 (13).
N-(4-Chlorophenyl)-3-(2-furyl)-2-propenethioamide (4c, C H ClNOS)
13 10
ꢂ
Orange crystals; mp 183 C; yield 70%; IR (KBr): ꢃꢁ ¼ 3245 (N–H), 3119 (C–H), 1691, 1637,
ꢁ
1
1
1
583 cm ; H NMR (DMSO-d ): ꢂ ¼ 6.64 (d, J ¼ 3.4 Hz, CH), 6.95 (d, J ¼ 3.4Hz, CH), 7.13 (d,
6
J ¼ 14.9Hz, CH vinyl), 7.47 (d, J ¼ 9.1 Hz, 2CH arom), 7.66 (d, J ¼ 14.9Hz, CH vinyl), 7.83 (s, CH),
1
3
7
.99 (d, J ¼ 9.1 Hz, 2CH arom), 11.69 (bs, NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 112.7, 115.5, 124.6,
6
1
25.8, 128.3, 129.1, 129.4, 138.4, 145.2, 151.1, 191.6 ppm; MS: m=z (%) ¼ 265.0 (36) [Mþ 2], 263.0
þꢃ
(
100) [M] , 230.0 (11), 209.0 (35), 137.0 (84), 114.0 (19), 109.0 (22), 65.1 (16).
General Procedure for the Reactions of Thioamides 3 with N-Arylmaleimides
3
A solution of 2 mmol of 3a and 2.4 mmol of N-phenylmaleimide (5) in 20 cm of dry acetonitrile
3
200 cm in the case of 3b) or acetone was stirred at 60 C for 96h and left at room temperature for
ꢂ
(
several days. Then the solvent was removed under reduced pressure and the residue was submitted to
column chromatography using CHCl or CHCl :CH OH ¼ 50:1 as eluent. The oily products were
3
3
3
recrystallized from t-butyl methyl ether.
(4RS,4aSR,7aSR)-6-Phenyl-2-(phenylimino)-4-(2-thienyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-6a, C H N O S )
23 18 2 2 2
ꢂ
Colorless crystals; mp 199–200 C; yield 83%; IR (KBr): ꢃꢁ ¼ 3099–3061, 2935 (C–H), 1711 (C¼O),
ꢁ
1
1
1
623, 1591cm ; H NMR (CDCl ): ꢂ ¼ 3.20 (dd, J ¼ 16.2, 8.0 Hz, 3-H), 3.28 (dd, J ¼ 16.2, 3.4Hz, 3-
3
H), 3.81 (dd, J ¼ 9.3, 6.1 Hz, 4a-H), 4.29 (m, 4-H), 4.49 (d, J ¼ 9.3 Hz, 7a-H), 6.89 (d, J ¼ 7.3 Hz, 2CH
arom), 6.96 (d, J ¼ 7.1Hz, 2CH arom), 7.00 (dd, J ¼ 5.1, 3.5Hz, CH), 7.04 (m, J ꢄ 3.5Hz, CH), 7.15
1
3
(
t, J ꢄ 7.3 Hz, CH arom), 7.29 (dd, J ¼ 5.1, 1.2 Hz, CH), 7.35–7.41 (m, 5CH arom) ppm; C NMR
(
CDCl ): ꢂ ¼ 37.2, 40.6, 42.2, 45.3, 119.5, 124.9, 125.5, 126.2, 127.0, 127.3, 129.0, 129.2, 129.3,
3
þꢃ
1
2
31.0, 139.7, 149.0, 160.4, 173.2 ppm; MS: m=z (%) ¼ 418.1 (100) [M] , 245.0 (21), 244.0 (13),
12.0 (99), 167.0 (15), 153.0 (18), 117.1 (15), 110.0 (33), 82.9 (15), 77.0 (28).
