N-Trifluoroacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline ozonides

Article abstract of DOI:10.1007/s11172-011-0024-z

A three-component condensation of aromatic amine, aldehyde, and cyclopentadiene with subsequent N-trifluoroacetylation leads to 4- and 4,8-substituted N-trifluoroacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c] quinolines. Ozonation of the double bond in the latter produced the corresponding isomeric stable ozonides having (1R*,4S*,5aR*, 6S*,11bR*)-configuration and differing in inversion at the carboxamide nitrogen atom.

Full text of DOI:10.1007/s11172-011-0024-z

Russian Chemical Bulletin, International Edition, Vol. 60, No. 1, pp. 160—167, January, 2011
160
NꢀTrifluoroacetylꢀ3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline ozonides
A. G. Tolstikov, R. G. Savchenko, D. V. Nedopekin, S. R. Afon´kina, E. S. Lukina, and V. N. Odinokov
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
141 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347) 284 2750. Eꢀmail: ink@anrb.ru
A threeꢀcomponent condensation of aromatic amine, aldehyde, and cyclopentadiene with
subsequent Nꢀtrifluoroacetylation leads to 4ꢀ and 4,8ꢀsubstituted Nꢀtrifluoroacetylꢀ3a,4,5,9bꢀ
tetrahydroꢀ3Hꢀcyclopenta[c]quinolines. Ozonation of the double bond in the latter produced
the corresponding isomeric stable ozonides having (1R*,4S*,5aR*,6S*,11bR*)ꢀconfiguration
and differing in inversion at the carboxamide nitrogen atom.
Key words: cycloaddition, cyclopentadiene, imines, 3a,4,5,9bꢀtetrahydroꢀ3Hꢀcycloꢀ
penta[c]quinolines, trifluoroacetamides, ozonolysis, ozonides, the Povarov reaction.
Valuable therapeutic properties of natural peroxides
produce an increased interest to the chemistry and pharꢀ
macology of their synthetic analogs.1—3 High antimalaria
activity of sesquiterpene lactone of artemisinine containꢀ
ing a peroxide bond in the form of 1,2,4ꢀtrioxane heteroꢀ
cycle4 stimulated a search for similar activity in its derivaꢀ
tives,5 partially synthetic analogs,6 and synthetic antiꢀ
malaria peroxides7 and ozonides.8—10 To improve antiꢀ
malaria and biopharmacological properties of synthetꢀ
ic peroxides and ozonides, their conjugates containing
weakly basic functional groups and heterocycles were
obtained.11—19
We have reported the synthesis of Nꢀacetylꢀ and Nꢀtriꢀ
fluoroacetylꢀ4ꢀphenylꢀ3a,4,5,9bꢀtetrahydroꢀ3Hꢀcycloꢀ
penta[c]quinoline ozonides.20 In the present work, we deꢀ
scribed a number of new ozonides of tetrahydroquinolines
annulated with cyclopentene, studied their stereochemꢀ
istry, and found how their conformational state depends
on the nature of substituents at positions 4 and 8 of the
starting compounds (Scheme 1).
Scheme 1
R1 = H (1, 9—13, 16—20, 23—27), CO2Me (2, 14, 21, 28); R2 = Ph (3, 9, 14, 16, 21, 23, 28), 3ꢀClC6H4 (4, 10, 17, 24), 4ꢀClC6H4 (5, 11,
18, 25), 4ꢀF3CC6H4 (6, 12, 19, 26), 4ꢀMeC6H4 (7, 13, 20, 27), CO2Et (8, 15, 22, 29)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 153—160, January, 2011.
1066ꢀ5285/11/6001ꢀ160 © 2011 Springer Science+Business Media, Inc.

Tetrahydroquinoline ozonides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
161
Substituted 3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]ꢀ
quinolines 9—15 were obtained by the Povarov reaction.21
Two approaches to their synthesis were tried: a [4+2]
cycloaddition of cyclopentadiene (CPD) to aromatic imiꢀ
nes (Schiff bases) and a threeꢀcomponent condensation of
an aromatic amine, aldehyde, and CPD using different
solvents (acetonitrile, 2,2,2ꢀtrifluoroethanol) and catalysts
(trifluoroacetic and sulfanilic acids, copper and ytterbium
triflates).21 The best results (high yields and purity of adꢀ
ducts 9—15) provided a oneꢀpot threeꢀcomponent reacꢀ
tion of arylammonium trifluoroacetate 1 or 2 generated
in situ with an equimolar amount of the corresponding
aldehyde 3—8 and a fiveꢀfold excess of CPD in MeCN.
Treatment of adducts 9—15 with trifluoroacetic anhydride
in CH2Cl2 in the presence of Et3N gave rise to the correꢀ
sponding trifluoroacetamides 16—22. Ozonolysis of comꢀ
pounds 16—22 in CH2Cl2 at 0 °C led to the target ozonꢀ
ides 23—29 (see Scheme 1).
Relative cisꢀorientation of protons at the chiral atom
C(3a), C(4), and C(9b) in the molecules of compounds
9—15 and their trifluoroacetamides 16—22 was inferred
from the spinꢀspin coupling constant values of vicinal protons
H(3a)—H(9b) (JH(9b),H(3a) = 8.0—9.6 Hz) and H(3a)—H(4)
(JH(4),H(3a) = 2.4—8.8 Hz) found from the 1H NMR specꢀ
tra recorded at –10 °C. Structure 9 was also confirmed by
the Xꢀray diffraction data.22
Broad signals for the atoms C(1), C(2) (δ 130.0—135.9),
and C(4) (δ 57.4—59.2) of compounds 16—22 in the
13C NMR spectra and the protons at these atoms in the
1H NMR spectra (δ 4.7—6.5) (Table 1) indicate a slow
inversion of the heterocycle in the NMR time scale (beꢀ
tween conformers with the pseudoaxial and pseudoequaꢀ
torial C(4)ꢀaryl group) and inversion at the N atom of the
1
heterocycle. At the same time, in the H and 13C NMR
spectra of the corresponding nonacylated adducts 9—15
the signals indicated are narrow, i.e., exchange between
Table 1. The 1H and 13C NMR spectra (δ, J/Hz) of Nꢀtrifluoroacetamides 17—22
Group or atom*
δ
δ
δ
δ
δ
δ
H
C
H
C
H
C
Compound 17
Compound 18
Compound 19
С(1)Н
С(2)Н
С(3)Н2
132.24 (br.s)
130.74 (br.s)
35.65
6.18 (br.s)
5.79 (br.s)
2.08 (d,
130.32 (br.s)
130.00 (br.s)
35.63
6.17 (br.s)
5.77 (br.s)
2.07 (d,
130.32 (br.s)
130.00 (br.s)
35.63
6.53 (br.s)
5.96 (br.s)
2.06 (d,
J =16);
J = 15);
J = 16);
2.64 (br.s)
3.58 (br.s)
6.18 (br.s)
00—
2.65 (br.s)
3.60 (br.s)
6.17 (br.s)
00—
2.66 (br.s.)
