and solvent-free 1:2 assembly of quinolines with aryltrifluoroacetylacetylenes to afford 3-arylethynyl

103 Pages·2017·3.86 MB·English

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.
This journal is © The Royal Society of Chemistry 2018
Catalyst-free 1:2 annulation of quinolines with trifluoroacetylacetylenes: an access to
functionalized oxazinoquinolines
Kseniya V. Belyaeva,a Lina P. Nikitina,a Andrei V. Afonin,a Alexander V. Vashchenko,a Vasiliy M.
Muzalevskiy,b Valentin G. Nenajdenko *b and Boris A. Trofimov*a
aA. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1
Favorsky Str., 664033, Irkutsk, Russia
bMoscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
E-mail: [email protected]
E-mail: [email protected]
Table of contents
General methods S2
General procedure and characterization data of compounds 3 and 5 S2-S16
Copies of all NMR spectra of compounds 3 and 5 S17-S101
X-ray diffraction structural analysis data S102-103
References S103
S1
General methods. NMR spectra were recorded on a Bruker DPX-400 spectrometer (400.1 MHz for 1H
and 100.6 MHz for 13C) and AV-400 spectrometers (40.5 MHz for 15N and 379.5 MHz for 19F) in CDCl .
3
The internal standards were HMDS (for 1H) or the residual solvent signals (for 13C), CH NO (for 15N)
3 2
and CFCl (for 19F). IR spectra were recorded on a two-beam Bruker Vertex 70 spectrometer. Elemental
3
analysis was carried out on a FLASH EA 1112 Series analyzer. Mass spectra were recorded on Mass
spectrometer Agilent 6210 HRMS-TOF-ESI. Electrostatic sputtering, registration of positive ions.
Sample Solvent - MeCN with the addition of 0.1% heptafluorobutanoic acid and with the addition of
calibration mixture for mass spectrometer. Melting points were determined on a Kofler hot stage
apparatus. Commercial samples of quinolines 1a-g and isoquinoline 4a were used.
Aryltrifluoroacetylacetylenes 2a-h1 and naphthyridines 4b,4c2 were obtained according to the literature
procedures. Monitoring of the reaction course was carried out by IR spectroscopy following the
disappearance of the absorption band of the C≡C bond in starting acetylene 2 at 2174-2202 cm-1. The
products 3a-o and 5a-c were purified by column chromatography. Column and thin-layer chromatography
were carried out on silica gel (0.06-0.2 mm) with chloroform/benzene/ethanol (20:4:1, for 3a,d,f,g,i,l,m,
5a) or hexane/dichloromethane (1:1 for 3b,c,e,h,j,k,n,o and 5b,c) mixtures as eluent.
General procedure and characterization data of compounds 3 and 5
7 6
6a
8 5
11 4a 4
9 10aN O
10 CF
1 3
i
2 3 12
13
p o i' o'
m O 14 CF3 m'
p'
2,2,2-Trifluoro-1-[1-phenyl-3-(phenylethynyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-
a]quinolin-2-yl]ethanone (3a). The mixture of acetylene 2a (0.119 g, 0.6 mmol) and quinoline 1a (0.039
g, 0.3 mmol) was stirred for 2 h at the room temperature in the argon atmosphere. The reaction mixture
was passed through a column (eluent – chloroform/benzene/ethanol) to obtain 1,3-oxazinoquinoline 3a
(0.118 g, 91%) as light-yellow powder, mp 180-181 oC (ethanol). Initial acetylene 2a was recovered
(0.021 g, conversion was 82%). IR (microlayer): 2235 (C≡C), 1713 (C=O), 1654 (C=C), 1204, 1180,
1154, 1095 (C-F) cm-1. (3S*,4aS*):(3R*,4aS*)-isomers ratio is 55:45 (1H NMR).
(3S*,4aS*)-3a: 1H NMR (400.1 MHz, CDCl ): δ 7.55-7.40 (m, 7H, H from Ph), 7.33-7.28 (m, 4H,
3 o,o’,m,p
H from Ph), 7.21 (d, 3J = 7.3 Hz, 1H, H-7), 6.95 (d, 3J = 9.8 Hz, 1H, H-6), 6.92 (m, 1H, H-8), 6.82
m,m’ 8,9 6,7
(m, 1H, H-9), 6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.16 (dd, 3J = 4.4 Hz, 3J = 9.8 Hz, 1H, H-5), 5.71
10,11 5a,6 6,7
(d, 3J = 4.4 Hz, 1H, H-4a) ppm.
5a,6
13C NMR (100.6 MHz, CDCl ): δ 184.6 (q, 2J = 35.7 Hz, C-14), 158.2 (C-1), 135.1 (C-10a), 134.0 (C
3 CF i
from Ph), 132.8 (C from Ph), 132.2 (C from Ph), 130.2 (C-2), 130.1 (C-6), 130.0 (C from Ph), 129.7
p o’ o,m
(C from Ph), 129.0 (C-9), 128.5 (C-7), 128.4 (C from Ph), 122.7 (C-8), 122.2 (C-6a), 120.9 (C from
p’ m’ i’
Ph), 120.7 (q, 1J = 284.4 Hz, CF ), 118.1 (C-10), 118.0 (C-5), 115.4 [C(O)CF ], 89.6 (C-13), 81.7 (C-
CF 3 3
12), 79.9 (q, 4J = 0.2 Hz, C-4a), 74.9 (q, 2J = 31.4 Hz, C-3) ppm.
CF CF
15N NMR (40.5 MHz, CDCl ): δ -260.9 (N-11) ppm.