(4RS,4aRS,7aRS)-6-Phenyl-2-(phenylimino)-4-(2-thienyl)-2,3,4,4a-tetrahydrothiopyrano
[
2,3-c]pyrrole-5,7(6H,7aH)-dione (exo-7a, C H N O S )
2
3 18 2 2 2
ꢂ
Colorless crystals; mp 221–223 C; yield 1.2%; IR (KBr): ꢃꢁ ¼ 3108, 3056, 2949, 2923, 2854 (C–H),
ꢁ
1
1
1
713 (C¼O), 1617, 1591 cm ; H NMR (CDCl ): ꢂ ¼ 3.02 (dd, J ¼ 15.8, 3.1 Hz, 3-H), 3.27 (dd,
3
J ¼ 15.8, 7.5 Hz, 3-H), 3.89 (dd, J ¼ 9.1, 4.8 Hz, 4a-H), 4.29 (m, 4-H), 4.49 (d, J ¼ 9.1 Hz, 7a-H), 6.77
d, J ¼ 7.3 Hz, 2CH arom), 7.04 (dd, J ¼ 5.1, 3.6Hz, CH), 7.12 (m, 2CH), 7.27–7.34 (m, 5CH) 7.43 (t,
(

Diastereoselective Hetero-Diels-Alder Reaction
105
1
3
J ꢄ 7.4 Hz, CH arom), 7.49 (dd, J ꢄ 7.6 Hz, CH arom) ppm; C NMR (CDCl ): ꢂ ¼ 36.3, 40.9, 41.9,
3
4
1
6.5, 119.5, 124.7, 124.9, 125.5, 127.2, 129.1, 129.2, 129.3, 131.2, 143.5, 148.8, 160.5, 173.2,
þꢃ
74.9ppm; MS: m=z (%) ¼ 418.1 (100) [M] , 386.1 (13), 385.1 (12), 315.0 (26), 245.0 (18), 212.0
(
56), 167.0 (38), 153.0 (32), 142.0 (22), 135.0 (11), 117.0 (15), 110.0 (46), 77.0 (39).
(4RS,4aSR,7aSR)-2-(4-Nitrophenylimino)-6-phenyl-4-(2-thienyl)-2,3,4,4a-tetrahydro-
thiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-6b, C H N O S )
23 17 3 4 2
ꢂ
Pale yellow crystals; mp 215–216 C; yield 17%; IR (KBr): ꢃꢁ ¼ 3109, 3072, 2918 (C–H), 1706 (C¼O),
ꢁ
1
1
1
625, 1587, 1511, 1492 cm ; H NMR (CDCl ): ꢂ ¼ 3.20–3.29 (m, J ¼ 16.2, 3.7, 4.9 Hz, 3-H), 3.83
3
(
dd, J ¼ 9.4, 6.2 Hz, 4a-H), 4.35 (m, 4-H), 4.56 (d, J ¼ 9.4 Hz, 7a-H), 6.92 (d, J ¼ 7.2 Hz, 2CH arom),
7
.00 (m, 4CH), 7.32 (dd, J ¼ 5.0, 1.0Hz, CH), 7.35–7.41 (m, 3CH arom), 8.26 (d, J ¼ 8.8 Hz, 2CH
1
3
arom) ppm; C NMR (CDCl ): ꢂ ¼ 37.1, 40.8, 42.2, 45.0, 120.0, 125.4, 125.8, 126.1, 127.1, 127.6,
3
þꢃ
1
29.1, 129.2, 130.9, 144.8, 154.7, 162.6, 172.7, 172.9 ppm; MS: m=z (%) ¼ 463.0 (53) [M] , 343.0
(
20), 317.0 (10), 315.0 (90), 311.0 (17), 290.0 (38), 289.0 (22), 257.0 (41), 211.0 (11), 173.1 (52),
1
68.0 (20), 167.0 (48), 153.0 (100), 142.0 (26), 137.0 (19), 135.0 (16).