3.67 (br.s)
6.53 (br.s)
00—
С(3а)Н
С(4)Н
С(5а)
40.33
58.49 (br.s)
137.91
40.14
58.25 (br.s)
134.38
45.21
58.49 (br.s)
139.94
С(6)Н—С(9)Н
126.68,
127.11,
129.11
6.69 (d, J = 8);
6.98 (t, J = 8);
7.33 (t, J = 8);
7.45 (d, J = 8)
00—
4.17 (d,
J = 8)
00—
126.66,
127.05,
128.12
7.16—7.44 (m)
124.84,
126.75,
127.18
6.98 (m);
7.57 (m)
С(9а)
С(9b)Н
125.91 (br.s)
46.53
125.96 (br.s)
45.24
00—
133.93
40.20
00—
4.14 (d,
J = 9.6)
—
4.20 (d,
J = 8)
00—
С(1´)
С(2´)Н
133.98
127.11
134.06
132.24
139.94
129.49
7.15 (m)
6.77 (d,
J = 8.4)
7.03
7.33 (m)
С(3´)Н
00—
00—
128.12
129.49
7.17 (m)
(d, J = 8.4)
00—
С(3´)
С(4´)Н
С(4´)
133.77
127.92
00—
00—
00—
00—
00—
7.15 (m)
00—
00—
00—
00—
00—
133.92
128.12
00—
127.93
129.49
00—
С(5´)Н
129.48
6.90 (m)
7.03 (d,
J = 8.4)
6.77 (d,
J = 8.4)
00—
7.33 (m)
С(6´)Н
128.24
00—
6.90 (m)
00—
130.53
00—
124.84
7.33 (m)
00—
С(4´)CF3
СОСF3
113.98 (q,
1JCF = 280.5)
155.71 (C=O);
116.67 (q, CF3,
1JCF = 289.3)
155.42 (C=O); 00—
116.68 (q, CF3,
1JCF = 288.7)
156.00 (C=O); 00—
116.67 (q, CF3,
1JCF = 288.5)
00—
(to be continued)

162
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
Tolstikov et al.
Table 1 (continued)
Group or atom*
δ
δ
δ
δ
δ
δ
C
H
C
H
C
H
Compound 20
Compound 21
Compound 22
С(1)Н
С(2)Н
С(3)Н2
135.86
134.38
35.85
6.20 (br.s)
5.76 (br.s)
2.63 (m);
2.42 (s);
132.30
130.50
35.86
6.22 (br.s)
5.76 (br.s)
1.74 (br.s);
2.67 (d.d,
J = 10.4,
132.68 (br.s)
131.15 (br.s)
35.25
5.91 (br.s)
5.83 (br.s)
2.71 (m)
2.34 (s)
J = 16.4)
3.65 (m)
5.76 (br.s)
00—
6.83 (d, J = 8);
7.83 (d, J = 8);
8.15 (s)
С(3а)Н
С(4)Н
С(5а)
С(6)Н—С(9)Н
40.53
59.07
137.56
126.44,
127.67,
128.76
3.71 (br.s)
6.20 (br.s)
00—
40.20
59.24
41.31
57.36
135.28
124.80,
126.42,
127.95
3.28 (m)
4.11 (m)
00—
138.41
127.77,
128.05,
128.23,
129.05
125.99
45.29
6.53—7.48 (m)
7.29 (m)
С(9а)
С(9b)Н
С(1´)
125.89
45.36
130.47
127.67
129.16
00—
00—
4.18 (d, J = 8.8)
00—
00—
4.21 (d, J = 8)
00—
124.80
45.25
00—
00—
00—
00—
00—
00—
00—
00—
4.00 (m)
00—
00—
00—
00—
00—
00—
00—
135.62
128.05
С(2´)Н
С(3´)Н
С(4´)Н
С(4´)
С(5´)Н
С(6´)Н
С(4´)Me
СОСF3
00—
7.06 (d, J = 8)
7.15 (t, J = 8)
6.83 (d, J = 8)
00—
00—
129.05
128.54
00—
5.43—7.48 (m)
00—
128.63
129.94
129.45
21.26
155.79 (q, C=O, 00—
2JCF = 36);
00—
129.05
128.05
7.15 (t, J = 8)
7.06 (d, J = 8)
00—
00—
2.19 (s)
00—
155.29 (m,
C=O);
00—
155.90 (m,
C=O);
00—
00—
00
00—
116.61 (q, CF3,
1JCF = 283)
00—
116.60 (q, CF3,
1JCF = 288.8)
166.40 (C=O); 3.95 (s, MeО)
52.29 (MeО)
116.54 (q, CF3,
1JCF = 288.4)
00—
8ꢀСО2Me
4ꢀСО2Et
00—
00—
00—
00—
00—
00—
168.10 (C=O); 4.00 (m, CH2);
61.38 (CH2);
13.80 (Me)
1.11 (t, Me,
J = 7)
* The atoms C(1´)—C(6´) are from the aryl group.
the conformers in the molecules of these compounds
is rapid, which is slowed down after introduction of the
Nꢀtrifluoroacetyl group.23
nides was confirmed by the presence of narrow signals in
their 13C NMR spectra (Table 2) in the region characterꢀ
istic of ozonides20,25 δ 98.9—101.5 (C(1) and C(4)) inꢀ
stead of broad signals for the atoms C(1) and C(2) in the
spectra of the starting compounds (δ 130.0—135.9). As it
has been noted earlier20 for ozonide 23, double sets of
In the 13C NMR spectra of compounds 16—22 reꢀ
corded at elevated temperature (+55 °C), the signals for
the atoms C(1), C(2), and C(4) become narrow, that eviꢀ
dences an increase in the rate of inversion at the N atom.
