Diels-alder reactions with cyclic sulfones: VIII. Organic catalysis in the synthesis of spiro[1-benzothiophene-4,5′-pyrimidine]-2′,4′, 6′-trione 1,1-dioxides and 2′-thioxospiro[1-benzothiophene-4, 5′-pyrimidine]-4′,6′-dione 1,1-dioxides

Article abstract of DOI:10.1134/S1070428009010126

5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-triones and 5-methylidene-2-thioxopyrimidine-4,6- diones in the presence of chiral amines or amino acids with high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spirofused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from 2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (-)-ephedrine or L-4-(tert-butyldimethylsiloxy) proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′, 6′-dione 1,1-dioxide with an enantiomeric excess of 80%.

Full text of DOI:10.1134/S1070428009010126

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 1, pp. 87–101. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © E.E. Shul’ts, G.N. Andreev, M.M. Shakirov, N.I. Komarova, I.Yu. Bagryanskaya, Yu.V. Gatilov, G.A. Tolstikov, 2009, published in
Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 1, pp. 94–107.
Diels–Alder Reactions with Cyclic Sulfones:
VIII.* Organic Catalysis in the Synthesis of Spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′-trione 1,1-Dioxides and 2′-Thioxo-
spiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-Dioxides
E. E. Shul’tsa, G. N. Andreevb, M. M. Shakirovb, N. I. Komarovaa, I. Yu. Bagryanskayaa,
Yu. V. Gatilova, and G. A. Tolstikova
a Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
b Ammosov Yakutian State University, ul. Belinskogo 58, Yakutsk, 677000 Sakha, Russia
Received June 28, 2007
Abstract—5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-tri-
ones and 5-methylidene-2-thioxopyrimidine-4,6-diones in the presence of chiral amines or amino acids with
high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spiro-
fused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydro-
thiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from
2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (–)-ephedrine or L-4-(tert-butyldimethyl-
siloxy)proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxide
with an enantiomeric excess of 80%.
DOI: 10.1134/S1070428009010126
5-Alkyl- and 5,5-dialkylbarbituric acids are widely
used as medical agents for the treatment of neuro-
logical diseases, depressions, and memory impairment
[2], as well as antitumor agents [3, 4]. In the recent
time, spiro-fused derivatives of barbituric acid attract
increasing attention from the viewpoint of their biolog-
ical activity [5, 6]. Derivatives of 2-thiobarbituric acids
are widely used as antibacterial agents [7], and they
inhibit reverse transcriptase and show strong inhibitory
activity against HIV-1 in vitro [8, 9]. Antiphlogistic
[10, 11], antitumor [12–14], and hypocholesteremic
agents [15] were found among compounds belonging
to the 1-benzothiophene 1,1-dioxide series. The
present study was aimed at developing synthetic ap-
proaches to hydrogenated 1-benzothiophene 1,1-di-
oxide derivatives containing spiro-fused barbituric and
thiobarbituric acid fragments.
1,1-dioxide (I) as diene and 5-methylidenebarbituric
and 5-methylidene-2-thiobarbituric acids II–VII as di-
enophiles. The reactions of diene I with dienophiles II
and III generated in situ from barbituric or 1,3-di-
methylbarbituric acid and formaldehyde solution were
carried out in aqueous acetonitrile in the presence of
L-proline (XIa) as catalyst. The process was strictly
regioselective, and the products were spiro-fused com-
pounds VIII and IX containing a 2,4,6-trioxopyrim-
idine fragment fused at the 5-position to C4 of
1-benzothiophene 1,1-dioxide fragment (yield 70–
80%; Scheme 1). Likewise, the reaction of compound I
with dienophile VI generated in a similar way from
5-methylidene-2-thiobarbituric acid gave 52% of thio-
barbituric acid derivative X. Apart from L-proline,
such chiral compounds as L-proline zinc(II) salt (XIb),
L-4-hydroxyproline (XIc), L-4-(tert-butyldimethyl-
siloxy)proline (XII), (+)-pseudoephedrine (XIII), and
1,3,3-triphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]-
oxazaborol-7-ium trifluoromethanesulfonate (XIV)
[16] were used to catalyze the reactions of diene I with
These compounds were synthesized by the Diels–
Alder reaction of 5-isopropenyl-2,3-dihydrothiophene
* For communication VII, see [1].
87

SHUL’TS et al.
88
Scheme 1.
CH2
6
O
O
R
N1'
Me
O
7
MeCN–H2O
-proline
O
R
O
R
5
6'
4'
CH2
Me
L
7a
3a
X
+
3'
N
2'
S
N
N
S
1
3
O
O
2
O
H
R
X
I
II, III, VI
VIII–X
II, VIII, X = O, R = Me; III, IX, X = O, R = H; VI, X, X = S, R = H.
R2
R3
R2
R3
4''
O
R1
R1
H
R1
5''
Me
O
R2
R3
1''
I
N
6''
O
O
Me
O
+
Me
O
Me
Me
O
H
N
O
N
N
Me
S
S
O
O
O
N
N
O
O
Me
Me
IVa–IVh
XVa–XVh
XVIa–XVIh
IV, XV, XVI, R1 = R2 = R3 = H (a); R1 = OMe, R2 = R3 = H (b); R1 = R2 = H, R3 = OMe (c); R1 = R2 = H, R3 = F (d); R1 = OH,
R2 = OMe, R3 = H (e); R1 = H, R2 = OH, R3 = OMe (f); R1 =H, R2 = R3 = OMe (g); R1 = R2 = R3 = OMe (h).
R2
R3
R2
R3
O
R1
R1
H
R1
H
R2
R3
I
HN
O
O
Me
O
+
Me
O
X
N
H
O
NH
NH
S
S
O
O
X
X
N
N
O
O
H
H
Va–Vc, VIIa, VIIb
XVIIa–XVIIc, XIXa, XIXb
XVIIIa–XVIIIc, XXa, XXb
V, XVII, XVIII, X = O, R1 = R2 = R3 = H (a); R1 = OMe, R2 = R3 = H (b); R1 = R2 = R3 = OMe (c); VII, XIX, XX, X = S,
R1 = R2 = R3 = OMe (a); R1 = OMe, R2 = R3 = H (b).
5-arylmethylidenehexahydropyrimidine-2,4,6-triones
IVa–IVh, Va, and Vb and 5-arylmethylidene-2-thioxo-
hexahydropyrimidine-4,6-dione VIIa.
acid derivatives IVc–IVf and IVh in the presence of
zinc salt XIb showed that the stereoselectivity depends
on the presence of an electron-withdrawing substituent
in the arylmethylidene fragment. The yield of stereo-
isomer XVd (R1 = R2 = H, R3 = F) is considerably
larger than the yield of XVc, XVe, XVf, and XVh.
Dienophiles Va and Vb prepared from barbituric acid
reacted with diene I to produce stereoisomer mixtures
XVIIa/XVIIIa and XVIIb/XVIIIb, respectively.
L-Proline derivatives XI and XII ensured higher
stereoselectivity and milder conditions of the cyclo-
addition. The reaction of I with thiobarbituric acid
derivative VIIa was completely stereoselective, and
the only product was stereoisomer XIXa (yield 25%).
The data in Table 1 show that the cycloaddition of
dienophile IVa to diene I gives a mixture of stereo-
isomers XVa and XVIa whose ratio appreciably
depends on the catalyst nature. The highest yield of
stereoisomer XVIa was observed in the reaction cata-
lyzed by L-proline zinc(II) salt (XIb). Analogous var-
iation in the ratio of stereoisomers XVb and XVIb was
typical of the reaction of I with IVb in going from
L-proline to its zinc salt as catalyst. Stereoisomer XVb
was formed as the only product in the reaction cata-
lyzed by 1,3,3-triphenyltetrahydro-3H-pyrrolo[1,2-c]-
[1,3,2]oxazaborol-7-ium trifluoromethanesulfonate
(XIV). The results of the reactions of I with barbituric
In the recent years, interest in asymmetric catalysis
by chiral amines has increased [17, 18]. Catalytic
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
89
Ph
Ph
H
X
Ph
OH
Me
Ph
OH
Me
OH
O
N+
H
COOY
B
N
N
OTf
MeNH
MeNH
H
H
Ph
XIa–XIc, XII
XIII
XIV
XXI
XXII
XI, X = Y = H (a); X = H, Y = Zn/2 (b); X = HO, Y = H (c); XII, X = t-BuMe2SiO, Y = H.
Diels–Alder reactions with relatively simple dienes
and dienophiles have been reported [19–21]. We pre-
sumed that Diels–Alder reactions between compounds
containing polar groups could involve intermediates
formed via interaction with chiral amines and that such
intermediates could be converted into optically active
final adducts. As catalysts in the Diels–Alder reactions
we used L-alanine, L-proline derivatives XIc and XII,
(+)-pseudoephedrine (XIII), (S)-(+)-prolinol (XXI),
and (–)-ephedrine (XXII). It was found that reactions
of diene I with 5-arylmethylidenebarbituric acids IVb,
IVe, Vb, and IVc generated in situ are stereoselective
and that in some cases these processes may be per-
formed with 100% stereoselectivity (Table 2). Thus
organic catalysis of three-component reactions is ob-
served. For example, the reaction of 1,3-dimethyl-
barbituric acid with 2-methoxybenzaldehyde and diene
I in the presence of amines or amino acids XI–XIII
and XXII yields exclusively 5β-stereoisomer XVa. In
analogous reaction with 2-hydroxy-3-methoxybenzal-
dehyde, adduct XVf was isolated as the only product.
The reactions of diene I with barbituric acid and
2-methoxy- or 2,3,4-trimethoxybenzaldehyde afforded
optically active adducts XVIIb and XVIIc. No stereo-
selectivity was observed in the reactions of diene I
with dienophiles IVf and VIIb (generated in situ) in
the presence of L-proline or (S)-(+)-prolinol (XXI).
The poor yield of compound XVe (45%) formed in
the reaction of I with IVe generated from dimethylbar-
bituric acid and salicylaldehyde should be noted.