3
19F NMR (376.5 MHz, CDCl ):δ -72.4 [s, C(O)CF ], -77.2 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3a as an isomer in a mixture with the (3S*,4aS*)-3a isomer (ratio is 55:45): 1H NMR (400.1
MHz, CDCl ): δ 7.55-7.40 (m, 7H, H from Ph), 7.33-7.28 (m, 4H, H from Ph), 7.18 (d, 3J =
3 o,o’,m,p m,m’ 8,9
7.3 Hz, 1H, H-7), 6.93 (d, 3J = 9.8 Hz, 1H, H-6), 6.86 (m, 1H, H-8), 6.85 (m, 1H, H-9), 6.34 (d, 3J =
6,7 10,11
8.3 Hz, 1H, H-10), 6.09 (dd, 3J = 4.6 Hz, 3J = 9.8 Hz, 1H, H-5), 5.91 (d, 3J = 4.6 Hz, 1H, H-4a)
5a,6 6,7 5a,6
ppm.
S2
13C NMR (100.6 MHz, CDCl ): δ 185.3 (2J = 36.8 Hz, C-14), 152.6 (C-1), 135.4 (C-10a), 134.3 (C
3 CF i
from Ph), 132.4 (C-2; C from Ph), 132.1 (C from Ph), 130.4 (C-6), 130.0 (C from Ph), 129.4 (C
o’ p o,m p’
from Ph), 129.0 (C-9), 128.6 (C-7), 128.5 (C from Ph), 122.4 (C-8), 122.3 (C-6a), 122.0 (q, 1J = 284.4
m’ CF
Hz, CF ), 121.4 (C from Ph), 117.7 (C-10), 117.5 (C-5), 114.9 [q, 1J = 291.1 Hz, C(O)CF ], 89.2 (C-
3 i’ CF 3
13), 81.7 (C-12), 80.6 (q, 4J = 2.4 Hz, C-4a), 73.4 (q, 2J = 31.4 Hz, C-3) ppm.
CF CF
15N NMR (40.5 MHz, CDCl ): δ -269.0 (N-11) ppm.
3
19F NMR (376.5 MHz, CDCl ):δ -73.4 [q, 6J = 2.2 Hz, C(O)CF ], -75.5 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 526.1236; found: 526.1215.
29 18 6 2
Found: C, 66.21; H, 3.25; F, 21.42; N, 2.58. Calc. for C H F NO (525.45): C, 66.29; H, 3.26; F, 21.69;
29 17 6 2
N, 2.67.
7 6
6a 5
8
11 4a
9 10aN O4
10 CF
1 3
i
2 3 12
p o 13i' o'
Me m O 14 CF3 m'
p' Me
2,2,2-Trifluoro-1-[1-(4-methylphenyl)-3-[(4-methylphenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-
[1,3]oxazino[3,2-a]quinolin-2-yl]ethanone (3b). Analogously, from quinoline 1a (0.0325 g, 0.25 mmol)
and acetylene 2b (0.106 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 24 h) 1,3-oxazinoquinoline 3b was
obtained. Eluent was mixture of hexane/dichloromethane. First fraction, yellow crystals, 0.110 g, mp 85-
87 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 40:60 (19F NMR). Second fraction, yellow
crystals, 0.017 g, mp 123-125 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 87:13. Total yield
0.127 g, 92%, (3S*,4aS*):(3R*,4aS*)-isomers ratio is 43:57 (19F NMR).
(3S*,4aS*)-3b: 1H NMR (400.1 MHz, CDCl ): δ 7.36 (m, 2H, H from Ph), 7.34 (m, 2H, H from Ph),
3 o o’
7.23 (d, 2H, H from Ph), 7.21 (d, 3J = 7.4 Hz, 1H, H-7), 7.11 (m, 2H, H from Ph), 6.94 (d, 3J = 9.8
m 7,8 m’ 5,6
Hz, 1H, H-6), 6.91 (m, 1H, H-8), 6.85 (m, 1H, H-9), 6.36 (d, 3J = 8.1 Hz, 1H, H-10), 6.17 (dd, 3J =
9,10 4a,5
4.7 Hz, 3J = 9.9 Hz, 1H, H-5), 5.71 (d, 3J = 4.7 Hz, 1H, H-4a), 2.41 (s, 3H, Me), 2.34 (s, 3H, Me’)
5,6 4a,5
ppm.
13C NMR (100.6 MHz, CDCl ): δ 184.4 (q, 2J = 35.8 Hz, C-14), 158.3 (C-1), 143.6 (C from Ph), 139.8
3 CF p
(C from Ph), 135.0 (C-10a), 132.1 (C from Ph), 131.1 (C from Ph), 130.5 (C from Ph), 129.9 (C-6),
p’ o’ i m
129.7 (C-2), 129.0 (C-9), 128.9 (C from Ph), 128.8 (C from Ph), 128.3 (C-7), 122.4 (C-8), 122.0 (C-
o m’
6a), 121.9 (q, 1J = 286.4 Hz, CF ), 117.9 (C-10), 117.8 (C-5), 117.7 (C from Ph), 115.3 [q, 1J =
CF 3 i’ CF
293.4 Hz, C(O)CF ], 89.6 (C-13), 81.0 (C-12), 79.6 (C-4a), 74.8 (q, 2J = 34.7 Hz, C-3), 21.6 (Me), 21.5
3 CF
(Me’) ppm.
19F NMR (376.3 MHz, CDCl ):δ -73.7 [s, C(O)CF ], -78.6 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3b: 1H NMR (400.1 MHz, CDCl ): δ 7.45 (m, 2H, H from Ph), 7.39 (m, 2H, H from Ph),
3 o o’
7.24 (m, 2H, H from Ph), 7.19 (d, 3J = 7.1 Hz, 1H, H-7), 7.13 (m, 2H, H from Ph), 6.96 (d, 3J = 9.8
m 7,8 m’ 5,6
Hz,1H, H-6), 6.89 (m, 1H, H-8), 6.85 (m, 1H, H-9), 6.39 (d, 3J = 8.1 Hz, 1H, H-10), 6.11 (dd, 3J =
9,10 4a,5
4.6 Hz, 3J = 9.7 Hz, 1H, H-5), 5.93 (d, 3J = 4.6 Hz, 1H, H-4a), 2.42 (s, 3H, Me), 2.35 (s, 3H, Me’)
5,6 4a,5
ppm.