(
4RS,4aSR,7aSR)-2-(Phenylimino)-4-(2-thienyl)-2,3,4,4a-tetrahydrothiopyrano
2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-9a) and (4RS,4aSR,7aSR)-2-(Phenylimino)-
-(2-thienyl)-2,3,4,4a-tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione
exo-10a, C H N O S ) – Diastereoisomeric Mixture of 9a and 10a
[
4
(
1
7 14 2 2 2
3
A mixture of 0.49g of 3a (2mmol) and 0.21 g of maleimide 8 (2.1mmol) in 15 cm of dry acetone was
refluxed for 36 h and left at room temperature for 7 days. The solvent was evaporated and the residue
was treated with CHCl . The crude product was filtered off and recrystallized from ethyl acetate:
3
ꢂ
acetone ¼ 1:1. Colorless crystals; mp 206–208 C; yield 63%; IR (KBr): ꢃꢁ ¼ 3464 (N–H), 3166, 3058,
ꢁ
1
1
2
931, 2744 (C–H), 1779, 1713 (C¼O), 1642, 1590cm . H NMR (DMSO-d ): 9a: ꢂ ¼ 2.91 (dd,
6
J ¼ 16.0, 8.2 Hz, 3-H), 3.17 (dd, J ¼ 16.0, 2.7 Hz, 3-H), 3.82 (dd, J ¼ 9.3, 6.7 Hz, 4a-H), 4.13 (m, 4-H),
4
.69 (d, J ¼ 9.3 Hz, 7a-H), 6.77 (d, J ¼ 7.4Hz, 2CH arom), 6.98 (m, 2CH), 7.12 (t, J ¼ 7.4 Hz, CH
arom), 7.36 (t, J ¼ 7.4 Hz, 2CH arom), 7.43 (dd, J ¼ 4.7, 1.5 Hz, CH), 11.54 (bs, NH) ppm; 10a:
ꢂ ¼ 2.84 (dd, J ¼ 16.3, 2.5 Hz, 3-H), 3.17 (m, 3-H), 3.77 (dd, J ¼ 9.2, 6.1 Hz, 4a-H), 3.97 (m, 4-H), 4.74
(
d, J ¼ 9.2Hz, 7a-H), 6.64 (d, J ¼ 7.6 Hz, 2CH arom), 6.86 (d, J ¼ 3.5Hz, CH), 6.91 (dd, J ¼ 5.1,
3
.5 Hz, CH), 7.04 (t, J ¼ 7.6Hz, CH arom), 7.27 (t, J ¼ 7.6 Hz, 2CH arom), 7.36 (m, CH), 11.54 (bs,
1
3
NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 35.6, 40.3, 42.5, 45.5, 119.2, 124.2, 125.1, 126.5, 129.1, 141.6,
6
þꢃ
1
49.3, 162.4, 175.9, 176.2ppm; MS: m=z (%) ¼ 342.1 (100) [M] , 239.0 (16), 224.0 (11), 222.1 (13),
2
12.0 (33), 167.0 (25), 153.0 (16), 142.0 (13).
(2RS,3RS,4RS)-5-(N-Acetyl-N-phenylamino)-2,3-bis(ethoxycarbonyl)-4-(2-thienyl)-3,4-
dihydro-2H-thiopyran; (endo-12a) and (2RS,3RS,4SR)-5-(N-Acetyl-N-phenylamino)-2,3-
bis(ethoxycarbonyl)-4-(2-thienyl)-3,4-dihydro-2H-thiopyran (exo-13a; C H NO S ) –
2
3
25
5 2
Diastereoisomeric Mixture of 12a and 13a
To a mixture of 0.49 g of diene 3a (2mmol), 0.38 g of diethyl fumarate (11, 2.2 mmol), and 0.32 g of
3
3
pyridine (4mmol) in 15 cm of dry acetone a solutionof 0.32 g of acetyl chloride (4mmol) in 5 cm of dry
acetone was added dropwise. Then the reaction mixture was refluxed for 24h. After evaporation of the
solvent, the oily residue was dissolved in CH Cl and washed with H O. The organic layer was dried
2
2,
2
(MgSO ). The solvent was removed, and the residue was purified by column chromatography using
4
CHCl as eluent and crystallized from t-butyl methyl ether:petrol ether ¼ 1:1. Pale yellow crystals; mp