Presumably, the formation of 5-arylmethylidenebar-
bituric acid IVe is accompanied by cyclization to
produce fused polycyclic compounds [22, 23] which
we failed to isolate. For example, our attempt to syn-
Table 1. Reaction conditions, yields, and ratios of spiro[1-benzothiophene-4,5′-pyrimidine]-2′,4′,6′-trione 1,1-dioxides XV–
XVIII and 2′-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxide XIXa in the reactions of diene I with
barbituric and thiobarbituric acid derivatives IVa–IVh, Va, Vb, and VIIa
Dienophile
Catalyst
Solvent
Temperature, °C
Products
Yield, %
Ratio
IVa
IVa
IVa
IVa
IVb
IVb
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVh
Va
XIa
XIb
XII
XIII
XIa
XIb
XIV
XIb
XIb
XIb
XIb
XIa
XIa
XIb
XIc
XII
XIa
XIa
PhH–CHCl3–H2O
Dioxane–H2O
Dioxane–H2O
Dioxane–H2O
PhH–CHCl3–H2O
Dioxane–H2O
CH2Cl2
060
100
XVa, XVIa
XVa, XVIa
XVa, XVIa
XVa, XVIa
XVb, XVIb
XVb, XVIb
XVb
47
69
70
52
35
55
70
58
65
47
52
27
32
67
58
71
32
25
5:1
2.5:1.0
9:1
7:1
6:1
2.5:1.0
–
100
100
060
100
(1) –50; (2) 42
100
Dioxane–H2O
Dioxane–H2O
Dioxane–H2O
Dioxane–H2O
PhH–CHCl3–H2O
PhH–CHCl3–H2O
Dioxane–H2O
Dioxane–H2O
Dioxane–H2O
DMF–H2O
XVc, XVIc
XVd, XVId
XVe, XVIe
XVf, XVIf
XVg, XVIg
XVh, XVIh
XVh, XVIh
XVIIa, XVIIIa
XVIIa, XVIIIa
XVIIb, XVIIIb
XIXa
4:1
8:1
3:1
3:1
5:1
6:1
3:1
8:1
9:1
3:1
–
100
100
100
060
060
100
100
Va
100
Vb
130
VIIa
DMF–H2O
130
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
90
Table 2. Synthesis of optically active spiro-fused barbituric acid derivatives
Initial reactantsa
Catalyst
Product
XVb
Yield, % [α]D20, deg
2-Methoxybenzaldehyde, 1,3-dimethyl-
barbituric acid, I
L-4-Hydroxyproline (XIc)
73
60
66
62
73
45
69
+18
+35
+30
+42
+36
+15
–
2-Methoxybenzaldehyde, 1,3-dimethyl-
barbituric acid, I
(+)-Pseudoephedrine (XIII)
L-Alanine
XVb
XVb
XVb
2-Methoxybenzaldehyde, 1,3-dimethyl-
barbituric acid, I
2-Methoxybenzaldehyde, 1,3-dimethyl-
barbituric acid, I
(–)-Ephedrine (XXII)
2-Methoxybenzaldehyde, 1,3-dimethyl-
barbituric acid, I
L-4-(tert-Butyldimethylsiloxy)- XVb
proline (XII)
2-Hydroxy-3-methoxybenzaldehyde,
1,3-dimethylbarbituric acid, I
(+)-Pseudoephedrine (XIII)
XVd
3-Hydroxy-4-methoxybenzaldehyde,
L-Proline
XVf, XVIf, 7:1
1,3-dimethylbarbituric acid, I
2-Methoxybenzaldehyde, barbituric acid, I
L-4-Hydroxyproline (XIc)
XVIIb
75
72
+18
+37
2,3,4-Trimethoxybenzaldehyde, barbituric
acid, I
L-4-(tert-Butyldimethylsiloxy)- XVIIc
proline (XII)
2-Methoxybenzaldehyde, 2-thiobarbituric
(S)-(+)-Prolinol (XXI)
XIXb, XXb, 5:1
55
–
acid, I
a
Dioxane–water, 4:1, 100°C, 21 h.
thesize 2-arylmethylidene-4,6-dimethylbarbituric acid
from salicylaldehyde derivative XXIII resulted in the
formation of oxadeazaflavin XXIV. The yield of the
latter attained 85% when excess dimethylbarbituric
acid was taken (Scheme 2).
We performed a series of experiments with diene I
and 5-(2-methoxybenzylidene)-2-thiobarbituric acid
(VIIb). The data in Table 3 show how the catalyst af-
fects the optical purity of adduct XIXb. It is seen that
the Diels–Alder reaction of I with thiobarbituric acid
Scheme 2.
O
Me
O
O
N
Me
O
t-Bu
N
O
Me
OAc
O
+
N
O
N
O
HO
Me
HO
Me
CHO
Bu-t
XXIII
O
2'
5'
Me
N1'
3'
N
Me
6'
4'
O
O
O
Me
O
5
4
6
9
AcO
3N
2
7
8
1
N
O
Bu-t
Me
XXIV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
91
Table 3. Yields and optical purity of (5R)-5-(2-methoxyphenyl)-7-methyl-2-thioxo-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-ben-
zothiophene-4,5′-pyrimidine]-4′,6′(1′H,3′H)-dione 1,1-dioxide (XIXb)a in the presence of different chiral catalysts
Yield of XIXb, %
Solvent
Temperature, °C
Catalyst
[α]D20, deg
chemical
eeb
Dioxane–H2O
Dioxane–H2O
Dioxane–H2O
DMF–H2O
100
100
100
130
XIc
75
68
60
39
20
80
86
04
0+27
0+78
+106
0+15
XII
XXII
XIb
a
5-(2-Methoxybenzylidene)-2-thioxohexahydropyrimidine-4,6-dione (VIIb) was prepared in situ from 2-methoxybenzaldehyde and thio-
barbituric acid.
According to the chiral HPLC data (Kromasil CHI-DMB).
b
VIIb could give compound XIXb with an ee (enantio-
meric excess) value of up to 86%.
ing vicinal coupling constants between protons on C5
and C6. Pseudoequatorial orientation of the aryl sub-
stituent in molecules XVIa–XVIc, XVIg, XVIh,
XVIIIa, XVIIIb, and XXb followed from the exist-
ence of axial–axial coupling between 5-H and 6-H
(–)-Ephedrine (XXII) and L-4-(tert-butyldimethyl-
siloxy)proline (XII) ensured high enantio- and dia-
stereoselectivity in the reaction under study. In our
experiments organic catalysis involved polyfunctional
dienes and dienophiles. We have found no published
data on analogous reactions with substrates of similar
complexity. The structure of the newly synthesized
compounds was determined on the basis of spectral
1
(J ≈ 11 Hz). In the H NMR spectra of (5S) isomers
XVIa–XVIc, XVIg, and XVIh, singlets from the
methyl groups on the nitrogen atoms were displaced
downfield (for example, δ 3.13 and 3.27 ppm for XVa
against δ 2.93 and 3.15 ppm for XVIa), presumably
due to magnetically anisotropic effect of the benzene
ring. The adducts in which the aryl group on C5 occu-
pies pseudoequatorial position were also characterized
by increased nonequivalence of protons on C6. The
1
data. The H NMR spectra of stereoisomeric adducts
displayed characteristic features which allowed us to
assign them to (5R) or (5S) isomers. The configuration
of substituents in the adducts was assigned by analyz-
C4″
F1
C3″
C9
C3″
C2″
C4″
C2″
C1″
C5″
C10
O4
C9
N3′
O5
O5
C5″
C4′
C4
C2′
C5
C6″
C1″
C5
C6″
O3
C6
N1′
S2
N3′
C6′
O3
C6
C3a
C4′
C2′
C4
C7
C7
N1′
C8
C3a
C1a
C6′
O4
C3
C1a
O2
C8
C3
S1
C2
S1
O1
C2
O1
O2
Fig. 1. Structure of the molecule of (5R)-5-(4-fluorophenyl)-
1′,3′,7-trimethyl-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzo-
thiophene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione 1,1-diox-
ide (XVd) according to the X-ray diffraction data.
Fig. 2. Structure of the molecule of (5R)-5-(2-methoxy-
phenyl)-7-methyl-2-thioxo-3,3a,5,6-tetrahydro-2H,2′H-spiro-
[1-benzothiophene-4,5′-pyrimidine]-4′,6′(1′H,3′H)-dione
1,1-dioxide (XIXb) according to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
92
above differences allowed us to estimate ratios of
stereoisomeric adducts in the reaction mixtures.
barbituric acid fragment is flattened, and the bond
lengths in molecules XVd and XIXb coincided within
3σ with the corresponding average values for the above
five structures. The dihedral angle between the ben-
zene ring and the plane including five atoms of the
pyrimidine ring is 34.2(2) and 26.5(1)° for compounds
XVd and XIXb, respectively. Supramolecular archi-
tecture of molecules XIXb in crystal is set by weak
N–H···O hydrogen bonds which give rise to three-di-
mensional network (N1′–H1′A···O2: H···O 2.08, N···O
2.934(3) Å, ∠ΝΗΟ 173°; N3′–H3′A···O1R: H···O 1.87,
N···O 2.731(4) Å, ∠ΝΗΟ 174°). No shortened inter-
molecular contacts were found in the crystalline struc-
ture of XVd.
Figures 1 and 2 show the structure of molecules
XVd and XIXb according to the X-ray diffraction
data. Molecules XVd and XIXb have similar steric
structures, and their geometric parameters coincide
within 3σ. We have found no structures with analogous
tetracyclic skeleton in the Cambridge Crystal Structure
Database [24]. The geometric parameters of the dioxo-
7-thiabicyclo[4.3.0]nonene fragment coincide within
3σ with those in 4-carbamoyl-7-methyl-2,3,3a,4,5,6-
hexahydro-1-benzothiophene-4-carboxylic acid 1,1-di-
oxide [1] and correspond to standard values [25].
Extension of the C5–C6 bond to 1.558(5) (XVd) and
1.540(4) Å (XIXb) against 1.529(4) Å [1] and of the
C5–C4 bond to 1.589(5) (XVd) and 1.600(4) Å (XIXb)
against 1.545(3) Å should be noted [1]. Most probably,
the observed extension of the C5–C6 and C5–C4 bonds
is related to interaction between the aryl substituent
and spiro-fused pyrimidine fragment. The cyclohexene
ring in both molecules adopts a distorted sofa con-
formation [26] where C3a, C1a, C7, C6, and C5 lie in one
plane [the mean-square deviations from that plane are
0.063 (XVd) and 0.031 Å (XIXb)]; C4 deviates from
that plane by 0.602(6) (XVd) and 0.622(5) Å (XIXb).
The thiophene ring has an envelope conformation with
the C3 atom deviating by 0.620(7) (XVd) or
0.622(5) Å (XIXb) from the plane formed by the
remaining four atoms (the mean-square deviations are
0.013 and 0.003 Å, respectively). The benzene ring is
almost orthogonal to the plane including five atoms of
the cyclohexene fragment: the corresponding dihedral
angle is 88.4(2) and 97.8(1)° for compounds XVd and
XIXb, respectively. The hexahydropyrimidine ring in
molecules XVd and XIXb is strongly flattened, the
torsion angles (in absolute values) range from 5.4(7) to
20.7(5)° (XVd) and from 5.5(5) to 30.6(3)° (XIXb).