13C NMR (100.6 MHz, CDCl ): δ 185.2 (q, 2J = 36.9 Hz, C-14), 152.6 (C-1), 142.6 (C from Ph), 139.5
3 CF p
(C from Ph), 135.4 (C-10a), 132.0 (C from Ph), 131.4 (C from Ph), 130.5 (C from Ph), 130.2 (C-6),
p’ o’ i m
130.0 (C-2), 129.0 (C-9), 128.9 (C from Ph), 128.8 (C from Ph), 128.4 (C-7), 123.1 (q, 1J = 289.3
o m’ CF
Hz, CF ), 122.1 (C-8), 122.0 (C-6a), 118.2 (C from Ph), 117.5 (C-10), 117.3 (C-5), 114.8 [q, 1J =
3 i’ CF
293.0 Hz, C(O)CF ], 86.2 (C-13), 80.4 (C-12), 80.2 (q, 4J = 2.2 Hz, C-4a), 73.2 (q, 2J = 31.7 Hz, C-
3 CF CF
3), 21.6 (Me), 21.5 (Me’) ppm.
19F NMR (376.3 MHz, CDCl ):δ -74.7 [q, J = 2.0 Hz, 3F, C(O)CF ], -76.9 (q, J = 2.0 Hz, 3F, CF ) ppm.
3 3 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 554.1549; found: 554.1550.
31 22 6 2
S3
7 6
6a 5
8
11 4a
9 10aN O4
10 CF
1 3
5' 6' 1' 2 3 12
4' 2' 131'' 2''
Me 3' O 14 CF3 Me
Me 6'' 3''
5'' 4'' Me
1-[1-(3,4-Dimethylphenyl)-3-[(3,4-dimethylphenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-
[1,3]oxazino[3,2-a]quinolin-2-yl]-2,2,2-trifluoroethanone (3c). Analogously, from quinoline 1a
(0.0325 g, 0.25 mmol) and acetylene 2c (0.122 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 24 h) 1,3-
oxazinoquinoline 3c was obtained as yellow crystals, 0.130 g, 89%, mp 104-106 °C (hexane),
(3S*,4aS*):(3R*,4aS*)-isomers ratio is 45:55 (19F NMR). Eluent was mixture of hexane/dichloromethane.
(3S*,4aS*)-3c: 1H NMR (400.1 MHz, CDCl ): δ 7.30-7.20 (m, 7H, H-7, H-2’, H-5’, H-6’, H-2’’, H-5’’,
3
H-6’’), 6.94 (m, 1H, H-6), 6.91 (m, 1H, H-8), 6.86 (m, 1H, H-9), 6.44 (d, 3J = 7.1 Hz, 1H, H-10), 6.19
9,10
(dd, 3J = 4.4 Hz, 3J = 9.8 Hz, 1H, H-5), 5.74 (d, 3J = 4.4 Hz, 1H, H-4a), 2.32 (s, 3H, Me-4’), 2.26
4a,5 5,6 4a,5
(s, 3H, Me-3’), 2.25 (s, 3H, Me-3’’), 2.23 (s, 3H, Me-4’’) ppm.
13C NMR (100.6 MHz, CDCl ): δ 185.2 (q, 2J = 35.8 Hz, C-14), 158.4 (C-1), 142.3 (C-4’), 138.5 (C-
3 CF
4’’), 138.2 (C-3’), 136.7 (C-3’’), 135.2 (C-10a), 133.1 (C-2’), 133.0 (C-2’’), 131.5 (C-1’), 131.0 (C-5’),
130.8 (C-2), 129.9 (C-6), 129.6 (C-5’’), 129.5 (C-6’), 129.4 (C-9), 128.8 (C-6’’), 128.3 (C-7), 122.2 (C-
8), 122.1 (C-6a), 121.9 (q, 1J = 286.0 Hz, CF ), 118.0 (C-1’’), 117.9 (C-10), 117.8 (C-5), 115.3 [q, 1J
CF 3 CF
= 293.0 Hz, C(O)CF ], 89.7 (C-13), 80.8 (C-12), 79.6 (C-4a), 74.8 (q, 2J = 34.3 Hz, C-3), 19.9 (Me-4’),
3 CF
19.7 (Me-3’, Me-3’’), 19.4 (Me-4’’) ppm.
19F NMR (376.3 MHz, CDCl ):δ -73.6 [s, C(O)CF ], -78.6 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3c: 1H NMR (400.1 MHz, CDCl ): δ 7.34 (m, 1H, H-2’), 7.30-7.20 (m, 6H, H-7, H-5’, H-6’,
3
H-2’’, H-5’’, H-6’’), 6.94 (m, 1H, H-6), 6.91 (m, 1H, H-8), 6.86 (m, 1H, H-9), 6.46 (d, 3J = 7.4 Hz,
9,10
1H, H-10), 6.12 (dd, 3J = 4.6 Hz, 3J = 9.8 Hz, 1H, H-5), 5.93 (d, 3J = 4.6 Hz, 1H, H-4a), 2.31 (s,
4a,5 5,6 4a,5
3H, Me-4’), 2.26 (s, 3H, Me-3’), 2.25 (s, 3H, Me-3’’), 2.23 (s, 3H, Me-4’’) ppm.
13C NMR (100.6 MHz, CDCl ): δ 185.2 (q, 2J = 36.9 Hz, C-14), 152.7 (C-1), 141.3 (C-4’), 138.5 (C-
3 CF
4’’), 138.2 (C-3’), 136.6 (C-3’’), 135.9 (C-10a), 133.1 (C-2’), 133.0 (C-2’’), 131.8 (C-1’), 131.0 (C-5’),
130.9 (C-2), 130.2 (C-6), 129.6 (C-5’’), 129.5 (C-6’), 129.4 (C-9), 128.8 (C-6’’), 128.3 (C-7), 123.1 (q,
1J = 289.3 Hz, CF ), 122.1 (C-6a), 122.0 (C-8), 118.5 (C-1’’), 117.6 (C-10), 117.3 (C-5), 114.8 [q, 1J
CF 3 CF
= 293.4 Hz, C(O)CF ], 86.3 (C-13), 80.3 (C-12), 80.1 (q, 4J = 2.6 Hz, C-4a), 73.2 (q, 2J = 31.0 Hz, C-
3 CF CF
3), 19.9 (Me-4’), 19.7 (Me-3’, Me-3’’), 19.4 (Me-4’’) ppm.