3
ꢂ
ꢁ
1
08–111 C; yield 31%; IR (KBr): ꢃꢁ ¼ 3105–3036, 2979, 2935 (C–H), 1735, 1725, 1698 (C¼O), 1637,
1
1
1
594 cm ; H NMR (DMSO-d , T ¼ 385 K): 12a: ꢂ ¼ 1.11 (t, J ¼ 7.1 Hz, CH ), 1.15 (t, J ¼ 7.1 Hz,
6
3

1
06
K. Bogdanowicz-Szwed and A. Budzowski
CH ), 2.15 (s, CH ), 3.25 (dd, J ¼ 11.0, 4.7Hz, 3-H), 3.99 (dq, J ¼ 10.8, 7.1 Hz, CH ), 4.10 (dq, J ¼ 10.9,
3
3
2
7
.1 Hz, CH ), 4.16 (d, J ¼ 11.0 Hz, 2-H), 4.53 (dd, J ¼ 6.4, 4.7 Hz, 4-H), 6.37 (d, J ¼ 6.4 Hz, 5-H), 6.82
2
(
d, J ¼ 3.5 Hz, CH), 6.97 (dd, J ¼ 5.1, 3.5 Hz, CH), 7.29 (t, J ¼ 7.1 Hz, CH arom), 7.33–7.41 (m, 5CH);
3a: ꢂ ¼ 1.02 (t, J ¼ 7.1 Hz, CH ), 1.11 (m, CH ), 2.12 (s, CH ), 3.12 (dd, J ¼ 9.4, 9.4 Hz, 3-H), 3.95 (m,
1
3
3
3
CH ), 3.99 (m, CH ), 4.33 (dd, J ¼ 9.4, 3.4Hz, 4-H), 4.45 (d, J ¼ 9.4 Hz, 2-H), 6.11 (d, J ¼ 3.4 Hz, 5-H),
2
2
1
3
C
6
.87 (d, J ¼ 3.6 Hz, CH), 6.94 (dd, J ¼ 5.2, 3.6 Hz, CH), 7.29 (m, CH), 7.33–7.41 (m, 5CH) ppm;
NMR (DMSO-d , T ¼ 385 K): ꢂ ¼ 13.6, 22.2, 37.3, 41.4, 45.9, 60.7, 61.5, 124.7, 125.9, 126.7, 126.9,
6
þꢃ
1
3
1
27.1, 128.8, 134.3, 140.9, 141.2, 168.7, 169.1, 169.8ppm; MS: m=z (%) ¼ 459.1 (87) [M] , 416.1 (18),
44.1 (30), 325.1 (10), 312.1 (42), 279.0 (35), 270.0 (28), 251.0 (27), 245.0 (26), 244.0 (31), 212.1 (100),
67.0 (11), 153.0 (53), 136.0 (10), 118.1 (13), 109.0 (11), 77.1 (26).
2
-(4-Methoxyphenylimino)-3-(2,5-dioxotetrahydropyrrol-3-yl)-4-(2-thienyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (14c, C H N O S )
22 19 3 5 2
3
A suspension of 0.55g of 3c (2mmol) and 0.21 g of 8 (2.1mmol) in 15cm of dry acetone was refluxed
for 48 h and left at room temperature for 2 weeks. The solvent was removed and the oily residue was left
3
for solidification. The crystalline product was treated with 10 cm of CHCl , filtered off, and crystallized
3
ꢂ
from ethyl acetate:acetone ¼ 1:1. Colorless crystals; mp 241–244 C; yield 31%; IR (KBr): ꢃꢁ ¼ 3464,
ꢁ
1
1
0
3
183 (N–H), 1778, 1708 (C¼O) cm ; H NMR (DMSO-d ): ꢂ ¼ 2.86–2.97 (m, 4 -H), 3.20–3.27 (m, 3-
6
0
H, 3 -H), 3.76 (s, CH O), 3.90 (dd, J ¼ 9.4, 6.0Hz, 4a-H), 4.30 (dd, J ꢄ 6.0, 6.2 Hz, 4-H), 4.69 (d,
3
J ¼ 9.2 Hz, 7a-H), 6.64 (d, J ¼ 8.8 Hz, 2CH arom), 6.92 (d, J ¼ 8.8 Hz, 2CH arom), 6.99 (dd, J ¼ 5.1,
3
.4 Hz, CH), 7.09 (dd, J ¼ 3.4, 1.0 Hz, CH), 7.43 (dd, J ¼ 5.1, 1.0 Hz, CH), 11.16 (bs, NH), 11.50 (bs,
13
NH) ppm; C NMR (DMSO-d ): ꢂ ¼ 35.4, 38.6, 42.2, 42.5, 50.9, 55.1, 114.2, 120.1, 125.7, 126.3, 128.1,
6
þꢃ
1
40.3, 142.1, 156.2, 161.4, 176.0, 176.3, 177.4, 178.3 ppm; MS: m=z (%) ¼ 469.0 (15) [M] , 372.0
(
100), 340.1 (28), 275.0 (17), 242.0 (47), 167.0 (16), 153.0 (25), 134.0 (55), 110.0 (29), 77.0 (12).