The hexahydropyrimidine ring in XIXb has a con-
formation similar to envelope, where the C4 atom
deviates by 0.413(5) Å from the plane formed by the
other five atoms in the ring (the mean-square deviation
is 0.017 Å). The conformation of analogous fragment
in molecule XVd resembles envelope to a lesser
extent: the C4 atom therein deviates from the plane
including the remaining five atoms (the mean-square
deviation is 0.060 Å) by only 0.195(6) Å. For com-
parison, we analyzed geometric parameters of five
structurally related spiro-fused dimethylbarbituric acid
derivatives, which were taken from the CCSD [27]:
DMBART10, LUQJIQ (two independent molecules),
OBICOR, and OKOCUM. In all cases, the dimethyl-
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded from
solutions in CDCl3 on Bruker AC-200 (200.13 MHz
1
for H and 50.32 MHz for 13C), AV-300 (300.13 MHz
for 1H and 75.47 MHz for 13C), AM-400 (400.13 MHz
for 1H and 100.78 MHz for 13C), and Bruker DRX-500
1
spectrometers (500.13 MHz for H and 125.76 MHz
for 13C). The molecular weights and elemental com-
positions were determined from the high-resolution
mass spectra (electron impact, 70 eV) which were
recorded on a Finnigan MAT-8200 mass spectrometer
(vaporizer temperature 270–300°C). The IR spectra
were measured in KBr on a Vector-22 instrument. The
UV spectra were obtained on an HP 8453 UV-Vis
spectrophotometer from solutions in ethanol (c =
10–4 M). The optical rotations were measured on
a Polar 3005 polarimeter.
The X-ray diffraction data for compounds XVd and
XIXb were acquired using a Bruker P4 diffractometer
(MoKα irradiation, graphite monochromator, 2θ/θ scan-
ning). Correction for absorption was introduced by an
empirical method using Ψ-curves. The structures were
solved by the direct method with the aid of SHELXS-
97 software package [28] and were refined by the
least-squares procedure in full-matrix anisotropic ap-
proximation using SHELXL-97 software [28]. The
parameters of hydrogen atoms were calculated in each
iteration cycle from the coordinates of the correspond-
ing carbon atoms. The crystallographic data for com-
pounds XVd and XIXb and parameters of X-ray dif-
fraction experiments are collected in Table 4. Com-
pound XIXb crystallized as solvate with DMSO, and
the sulfur atom in the solvate DMSO molecule was
disordered by two positions, S1R and S1RA with a pop-
ulation ratio of 0.76:0.24. The geometric parameters,
conformations, and intermolecular interactions were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
93
Table 4. Crystallographic data for compounds XVd and
XIXb and parameters of X-ray diffraction experiments
analyzed with the aid of PLATON program [29]. The
complete sets of crystallographic data for compounds
XVd and XIXb were deposited to the Cambridge
Crystallographic Data Centre (entry nos. CCDC
655 855 and CCDC 655 856, respectively; http://
www.ccdc.cam.ac.uk/ data_request/cif deposit).
Parameter
Formula
XVd
XIXb·DMSO
C20H21N2O5FS C19H17N2O5S2·
C2H6OS
Temperature, °C
Molecular weight
Crystal system
Space group
θ range, deg
Unit cell parameters:
a, Å
23
23
The progress of reactions was monitored by thin-
layer chromatography on Silufol UV-254 plates; spots
were detected by treatment with iodine vapor. The
products were isolated by column chromatography on
silica gel using chloroform–ethanol was eluent.
420.45
Rhombic
Pbca
497.64
Triclinic
P-1
2.1–25.5
2.1–26.0
The optical purity of compound XIXb was deter-
mined by chiral HPLC on a Millikhrom 1 chromato-
graph; Kromasil CHI-DMB column, 64×2 mm, grain
size 10 μm; eluent 10% of isopropyl alcohol in hexane,
flow rate 100 μl/min; UV detector, λ 210 nm. The
retention time of the (S) enantiomer was 8.9 min, and
that for the (R) enantiomer was 11.4 min.
11.043(2)
17.902(3)
19.484(3)
90
09.231(1)
10.045(1)
12.782(1)
83.590(10)
82.072(9)0
79.443(9)0
1149.5(2)
2
b, Å
c, Å
α, deg
β, deg
90
γ, deg
V, Å3
90
L-Proline, L-alanine, and L-4-hydroxyproline from
Reanal (Hungary), [α]D20 (water) = –84, –23, and –73°,
respectively, and (S)-(+)-prolinol (XXI) from
Lancaster ([α]D20 = +31°, toluene) were used. L-4-(tert-
Butyldimethylsiloxy)proline (XII) was synthesized ac-
cording to the procedure reported in [30]. 1,3,3-Tri-
phenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborol-
7-ium trifluoromethanesulfonate (XIV) [31] was pre-
pared as described in [32]. L-Proline zinc(II) salt was
synthesized according to [33]. (+)-Pseudoephedrine
{XIII, (1S,2S)-2-methylamino-1-phenylpropan-1-ol,
3852(1)
8
Z
d
calc, g/cm3
1.450
0.214
1.438
µ, mm–1
0.150
Crystal habit, mm
1.00×0.12×0.04 0.76×0.42×0.21
Total number of
reflections
3578
4807
Number of independent
reflections
3677
4509
Correction for
absorption
Empirical
Empirical
mp 118–119°C; sublimed at 100°C (12 mm) after re-
20
578
crystallization from benzene; [α] = +53° (c = 3,
Transmission
0.52–0.85
1712
0.66–0.90
3551
EtOH)} was isolated from Ephedra equisetina Bunge
[34]. (–)-Ephedrine [XXII, (1R,2S)-2-methylamino-1-
phenylpropan-1-ol, mp 38–39°C (from hexane)] was
Number of reflections
with I > 2σ(I)
Number of refined
parameters
0262
0299
isolated from the corresponding hydrochloride
20
578
{mp 216–217°C (from EtOH), [α] = –36° (c = 2,
R1 [reflections with
F > 4σ(F)]
0.0573
0.0588
H2O)} which was isolated from alkaloids of Ephedra
equisetina Bunge [34, 35]}.
wR2 (all reflections)
0.1944
0.9500
0.1749
1.0800
5-Arylmethylideneperhydropyrimidine-2,4,6-tri-
ones IVa–IVh, Va, and Vb and 2-thioxo-5-(2,3,4-tri-
methoxybenzylidene)perhydropyrimidine-4,6-dione
(VIIa) were synthesized by the Knoevenagel conden-
sation of N,N-dimethylbarbituric, barbituric, or thio-
barbituric acid with the corresponding aromatic alde-
hyde in water in the presence of a phase-transfer
catalyst. A mixture of 10 mmol of aromatic aldehyde,
10 mmol of 1,3-dimethylbarbituric acid, and 0.17 g of
benzyl(trimethyl)ammonium chloride in 40 ml of
water was stirred for 4–5 h at 90°C. The mixture was
cooled, and the precipitate was filtered off and recrys-
Goodness of fit
tallized from ethyl acetate. Yield 83–99%; IVa,
mp 250–252°C (for spectral parameters, see [36]);
IVb, mp 161–162°C (cf. [36]); IVc, mp 134–135°C
(cf. [36]); IVe, mp 180–181°C (cf. [37]); Va, mp 270–
272°C (cf. [38]); Vb, mp 267–268°C (cf. [38]).
5-(4-Fluorobenzylidene)-1,3-dimethylhexahydro-
pyrimidine-2,4,6-trione (IVd). Yield 95%, mp 153–
156°C. IR spectrum, ν, cm–1: 759, 793, 851, 980, 1152,
1170, 1359, 1663, 1730. UV spectrum, λmax, nm
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
94
1
(logε): 203 (3.35), 254 (3.19), 331 (2.64). H NMR
spectrum (CDCl3), δ, ppm: 3.36 s (3H, CH3N), 3.39 s
(3H, CH3N), 7.11 d and 7.14 d (1H each, 2′-H, 6′-H),
8.16 d and 8.18 d (1H each, 3′-H, 5′-H), 8.49 s (1H,
CH=). 13C NMR spectrum, δC, ppm: 28.23 q (CH3),
28.91 q (CH3), 115.33 d and 115.54 d (C3′, C5′), 116.79 s
(C1′), 128.68 s (C5), 136.52 d and 136.61 d (C2′, C6′),
151.00 s (C2), 157.54 d (CH=), 160.32 s (C4′),
162.31 s and 163.95 s (C4, C6). Found: m/z 261.06849
[M]+. C13H10FN2O3. Calculated: M 261.06754.
61.92 s (OCH3), 106.17 s (C5′), 117.27 d (C1′), 119.58 s
(C5), 129.57 d (C6′), 141.02 s (C3′), 151.35 s (C2),
154.01 d (CH=), 155.95 s (C4′), 158.76 s (C2′), 160.69 s
(C=O), 162.81 s (C=O).
2-Thioxo-5-(2,3,4-trimethoxybenzylidene)hexa-
hydropyrimidine-4,6-dione (VIIa). Yield 96%,
1
mp 220–222°C. H NMR spectrum (DMSO-d6), δ,
ppm: 3.76 s (3H, OCH3), 3.86 s (3H, OCH3), 3.90 s
(3H, OCH3), 6.92 d (1H, 5′-H), 8.41 d (1H, 6′-H),
8.50 s (1H, CH=), 11.50 br.s (2H, NH). Found, %:
C 52.66; H 4.43; N 8.92; S 9.48. C14H14N2O5S. Calcu-
lated, %: C 52.17; H 4.34; N 8.69; S 9.94.
5-(3-Hydroxy-4-methoxybenzylidene)-1,3-di-
methylhexahydropyrimidine-2,4,6-trione (IVf).
Yield 90%, mp 214–215°C (from ethyl acetate). IR
spectrum, ν, cm–1: 791, 812, 900, 989, 1015, 1134,
1153, 1273, 1511, 1576, 1654, 1727, 3126. UV spec-
trum, λmax, nm (logε): 231 (3.23), 262 (3.16), 315
1′,3′,7-Trimethyl-3,3a,5,6-tetrahydro-2H,2′H-
spiro[1-benzothiophene-4,5′-pyrimidine]-
2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (VIII). An aque-
ous formaldehyde solution, 2.5 ml, was added to a mix-
ture of 0.79 g (5 mmol) of N,N′-dimethylbarbituric
acid, 0.76 g (4.8 mmol) of diene I, 0.10 g of L-proline,
7 ml of acetonitrile, and 1.5 ml of water. The mixture
was stirred for 4 h at 20°C, diluted with 10 ml of
water, and extracted with chloroform, the extract was
evaporated, and the residue was recrystallized from
ethyl acetate. Yield 1.25 g (80%), mp 265–266°C.