Similar changes in the character of signals for the protons
H(1) and H(2) are observed in the 1H NMR spectra, howꢀ
ever, the signal for the proton H(4) remains broadened,
that is due to the higher barrier of the ring inversion.24
Ozonation of compounds 16—22 in CH2Cl2 at 0 °C
occurs at the C(1)—C(2) endocyclic double bond and leads
to the corresponding ozonides 23—29 (the synthesis and
characteristics of ozonide 23 have been described earliꢀ
er20). The presence of 1,2,4ꢀtrioxolane ring in the ozoꢀ
1
signals are observed in the H and 13C NMR spectra of
compounds 24—28 with an aryl group at position 6, that
evidences formation of a mixture of two ozonides: with
pseudoaxial (conformers a) and pseudoequatorial (conꢀ
formers b) position of the aryl group. Proportion of conꢀ
formers a and b in ozonides 23—28 depends on the nature
of a substituents in the aryl group, as well as on the presꢀ
ence of substituent at the atom C(10). From the relative
intensity of two signals for the proton H(1) (see Table 2,
the more highꢀfield signal is assigned, according to the

Tetrahydroquinoline ozonides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
163
Table 2. The 1H and 13C NMR spectra (δ, J/Hz) of ozonides 24—28 (conformers a and b)* and 29
Group or atom**
δ
δ
δ
δ
δ
δ
H
C
H
C
H
C
Compound
Compound
Compound
24а [24b]
25а [25b]
26а [26b]
C(1)H
C(4)H
C(5)H2
99.08
[101.06]
6.37 (br.s)
[6.47 (s)]
99.09
[101.10]
6.38 (br.s)
[6.47 (s)]
99.02
[101.03]
6.37 (d,
JH(1),H(11b) = 2.4);
[6.50 (s)]
5.79 (d,
JH(4),H(5) = 3.6)
[5.60 (s)]
1.78 (m);
2.28 (m)
3.34 (m)
5.90 (d,
99.08
[101.06]
5.79 (d,
99.09
[101.06]
5.80 (d,
99.18
[101.03]
JH(4),H(5) = 3.6)
[5.61 (s)]
1.77 (m);
2.27 (m)
3.29 (m)
5.87 (d,
JH(6),H(5а) = 11.2) [58.75]
00—
6.18 (m)
JH(4),H(5) = 4)
[5.61 (s)]
1.74 (m);
2.25 (m)
3.28 (m)
5.89 (d,
JH(6),H(5а) = 11.2) [59.00]
00—
6.14 (m)
30.22
30.27
29.34
C(5a)H
C(6)H
32.83
31.24
57.88 (br.s)
29.68
58.06 (br.s)
58.14 (br.s)
[58.86]
137.16
126.64,
127.65,
127.84,
127.97
130.09
38.39
JH(6),H(5а) = 10.8)
00—
7.38 (m)
C(7a)
C(8)H—C(11)H
136.67
126.51,
127.66,
127.93,
128.25
133.67
38.40
139.15
124.95,
125.20,
126.50,
126.67
131.45
38.37
C(11a)
C(11b)H
00—
3.58 (dd,
00—
3.57 (dd,
00—
3.58 (dd,
[39.06]
JH(11b),H(5a) = 10.8, [39.05]
JH(11b),H(1) = 3.4)
[3.14 (m)]
JH(11b),H(5a) = 10.8, [39.09]
JH(11b),H(1) = 3.4)
[3.12 (m)]
JH(11b),H(5a) = 10.8,
JH(11b),H(1) = 2.4)
[3.16 (m)]
00—
C(1´)
135.62
128.45
00—
00—
135.57
128.50
128.83
00—
00—
135.57
127.77
128.01
00—
C(2´)H
C(3´)H
C(3´)
C(4´)H
C(4´)
6.18 (m)
00—
6.14 (m)
6.14 (m)
00—
7.38 (m)
7.38 (m)
00—
133.81
129.20
00—
00—
6.18 (m)
00—
00—
00—
00—
00—
134.31
129.10,
131.08
00—
00—
131.45
00—
C(5´)H, C(6´)H
127.65,
126.64
00—
6.18 (m)
6.14 (m)
130.08,
7.38 (m)
130.19
C(4´)CF3
00—
00—
00—
122.49 (q,
1JCF = 272)
156.00 (q,
2JCF = 36);
115.92 (q,
1JCF = 289)
00—
00—
CF3CO
155.61
(q, C=O,
2JCF = 37);
116.52 (q, CF3,
1JCF = 289)
155.55 (q, C=O, 00—
2JCF = 36)
[156.91 (q, C=O,
1JCF = 36)];
116.51 (q, CF3,
1JCF = 288)
10ꢀСO2Me
4ꢀCO2Et
00—
00—
00—
00—
165.96 (C=O);
52.45 (Me—O)
00—
3.96 (s, Me—O)
00—
00—
00—
167.60
4.14 (m,
(C=O); 61.78 CH2—O);
(CH2—O);
13.72 (Me)
1.18 (m, Me)
Compound
27а [27b]
Compound
28а [28b]
Compound
29
C(1)H
C(4)H
98.93
[101.15]
6.41 (br.s)
[6.47 (s)]
98.87
99.09
6.44 (d,
JH(1),H(11b) = 2.8)
[6.54 (s)]
101.49
6.06 (s)
5.85 (s)
99.21
5.82 (d,
5.81 (d,
99.62
[101.31]
JH(4),H(5) = 5.2)
[5.60 (br.s)]
JH(4),H(5) = 5.2)
[5.62 (s)]
(to be continued)

164
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
Tolstikov et al.