Reactions of Thioamides 4 with N-Arylmaleimides
All the reactions of 4a–4c with 5 or 15 were carried out according to the procedure described for 3
using acetonitrile as solvent. The obtained products were separated by column chromatography and
crystallized from t-butyl methyl ether:petrol ether ¼ 1:1.
(4RS,4aSR,7aSR)-4-(2-Furyl)-2-(4-methylphenylimino)-6-phenyl-2,3,4,4a-tetrahydro-
thiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-16b, C H N O S)
4 20 2 3
2
ꢂ
Colorless crystals; mp 188–190 C; yield 60%; IR (KBr): ꢃꢁ ¼ 3479 (N–H), 2933 (C–H), 1710 (C¼O),
ꢁ
1
1
1
2
7
627 cm ; H NMR (CDCl ): ꢂ ¼ 2.33 (s, CH ), 3.03 (dd, J ¼ 16.4, 9.3 Hz, 3-H), 3.24 (dd, J ¼ 16.4,
3
3
.5 Hz, 3-H), 3.88 (dd, J ¼ 9.5, 6.1 Hz, 4a-H), 3.99 (ddd, J ¼ 9.3, 6.1, 2.5 Hz, 4-H), 4.43 (d, J ¼ 9.5 Hz,
a-H), 6.26 (d, J ¼ 3.3 Hz, CH), 6.37 (dd, J ¼ 3.3, 1.9 Hz, CH), 6.76 (d, J ¼ 8.1 Hz, 2CH arom), 7.15
13
(
d, J ¼ 8.1 Hz, 2CH arom), 7.19 (d, J ¼ 7.5 Hz, 2CH arom), 7.35–7.46 (m, 4CH arom) ppm; C NMR
(
CDCl ): ꢂ ¼ 21.2, 35.6, 38.2, 42.7, 43.4, 76.8, 108.0, 111.0, 119.7, 126.4, 129.2, 129.5, 130.1, 131.4,
3
þꢃ
1
34.8, 142.3, 146.6, 151.8, 161.2, 173.5, 173.8 ppm; MS: m=z (%) ¼ 416.1 (24) [M] , 131.1 (10), 84.9
(
30), 82.9 (49), 73.0 (100), 57.0 (22).