1H NMR spectrum (CDCl3), δ, ppm: 1.80 m (1H, 3-H),
1.90–2.10 m (2H, 3-H, 5-H), 2.11 d (3H, CH3, J =
2.2 Hz), 2.21 m (1H, 5-H), 2.38 m (2H, 6-H), 2.92 m
(1H, 2-H), 3.12 m (1H, 2-H), 3.24 s (3H, CH3N), 3.31 s
(3H, CH3N), 3.52 m (1H, 3a-H). 13C NMR spectrum,
δC, ppm: 17.87 s (CH3), 21.60 t (C3), 28.55 s (CH3),
29.19 s (CH3), 29.96 t (C5), 32.91 t (C6), 41.25 d (C3a),
50.33 t (C2), 52.23 s (C4), 131.47 s (C1a), 139.91 s (C7),
150.54 s (C2′), 167.06 s (C4′), 170.42 s (C6′). Mass
spectrum, m/z (Irel, %): 326 (100) [M]+, 262 (34),
247 (78), 234 (54), 207 (30), 181 (49), 169 (71), 147
(46), 120 (56), 94 (94). C14H18N2O5S. Calculated:
M 326.09363.
1
(2.84), 401 (2.61). H NMR spectrum (CDCl3), δ,
ppm: 3.37 s (3H, CH3N), 3.39 s (3H, CH3N), 3.98 s
(3H, OCH3), 5.70 br.s (1H, OH), 6.92 d (1H, 5′-H, J =
8.2 Hz), 7.79 d.d (1H, 6′-H, J = 1.8, 8.2 Hz), 8.05 d
(1H, 2′-H, J = 1.8 Hz), 8.44 s (1H, CH=). 13C NMR
spectrum, δC, ppm: 28.23 q (CH3), 28.91 q (CH3),
57.06 q (OCH3), 109.90 d (C2′), 114.93 s (C1′),
120.13 d (C6′), 126.28 s (C5), 131.05 d (C5′), 145.05 s
(C3′), 151.35 s (C2), 158.94 d (CH=), 160.72 s (C4′),
162.98 s and 164.28 s (C4, C6).
5-(3,4-Dimethoxybenzylidene)-1,3-dimethylhexa-
hydropyrimidine-2,4,6-trione (IVg). Yield 83%,
mp 208–210°C (from ethyl acetate). H NMR spec-
1
trum (CDCl3), δ, ppm: 3.38 s (3H, CH3N), 3.40 s (3H,
CH3N), 3.95 s (3H, OCH3), 3.99 s (3H, OCH3), 6.92 d
(1H, 5′-H, J = 8.2 Hz), 7.78 d.d (1H, 6′-H, J = 8.2,
1.8 Hz), 8.37 d (1H, 2′-H, J = 1.8 Hz), 8.47 s (1H,
CH=). 13C NMR spectrum, δC, ppm: 28.18 s (NCH3),
28.67 s (NCH3), 58.67 s (OCH3), 60.28 s (OCH3),
109.62 d (C2′), 110.51 d (C5′), 120.88 d (C6′), 121.57 s
(C1′), 127.81 s (C5), 147.16 s and 150.48 s (C3′, C4′),
151.51 s (C2), 155.12 d (CH=), 160.69 s (C=O),
162.81 s (C=O).
7-Methyl-3,3a,5,6-tetrahydro-2H, 2′H-
spiro[1-benzothiophene-4,5′-pyrimidine]-
2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (IX) was synthe-
sized in a similar way. Yield 70%, mp 240–241°C
(from ethanol). 13C NMR spectrum (DMSO-d6), δC,
ppm: 17.34 s (CH3), 21.69 t (C3), 29.06 t (C5), 30.97 t
(C6), 40.95 d (C3a), 51.12 t (C2), 53.02 s (C4), 131.64 s
(C1a), 138.67 s (C7), 150.77 s (C2′), 168.26 s (C4′),
170.42 s (C6′). Found: m/z 298.06464 [M]+.
C12H14N2O5S. Calculated: M 298.06234.
1,3-Dimethyl-5-(2,3,4-trimethoxybenzylidene)-
hexahydropyrimidine-2,4,6-trione (IVh). Yield 96%,
mp 218–221°C. IR spectrum, ν, cm–1: 702, 736, 755,
927, 991, 1090, 1151, 1289, 1308, 1551, 1590, 1670,
1680, 1723. UV spectrum, λmax, nm (logε): 226 (2.92),
1
257 (2.81), 388 (3.48). H NMR spectrum (CDCl3), δ,
ppm: 3.32 s (3H, CH3N), 3.37 s (3H, CH3N), 3.82 s
(3H, OCH3), 3.92 s (3H, OCH3), 3.96 s (3H, OCH3),
6.70 d (1H, J = 8.2 Hz), 8.27 d (1H, J = 8.2 Hz), 8.82 s
(1H, CH=). 13C NMR spectrum, δC, ppm: 28.17 s
(CH3), 28.77 s (CH3), 56.05 s (OCH3), 60.76 s (OCH3),
7-Methyl-2′-thioxo-3,3a,5,6-tetrahydro-
2H,2′H-spiro[1-benzothiophene-4,5′-pyrimidine]-
4′,6′(1′H,3′H)-dione 1,1-dioxide (X). Yield 52%,
mp 226–229°C (from ethyl acetate). 13C NMR spec-
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DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
95
trum (DMSO-d6), δC, ppm: 17.34 s (CH3), 21.52 t (C3),
29.96 t (C5), 30.51 t (C6), 41.33 d (C3a), 50.03 t (C2),
51.22 s (C4), 131.27 s (C1a), 139.09 s (C7), 166.36 s
(C4′), 170.06 s (C6′) 178.54 s (C2′). Mass spectrum,
m/z (Irel, %): 314 (6) [M]+, 167 (5), 149 (13), 44 (100).
C12H14N2O4S2. Calculated: M 314.03949.
d. A mixture of 3 mmol of barbituric, thiobarbituric,
or N,N′-dimethylbarbituric acid, 3.2 mmol of the corre-
sponding aromatic aldehyde, 0.6 mmol of catalyst (see
Tables 2, 3), and 0.43 g (2.7 mmol) of diene I in aque-
ous dioxane (15:3 by volume) was heated in a sealed
ampule for 21 h at a bath temperature of 130°C. The
ampule was cooled and opened, and the mixture was
poured on a Petri dish and allowed to evaporate in air.
The dry residue was dissolved in a minimal amount of
chloroform, and the solution was applied to a column
charged with silica gel. After chromatographic separa-
tion, the product (compound XVb or XVf) was recrys-
tallized from ethanol. To isolate compounds XVIIb,
XVIIc, XIXb, and XXb, the dry residue was dissolved
in ethanol, and the undissolved material was filtered
off and additionally purified by recrystallization. The
yields and optical rotations of the products are given in
Tables 2 and 3.
Reactions of 5-benzylidenebarbituric and -2-thio-
barbituric acids with 5-isopropenyl-2,3-dihydro-
thiophene 1,1-dioxide (I) (general procedures).
a. A mixture of 5 mmol of compound IVa, IVb, IVg,
IVh, Vb, or VIIa, 4.8 mmol of diene I, 0.10 g of
L-proline, and 0.08 g of benzyl(trimethyl)ammonium
chloride in benzene–chloroform–water (5:3:1 by vol-
ume) or in aqueous dimethylformamide (1:10 by vol-
ume) was heated for 32–36 h under reflux. The mix-
ture was evaporated, and the residue was subjected to
column chromatography on silica gel using chloro-
form–ethanol as eluent to isolate (in order of elution)
unreacted dienophile IVa, IVb, IVg, IVh, Vb, or
VIIa, stereoisomer mixture XVa/XVIa, XVb/XVIb,
or XVh, XVIh), (5S) isomer XVIa, XVIg, or XVIIIb,
and (5R) isomer XVa, XVg, XVIIb, or XIXa.
(5R)-1′,3′,7-Trimethyl-5-phenyl-3,3a,5,6-tetra-
hydro-2H,2′H-spiro[1-benzothiophene-4,5′-pyrimi-
dine]-2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (XVa).
mp 223–225°C (from ethyl acetate). IR spectrum, ν,
cm–1: 704, 740, 852, 1070, 1128, 1287, 1300, 1500,
1630, 1676, 1747. UV spectrum: λmax 206 nm
b. A mixture of 3 mmol of 5-benzylidene-1,3-di-
methylperhydropyrimidine-2,4,6-trione IVa–IVf, IVh,
or Va, 2.7 mmol (0.43 g) of 5-isopropenyl-2,3-dihy-
drothiophene 1,1-dioxide (I), and 0.06 mmol of chiral
catalyst XIb, XIc, XII, or XIII in aqueous dioxane
(10:3 by volume) was heated for 20–38 h under reflux.
When the reaction was complete (TLC), the mixture
was cooled, and the precipitate was filtered off and
recrystallized from ethyl acetate to isolate compound
XVa, XVIIa, or XVIIIa. The mother liquor was com-
bined with the filtrate and evaporated, and the residue
was subjected to column chromatography on silica gel
to isolate (in order of elution) unreacted dienophile,
(5S) isomer XVIb, XVIc, or XVIh, and (5R) isomer
XVb or XVh.
1
(log ε 3.29). H NMR spectrum (CDCl3), δ, ppm:
2.05 m (2H, 3-H), 2.19 d (3H, CH3, J = 2.2 Hz),
2
2.59 m (2H, 6-H, J = 2.6, 2.8, J = 18.6 Hz), 2.98 m
(1H, 2-H), 3.13 s (3H, CH3), 3.20 d.d.d (1H, 2-H, J =
2.6, 6.7, 13.0 Hz), 3.27 s (3H, CH3), 3.35 d.d (1H, 5-H,
J = 2.8, 5.9 Hz), 3.47 m (1H, 3a-H), 6.93 m (2H,
Harom), 7.27 m (3H, Harom). 13C NMR spectrum, δC,
ppm: 17.99 q (CH3), 21.87 t (C3), 29.50 q (CH3),
29.54 q (CH3), 36.17 d (C3a), 36.52 t (C6), 49.72 d
(C5), 50.70 t (C2), 58.70 s (C4), 128.58 (C2″, C6″),
128.72 d (C4″), 129.22 d (C3″, C5″), 133.01 s (C7a),
137.92 s (C1″), 138.73 s (C7), 150.60 s (C2′), 168.10 s
and 168.41 s (C4′, C6′). Mass spectrum, m/z (Irel, %):
402 (10) [M]+, 338 (29), 309 (100), 247 (32), 165
(29), 142 (37), 91 (51). C20H22N2O5S. Calculated:
M 402.12493.
c. A solution of 0.13 g (0.04 mmol) of compound
XIV (prepared in situ [31]) in 10 ml of methylene
chloride was cooled to –50°C, a solution of 0.73 g
(3 mmol) of pyrimidine-2,4,6-trione IVb and 0.43 g
(2.7 mmol) of diene I in 10 ml of methylene chloride
was added dropwise, and the mixture was stirred for
4 h at –50°C, for 2 h at 20°C, and for 40 h on heating
under reflux (TLC). The resulting solution was cooled,
diluted with water, and extracted with methylene
chloride, the extract was washed with water, dried over
MgSO4, and evaporated, and the residue was subjected
to chromatography on silica gel. The product was
additionally recrystallized from ethanol. Yield of XVb
0.82 g (70%).