Table 2 (continued)
Group or atom**
δ
δ
δ
δ
δ
δ
C
H
C
H
C
H
Compound
27а [27b]
Compound
28а [28b]
Compound
29
C(5)H2
30.51
[32.94]
31.23
58.46 (br.s)
[59.34 (s)]
137.75
126.33,
126.53,
127.36,
127.77
1.77 (m);
2.28 (m)
3.30 (m)
5.90 (d,
JH(6),H(5а) = 10.8)
00—
30.24
31.38
1.84 (m);
2.28 (m)
3.32 (m)
5.90 (d,
JH(6),H(5а) = 10.8) (br.s)
00—
28.96
2.39 (m);
2.57 (m)
3.27 (m)
4.91 (m)
C(5a)H
C(6)H
32.83
58.08
58.86 (br.s)
C(7a)
C(8)H—C(11)H
140.06
126.50,
127.89,
128.17,
131.33
134.95
38.49
136.22
126.78,
127.27
00—
7.41 (m)
7.03 (m)
7.09 (m)
C(11a)
C(11b)H
131.77
38.72
[39.15]
00—
3.58 (dd,
00—
3.60 (dd,
JH(11b),H(5a) =11.2,
JH(11b),H(1) = 2.4)
00—
127.48
38.04
00—
3.48 (d,
JH(11b),H(5a)
= 8.4)
J
H(11b),H(5a) = 11.6,
=
JH(11b),H(1) = 3.2)
00—
C(1´)
134.97
[135.15]
127.87
128.46
133.81
00—
138.42
00—
00—
C(2´)H
C(3´)H
C(3´)
C(4´)Н
C(4´)
7.03 (m)
7.03 (m)
00—
00—
00—
128.46
128.78
00—
129.19
00—
129.90,
129.58
00—
7.09 (m)
7.09 (m)
00—
7.09 (m)
00—
00—
00—
00—
00—
00—
00—
00—
00—
00—
00—
00—
00—
135.96
C(5´)H, C(6´)H 128.96,
7.03 (m)
7.09 (m)
129.90
21.25
[21.45]
155.47 (q, C=O, 00—
2JCF = 36);
С(4´)Me
2.19 (s)
00—
00—
00—
00—
CF3CO
155.51 (q, C=O, 00—
2JCF = 37);
116.54 (q, CF3,
1JCF = 289)
156.53
(m, C=O);
116.40
(q, CF3,
1JCF = 288
00—
116.61 (q, CF3,
1JCF = 283)
10ꢀСO2Me
4ꢀCO2Et
00—
00—
00—
00—
165.96 (C=O);
52.45 (Me—O)
00—
3.96 (s, Me—O)
00—
00—
167.60
4.14 (m,
(C=O);
61.78
CH2—O);
1.18 (m, Me)
(CH2—O);
13.72 (Me)
* If signals for conformers a and b overlap, only one δC and δH value is given.
** The atoms C(1´)—C(6´) are from the aryl group.
literature data,20 to the major conformer a) or H(4) (the
signal for the major conformer a is found more downfield)
it follows that the ratio of conformers a and b in ozonides
23—28 is ∼70 : 30 (23),20 92 : 8 (24), 88 : 12 (25 and 26),
89 : 11 (27), 99 : 1 (28). Due to the pseudoaxial position
of the trifluoroacetyl group intrinsic to conformers b, this
group is close to the trioxolane ring, that makes the conꢀ
formational transformations difficult to occur because of
the donorꢀacceptor interaction of pꢀelectrons of the
O atoms of the trioxolane ring with strongly electronegaꢀ
tive F atoms of the trifluoromethyl group.20 A narrow sigꢀ
nal for the atom C(6) (δ 58.8—59.3) neighboring to the
N atom indicates degree of rigidity of conformers b, whereꢀ
as this signal is broadened in the spectra of conformers a,
that shows the presence of the exchange process between
energetically close conformers.
In ozonides 23—29, the protons at the chiral vicinal
atoms C(5a), C(6), and C(11b) are cisꢀoriented with

Tetrahydroquinoline ozonides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
165
J = 7.6 Hz); 7.35 (br.s, 1 H, HAr(6´)); 7.36 (br.s, 1 H, HAr(5´));
7.38 (br.s, 1 H, HAr(4´)); 7.52 (br.s, 1 H, HAr(2´)). 13C NMR
(CDCl3), δ: 31.48 (C(3)); 45.91 (C(3a)); 46.31 (C(9b)); 57.66
(C(4)); 116.12 (C(9)); 119.51 (C(7)); 124.77 (C(4´)); 126.01
(C(9a)); 126.47 (C(8)); 126.69 (C(5´)); 127.48 (C(6´); 129.07
(C(6)); 129.86 (C(2´)); 130.31 (C(2)); 134.04 (C(1)); 134.50
(C(3´)); 145.11(C(1´)); 145.22 (C(5a)). Trifluoroacetic anhydride
(TFAA) (0.34 mL, 2.4 mmol) and triethylamine (0.33 mL,
2.4 mmol) were added to a solution of compound 10 (0.56 g,
2.0 mmol) in anhydrous CH2Cl2 (10 mL). The reaction mixture
was stirred until the starting compound disappeared (2 min, TLC
monitoring, nꢀhexane—ethyl acetate, 3 : 1). The solvent was
evaporated, the residue was diluted with saturated aq. NaHCO3
until neutrality (∼5 mL) and extracted with ethyl acetate. The
organic layer was concentrated, the residue was subjected to
column chromatography (a column 20 mm in diameter, 5—10 g
of SiO2, light petroleum (b.p. 70—100 °C) was an eluent).
The yield of trifluoroacetamide 17 was 0.73 g (97%), Rf 0.61
(nꢀhexane—ethyl acetate, 3 : 1), m.p. 50—52 °C. Found (%):
C, 63.73; H, 3.85; Cl, 9.62; N, 3.74. C20H15ClF3NO. Calculatꢀ
ed (%): C, 63.58; H, 4.00; Cl, 9.38; N, 3.71.
respect to each other, which is indicated by their spinꢀ
spin coupling constant values (JH(6),H(5a) ≈ 11 Hz,
JH(11b),H(5a) = 8.4—11.6 Hz) (see Table 2). Based on the
1H and 13C NMR spectra and the Xꢀray diffraction data
obtained earlier20 for Nꢀacetoxy ozonide related to comꢀ
pound 23, the structure of (1R*,4S*,5aR*,6S*,11bR*)ꢀ6ꢀ
arylꢀ7ꢀtrifluoroacetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀ
epoxy[1,2]dioxepino[5,4ꢀc]quinoline is assigned to ozoꢀ
nides 24—28 (a methoxycarbonyl group at the atom C(10)
is additionally present in compound 28, whereas comꢀ
pound 29 has a CO2Et group instead of the aryl group at
position C(6)).
In conclusion, a threeꢀcomponent condensation of
arylammonium trifluoroacetate, an aldehyde, and cycloꢀ
pentadiene in MeCN with subsequent Nꢀtrifluoroacetylaꢀ
tion and ozonolysis furnishes new stable ozonides — promꢀ
ising antimalaria peroxideꢀtype agents.