19F NMR (376.3 MHz, CDCl ):δ -74.6 [q, 6J = 2.2 Hz, C(O)CF ], -76.9 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 582.1862; found: 582.1867.
33 26 6 2
7 6
6a 5
8
11 4a 4
9 10aN O
10 CF
1 3
i
2 3 12
p o 13i' o'
t-Bu m O 14 CF3 m'
p' Bu-t
1-[1-(4-tert-Butylphenyl)-3-[(4-tert-butylphenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-
[1,3]oxazino[3,2-a]quinolin-2-yl]-2,2,2-trifluoroethanone (3d). Analogously, from quinoline 1a (0.013
g, 0.1 mmol) and acetylene 2d (0.051 g, 0.2 mmol) in 0.1 ml MeCN (20-24 oC, 24 h) 1,3-
S4
oxazinoquinoline 3d (0.048 g, 75%) was obtained as a yellow oil. Eluent was mixture of
chloroform/benzene/ethanol. Initial acetylene 2d was recovered (0.007 g, conversion was 86%). IR
(microlayer): 2235 (C≡C), 1711 (C=O), 1655, 1607 (C=C), 1205, 1156, 1090 (C-F) cm-1.
(3S*,4aS*):(3R*,4aS*)-isomers ratio is 50:50 (1H NMR).
(3S*,4aS*)-3d: 1H NMR (400.1 MHz, CDCl ): δ 7.45-7.35 (m, 6H, H from Ph), 7.30 (m, 2H, H
3 o,o’,m m’
from Ph), 7.18 (d, 3J = 7.3 Hz, 1H, H-7), 6.92 (d, 3J = 9.9 Hz, 1H, H-6), 6.89 (m, 1H, H-8), 6.81 (m,
8,9 6,7
1H, H-9), 6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.14 (dd, 3J = 4.4 Hz, 3J = 9.9 Hz, 1H, H-5), 5.70 (d,
10,11 5a,6 6,7
3J = 4.4 Hz, 1H, H-4a), 1.29 (s, 9H, 3Me from t-Bu), 1.26 (s, 9H, 3Me’ from t-Bu’) ppm.
5a,6
13C NMR (100.6 MHz, CDCl ): δ 185.0 (q, 2J = 35.4 Hz, C-14), 158.1 (C-1), 156.8 (C from Ph), 153.0
3 CF p
(C from Ph), 135.3 (C-10a), 132.0 (C from Ph), 131.2 (C from Ph), 130.4 (C-2), 130.1 (C-6), 129.0
p’ o’ i
(C-9), 128.5 (C from Ph; C-7), 126.9 (C from Ph), 125.4 (C from Ph), 122.5 (C-8), 122.2 (C-6a),
o m m’
122.1 (q, 1J = 284.4 Hz, CF ), 118.1 (C-5; C-10), 118.0 (C from Ph), 115.0 [q, 1J = 291.1 Hz,
CF 3 i’ CF
C(O)CF ], 89.7 (C-13), 80.7 (C-12), 80.4 (C-4a), 75.0 (q, 2J = 31.5 Hz, C-3), 35.3 (C from t-Bu), 35.0
3 CF
(C’ from t-Bu), 31.3 (3Me from t-Bu), 31.2 (3Me’ from t-Bu’) ppm.
19F NMR (376.5 MHz, CDCl ):δ -73.5 [s, C(O)CF ], -75.5 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3d: 1H NMR (400.1 MHz, CDCl ): δ 7.45-7.35 (m, 6H, H from Ph), 7.30 (m, 2H, H
3 o,o’,m m’
from Ph), 7.16 (d, 3J = 7.3 Hz, 1H, H-7), 6.90 (d, 3J = 9.7 Hz, 1H, H-6), 6.87 (m, 1H, H-8), 6.85 (m,
8,9 6,7
1H, H-9), 6.34 (d, 3J = 8.0 Hz, 1H, H-10), 6.10 (dd, 3J = 4.6 Hz, 3J = 9.7 Hz, 1H, H-5), 5.89 (d,
10,11 5a,6 6,7
3J = 4.6 Hz, 1H, H-4a), 1.27 (s, 9H, 3Me from t-Bu), 1.26 (s, 9H, 3Me’ from t-Bu’) ppm.
5a,6
13C NMR (100.6 MHz, CDCl ): δ 185.3 (q, 2J = 35.4 Hz, C-14), 155.9 (C from Ph), 152.8 (C from
3 CF p p’
Ph), 152.6 (C-1), 135.7 (C-10a), 132.1 (C from Ph), 131.5 (C from Ph), 130.4 (C-2), 130.1 (C-6), 129.0
o’ i
(C-9), 128.5 (C from Ph; C-7), 126.9 (C from Ph), 125.5 (C from Ph), 123.3 (q, 1J = 284.4 Hz, CF ),
o m m’ CF 3
122.3 (C-6a), 122.2 (C-8), 118.5 (C from Ph), 117.7 (C-10), 117.6 (C-5), 114.6 [q, 1J = 291.1 Hz,
i’ CF
C(O)CF ], 86.4 (C-13), 81.4 (C-12), 79.8 (q, 4J = 2.6 Hz, C-4a), 73.4 (q, 2J = 31.4 Hz, C-3), 35.2 (C
3 CF CF
from t-Bu), 35.0 (C’ from t-Bu), 31.3 (3Me from t-Bu), 31.2 (3Me’ from t-Bu’) ppm.