(5S)-1′,3′,7-Trimethyl-5-phenyl-3,3a,5,6-tetrahy-
dro-2H,2′H-spiro[1-benzothiophene-4,5′-pyrimi-
dine]-2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (XVIa).
mp 251–253°C (from ethyl acetate). IR spectrum, ν,
cm–1: 1449, 1677 (C=Carom); 1131, 1294 (SO2); 1745
(C=O). UV spectrum: λmax 206 nm (log ε 3.30).
1H NMR spectrum (CDCl3), δ, ppm: 1.78 m and
2.00 m (1H each, 3-H), 2.20 d (3H, CH3, J = 2.2 Hz),
2.53 d.d.d (1H, 6-H, J = 0.6, 2.1, 5.4, 19.0 Hz), 2.85 m
2
(1H, 6-H, J = 19.0 Hz), 2.93 s (3H, CH3), 3.00 t (1H,
2-H, J = 13.1, 6.8 Hz), 3.15 s (3H, CH3), 3.17 m (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
96
2-H, J = 1.5, 6.8, 13.1 Hz), 3.52 m (1H, 5-H, J = 5.4,
11.7 Hz), 3.89 m (1H, 3a-H), 6.94 m (2H, Harom),
7.25 m (3H, Harom). 13C NMR spectrum, δC, ppm:
17.89 q (CH3), 21.97 t (C3), 28.02 q (CH3), 28.49 q
(CH3), 36.55 t (C6), 43.80 d (C3a), 50.14 d (C5), 50.96 t
(C2), 57.62 s (C4), 127.20 d (C2″, C6″), 128.73 d (C3″,
C5″), 128.92 d (4″), 131.44 s (C7a), 136.18 s (C1″),
140.41 s (C7), 149.68 s (C2′), 166.33 s and 169.87 s
(C4′, C6′). Mass spectrum, m/z (Irel, %): 402 (71) [M]+,
338 (25) 309 (100), 298 (35), 247 (34), 91 (46).
C20H22N2O5S. Calculated: M 402.12493.
(C2″), 167.08 s and 170.43 s (C4′, C6′). Mass spectrum,
m/z (Irel, %): 432 (43) [M]+, 340 (87), 298 (53), 247
(33), 121 (100), 119 (32), 91 (89). C21H24N2O6S. Cal-
culated: M 432.13550.
(5R)-5-(4-Methoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVc). mp 215–217°C (from ethyl ace-
tate). 1H NMR spectrum (CDCl3), δ, ppm: 2.09 m (2H,
3-H), 2.19 d (3H, CH3, J = 2.6 Hz), 2.52 d.d (1H, 6-H,
J = 2.4, 3.4, 18.2 Hz), 2.58 m (1H, 6-H), 2.99 m (1H,
2-H), 3.16 s (3H, CH3), 3.20 m (1H, 2-H), 3.28 s (3H,
CH3), 3.34 d.d (1H, 5-H, J = 3.4, 6.0 Hz), 3.42 m (1H,
3a-H), 3.75 s (3H, OCH3), 6.79 d (2H, 3″-H, 5″-H, J =
8.2 Hz), 6.86 d (2H, 2″-H, 6″-H, J = 8.2 Hz). 13C NMR
spectrum, δC, ppm: 18.07 q (CH3), 21.36 t (C3),
28.95 q (CH3), 29.85 q (CH3), 35.76 d (C3a), 36.79 t
(C6), 49.04 d (C5), 50.66 t (C2), 55.09 q (OCH3),
58.76 s (C4), 114.58 d (C3″, C5″), 128.68 d (C2″, C6″),
129.69 s (C1″), 132.89 s (C7a), 140.62 s (C7), 150.73 s
(C2′), 159.52 s (C4″), 168.05 s and 168.43 s (C4′, C6′).
Mass spectrum, m/z (Irel, %): 432 (46) [M]+, 340 (100),
298 (68), 121 (95), 91 (69). C21H24N2O6S. Calculated:
M 432.13550.
(5R)-5-(2-Methoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVb). mp 278–280°C (from ethanol). IR
spectrum, ν, cm–1: 727, 754, 1113, 1125, 1291, 1488,
1682, 1746. UV spectrum, λmax, nm (logε): 206 (3.25),
278 (1.07). 1H NMR spectrum (CDCl3), δ, ppm: 1.99 m
(2H, 3-H), 2.22 d (3H, CH3, J = 2.5 Hz), 2.43 d.d.d
(1H, 6-H, J = 2.4, 3.3, 18.3 Hz), 2.58 m (1H, 6-H, 2J =
18.3 Hz), 3.0 m (1H, 2-H), 3.07 s (3H, CH3), 3.20 m
(1H, 2-H), 3.32 s (3H, CH3), 3.54 m (1H, 3a-H), 3.73 s
(3H, OCH3), 4.15 m (1H, 5-H, J = 3.3, 6.0 Hz), 6.75 d
(1H, 3″-H, J = 8.2 Hz), 6.90 t (1H, 4″-H, J = 8.0,
8.2 Hz), 7.12 t (1H, 5″-H, J = 7.5, 8.0 Hz), 7.30 d
(1H, 6″-H, J = 7.5 Hz). 13C NMR spectrum, δC, ppm:
17.94 q (CH3), 21.09 t (C3), 28.85 q (CH3), 29.01 q
(CH3), 36.61 d (C3a), 37.37 t (C6), 39.96 d (C5), 50.52 t
(C2), 55.68 q (OCH3), 57.92 s (C4), 109.89 d (C3″),
121.55 d (C6″), 126.13 s (C1″), 127.66 d and 129.37 d
(C4″, C5″), 132.95 s (C7a), 138.73 s (C7), 150.81 s (C2′),
156.16 s (C2″), 167.70 s and 168.82 s (C4′, C6′). Mass
spectrum, m/z (Irel, %): 432 (46) [M]+, 340 (100), 298
(68), 121 (95), 91 (69). 432.13501. C21H24N2O6S. Cal-
culated: M 432.13550.
(5S)-5-(4-Methoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVIc). mp 198–202°C. IR spectrum, ν,
cm–1: 733, 754, 839, 1032, 1113, 1127, 1302, 1515,
1
1584, 1610, 1675, 1750, 3546, 3627. H NMR spec-
trum (CDCl3), δ, ppm: 1.78 m and 2.01 m (1H each,
3-H), 2.19 d (3H, CH3, J = 2.6 Hz), 2.48 d.d.d (1H,
2
6-H, J = 2.2, 3.6, 18.8 Hz), 2.82 m (1H, 6-H, J =
18.8 Hz), 2.95 s (3H, CH3), 2.98 m (1H, 2-H), 3.14 s
(3H, CH3), 3.20 m (1H, 2-H), 3.68 d.d (1H, 5-H, J =
3.6, 11.2 Hz), 3.85 m (1H, 3a-H), 3.73 s (3H, OCH3),
6.73 d (2H, 3″-H, 5″-H, J = 8.0 Hz), 6.86 d (2H, 2″-H,
6″-H, J = 8.0 Hz). 13C NMR spectrum, δC, ppm: 17.84 q
(CH3), 21.97 t (C3), 28.00 q (CH3), 28.91 q (CH3),
36.79 t (C6), 43.84 d (C3a), 49.29 d (C5), 50.95 t (C2),
55.14 q (OCH3), 57.75 s (C4), 114.00 d (C3″, C5″),
127.95 s (C1″), 128.31 d (C2″, C6″), 131.35 s (C7a),
140.54 s (C7), 149.72 s (C2′), 159.73 s (C4″), 166.42 s
and 170.01 s (C4′, C6′). Mass spectrum, m/z (Irel, %):
432 (43) [M]+, 340 (87), 298 (53), 247 (33), 121
(100), 119 (32), 91 (89). C21H24N2O6S. Calculated:
M 432.13550.
(5S)-5-(2-Methoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1
1,1-dioxide (XVIb). mp 188–205°C. H NMR spec-
trum (CDCl3), δ, ppm: 1.75 m and 1.90 m (1H each,
3-H), 2.13 d (3H, CH3, J = 2.2 Hz), 2.50 m (1H, 6-H),
2.86 s (3H, CH3), 2.88–3.16 m (3H, 2-H, 6-H), 3.05 s
(3H, CH3), 3.50 m (1H, 5-H), 3.70 s (3H, OCH3),
3.90 m (1H, 3a-H), 6.60 d (1H, 3″-H, J = 8.0 Hz),
6.80 m (2H, 4″-H, 5″-H), 7.16 d (1H, 6″-H, J =
7.8 Hz). 13C NMR spectrum, δC, ppm: 17.79 q (CH3),
21.01 t (C3), 27.98 q (CH3), 29.13 q (CH3), 36.21 t
(C6), 39.87 d (C3a), 43.04 d (C5), 50.99 t (C2), 56.71 q
(OCH3), 60.17 s (C4), 110.73 d (C3″), 120.41 d (C6″),
124.35 s (C1″), 127.56 d and 129.29 d (C4″, C5″),
131.59 s (C7a), 139.99 s (C7), 150.54 s (C2′), 156.92 s
(5R)-5-(4-Fluorophenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVd). mp 199–200°C (from ethyl
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
97
acetate). IR spectrum, ν, cm–1: 733, 758, 842, 1108,
1127, 1284, 1302, 1511, 1604, 1677, 1700, 1749.
1H NMR spectrum (CDCl3), δ, ppm: 2.02 m (2H, 3-H),
2.21 d (3H, CH3, J = 2.5 Hz), 2.58 m (2H, 6-H),
3.06 m (1H, 2-H), 3.16 s (3H, CH3), 3.20 m (1H, 2-H),
3.29 s (3H, CH3), 3.38 d.d (1H, 5-H, J = 3.0, 6.0 Hz),
3.43 m (1H, 3a-H), 6.91–7.01 m (4H, FC6H4). 13C NMR
spectrum, δC, ppm: 18.01 q (CH3), 21.44 t (C3),
28.94 q (CH3), 30.71 q (CH3), 35.93 d (C3a), 36.59 t
(C6), 48.64 d (C5), 50.62 t (C2), 58.42 s (C4), 115.84 d
and 116.05 d (C3″, C5″), 129.06 d and 129.14 d (C2″,
C6″), 132.98 s (C7a), 133.72 s (C1″), 138.47 s (C7),
150.73 s (C2′), 161.23 s (C4″), 167.87 s and 168.31 s
(C4′, C6′). Mass spectrum, m/z (Irel, %): 420 (36) [M]+,
356 (23), 327 (100), 297 (75), 247 (32), 109 (55).