Experimental
(3aR*,4S*,9bS*)ꢀ4ꢀ(4ꢀChlorophenyl)ꢀ5ꢀtrifluoroacetylꢀ
3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (18). Trifluoroꢀ
acetic acid (0.23 mL, 3.0 mmol) was added to a solution of
aniline (1) (0.27 mL, 3.0 mmol) in anhydrous acetonitrile
(20 mL), followed by addition of freshly distilled CPD (1.23 mL,
15 mmol) at 0 °C and 4ꢀchlorobenzaldehyde (5) (0.34 mL,
3.0 mmol). The mixture was stirred for 0.5 h and further treated
as described in the synthesis of compound 10. The yield of comꢀ
pound 11 was 0.76 g (90%), Rf 0.58 (nꢀhexane—ethyl acetate,
3 : 1), m.p. 138—140 °C (from nꢀhexane) (the data in Ref. 26:
m.p. 141—142 °C). 1H NMR (CDCl3), δ (cf. Ref. 26): 1.86 (dd,
1 H, Ha(3), J = 8.8 Hz, J = 16.4 Hz); 2.65 (m, 1 H, He(3)); 3.02
(q, 1 H, H(3a), J = 9.2 Hz); 3.73 (br.s, 1 H, H(5)); 4.17 (d, 1 H,
H(9b), J = 8.8 Hz); 4.66 (d, 1 H, H(4), J = 2.8 Hz); 5.71 (s, 1 H,
H(2)); 5.92 (s, 1 H, H(1)); 6.68 (d, 1 H, H(9), J = 7.6 Hz); 6.83
(t, 1 H, H(7), J = 7.6 Hz); 7.06 (t, 1 H, H(8), J = 7.6 Hz); 7.12
(d, 1 H, H(6), J = 7.6 Hz); 7.39 (d, 2 H, HAr(2´), HAr(6´),
J = 8.0 Hz); 7.42 (d, 2 H, HAr(3´), HAr(5´), J = 8.0 Hz).
13C NMR (CDCl3), δ (cf. Ref. 26): 31.45 (C(3)); 45.97 (C(3a));
46.31 (C(9b)); 57.53 (C(4)); 116.07 (C(9)); 119.46 (C(7)); 126.02
(C(9a)); 126.45 (C(8)); 127.90 (C(3´), C(5´)); 128.71 (C(2´),
C(6´)); 129.07 (C(6)); 130.30 (C(2)); 132.91 (C(4´)); 134.07
(C(1)); 141.43 (C(1´)); 145.32 (C(5a)). Compound 11 (0.56 g,
2.0 mmol), TFAA (0.34 mL, 2.4 mmol), and Et3N (0.33 mL,
2.4 mmol) under conditions for the synthesis of trifluoroacetate
17 furnished amorphous trifluoroacetamide 18 (34 g, 90%),
Rf 0.53 (nꢀhexane—ethyl acetate, 3 : 1). Found (%): C, 63.57;
H, 3.79; Cl, 9.43; N, 3.62. C20H15ClF3NO. Calculated (%):
C, 63.58; H, 4.00; Cl, 9.38; N, 3.71.
1
H and 13C NMR spectra were recorded on a Bruker Avanceꢀ
400 (400.13 (1H) and 100.62 (13C) MHz) spectrometer in CDCl3
using Me4Si as an internal standard. The homoꢀ and heteronuꢀ
clear procedures DEPTꢀ135°, COSY, HSQC, HMBC correꢀ
sponded to the standard Bruker procedures. Melting points were
measured on a smallꢀsize Boetius heating stage. Elemental analꢀ
ysis was performed on a Carlo Erba EAꢀ1108 CHNSꢀOꢀanalyꢀ
ser. Silica gel KSKG (100/200) was used for column chromatoꢀ
graphy. Plates with SiO2 (Silufol) were used for the monitoring
by TLC, a solution of vanillin in ethanol acidified with sulfuric
acid was used for visualization.
The starting compounds 1—7 were purchased from Acros
Organics, compound 8 from Fluka. The 1H and 13C NMR specꢀ
tra of compounds 17—22 are given in Table 1, of compounds
24—29 in Table 2, the NMR spectra of compounds 16 and 23
have been reported earlier.20
(3aR*,4S*,9bS*)ꢀ4ꢀ(3ꢀChlorophenyl)ꢀ5ꢀtrifluoroacetylꢀ
3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (17). Trifluoroꢀ
acetic acid (TFA) (0.23 mL, 3 mmol) was added to a solution of
aniline (1) (0.27 mL, 3.0 mmol) in anhydrous MeCN (30 mL),
followed by addition of freshly distilled cyclopentadiene (CPD)
(1.23 mL, 15 mmol) at 0 °C and 3ꢀchlorobenzaldehyde (4)
(0.34 mL, 3 mmol). The reaction mixture was stirred at ∼20 °C
until the starting aniline disappeared (0.25 h, TLC monitoring,
nꢀhexane—ethyl acetate, 3 : 1). The solvent was evaporated, the
residue was diluted with saturated aqueous NaHCO3 until neuꢀ
trality (∼6 mL) and extracted with ethyl acetate. The organic
layer was concentrated, the residue was subjected to column
chromatography (a column 20 mm in diameter, 5—10 g of SiO2,
nꢀhexane was an eluent). The yield of compound 10 was 0.83 g
(98%), Rf 0.70 (nꢀhexane—ethyl acetate, 3 : 1), m.p. 118—120 °C
(from nꢀhexane). Found (%): C, 76.68; H, 5.60; Cl, 12.82;
N, 4.73. C18H16ClN. Calculated (%): C, 76.72; H, 5.72; Cl, 12.58;
N, 4.97. 1H NMR (CDCl3), δ: 1.88 (dd, 1 H, Ha(3), J = 8.4 Hz,
J = 16.0 Hz); 2.67 (m, 1 H, He(3)); 3.05 (q, 1 H, H(3a),
J = 8.8 Hz); 3.75 (br.s, 1 H, H(5)); 4.17 (d, 1 H, H(9b), J = 8.8 Hz);
4.66 (d, 1 H, H(4), J = 2.8 Hz); 5.72 (s, 1 H, H(2)); 5.92 (s, 1 H,
H(1)); 6.69 (d, 1 H, H(9), J = 7.6 Hz); 6.84 (t, 1 H, H(7),
J = 7.6 Hz); 7.07 (t, 1 H, H(8), J = 7.6 Hz); 7.13 (d, 1 H, H(6),
(3aR*,4S*,9bS*)ꢀ5ꢀTrifluoroacetylꢀ4ꢀ(4ꢀtrifluoromethylpheꢀ
nyl)ꢀ3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (19). Triꢀ
fluoroacetic acid (0.31 mL, 4.0 mmol) was added to a solution of
aniline (1) (0.36 mL, 4.0 mmol) in anhydrous MeCN (15 mL),
followed by addition of freshly distilled CPD (1.64 mL, 20 mmol)
at 0 °C and 4ꢀtrifluoromethylbenzaldehyde (6) (0.55 g, 4 mmol).