(4RS,4aSR,7aSR)-2-(4-Chlorophenylimino)-4-(2-furyl)-6-phenyl-2,3,4,4a-tetrahydro-
thiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-16c, C H ClN O S)
4
2
19
2 3
ꢂ
Colorless crystals; mp 212 C; yield 70%; IR (KBr): ꢃꢁ ¼ 3486 (N–H), 2923 (C–H), 1717(C¼O),
ꢁ
1
1
1
624 cm H NMR (CDCl ): ꢂ ¼ 2.36 (s, CH ), 3.03 (dd, J ¼ 16.3, 9.2 Hz, 3-H), 3.19 (dd,
J ¼ 16.3, 2.6 Hz, 3-H), 3.85 (dd, J ¼ 9.4, 6.0Hz, 4a-H), 3.99 (ddd, J ¼ 9.2, 6.0, 2.6 Hz, 4-H), 4.44
d, J ¼ 9.4Hz, 7a-H), 6.25 (d, J ¼ 3.2 Hz, CH), 6.37 (dd, J ¼ 3.2, 1.8Hz, CH), 6.78 (d, J ¼ 8.6Hz, 2CH
;
3
3
(

Diastereoselective Hetero-Diels-Alder Reaction
107
arom), 7.04 (d, J ¼ 8.3 Hz, 2CH arom), 7.23 (d, J ¼ 8.3 Hz, 2CH arom), 7.30 (d, J ¼ 8.6 Hz, 2CH
1
3
arom), 7.39 (d, J ¼ 1.8 Hz, CH) ppm; C NMR (CDCl ): ꢂ ¼ 21.2, 35.3, 38.2, 42.5, 43.2, 107.9, 110.7,
3
1
21.0, 125.9, 128.6, 129.4, 129.8, 130.2, 139.1, 142.1, 147.4, 151.4, 162.3, 173.1, 173.4 ppm; MS: m=z
þꢃ
(
(
%) ¼ 452.0 (37) [M þ 2], 450.0 (100) [M] , 422.1 (13), 313.0 (36), 230.0 (27), 187.1 (34), 151.0
62), 137.0 (18), 111.0 (12), 94.0 (26).
(4RS,4aSR,7aSR)-4-(2-Furyl)-6-(4-methylphenyl)-2-(phenylimino)-2,3,4,4a-tetrahydro-
thiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-18a, C H N O S)
24 20 2 3
ꢂ
Colorless crystals; mp 175–178 C; yield 27%; IR (KBr): ꢃꢁ ¼ 3483 (N–H), 3112, 2927 (C–H), 1716
ꢁ
1
1
(
C¼O), 1625, 1592, 1513cm ; H NMR (CDCl ): ꢂ ¼ 2.36 (s, CH ), 3.04 (dd, J ¼ 16.5, 9.3 Hz, 3-H),
3
3
3
.23 (dd, J ¼ 16.5, 2.6 Hz, 3-H), 3.85 (dd, J ¼ 9.5, 6.0 Hz, 4a-H), 3.98 (ddd, J ¼ 9.3, 6.0, 2.6 Hz, 4-H),
.42 (d, J ¼ 9.5 Hz, 7a-H), 6.26 (dd, J ¼ 3.3, 0.7 Hz, CH), 6.37 (dd, J ¼ 3.3, 1.8 Hz, CH), 6.84 (d,
4
J ¼ 8.4 Hz, 2CH arom), 7.05 (d, J ¼ 8.3 Hz, 2CH arom), 7.13 (t, J ¼ 7.4 Hz, CH arom), 7.22 (d,
1
3
C
J ¼ 8.3 Hz, 2CH arom), 7.34 (dd, J ¼ 7.4, 8.4 Hz, 2CH arom), 7.39 (dd, J ¼ 1.8, 0.7 Hz) ppm;
NMR (CDCl ): ꢂ ¼ 21.2, 35.4, 38.1, 42.5, 43.2, 76.8, 107.8, 110.7, 119.5, 124.8, 125.9, 128.6, 129.3,
3
þꢃ
1
29.8, 139.0, 142.0, 149.0, 151.6, 161.2, 173.2, 173.6 ppm; MS: m=z (%) ¼ 416.1 (100) [M] , 388.1
(
32), 313.1 (34), 201.1 (14), 196.1 (21), 187.1 (24), 151.0 (23), 137.0 (18), 132.0 (26), 123.0 (14),
1
17.0 (45), 104.0 (24), 94.0 (26), 91.0 (31), 77.0 (72), 65.0 (22).