C20H21FN2O5S. Calculated: M 420.11551.
J = 2.1 Hz). 6.73 d (1H, 5″-H, J = 8.1 Hz). 13C NMR
spectrum, δC, ppm: 18.06 q (CH3), 21.49 t (C3),
28.92 q (CH3), 29.01 q (CH3), 35.90 d (C3a), 36.75 t
(C6), 49.27 d (C5), 50.68 t (C2), 55.77 q (OCH3), 58.78 s
(C4), 110.82 d (C5″), 113.91 d (C2″), 118.76 d (C6″),
130.87 s (C1″), 132.89 s (C7a), 138.53 s (C7), 145.86 s
and 146.60 s (C3″, C4″), 150.73 s (C2′), 168.10 s (C4′),
168.51 s (C6′). Mass spectrum, m/z (Irel, %): 448
(51) [M]+, 356 (56), 298 (56), 188 (51), 137 (100).
C21H24N2O7S. Calculated: M 448.13041.
(5R)-5-(3,4-Dimethoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVg). mp 249–251°C (from ethanol).
1H NMR spectrum (CDCl3), δ, ppm: 2.01 m (2H, 3-H),
2.21 d (3H, CH3, J = 2.1 Hz), 2.58 m (2H, 6-H),
2.98 m (1H, 2-H), 3.18 s (3H, CH3), 3.25 m (1H, 2-H),
3.28 s (3H, CH3), 3.43 d.d (1H, 5-H, J = 2.8, 6.2 Hz),
3.48 m (1H, 3a-H), 3.77 s (3H, OCH3), 3.83 s (3H,
OCH3), 6.48 d (1H, 2″-H, J = 2.0 Hz), 6.50 d.d (1H,
6″-H, J = 2.0, 8.2 Hz), 6.75 d (1H, 5″-H, J = 8.2 Hz).
13C NMR spectrum, δC, ppm: 18.03 q (CH3), 21.48 t
(C3), 28.94 q (CH3), 29.04 q (CH3), 36.15 d (C3a),
36.17 t (C6), 49.38 d (C5), 50.83 t (C2), 55.72 q
(OCH3), 55.75 q (OCH3), 58.71 s (C4), 110.36 d (C2″),
111.15 d (C5″), 119.82 d (C6″), 130.00 s (C1″), 133.16 s
(C7a), 138.56 s (C7), 149.06 s and 149.08 s (C3″,
C4″), 150.71 s (C2′), 168.06 s (C4′), 168.39 s (C6′). Mass
spectrum, m/z (Irel, %): 462 (71) [M]+, 369 (30), 202
(37), 191 (86), 151 (100). C22H26N2O7S. Calculated:
M 462.14606.
(5R)-5-(2-Hydroxy-3-methoxyphenyl)-1′,3′,7-tri-
methyl-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzo-
thiophene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVe). mp 228–231°C (from ethyl ace-
tate). 1H NMR spectrum (CDCl3), δ, ppm: 2.02 m (2H,
3-H), 2.20 d (3H, CH3, J = 2.5 Hz), 2.40 d.d (1H, 6-H,
J = 2.9, 18.4 Hz), 2.61 d.d.d (1H, 6-H, J = 0.6, 2.0, 6.7,
18.4 Hz), 2.98 m (1H, 2-H), 3.13 s (3H, CH3), 3.18 m
(1H, 2-H), 3.31 s (3H, CH3), 3.54 m (1H, 3a-H), 3.86 s
(3H, OCH3), 3.89 d.d (1H, 5-H, J = 2.9, 6.7 Hz), 5.79 s
(1H, OH), 6.71 d (2H, 4″-H, J = 8.0 Hz), 6.79 t (1H,
5″-H, J = 8.2, 8.0 Hz). 6.84 d (1H, 6″-H, J = 8.2 Hz).
13C NMR spectrum, δC, ppm: 17.83 q (CH3), 21.01 t
(C3), 28.98 q (CH3), 29.17 q (CH3), 36.06 d (C3a),
37.06 t (C6), 39.88 d (C5), 50.46 t (C2), 55.91 q
(OCH3), 57.68 s (C4), 110.05 d (C5″), 119.29 d (C4″),
120.54 d (C5″), 123.95 s (C1″), 132.99 s (C7a), 138.71 s
(C7), 142.99 s (C3″), 145.79 d (C2″), 150.81 s (C2′),
167.58 s (C4′), 168.46 s (C6′). Mass spectrum, m/z (Irel,
%): 448 (100) [M]+, 356 (82), 298 (61). C21H24N2O7S.
Calculated: M 448.13041.
(5S)-5-(3,4-Dimethoxyphenyl)-1′,3′,7-trimethyl-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVIg). mp 205–208°C (from ethanol).
1H NMR spectrum (CDCl3), δ, ppm: 1.75 m and
2.00 m (1H each, 3-H), 2.20 d (3H, CH3, J = 2.3 Hz),
2.50 d.d (1H, 6-H, J = 3.9, 18.2 Hz), 2.80 m (1H, 6-H),
2.90 m (1H, 2-H), 3.00 s (3H, CH3), 3.20 m (1H, 2-H),
3.18 s (3H, CH3), 3.30 m (1H, 5-H, J = 3.9, 11.3 Hz),
3.48 m (1H, 3a-H), 3.80 s (6H, OCH3), 6.43 d (1H,
2″-H, J = 2.2 Hz), 6.47 d.d (1H, 6″-H, J = 2.2, 8.0 Hz),
6.78 d (1H, 5″-H, J = 8.0 Hz). 13C NMR spectrum, δC,
ppm: 18.12 q (CH3), 23.07 t (C3), 28.00 q (CH3),
28.60 q (CH3), 36.99 t (C6), 40.18 d (C3a), 49.54 d
(C5), 50.90 t (C2), 55.81 q and 55.84 q (OCH3), 57.68 s
(C4), 110.80 d (C2″), 114.51 d (C5″), 120.21 d (C6″),
130.12 s (C7a), 134.08 s (C1″), 139.12 s (C7), 146.42 s
(C3″), 149.08 s (C2′), 151.15 s (C4″), 164.99 s and
169.12 s (C4′, C6′). Found: m/z 462.14660 [M]+.
C22H26N2O7S. Calculated: M 462.14606.
(5R)-5-(3-Hydroxy-4-methoxyphenyl)-1′,3′,7-tri-
methyl-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzo-
thiophene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVf). mp 208–211°C (from ethanol). IR
spectrum, ν, cm–1: 733, 756, 1050, 1129, 1287, 1511,
1
1589, 1681, 1700, 1752, 3501. H NMR spectrum
(CDCl3), δ, ppm: 2.05 m (2H, 3-H), 2.19 d (3H, CH3,
J = 2.5 Hz), 2.52 d.d (1H, 6-H, J = 2.5, 18.5 Hz),
2.61 d.d.d (1H, 6-H, J = 2.5, 6.0, 18.5 Hz), 3.01 m
(1H, 2-H), 3.18 s (3H, CH3), 3.20 m (1H, 2-H), 3.28 s
(3H, CH3), 3.36 d.d (1H, 5-H, J = 2.5, 6.0 Hz), 3.48 m
(1H, 3a-H), 3.84 s (3H, OCH3), 5.81 s (1H, OH),
6.43 d.d (1H, 6″-H, J = 2.1, 8.1 Hz), 6.48 d (1H, 2″-H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
98
817, 1034, 1095, 1123, 1294, 1496, 1599, 1685,
1715, 1753, 3093, 3214, 3436. H NMR spectrum
(5R)-1′,3′,7-Trimethyl-5-(2,3,4-trimethoxyphen-
1
yl)-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVh). mp 280–281°C (from ethyl ace-
tate). IR spectrum, ν, cm–1: 720, 728, 748, 1040, 1092,
(DMSO-d6), δ, ppm: 1.96 m (2H, 3-H), 2.06 d (3H,
CH3, J = 1.7 Hz), 2.53 m (2H, 6-H), 3.05 m (1H, 2-H),
3.22 m (1H, 2-H), 3.42 m (1H, 3a-H), 3.62 d (1H, 5-H,
J = 2.8, 6.0 Hz), 7.12 m (2H, Harom), 7.32 m (3H,
Harom), 11.12 br.s (2H, NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 17.69 q (CH3), 21.55 t (C3),
35.42 d (C3a), 36.05 t (C6), 46.73 d (C5), 50.66 t (C2),
56.82 s (C4), 127.67 d (C4″), 127.85 d (C2″, C6″),
128.50 d (C3″, C5″), 133.36 s (C7a), 137.95 s (C1″),
139.19 s (C7), 149.83 s (C2′), 169.57 s and 169.97 s
(C4′, C6′). Found: m/z 374.09357 [M]+. C18H18N2O5S.
Calculated: M 374.09363.
(5S)-7-Methyl-5-phenyl-3,3a,5,6-tetrahydro-
2H,2′H-spiro[1-benzothiophene-4,5′-pyrimidine]-
2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (XVIIIa).
mp 196–200°C (decomp.; from ethanol). 1H NMR spec-
trum (DMSO-d6), δ, ppm: 1.68 m and 1.92 m (1H
each, 3-H), 2.04 d (3H, CH3, J = 2.5 Hz), 2.53 m and
2.80 m (1H each, 6-H), 3.09 m and 3.20 m (1H each,
2-H), 3.54 m (1H, 5-H, J = 5.8, 11.8 Hz), 3.70 m
(1H, 3a-H), 7.12 m (2H, Harom), 7.32 m (3H, Harom),
11.12 br.s (2H, NH). 13C NMR spectrum, δC, ppm:
17.51 q (CH3), 21.93 t (C3), 36.80 t (C6), 44.21 d (C3a),
47.03 d (C5), 50.26 t (C2), 56.71 s (C4), 127.25 d (C2″,
C6″), 127.76 d (C4″), 128.89 d (C3″, C5″), 131.44 s (C7a),
137.55 s (C1″), 140.11 s (C7), 149.14 s (C2′), 168.57 s
and 171.34 s (C4′, C6′). Mass spectrum, m/z (Irel, %):
374 (26) [M]+, 179 (19), 153 (23), 91 (100).
C18H18N2O5S. Calculated: M 374.09363.