The mixture was stirred for 1 h and further treated as described
in the synthesis of compound 10. The yield of compound 12 was
1.08 g (86%), Rf 0.67 (nꢀhexane—ethyl acetate, 3 : 1), m.p.
108—110 °C. Found (%): C, 72.42; H, 5.00; N, 4.50. C19H16F3N.
Calculated (%): C, 72.37; H, 5.11; N, 4.44). 1H NMR (CDCl3),

166
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
Tolstikov et al.
δ: 1.85 (dd, 1 H, Ha(3), J = 8.8 Hz, J = 16.4 Hz); 2.68 (m, 1 H,
He(3)); 3.08 (q, 1 H, H(3a), J = 8.8 Hz); 3.78 (br.s, 1 H, H(5));
4.21 (d, 1 H, H(9b), J = 8.8 Hz); 4.76 (d, 1 H, H(4), J = 2.4 Hz);
5.72 (s, 1 H, H(2)); 5.94 (s, 1 H, H(1)); 6.71 (d, 1 H, H(9),
J = 8.0 Hz); 6.86 (t, 1 H, H(7), J = 8.0 Hz); 7.08 (t, 1 H, H(8),
J = 8.0 Hz); 7.15 (d, 1 H, H(6), J = 8.0 Hz); 7.63 (d, 2 H, HAr(2´),
HAr (6´), J = 8.4 Hz); 7.71 (d, 2 H, HAr(3´), HAr(5´), J = 8.4 Hz).
13C NMR (CDCl3), δ: 31.43 (C(3)); 45.87 (C(9b)); 46.32 (C(3a));
57.84 (C(4)); 113.89 (CF3, J = 280.5 Hz); 116.15 (C(9)); 119.63
(C(7)); 125.50 (C(6´)); 125.54 (C(9a)); 126.01 (C(2´)); 126.51
(C(8)); 126.89 (C(6), C(3´), C(5´)); 129.09 (C(2)); 130.22 (C(1));
134.04 (C(4´)); 145.12 (C(1´)); 147.00 (C(5a)). Compound 12
(0.63 g, 2.0 mmol), TFAA (0.34 mL, 2.4 mmol), and Et3N
(0.33 mL, 2.4 mmol) under conditions for the synthesis of comꢀ
pound 17 furnished amorphous trifluoroacetamide 19 (0.72 g,
88%), Rf 0.62 (nꢀhexane—ethyl acetate, 3 : 1). Found (%):
C, 61.41; H, 3.57; N, 3.62. C21H15F6NO. Calculated (%):
C, 61.32; H, 3.68; N, 3.41.
(3aR*,4S*,9bS*)ꢀ4ꢀ(4ꢀMethylphenyl)ꢀ5ꢀtrifluoroacetylꢀ
3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (20). Freshly
distilled CPD (2.05 mL, 25 mmol) was added to a solution of
aniline (1) (0.46 mL, 5.0 mmol) and TFA (0.39 mL, 5.0 mmol)
in anhydrous MeCN (50 mL) at 0 °C, followed by addition of
4ꢀmethylbenzaldehyde (7) (0.59 mL, 5.0 mmol), the mixture
was stirred for 3 h and further treated as described for the syntheꢀ
sis of compound 10. The yield of compound 13 was 0.78 g (60%),
Rf 0.56 (nꢀhexane—ethyl acetate, 3 : 1), m.p. 100—102 °C (from
nꢀhexane) (the data in Ref. 26: m.p. 64—65 °C). 1H NMR
(CDCl3), δ (cf. Ref. 26): 1.97 (dd, 1 H, Ha(3), J = 8.8 Hz,
J = 16.0 Hz); 2.52 (s, 3 H, MeC(4´)); 2.79 (m, 1 H, He(3)); 3.14
(q, 1 H, H(3a), J = 8.8 Hz); 3.83 (m, 1 H, H(5)); 4.24 (d, 1 H,
H(9b), J = 8.0 Hz); 4.72 (br.s, 1 H, H(4)); 5.79 (s, 1 H, H(2));
5.98 (s, 1 H, H(1)); 6.71 (d, 1 H, H(9), J = 8.0 Hz); 6.86 (t, 1 H,
H(7), J = 8.0 Hz); 7.08 (t, 1 H, H(8), J = 8.0 Hz); 7.15 (d, 1 H,
H(6), J = 8.0 Hz); 7.63 (d, 2 H, HAr(2´), HAr(6´), J = 8.4 Hz);
7.71 (d, 2 H, HAr(3´), HAr(5´), J = 8.4 Hz). 13C NMR (CDCl3),
δ (cf. Ref. 26): 21.71 (Me); 31.67 (C(3)); 43.22 (C(3a)); 46.16
(C(9b)); 58.18 (C(4)); 116.06 (C(9)); 119.26 (C(7)); 123.67
(C(5´)); 126.25 (C(6)); 126.44 (C(6´)); 126.60 (C(8)); 127.34
(C(9a)); 128.22 C(3´)); 128.67 (C(2´)); 130.51 (C(2)); 132.16
(C(1)); 142.96 (C(4´)); 145.83 (C(1´)); 148.37 (C(5a)). Comꢀ
pound 13 (0.52 g, 2.0 mmol), TFAA (0.34 mL, 2.4 mmol), and
Et3N (0.33 mL, 2.4 mmol) under conditions for the synthesis of
trifluoroacetamide 17 furnished amorphous product 20 (0.64 g,
90%), Rf 0.50 (nꢀhexane—ethyl acetate, 3 : 1). Found (%):
C, 70.57; H, 4.96; N, 3.89. C21H18F3NO. Calculated (%):
C, 70.58; H, 5.08; N, 3.92.