19F NMR (376.5 MHz, CDCl ):δ -72.4 [q, 6J = 2.2 Hz, C(O)CF ], -77.2 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 638.2488; found: 638.2462.
37 34 6 2
Found: C, 69.40; H, 5.15; N, 2.08; F, 17.69. Calc. for C H F NO (637.67): C, 69.69; H, 5.22; N, 2.20;
37 33 6 2
F, 17.88.
7 6
6a 5
8
11 4a 4
9 10aN O
10 CF
1 3
i
2 3 12
p o 13i' o'
Cl m O 14 CF3 m'
p' Cl
1-[1-(4-Chlorophenyl)-3-[(4-chlorophenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-
a]quinolin-2-yl]-2,2,2-trifluoroethanone (3e). Analogously, from quinoline 1a (0.0325 g, 0.25 mmol)
and acetylene 2e (0.117 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 24 h) 1,3-oxazinoquinoline 3e was
obtained. Eluent was mixture of hexane/dichloromethane. First fraction, yellow crystals, 0.124 g, mp 197-
199 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 50:50 (19F NMR). Second fraction, yellow
crystals, 0.012 g, mp 190-191 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 100:0. Total yield
0.134 g, 90%, (3S*,4aS*):(3R*,4aS*)-isomers ratio is 55:45 (19F NMR).
(3S*,4aS*)-3e: 1H NMR (400.1 MHz, CDCl ): δ 7.42 (m, 4H, H from Ph), 7.37 (m, 2H, H from Ph),
3 o, o’ m
7.29 (m, 2H, H from Ph), 7.23 (d, 3J = 7.3 Hz, 1H, H-7), 6.97 (d, 1H, H-6), 6.92(m, 1H, H-8), 6.90
m’ 7,8
(m, 1H, H-9), 6.31 (d, 3J = 8.0 Hz, 1H, H-10), 6.17 (dd, 3J = 4.4 Hz, 3J = 9.8 Hz, 1H, H-5), 5.67
9,10 4a,5 5,6
(d, 3J = 4.4 Hz, 1H, H-4a) ppm.
4a,5
13C NMR (100.6 MHz, CDCl ): δ 184.2 (q, 2J = 36.1 Hz, C-14), 156.9 (C-1), 139.2 (C from Ph), 135.5
3 CF p
(C-10a), 135.0 (C from Ph), 133.3 (C from Ph), 132.2 (C from Ph), 131.0 (C-2), 130.3 (C from Ph),
p’ o’ i o,m
S5
130.1 (C-6), 129.1 (C-9), 128.6 (C from Ph), 128.5 (C-7), 122.9 (C-8), 122.1 (C-6a), 121.7 (q, 1J =
m’ CF
286.0 Hz, CF ), 119.1 (C from Ph ), 117.8 (C-10), 117.7 (C-5), 115.2 [q, 1J = 293.8 Hz, C(O)CF ],
3 i’ CF 3
88.4 (C-13), 81.8 (C-12), 79.8 (C-4a), 74.6 (q, 2J = 35.0 Hz, C-3) ppm.
CF
19F NMR (376.3 MHz, CDCl ):δ -73.7 [s, C(O)CF ], -78.6 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3e: 1H NMR (400.1 MHz, CDCl ): δ 7.45 (m, 2H, H from Ph), 7.43 (m, 4H, H from Ph),
3 m o,o’
7.30 (m, 2H, H from Ph), 7.21 (d, 3J = 7.3 Hz, 1H, H-7), 6.97 (d, 1H, H-6), 6.92(m, 1H, H-8), 6.90
m’ 7,8
(m, 1H, H-9), 6.35 (d, 3J = 7.2 Hz, 1H, H-10), 6.11 (dd, 3J = 4.5 Hz, 3J = 9.7 Hz, 1H, H-5), 5.91
9,10 4a,5 5,6
(d, 3J = 4.5 Hz, 1H, H-4a) ppm.
4a,5
13C NMR (100.6 MHz, CDCl ): δ 185.1 (q, 2J = 37.2 Hz, C-14), 151.1 (C-1), 138.4 (C from Ph), 135.8
3 CF p
(C-10a), 134.5 (C from Ph), 133.4 (C from Ph), 132.5 (C from Ph), 131.2 (C-6), 131.1 (C-2), 130.3
p’ o’ i
(C from Ph), 129.0 (C-9), 128.7 (C from Ph), 128.6 (C-7), 123.0 (q, 1J = 289.3 Hz, CF ), 122.5 (C-
o,m m’ CF 3
8), 122.2 (C-6a), 119.6 (C from Ph), 117.4 (C-10), 117.2 (C-5), 114.7 [q, 1J = 293.0 Hz, C(O)CF ],
i’ CF 3
85.1 (C-13), 82.1 (C-12), 80.3 (q, 4J = 2.6 Hz, C-4a), 73.1 (q, 2J = 31.7 Hz, C-3) ppm.
CF CF
19F NMR (376.3 MHz, CDCl ):δ -74.7 [q, 6J = 2.2 Hz, C(O)CF ], -76.9 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H Cl F NO +: 594.0457; found: 594.0461.
29 16 2 6 2
7 6
6a 5
8
11 4a
9 10aN O4
10 CF
1 3
i
2 3 12
p o 13i' o'
Br m O 14 CF3 m'
p' Br
1-[1-(4-Bromophenyl)-3-[(4-bromophenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-
a]quinolin-2-yl]-2,2,2-trifluoroethanone (3f). Analogously, from quinoline 1a (0.039 g, 0.3 mmol) and
acetylene 2f (0.166 g, 0.6 mmol) in 0.3 ml MeCN (20-24 oC, 4 h) 1,3-oxazinoquinoline 3f (0.114 g, 56%)
was obtained as a yellow oil. Eluent was mixture of chloroform/benzene/ethanol. IR (microlayer): 2237
(C≡C), 1712 (C=O), 1655 (C=C), 1204, 1158, 1098 (C-F) cm-1. (3S*,4aS*):(3R*,4aS*)-isomers ratio is
60:40 (1H NMR).