(4RS,4aSR,7aSR)-4-(2-Furyl)-2-(4-methylphenylimino)-6-(4-methylphenyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-18b, C H N O S)
25 22 2 3
ꢂ
Colorless crystals; mp 203–205 C; yield 71%; IR (KBr): ꢃꢁ ¼ 34879, (N–H), 3112–2925 (C–H), 1785,
ꢁ
1
1
1
9
2
714 (C¼O), 1615 cm ; H NMR (CDCl ): ꢂ ¼ 2.33 (s, CH ), 2.36 (s, CH ), 3.03 (dd, J ¼ 16.4,
3
3
3
.3 Hz, 3-H), 3.22 (dd, J ¼ 16.4, 2.6 Hz, 3-H), 3.86 (dd, J ¼ 9.4, 6.0 Hz, 4a-H), 3.98 (ddd, J ¼ 9.4, 6.0,
.6 Hz, 4-H), 4.41 (d, J ¼ 9.4 Hz, 7a-H), 6.25 (d, J ¼ 3.4Hz, CH), 6.36 (dd, J ¼ 3.4, 1.8 Hz, CH), 6.75
(
d, J ¼ 8.1 Hz, 2CH arom), 7.05 (d, J ¼ 8.2 Hz, 2CH arom), 7.14 (d, J ¼ 8.1 Hz, 2CH arom), 7.22 (d,
13
J ¼ 8.2 Hz, 2CH arom), 7.39 (d, J ¼ 1.8 Hz, CH) ppm; C NMR (CDCl ): ꢂ ¼ 20.9, 21.1, 35.3, 38.0,
3
4
1
2.5, 43.2, 107.7, 110.6, 119.4, 125.9, 128.6, 129.7, 134.4, 139.0, 142.0, 146.4, 151.6, 160.8, 173.2,
þꢃ
73.5ppm; MS: m=z (%) ¼ 430.1 (100) [M] , 402.1 (18), 313.1 (23), 210.1 (19), 187.1 (18), 152.0
(
12), 151.0 (16), 131.1 (52), 94.0 (14), 91.0 (29), 73.1 (58).
(4RS,4aRS,7aRS)-4-(2-Furyl)-2-(4-methylphenylimino)-6-(4-methylphenyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (exo-19b, C H N O S)
25 22 2 3
ꢂ
Pale yellow crystals; mp 164–168 C; yield 1%; IR (KBr): ꢃꢁ ¼ 3480, 3366 (N–H), 3116–2921 (C–H),
ꢁ
1
1
1
2
6
785, 1716 (C¼O), 1625cm ; H NMR (CDCl ): ꢂ ¼ 2.31 (s, CH ), 2.39 (s, CH ), 2.88 (dd, J ¼ 15.9,
3
3
3
.8 Hz, 3-H), 3.26 (dd, J ¼ 15.9, 6.7Hz, 3-H), 3.98–4.04 (m, 4-H, 4a-H), 4.36 (d, J ¼ 8.9 Hz, 7a-H),
.34 (d, J ¼ 3.2 Hz, CH), 6.40 (dd, J ¼ 3.2, 1.8 Hz, CH), 6.69 (d, J ¼ 8.1 Hz, 2CH arom), 7.11 (d,
J ¼ 8.1 Hz, 2CH arom), 7.19 (d, J ¼ 8.2 Hz, 2CH arom), 7.28 (d, J ¼ 8.2 Hz, 2CH arom), 7.42 (d,
1
3
J ¼ 1.8 Hz, CH) ppm; C NMR (CDCl ): ꢂ ¼ 20.9, 21.1, 34.7, 38.1, 41.7, 42.9, 107.2, 110.7, 119.4,
3
1
25.9, 128.6, 129.7, 129.8, 134.4, 139.2, 142.0, 146.3, 152.8, 160.3, 173.6, 175.1ppm; MS: m=z
þꢃ
(
%) ¼ 430.1 (100) [M] , 402.1 (22), 215.1 (19), 210.1 (50), 187.1 (63), 131.1 (65), 121.0 (13),
1
17.1 (11), 94.0 (49), 91.0 (30).