H(9)). 13C NMR (CDCl3), δ: 31.52 (C(3)); 45.78 (C(3a)); 45.89
(C(9b)); 51.63 (MeO); 57.52 (C(4)); 115.13 (C(6)); 120.23
(C(8)); 125.07 (C(9a)); 126.40 C(3´), C(5´)); 127.53 (C(7));
128.41 (C(4´)); 128.64 (C(2´), C(6´)); 130.49 (C(2)); 131.19
(C(9)); 133.91 (C(1)); 142.03 (C(1´)); 149.95 (C(5a)); 167.63
(C=O). Compound 14 (0.61 g, 2.0 mmol), TFAA (0.34 mL,
2.4 mmol), and Et3N (0.33 mL, 2.4 mmol) under conditions for
the synthesis of trifluoroacetamide 17 furnished product 21
(0.72 g, 90%), Rf 0.50 (nꢀhexane—ethyl acetate, 3 : 1), m.p.
61—63 °C. Found (%): C, 65.80; H, 4.40; N, 3.62. C22H18F3NO3.
Calculated (%): C, 65.83; H, 4.52; N, 3.49.
(3aR*,4S*,9bS*)ꢀ4ꢀEthoxycarbonylꢀ5ꢀtrifluoroacetylꢀ
3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (22). Trifluoroꢀ
acetic acid (0.77 mL, 10 mmol) was added to a solution of aniline
(1) (0.91 mL, 10 mmol) in anhydrous MeCN (60 mL), followed
by addition of freshly distilled CPD (4.1 mL, 50 mmol) at 0 °C
and ethyl glyoxylate (8) (50% solution in toluene) (2 mL,
10 mmol). After the reaction was performed, the mixture was
treated as described for the synthesis of compound 10. The yield
of compound 15 was 1.36 g (56%), Rf 0.63 (nꢀhexane—ethyl
acetate, 3 : 1), m.p. 60—62 °C (from nꢀhexane). Found (%):
C, 74.00; H, 6.78; N, 5.96. C15H17NO2. Calculated (%): C, 74.05;
H, 7.04; N, 5.76. 1H NMR (CDCl3), δ: 1.37 (m, Me); 2.38
(m, 1 H, H(3)); 2.54 (m, 1 H, H(3)); 3.39 (q, 1 H, H(3a),
J = 8.8 Hz); 4.12 (br.s, 1 H, H(5)); 4.13 (m, CH2O); 4.25 (d, 1 H,
H(9b), J = 8.0 Hz); 4.35 (d, 1 H, H(4), J = 7.2 Hz); 5.71 (s, 1 H,
H(2)); 5.78 (s, 1 H, H(1)); 6.68 (d, 1 H, H(9), J = 7.6 Hz); 6.77
(t, 1 H, H(7), J = 7.6 Hz); 7.01 (t, 1 H, H(8), J = 7.6 Hz); 7.05
(d, 1 H, H(6), J = 7.6 Hz). 13C NMR (CDCl3), δ: 14.32
(MeCH2O); 32.70 (C(3)); 40.82 (C(3a); 46.45 (C(9b)); 56.51
(C(4)); 61.22 (CH2O); 115.79 (C(6)); 119.25 (C(7)); 125.98
(C(9a)); 126.50 (C(9)); 128.67 (C(8)); 129.82 (C(1)); 134.28
(C(2)); 144.00 (C(5a)); 171.95 (C=O). Compound 15 (1.22 g,
5.0 mmol), TFAA (0.85 mL, 5 mmol), Et3N (0.69 mL, 5 mmol),
and anhydrous CH2Cl2 (30 mL) under conditions for the syntheꢀ
sis of trifluoroacetamide 17 furnished product 22 (1.02 g, 60%),
Rf 0.64 (nꢀhexane—ethyl acetate, 3 : 1), m.p. 86—88 °C. Found (%):
C, 60.45; H, 4.67; N, 4.38. C17H16F3NO3. Calculated (%):
C, 60.18; H, 4.75; N, 4.13.
(1R*,4S*,5aR*,6S*,11bR*)ꢀ6ꢀ(3ꢀChlorophenyl)ꢀ7ꢀtrifluoroꢀ
acetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]dioxepinoꢀ
[5,4ꢀc]quinoline (24). The ozoneꢀoxygen mixture (the ozonator
productivity was (30 mmol of O3) h–1) was passed through
a solution of compound 17 (0.57 g, 1.5 mmol) in anhydrous
CH2Cl2 (20 mL) at 0 °C with stirring until the starting comꢀ
pound disappeared (∼3 min, TLC monitoring). The reaction mixꢀ
ture was purged with argon and concentrated. The residue
was subjected to column chromatography (10 g of SiO2 with
CHCl3 as an eluent). The yield of ozonide 24 was 0.47 g (73%),
Rf 0.28 (CHCl3), m.p. 48—50 °C, the ratio of conformers
24a : 24b = 92 : 8 (from relative intensities of signals for the atom
H(1) (δ 6.37 and 6.47) or H(4) (δ 5.79 and 5.61)). Found (%):
C, 56.60; H, 3.41; Cl, 8.42; N, 3.20. C20H15ClF3NO4. Calculatꢀ
ed (%): C, 56.42; H, 3.55; Cl, 8.33; N, 3.29.
(1R*,4S*,5aR*,6S*,11bR*)ꢀ6ꢀ(4ꢀChlorophenyl)ꢀ7ꢀtrifluoroꢀ
acetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]dioxepinoꢀ
[5,4ꢀc]quinoline (25). Ozonation of compound 18 (0.57 g, 1.5 mmol)
and subsequent treatment as described in the preceding experiꢀ
ment yielded ozonide 25 (0.22 g, 34%), Rf 0.27 (CHCl3), m.p.
58—60 °C, the ratio of conformers 25a : 25b = 88 : 12 (from relꢀ
ative intensities of signals for the atom H(1) (δ 6.38 and 6.47) or
(3aR*,4S*,9bS*)ꢀ8ꢀMethoxycarbonylꢀ4ꢀphenylꢀ5ꢀtrifluoroꢀ
acetylꢀ3a,4,5,9bꢀtetrahydroꢀ3Hꢀcyclopenta[c]quinoline (21).
The reaction of methyl 4ꢀaminobenzoate (7) (0.75 g, 5.0 mmol),
TFA (0.39 mL, 5.0 mmol), freshly distilled CPD (2.05 mL,
25 mmol), and benzaldehyde (3) (0.51 mL, 5 mmol) under conꢀ
ditions for the synthesis of compound 10 yielded compound 14
(1.2 g, 78%), Rf 0.60 (nꢀhexane—ethyl acetate, 3 : 1), m.p.