(3S*,4aS*)-3f: 1H NMR (400.1 MHz, CDCl ): δ 7.55 (m, 2H, H from Ph), 7.42 (m, 2H, H from Ph),
3 m m’
7.35-7.27 (m, 4H, H from Ph), 7.20 (m, 1H, H-7), 6.90 (m, 3H, H-6, H-8, H-9), 6.30 (m, 1H, H-10),
o,o’
6.14 (dd, 3J = 4.4 Hz, 3J = 9.6 Hz, 1H, H-5), 5.66 (d, 3J = 4.4 Hz, 1H, H-4a) ppm.
5a,6 6,7 5a,6
13C NMR (100.6 MHz, CDCl ): δ 184.0 (q, 2J = 35.5 Hz, C-14), 157.0 (C-1), 135.1 (C-10a), 133.8 (C
3 CF o’
from Ph), 133.4 (C from Ph), 132.8 (C from Ph), 131.8 (C from Ph), 130.2 (C-6), 129.3 (C-9), 128.7
m i o,m’
(C-7), 128.5 (C-2), 127.9 (C from Ph), 124.3 (C from Ph), 123.2 (C-8), 122.3 (C-6a), 121.8 (q, 1J =
p p’ CF
284.6 Hz, CF ), 119.7 (C from Ph), 118.0 (C-10), 117.8 (C-5), 115.5 [q, 1J = 291.3 Hz, C(O)CF ], 88.7
3 i’ CF 3
(C-13), 82.0 (C-12), 80.0 (C-4a), 75.0 (q, 2J = 31.0 Hz, C-3) ppm.
CF
19F NMR (376.5 MHz, CDCl ):δ -72.2 [s, C(O)CF ], -77.1 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3f: 1H NMR (400.1 MHz, CDCl ): δ 7.55 (m, 2H, H from Ph), 7.42 (m, 2H, H from Ph),
3 m m’
7.35-7.27 (m, 4H, H from Ph), 7.20 (m, 1H, H-7), 6.90 (m, 3H, H-6, H-8, H-9), 6.30 (m, 1H, H-10),
o,o’
6.07 (dd, 3J = 4.4 Hz, 3J = 9.6 Hz, 1H, H-5), 5.86 (d, 3J = 4.4 Hz, 1H, H-4a) ppm.
5a,6 6,7 5a,6
13C NMR (100.6 MHz, CDCl ): δ 185.2 (q, 2J = 36.4 Hz, C-14), 151.3 (C-1), 135.2 (C-10a), 133.6 (C
3 CF o’
from Ph), 133.4 (C from Ph), 133.1 (C from Ph), 131.7 (C from Ph), 131.4 (C from Ph), 130.4 (C-6),
m i m’ o
129.3 (C-9), 128.8 (C-7), 128.5 (C-2), 127.0 (C from Ph), 124.0 (C from Ph), 122.7 (C-8), 122.3 (C-
p p’
6a), 122.2 (q, 1J = 284.2 Hz, CF ), 120.2 (C from Ph), 117.4 (C-10), 117.0 (C-5), 115.0 [q, 1J =
CF 3 i’ CF
290.8 Hz, C(O)CF ], 85.3 (C-13), 82.6 (C-12), 80.5 (q, 4J = 2.0 Hz, C-4a), 73.5 (q, 2J = 31.5 Hz, C-3)
3 CF CF
ppm.
19F NMR (376.5 MHz, CDCl ):δ -73.2 [q, 6J = 2.2 Hz, C(O)CF ], -75.4 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H Br F NO +: 681.9446; found: 681.9415.
29 16 2 6 2
S6
Found: C, 50.69; H, 2.14; N, 1.98; Br, 23.48; F, 16.94. Calc. for C H Br F NO (683.24): C, 50.98; H,
29 15 2 6 2
2.21; N, 2.05; Br, 23.39; F, 16.68.
7 6
6a 5
8
11 4a
9 10aN O4
10 CF
1 3
i
2 3 12
p o 13i' o'
MeO m O 14 CF3 m'
p' OMe
2,2,2-Trifluoro-1-[1-(4-methoxyphenyl)-3-[(4-methoxyphenyl)ethynyl]-3-(trifluoromethyl)-3H,4aH-
[1,3]oxazino[3,2-a]quinolin-2-yl]ethanone (3g). Analogously, from quinoline 1a (0.039 g, 0.3 mmol)
and acetylene 2g (0.137 g, 0.6 mmol) in 0.3 ml MeCN (20-24 oC, 3 h) 1,3-oxazinoquinoline 3g (0.123 g,
74%) was obtained as a bright-yellow oil. Eluent was mixture of chloroform/benzene/ethanol. Initial
acetylene 2g was recovered (0.008 g, conversion was 94%). IR (microlayer): 2232 (C≡C), 1705 (C=O),
1655, 1604 (C=C), 1202, 1177, 1158, 1095 (C-F) cm-1. (3S*,4aS*):(3R*,4aS*)-isomers ratio is 50:50 (1H
NMR).
(3S*,4aS*)-3g: 1H NMR (400.1 MHz, CDCl ): δ 7.45-7.35 (m, 4H, H from Ph), 7.19 (d, 3J = 7.0 Hz,
3 o,o’ 8,9
1H, H-7), 6.95-6.80 (m, 7H, H-6, H-8, H-9, H from Ph), 6.37 (d, 3J = 8.0 Hz, 1H, H-10), 6.14 (dd,
m,m’ 10,11
3J = 4.4 Hz, 3J = 9.6 Hz, 1H, H-5), 5.69 (d, 3J = 4.4 Hz, 1H, H-4a), 3.82 (s, 3H, OMe), 3.76 (s,
5a,6 6,7 5a,6
3H, OMe’) ppm.