(4RS,4aSR,7aSR)-2-(4-Chlorophenylimino)-4-(2-furyl)-6-(4-methylphenyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (endo-18c, C H ClN O S)
2
4
19
2 3
ꢂ
Colorless crystals; mp 202 C; yield 70%; IR (KBr): ꢃꢁ ¼ 3486 (N–H), 2923 (C–H), 1717(C¼O),
ꢁ
1
1
1
624 cm
;
H NMR (CDCl ): ꢂ ¼ 2.36 (s, CH ), 3.03 (dd, J ¼ 16.3, 9.2 Hz, 3-H), 3.19 (dd,
3
3

1
08 K. Bogdanowicz-Szwed and A. Budzowski: Diastereoselective Hetero-Diels-Alder Reaction
J ¼ 16.3, 2.6 Hz, 3-H), 3.85 (dd, J ¼ 9.4, 6.0 Hz, 4a-H), 3.99 (ddd, J ¼ 9.2, 6.0, 2.6 Hz, 4-H), 4.44 (d,
J ¼ 9.4 Hz, 7a-H), 6.25 (d, J ¼ 3.2 Hz, CH), 6.37 (dd, J ¼ 3.2, 1.8 Hz, CH), 6.78 (d, J ¼ 8.6 Hz, 2CH
arom), 7.04 (d, J ¼ 8.3 Hz, 2CH arom), 7.23 (d, J ¼ 8.3 Hz, 2CH arom), 7.30 (d, J ¼ 8.6 Hz, 2CH
1
3
arom), 7.39 (d, J ¼ 1.8 Hz, CH arom) ppm; C NMR (CDCl ): ꢂ ¼ 21.2, 35.3, 38.2, 42.5, 43.2, 107.9,
3
1
10.7, 121.0, 125.9, 128.6, 129.4, 129.8, 130.2, 139.1, 142.1, 147.4, 151.4, 162.3, 173.1, 173.4ppm;
þꢃ
MS: m=z (%) ¼ 452.0 (37) [Mþ 2], 450.0 (100) [M] , 422.1 (13), 313.0 (36), 230.0 (27), 187.1 (34),
1
51.0 (62), 137.0 (18), 111.0 (12), 94.0 (26).
(4RS,4aRS,7aRS)-2-(4-Chlorophenylimino)-4-(2-furyl)-6-(4-methylphenyl)-2,3,4,4a-
tetrahydrothiopyrano[2,3-c]pyrrole-5,7(6H,7aH)-dione (exo-19c, C H ClN O S)
2
4
19
2 3
ꢂ
Pale yellow crystals; mp 172–175 C; yield 1%; IR (KBr): ꢃꢁ ¼ 3482 (N–H), 3116–2921 (C–H), 1786,
ꢁ
1
1
1
715 (C¼O), 1625cm ; H NMR (CDCl ): ꢂ ¼ 2.39 (s, CH ), 2.86 (dd, J ¼ 16.1, 2.8 Hz, 3-H), 3.27
3
3
(
dd, J ¼ 16.1, 6.4 Hz, 3-H), 4.03 (dd, J ¼ 9.0, 4.2Hz, 4a-H), 4.04–4.07 (m, 4-H), 4.38 (d, J ¼ 9.0 Hz,
7
a-H), 6.33 (d, J ¼ 3.2 Hz, CH), 6.41 (dd, J ¼ 3.2, 2.0 Hz, CH), 6.71 (d, J ¼ 8.8 Hz, 2CH arom), 7.19
13
(
d, J ¼ 8.4 Hz, 2CH arom), 7.26–7.31 (m, 4CH arom), 7.43 (d, J ¼ 2.0 Hz, CH) ppm; C NMR
(
CDCl ): ꢂ ¼ 21.2, 34.8, 38.1, 41.7, 42.7, 107.2, 110.8, 121.0, 125.9, 128.6, 129.4, 129.9, 130.2,
3
1
39.3, 142.1, 147.3, 152.6, 161.8, 173.5, 175.0 ppm; MS: m=z (%) ¼ 452.0 (16) [Mþ 2], 450.1 (41)
þꢃ
[
M] , 265.0 (14), 263.0 (38), 232.0 (12), 230.0 (36), 209.0 (12), 187.1 (100), 153.0 (25), 151.0 (43),
1
37.0 (51), 133.1 (21), 132.1 (15).
References
[
[
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[
[
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[
[
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[
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