1
1128, 1295, 1495, 1597, 1688, 1700, 1748. H NMR
spectrum (CDCl3), δ, ppm: 1.98 m (2H, 3-H), 2.20 d
(3H, CH3, J = 2.0 Hz), 2.44 d.d (1H, 6-H, J = 2.7,
18.6 Hz), 2.61 d.d.d (1H, 6-H, J = 4.2, 6.5, 18.6 Hz),
3.01 d.d.d (1H, 2-H, J = 7.7, 11.9, 13.2 Hz), 3.12 s
(3H, CH3), 3.18 m (1H, 2-H, J = 2.7, 6.2, 13.2 Hz),
3.30 s (3H, CH3), 3.39 m (1H, 3a-H), 3.73 d.d (1H,
5-H, J = 2.7, 6.5 Hz), 3.76 s (3H, OCH3), 3.77 s (3H,
OCH3), 3.81 s (3H, OCH3), 6.63 d (1H, 5″-H, J =
8.4 Hz), 6.80 d (1H, 6″-H, J = 8.4 Hz). 13C NMR spec-
trum, δC, ppm: 17.97 q (CH3), 20.92 t (C3), 29.05 q
(CH3), 29.08 q (CH3), 36.37 d (C3a), 37.26 t (C6),
40.97 d (C5), 50.47 t (C2), 55.71 q (CH3), 58.01 s (C4),
60.56 q (CH3), 60.95 q (CH3), 107.23 d (C5″), 121.79 d
(C6″), 123.30 s (C1″), 132.88 s (C7a), 138.99 s (C7),
141.14 s (C4″), 150.85 s (C2′), 151.29 s and 153.39 s
(C2″, C3″), 167.76 s (C4′), 168.65 s (C6′). Mass spec-
trum, m/z (Irel, %): 492 (65) [M]+, 400 (36), 337 (40),
298 (48), 221 (90), 181 (100). C23H28N2O8S. Calculat-
ed: M 492.15662.
(5S)-1′,3′,7-Trimethyl-5-(2,3,4-trimethoxyphen-
yl)-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVIh). mp 185–187°C (from ethanol). IR
spectrum, ν, cm–1: 728, 754, 1099, 1131, 1288, 1302,
1
1498, 1599, 1681, 1746. H NMR spectrum (CDCl3),
(5R)-5-(2-Methoxyphenyl)-7-methyl-3,3a,5,6-
tetrahydro-2H,2′H-spiro[1-benzothiophene-4,5′-
pyrimidine]-2′,4′,6′(1′H,3′H)-trione 1,1-dioxide
(XVIIb). mp 208–211°C (decomp.; from ethanol). IR
spectrum, ν, cm–1: 757, 1026, 1052, 1122, 1294, 1493,
1600, 1615, 1678, 1716, 1753, 3024, 3202, 3397.
1H NMR spectrum (DMSO-d6), δ, ppm: 2.08 m (2H,
3-H), 2.22 d (3H, CH3, J = 2.0 Hz), 2.53 d.d (1H, 6-H,
δ, ppm: 1.82 m and 2.01 m (1H each, 3-H), 2.19 d (3H,
CH3, J = 2.7 Hz), 2.40 d.d (1H, 6-H, J = 3.7, 19.0 Hz),
2.81 m (1H, 6-H), 2.98 m (1H, 2-H), 2.96 s (3H, CH3),
3.17 m (1H, 2-H), 3.20 s (3H, CH3), 3.77 s (3H,
OCH3), 3.81 s (3H, OCH3), 3.82 s (3H, OCH3),
3.89 d.d (1H, 5-H, J = 3.7, 11.5 Hz), 3.94 m (1H,
3a-H), 6.49 d (1H, 6″-H, J = 8.7 Hz), 6.52 d (1H, 5″-H,
J = 8.7 Hz). 13C NMR spectrum, δC, ppm: 17.89 q
(CH3), 21.85 t (C3), 28.28 q (CH3), 28.72 q (CH3),
37.25 t (C6), 40.12 d (C3a), 43.67 d (C5), 51.05 t (C2),
55.88 q (OCH3), 56.21 s (C4), 60.68 q (OCH3), 61.32 q
(OCH3), 106.95 d (C5″), 121.95 d (C6″), 122.56 s (C1″),
131.63 s (C7a), 140.38 s (C7), 142.22 s (C4″), 150.19 s
(C2′), 151.97 s and 153.79 s (C2″, C3″), 166.55 s
(C4′), 169.41 s (C6′). Found: m/z 492.15630 [M]+.
C23H28N2O8S. Calculated: M 492.15662.
2
J = 3.2, 18.6 Hz), 2.75 m (1H, 6-H, J = 18.6 Hz),
3.10 m and 3.22 m (1H, 2-H), 3.42 m (1H, 3a-H),
3.68 s (3H, CH3), 4.04 d (1H, 5-H, J = 5.8, 3.2 Hz),
6.72 d (1H, 3″-H, J = 8.2 Hz), 6.83 t (1H, 5″-H, J =
8.0, 8.6 Hz), 7.00 d (1H, 6″-H, J = 8.6 Hz), 7.16 t (1H,
13
4″-H, J = 8.0, 8.2 Hz), 10.82 br.s (2H, NH). C NMR
spectrum, δC, ppm: 18.08 q (CH3), 21.56 t (C3), 37.66 d
(C3a), 38.44 t (C6), 40.32 d (C5), 51.89 t (C2), 56.01 q
(OCH3), 58.08 s (C4), 111.45 d (C3″), 122.04 d (C5″),
127.27 d (C6″), 128.55 s (C1″), 130.19 d (C4″), 133.12 s
(C7a), 139.70 s (C7), 149.86 s (C2′), 158.18 s (C2″),
169.94 s and 170.48 s (C4′, C6′). Found: m/z 404.10370
[M]+. C19H20N2O6S. Calculated: M 404.10420.
(5R)-7-Methyl-5-phenyl-3,3a,5,6-tetrahydro-
2H,2′H-spiro[1-benzothiophene-4,5′-pyrimidine]-
2′,4′,6′(1′H,3′H)-trione 1,1-dioxide (XVIIa). mp 248–
250°C (decomp.; from ethanol). IR spectrum, ν, cm–1:
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DIELS–ALDER REACTIONS WITH CYCLIC SULFONES: VIII.
99
(5S)-5-(2-Methoxyphenyl)-7-methyl-3,3a,5,6-
tetrahydro-2H,2′H-spiro[1-benzothiophene-4,5′-
pyrimidine]-2′,4′,6′(1′H,3′H)-trione 1,1-dioxide
(XVIIIb). mp 228–232°C (decomp.; from ethanol). IR
spectrum, ν, cm–1: 759, 1026, 1120, 1289, 1340, 1492,
1589, 1601, 1698, 1724, 1751, 3104, 3219, 3431.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.86 m and
2.06 m (1H each, 3-H), 2.09 d (3H, CH3, J = 2.0 Hz),
2.43 m (2H, 6-H), 3.05 m and 3.20 m (1H each, 2-H),
3.42 m (1H, 3a-H), 3.62 d (1H, 5-H, J = 4.0, 11.2 Hz),
3.78 s (3H, CH3), 6.79 m (2H, 3″-H, 5″-H), 6.90 d (1H,
6″-H, J = 8.5 Hz), 7.16 t (1H, 4″-H, J = 8.2, 8.2 Hz),
11.32 br.s (2H, NH). 13C NMR spectrum, δC, ppm:
17.81 q (CH3), 21.85 t (C3), 36.19 d (C3a), 36.92 t (C6),
40.13 d (C5), 50.58 t (C2), 55.21 q (OCH3), 56.71 s
(C4), 110.11 d (C3″), 120.38 d (C5″), 127.27 d (C6″),
128.88 s (C1″), 131.54 d (C4″), 132.04 s (C7a), 139.51 s
(C7), 150.08 s (C2′), 156.88 s (C2″), 169.27 s and
172.28 s (C4′, C6′). Mass spectrum, m/z (Irel, %): 404
(24) [M]+, 311 (21), 172 (22), 161 (22), 121 (100).
C19H20N2O6S. Calculated: M 404.10420.
18.5 Hz), 2.50 m (1H, 6-H), 3.09 m and 3.22 m (1H
each, 2-H), 3.48 m (1H, 3a-H), 3.69 s (3H, OCH3),
3.76 s (3H, OCH3), 3.78 s (3H, OCH3), 3.82 d.d
(1H, 5-H, J = 5.6, 2.8 Hz), 6.69 d and 6.75 d (1H each,
5″-H, 6″-H, J = 8.2 Hz), 12.3 br.s (2H, NH). 13C NMR
spectrum, δC, ppm: 17.54 q (CH3), 20.88 t (C3),
35.60 d (C3a), 36.78 t (C6), 39.90 d (C5), 50.43 t (C2),
55.70 q (OCH3), 57.09 s (C4), 60.27 q (OCH3), 60.79 q
(OCH3), 107.49 d (C5″), 121.42 d (C6″), 123.92 s (C1″),
133.09 s (C7a), 138.18 s (C7), 140.51 s (C3″), 151.11 s
(C2″), 152.89 s (C4″), 167.24 s and 167.93 s (C4′, C6′),
178.63 s (C2′). Mass spectrum, m/z (Irel, %): 480 (55)
[M]+, 337 (59), 291 (41), 232 (43), 221 (82), 194 (65),
181 (100). C21H24N2O7S2. Calculated: M 480.10248.
(5R)-5-(2-Methoxyphenyl)-7-methyl-2-thioxo-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-4′,6′(1′H,3′H)-dione 1,1-di-
oxide (XIXb). mp 213–220°C (decomp.; from EtOH–
DMSO, 1:1). IR spectrum, ν, cm–1: 728, 756, 1006,
1095, 1116, 1128, 1291, 1297, 1300, 1495, 1548, 1609,
1
1665, 1706, 3183, 3280, 3391. H NMR spectrum
(DMSO-d6), δ, ppm: 1.99 m (2H, 3-H), 2.07 d (3H,
CH3, J = 2.0 Hz), 2.33 m (1H, 6-H, J = 18.8 Hz),
(5R)-7-Methyl-5-(2,3,4-trimethoxyphenyl)-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1,1-dioxide (XVIIc). mp 229–232°C (decomp.). IR
spectrum, ν, cm–1: 700, 742, 1064, 1121, 1286, 1496,
1500, 1605, 1705, 1740, 1752, 3102, 3198, 3427.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.96 m (2H,
3-H), 2.05 d (3H, CH3, J = 2.0 Hz), 2.41 d.d (1H, 6-H,
2
2.55 m (1H, 6-H), 2.99 m and 3.20 m (1H each, 2-H),
3.60 m (1H, 3a-H), 3.68 s (3H, OCH3), 4.02 d.d (1H,
5-H, J = 6.0, 2.8 Hz), 6.86 m (3H, 3″-H, 4″-H, 6″-H),
7.32 t (1H, 5″-H, J = 8.6, 8.0 Hz), 9.5 br.s and
11.12 br.s (1H each, NH). 13C NMR spectrum, δC,
ppm: 17.63 q (CH3), 21.62 t (C3), 35.32 d (C3a), 36.48 t
(C6), 44.60 d (C5), 50.38 t (C2), 55.11 q (OCH3),
57.09 s (C4), 109.83 d (C3″), 120.63 d (C6″), 126.48 s
(C1″), 127.69 d (C4″), 128.80 d (C5″), 132.74 s (C7a),
138.36 s (C7), 156.52 s (C2″), 166.87 s and 167.76 s
(C4′, C6′), 178.27 s (C2′). Found: m/z 420.08004 [M]+.