13C NMR (100.6 MHz, CDCl ): δ 184.5 (q, 2J = 35.5 Hz, C-14), 163.4 (C from Ph), 160.6 (C from
3 CF p p’
Ph), 158.3 (C-1), 135.3 (C-10a), 133.8 (C from Ph), 132.1 (C from Ph), 130.1 (C-6), 129.0 (C-9), 128.5
o’ o
(C-2; C-7), 126.4 (C from Ph), 122.6 (C-8), 122.2 (C-6a), 120.7 (q, 1J = 284.7 Hz, CF ), 118.1 (C-10),
i CF 3
118.0 (C-5), 115.4 (C from Ph), 115.1 [q, 1J = 291.0 Hz, C(O)CF ], 114.0 (C from Ph), 113.1 (C
m CF 3 m’ i’
from Ph), 89.6 (C-13), 80.7 (C-12), 79.7 (C-4a), 74.8 (q, 2J = 31.2 Hz, C-3), 55.6 (OMe), 55.4 (OMe’)
CF
ppm.
19F NMR (376.5 MHz, CDCl ):δ -72.2 [s, C(O)CF ], -77.4 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3g: 1H NMR (400.1 MHz, CDCl ): δ 7.45-7.35 (m, 4H, H from Ph), 7.15 (d, 3J = 6.8 Hz,
3 o,o’ 8,9
1H, H-7), 6.95-6.80 (m, 7H, H-6, H-8, H-9, H from Ph), 6.37 (d, 3J = 8.0 Hz, 1H, H-10), 6.06 (dd,
m,m’ 10,11
3J = 4.4 Hz, 3J = 9.4 Hz, 1H, H-5), 5.88 (d, 3J = 4.4 Hz, 1H, H-4a), 3.82 (s, 3H, OMe), 3.76 (s,
5a,6 6,7 5a,6
3H, OMe’) ppm.
13C NMR (100.6 MHz, CDCl ): δ 185.4 (q, 2J = 36.2 Hz, C-14), 162.7 (C from Ph), 160.5 (C from
3 CF p p’
Ph), 152.5 (C-1), 135.7 (C-10a), 133.9 (C from Ph), 132.1 (C from Ph), 130.3 (C-6), 129.0 (C-9),
o’ o
128.6 (C-7), 128.5 (C-2), 126.7 (C from Ph), 122.3 (C-6a; C-8), 122.1 (q, 1J = 284.7 Hz, CF ), 117.7
i CF 3
(C-10), 117.6 (C-5), 115.4 (C from Ph), 114.9 [q, 1J = 290.8 Hz, C(O)CF ], 114.1 (C from Ph),
m CF 3 m’
113.6 (C from Ph), 86.2 (C-13), 80.3 (q, 4J = 2.6 Hz, C-4a), 80.1 (C-12), 73.3 (q, 2J = 31.1 Hz, C-3),
i’ CF CF
55.6 (OMe’), 55.4 (OMe) ppm.
19F NMR (376.5 MHz, CDCl ):δ -73.4 [q, 6J = 2.2 Hz, C(O)CF ], -75.5 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 586.1448; found: 586.1423.
31 22 6 4
Found: C, 63.30; H, 3.48; N, 2.68; F, 19.13. Calc. for C H F NO (585.50): C, 63.59; H, 3.62; N, 2.39;
31 21 6 4
F, 19.47.
S7
7 6
6a 5
8
11 4a
9 10aN O4
10 CF
1 3
i
2 3 12
p o 13i' o'
MeS m O 14 CF3 m'
p' SMe
2,2,2-Trifluoro-1-[1-[4-(methylthio)phenyl]-3-{[4-(methylthio)phenyl]ethynyl}-3-(trifluoromethyl)-
3H,4aH-[1,3]oxazino[3,2-a]quinolin-2-yl]ethanone (3h). Analogously, from quinoline 1a (0.0325 g,
0.25 mmol) and acetylene 2h (0.122 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 24 h) 1,3-oxazinoquinoline
3h was obtained. Eluent was mixture of hexane/dichloromethane. First fraction, yellow-brown crystals,
0.012 g, mp 88-90 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 13:87 (19F NMR). Second
fraction, yellow-brown crystals, 0.118 g, mp 131-133 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is
50:50. Total yield 0.130 g, 84%, (3S*,4aS*):(3R*,4aS*)-isomers ratio is 45:55 (19F NMR).
(3S*,4aS*)-3h: 1H NMR (400.1 MHz, CDCl ): δ 7.44 (m, 2H, H from Ph), 7.38 (m, 2H, H from Ph),
3 o o’
7.25 (m, 2H, H from Ph), 7.21 (m, 1H, H-7), 7.16 (m, 2H, H from Ph), 6.96 (m, 1H, H-6), 6.93 (m, 1H,
m m’
H-8), 6.89 (m, 1H, H-9), 6.42 (d, 3J = 8.2 Hz, 1H, H-10), 6.19 (dd, 3J = 4.6 Hz, 3J = 10.2 Hz, 1H,
9,10 4a,5 5,6
H-5), 5.73 (d, 3J = 4.6 Hz, 1H, H-4a), 2.51 (s, 3H, SMe), 2.46 (s, 3H, SMe’) ppm.
4a,5
13C NMR (100.6 MHz, CDCl ): δ 184.2 (q, 2J = 36.5 Hz, C-14), 157.9 (C-1), 145.9 (C from Ph), 141.1
3 CF p
(C from Ph), 134.9 (C-10a), 132.4 (C from Ph), 132.3 (C from Ph), 130.2 (C from Ph), 130.1
p’ o’ m m’
(Cfrom Ph), 130.0 (C-2), 129.9 (C-6), 128.9 (C-9, C from Ph), 128.4 (C-7), 126.1 (C-8), 122.6 (C-6a),
i o
121.8 (q, 1J = 286.8 Hz, CF ), 117.8 (C-5, C-10), 116.7 (C from Ph), 114.8 [q, 1J = 293.4 Hz,
CF 3 i’ CF
C(O)CF ], 89.2 (C-13), 81.6 (C-12), 79.7 (C-4a), 74.8 (q, 2J = 34.6 Hz, C-3), 15.0 (SMe), 14.6 (SMe’)
3 CF
ppm.