127—129 °C. Found (%): C, 78.63; H, 6.20; N, 4.52. C20H19NO2.
Calculated (%): C, 78.66; H, 6.27; N, 4.59. 1H NMR (CDCl3),
δ: 1.83 (m, 1 H, Ha(3)); 2.60 (m, 1 H, He(3)); 3.03 (q, 1 H,
H (3a), J = 8.8 Hz); 3.87 (s, MeO); 4.14 (d, 1 H, H(9b),
J = 8.4 Hz); 4.71 (d, 1 H, H(4), J = 2.4 Hz); 5.68 (s, 1 H, H(2));
5.93 (s, 1 H, H(1)); 6.61 (d, 1 H, H(6), J = 8.0 Hz); 7.33 (m, 6 H,
H(7), HAr(2´), HAr(3´), HAr(4´), HAr(6´), HAr(5´)); 7.84 (s, 1 H,

Tetrahydroquinoline ozonides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
167
H(4) (δ 5.80 and 5.61)). Found (%): C, 56.42; H, 3.42; Cl, 8.12;
N, 3.50. C20H15ClF3NO4. Calculated (%): C, 56.42; H, 3.55;
Cl, 8.33; N, 3.29.
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(1R*,4S*,5aR*,6S*,11bR*)ꢀ7ꢀTrifluoroacetylꢀ6ꢀ(4ꢀtrifluoꢀ
romethylphenyl)ꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]ꢀ
dioxepino[5,4ꢀc]quinoline (26). The reaction of compound 19
(0.62 g, 1.5 mmol) as described in the synthesis of ozonide 24
gave ozonide 26 (0.49 g, 71%), Rf 0.50 (CHCl3), m.p. 36—38 °C,
the ratio of conformers 26a : 26b = 88 : 12 (from relative intenꢀ
sities of signals for the atom H(1) (δ 6.37 and 6.50) or H(4)
(δ 5.79 and 5.60)). Found (%): C, 54.92; H, 3.18; N, 3.18.
C21H15F6NO4. Calculated (%): C, 54.91; H, 3.29; N, 3.05.
(1R*,4S*,5aR*,6S*,11bR*)ꢀ6ꢀ(4ꢀMethylphenyl)ꢀ7ꢀtrifluoꢀ
roacetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]dioxeꢀ
pino[5,4ꢀc]quinoline (27). The reaction of compound 20 (0.54 g,
1.5 mmol) as described in the synthesis of ozonide 24 gave ozonꢀ
ide 27 (0.21 g, 34%), Rf 0.38 (CHCl3), m.p. 50—52 °C, the ratio
of conformers 27a : 27b = 89 : 11 (from relative intensities of sigꢀ
nals for the atom H(1) (δ 6.41 and 6.47) or H(4) (δ 5.82 and
5.60)). Found (%): C, 62.31; H, 4.37; N, 3.87. C21H18F3NO4.
Calculated (%): C, 62.22; H, 4.48; N, 3.46.
14. Y. Li, Z.ꢀS. Yang, H. Zhang, B.ꢀJ. Cao, F.ꢀD. Wang,
Y. Zhang, Y.ꢀL. Shi, J.ꢀD. Yang B.ꢀA. Wu, Bioorg. Med.
Chem., 2003, 11, 4363.
(1R*,4S*,5aR*,6S*,11bR*)ꢀ10ꢀMethoxycarbonylꢀ6ꢀphenylꢀ
7ꢀtrifluoroacetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]ꢀ
dioxepino[5,4ꢀc]quinoline (28). The reaction of compound 21
(0.60 g, 1.5 mmol) as described in the synthesis of ozonide 24
gave ozonide 28 (0.08 g, 18%), Rf 0.23 (CHCl3), m.p. 62—64 °C,
the ratio of conformers 28a : 28b = 99 : 1 (from relative intensiꢀ
ties of signals for the atom H(1) (δ 6.44 and 6.54) or H(4) (δ 5.81
and 5.62)). Found (%): C, 59.25; H, 4.01; N, 3.02. C22H18F3NO6.
Calculated (%): C, 58.80; H, 4.04; N, 3.12.
(1R*,4S*,5aR*,6S*,11bR*)ꢀ6ꢀEthoxycarbonylꢀ7ꢀtrifluoroꢀ
acetylꢀ4,5,5a,6,7,11bꢀhexahydroꢀ1Hꢀ1,4ꢀepoxy[1,2]dioxepinoꢀ
[5,4ꢀc]quinoline (29). The reaction of compound 22 (1.02 g,
3.0 mmol) as described in the synthesis of ozonide 24 gave ozonꢀ
ide 29 (0.14 g, 12%), Rf 0.19 (CHCl3), m.p. 48—50 °C. Found (%):
C, 52.80; H, 4.12; N, 3.58. C17H16F3NO6. Calculated (%):
C, 52.72; H, 4.16; N, 3.62.
15. C. Singh, H. Malik, S. K. Puri, Bioorg. Med. Chem. Lett.,
2004, 14, 459.
16. V. T. Khac, T. N. Van, S. T. Van, Bioorg. Med. Chem. Lett.,
2005, 15, 2629.
17. A. Robert, O. DechyꢀCabaret, J. Cazelles, B. Meunier, Acc.
Chem. Res., 2002, 35, 167.
18. R. K. Haynes, B. Fugmann, J. Stetter, K. Rieckmann, H.ꢀD.
Heilmann, H.ꢀW. Chan, M.ꢀK. Cheung, W.ꢀL. Lam, H.ꢀN.
Wong, S. L. Croft, L. Vivas, L. Rattray, L. Stewart, W. Peꢀ
ters, B. L. Robinson, M. D. Edstein, B. Kotecka, D. E. Kyle,
B. Beckermann, M. Gerisch, M. Radtke, G. Schmuck,
W. Steinke, U. Wollborn, K. Schmeer, A. Rцmer, Angew.
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The authors are grateful to Professor L. M. Khalilov
for the discussion on 1H and 13C NMR spectra.
This work was financially supported by the Presidium
of the Russian Academy of Sciences (Program "Fundaꢀ
mental Sciences to Medicine").
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Received April 5, 2010;
in revised form November 15, 2010