C19H20N2O5S2. Calculated: M 420.08136.
2
J = 2.8, 18.7 Hz), 2.55 m (1H, 6-H, J = 18.7 Hz),
3.08 m and 3.15 m (1H each, 2-H), 3.50 m (1H, 3a-H),
3.69 s (OCH3), 3.79 s (3H, OCH3), 3.81 s (3H, OCH3),
3.81 d.d (1H, 5-H, J = 2.8, 5.8 Hz), 6.71 d and 6.73 d
(1H each, 5″-H, 6″-H, J = 8.6 Hz), 12.7 br.s (2H, NH).
13C NMR spectrum, δC, ppm: 17.45 q (CH3), 20.97 t
(C3), 36.55 d (C3a), 36.90 t (C6), 39.90 d (C5), 50.46 t
(C2), 56.69 q (OCH3), 56.40 s (C4), 60.11 q (OCH3),
60.49 q (OCH3), 107.62 d (C5″), 121.62 d (C6″),
124.44 s (C1″), 132.88 s (C7a), 138.61 s (C7), 140.71 s
(C3″), 149.68 s (C4″), 151.10 s (C2′), 152.78 s (C2″),
169.32 s and 170.17 s (C4′, C6′). Mass spectrum, m/z
(Irel, %): 464 (3) [M]+, 306 (18), 275 (100), 232 (54).
C21H24N2O8S. Calculated: M 464.12532.
(5S)-5-(2-Methoxyphenyl)-7-methyl-2-thioxo-
3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzothio-
phene-4,5′-pyrimidine]-4′,6′(1′H,3′H)-dione 1,1-di-
oxide (XXb). mp 232–238°C (decomp.; from ethanol).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.64 m and
1.92 m (1H each, 3-H), 2.02 d (3H, CH3, J = 2.2 Hz),
2
2.40 m (1H, 6-H, J = 18.5 Hz), 2.80 m (1H, 6-H),
3.15 m (1H, 2-H), 3.50 m (2H, 2-H, 3a-H), 3.88 s (3H,
OCH3), 3.92 d.d (1H, 5-H, J = 11.6, 5.8 Hz), 6.70 d
(1H, 3″-H, J = 8.2 Hz), 6.80 t (1H, 4″-H, J = 8.6,
8.2 Hz), 6.86 d (1H, 6″-H, J = 8.0 Hz), 7.22 t (1H,
5″-H, J = 8.6, 8.0 Hz), 12.05 br.s and 12.25 br.s (1H
each, NH). 13C NMR spectrum, δC, ppm: 17.47 q
(CH3), 20.74 t (C3), 36.54 t (C6), 37.95 d (C3a), 43.16 d
(C5), 50.80 t (C2), 55.24 s (C4), 55.59 q (OCH3),
111.05 d (C3″), 120.35 d (C6″), 125.19 s (C1″), 126.92 d
(5R)-7-Methyl-2-thioxo-5-(2,3,4-trimethoxy-
phenyl)-3,3a,5,6-tetrahydro-2H,2′H-spiro[1-benzo-
thiophene-4,5′-pyrimidine]-4′,6′(1′H,3′H)-dione
1,1-dioxide (XIXa). mp 249–252°C (decomp.). IR
spectrum, ν, cm–1: 1096, 1121, 1134, 1295, 1524,
1
1599, 1650, 1675, 1718, 3185, 3235, 3415. H NMR
spectrum (DMSO-d6), δ, ppm: 1.95 m (2H, 3-H),
2
2.03 d (3H, CH3, J = 2.0 Hz), 2.33 m (1H, 6-H, J =
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

SHUL’TS et al.
100
(C4″), 129.09 d (C5″), 131.36 s (C7a), 140.71 s (C7),
157.04 s (C2″), 166.28 s and 169.16 s (C4′, C6′), 177.81 s
(C2′). Mass spectrum, m/z (Irel, %): 420 (12) [M]+, 328
(31), 121 (39), 91 (30), 66 (100). C19H20N2O5S2. Cal-
culated: M 420.08136.
3. Maquoi, E., Sounni, N.E., Devy, L., Oliver, F., Fran-
kenne, F., Krell, H.-W., Grams, F., Foidart, J.-M., and
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sky, J.L., and Schultz, M.J., WO Patent no. 2006-
104715, 2006; Chem. Abstr., 2006, vol. 145,
no. 397552k.
5. Pedras, M.S.C., Suchy, M., and Ahiahonu, P.W.K., Org.
Biomol. Chem., 2006, vol. 4, p. 691.
6. Nilsson, I. and Polla, M., WO Patent no. 2006-135312,
2006; Chem. Abstr., 2007, vol. 146, no. 81882x.
7. Ali, S. and Alam, M., Arch. Pharmacol. Res., 1994,
vol. 17, p. 131.
8. Larsen, J.S., Abdel Aal, M.T., Pedersen, E.V., and
3-[9-tert-Butyl-1,3-dimethyl-2,4-dioxo-5-(1,3-di-
methyl-2,4,6-trioxohexahydropyrimidin-5-yl)-
2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidine-
7-yl]propyl acetate (XXIV). A mixture of 0.25 g
(0.9 mmol) of aldehyde XXIII, 0.2 g (1.3 mmol) of
1,3-dimethylbarbituric acid, 0.14 g (0.89 mmol) of
diene I, and 0.024 g (0.18 mmol) of L-4-hydroxy-
proline in 10 ml of dioxane–water (8:2) was heated for
8 h under reflux, an additional 0.12 g of 1,3-dimethyl-
barbituric acid was added, and the mixture was heated
for 12 h more under reflux. The mixture was then
evaporated, and the residue was subjected to chroma-
tography on silica gel to isolate (in order of elution)
0.12 g of unreacted diene I and 0.42 g (85%) of
compound XXIV with mp 175–177°C (from ethyl
acetate). IR spectrum, ν, cm–1: 754, 1035, 1110, 1123,
1180, 1213, 1227, 1377, 1493, 1595, 1600, 1660, 1670,
Nielsen, C., J. Heterocycl. Chem., 2001, vol. 38, p. 679.
9. Mai, A., Sbardella, G., Artico, M., Ragno, R, Massa, S.,
Novellino, E., Greco, G., Lavecchia, A., Musiu, C., La
Colla, M., Murgioni, C., La Colla, P., and Loddo, R.,
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10. Tolstikov, G.A., Shul’ts, E.E., Vafina, G.F., Tolstiko-
va, T.G., Davydova, V.A., Ismagilova, A.F., Spiri-
khin, L.V., Zarudii, F.S., and Lazareva, D.N., Khim.-
Farm. Zh., 1991, no. 11, p. 39.
11. Svoboda, J., Stadler, M., Jandera, A., Panajotova, V.,
and Kuchar, M., Collect. Czech. Chem. Commun., 2000,
vol. 65, p. 1082.
1
1676, 1680, 1700, 1720, 1747. H NMR spectrum, δ,
ppm: 1.41 s (9H, Bu-t), 1.85 m (2H, CH2), 2.03 s (3H,
CH3), 2.57 m (2H, 7-CH2), 2.97 s (3H, 1′-CH3), 3.22 s
(3H, 3′-CH3), 3.35 s (3H, 1-CH3), 3.57 s (3H, 3-CH3),
3.92 d (1H, 5-H, J = 1.2 Hz), 4.00 m (2H, CH2C=O),
4.99 d (1H, 5′-H, J = 1.2 Hz), 6.78 d (1H, 6-H, J =
12. Encio, I., Morre, D.J., Villar, R., Gil, M.J., and Marti-
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Scozzafava, A., Vullo, D., and Supuran, C.T., Bioorg.
Med. Chem. Lett., 2005, vol. 15, p. 4872.
13
1.8 Hz), 7.07 d (1H, 8-H, J = 1.8 Hz). C NMR spec-
trum, δC, ppm: 20.47 q (CH3), 27.65 q (CH3N), 27.69 q
(CH3N), 27.88 q (CH3N), 29.33 q [(CH3)3C], 29.65 t
(CH2), 29.85 s (1′-CH3), 31.18 t (CH2), 34.25 s
[(CH3)3C], 37.85 d (C5), 53.89 d (C5′), 62.96 t (CH2),
85.29 s (C4a), 119.24 s (C5a), 125.14 d (C6), 126.99 d
(C8), 137.37 d (C9), 138.14 s (C7), 146.38 s (C9a),
150.14 s (C2), 150.69 s (C2′), 154.05 s (C10a), 161.25 s
(C4), 166.52 s and 166.77 s (C4′, C6′), 170.52 s (C=O).
Mass spectrum, m/z (Irel, %): 554 (2) [M]+, 552 (5),
342 (10), 312 (16), 43 (14). C28H34N4O8. Calculated:
M 554.23764.
14. Iley, J., Moreira, R., Martins, L., Guedes, R.C., and
Soares, C.M., Bioorg. Med. Chem. Lett., 2006, vol. 16,
p. 2738.
15. Aebi, J., Ackermann, J., Dehmlow, G., Maerki, H.P., and
Morand, O., WO Patent no. 02-36584, 2002; Chem.
Abstr., 2002, vol. 136, no. 369719r.
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2004, vol. 126, p. 13708.
17. Dalko, P.I. and Moisan, L., Angew. Chem., Int. Ed.,
2004, vol. 43, p. 5138.
18. List, B., Tetrahedron, 2002, vol. 58, p. 5573; List, B.,
Chem. Commun., 2006, p. 819.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 06-03-32150, 05-03-32365).
19. Notz, W., Tanaka, F., and Barbas, C.F., III, Acc. Chem.
Res., 2004, vol. 37, p. 580; Northrup, A.B. and
MacMillan, D.W.C., J. Am. Chem. Soc., 2002, vol. 124,
p. 2458.
20. Wabnitz, T.C., Saaby, S., and Jorgensen, K.A., Org.
Biomol. Chem., 2004, vol. 2, p. 828; Abraham, C.J.,
Paull, D.H., Scerba, M.T., Grebinski, J.W., and
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