19F NMR (376.3 MHz, CDCl ):δ -73.6 [s, C(O)CF ], -78.7 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3h: 1H NMR (400.1 MHz, CDCl ): δ 7.44 (m, 2H, H from Ph), 7.40 (m, 2H, H from Ph),
3 o o’
7.25 (m, 2H, H from Ph), 7.23 (m, 1H, H-7), 7.18 (m, 2H, H from Ph), 6.96 (m, 1H, H-6), 6.93 (m, 1H,
m m’
H-8), 6.89 (m, 1H, H-9), 6.42 (d, 3J = 8.4 Hz, 1H, H-10), 6.11 (dd, 3J = 4.7 Hz, 3J = 10.1 Hz, 1H,
9,10 4a,5 5,6
H-5), 5.92 (d, 3J = 4.7 Hz, 1H, H-4a), 2.20 (s, 3H, SMe), 2.46 (s, 3H, SMe’) ppm.
4a,5
13C NMR (100.6 MHz, CDCl ): δ 185.1 (q, 2J = 37.6 Hz, C-14), 152.0 (C-1), 144.7 (C from Ph), 140.8
3 CF p
(C from Ph), 135.3 (C-10a), 132.4 (C from Ph), 130.2 (C from Ph), 129.9 (C-2, C-6), 129.7 (C
i’,p’ m,o’ m’ i
from Ph), 128.9 (C-9, C from Ph), 128.5 (C-7), 125.4 (C-8), 123.0 (q, 1J = 289.3 Hz, CF ), 122.2 (C-
o CF 3
6a), 117.3 (C-5, C-10), 114.4 [q, 1J = 293.0 Hz, C(O)CF ], 85.8 (C-13), 81.0 (C-12), 80.2 (q, 4J = 2.6
CF 3 CF
Hz, C-4a), 74.8 (q, 2J = 31.3 Hz, C-3), 15.0 (SMe), 14.6 (SMe’) ppm.
CF
19F NMR (376.3 MHz, CDCl ):δ -74.7 [q, 6J = 2.2 Hz, C(O)CF ], -76.9 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO S +: 618.0991; found: 618.0990.
31 22 6 2 2
7 6
6a 5 Me
8
11 4a 4
9 10aN O
10 CF
1 3
i
2 3 12
p o 13i' o'
MeO m O 14 CF3 m'
p' OMe
2,2,2-Trifluoro-1-[1-(4-methoxyphenyl)-3-[(4-methoxyphenyl)ethynyl]-5-methyl-3-
(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-2-yl]ethanone (3i). Analogously, from
quinoline 1b (0.021 g, 0.15 mmol) and acetylene 2g (0.068 g, 0.3 mmol) (20-24 oC, 6 h) 1,3-
S8
oxazinoquinoline 3i (0.072 g, 80%) was obtained as a yellow oil. Eluent was mixture of
chloroform/benzene/ethanol. Initial acetylene 2g was recovered (0.009 g, conversion was 87%). IR
(microlayer): 2231 (C≡C), br 1694 (C=O), 1604 (C=C), 1177, 1074 (C-F) cm-1. (3S*,4aS*):(3R*,4aS*)-
isomers ratio is 75:25 (1H NMR).
(3S*,4aS*)-3i: 1H NMR (400.1 MHz, CDCl ): δ 7.39 (m, 4H, H from Ph), 7.12 (d, 3J = 7.0 Hz, 1H,
3 o,o’ 8,9
H-7), 6.95-6.75 (m, 6H, H-8, H-9, H from Ph), 6.63 (s, 1H, H-6), 6.32 (d, 3J = 8.0 Hz, 1H, H-10),
m,m’ 10,11
5.46 (s, 1H, H-4a), 3.84 (s, 3H, OMe), 3.79 (s, 3H, OMe’), 2.17 (s, 3H, Me) ppm.
13C NMR (100.6 MHz, CDCl ): δ 184.4 (q, 2J = 35.3 Hz, C-14), 163.4 (C from Ph), 160.6 (C from
3 CF p p’
Ph), 158.2 (C-1), 134.1 (C-10a), 133.8 (C from Ph), 132.2 (C from Ph), 128.5 (C-2; C-9), 127.8 (C-7),
o’ o
127.6 (C-5), 127.5 (C from Ph), 125.7 (C-6), 123.2 (C-8), 122.7 (C-6a), 120.4 (q, 1J = 284.4 Hz, CF ),
i CF 3
117.8 (C-10), 115.4 (C from Ph), 114.9 [q, 1J = 290.7 Hz, C(O)CF ], 114.1 (C from Ph), 113.3 (C
m CF 3 m’ i’
from Ph), 89.3 (C-13), 83.5 (C-4a), 80.2 (C-12), 74.7 (q, 2J = 31.0 Hz, C-3), 55.7 (OMe), 55.5 (OMe’),
CF
19.4 (Me) ppm.
19F NMR (376.5 MHz, CDCl ): δ -72.0 [s, C(O)CF ], -77.2 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3i: 1H NMR (400.1 MHz, CDCl ): δ 7.39 (m, 4H, H from Ph), 7.09 (d, 3J = 7.0 Hz, 1H,
3 o,o’ 8,9
H-7), 6.95-6.75 (m, 6H, H-8, H-9, H from Ph), 6.61 (s, 1H, H-6), 6.32 (d, 3J = 8.0 Hz, 1H, H-10),
m,m’ 10,11
5.70 (s, 1H, H-4a), 3.84 (s, 3H, OMe), 3.78 (s, 3H, OMe’), 2.13 (s, 3H, Me) ppm.
The signals of (3R*,4aS*)-3n in the 13C NMR spectrum are overlapped with those of the major isomer.
19F NMR (376.5 MHz, CDCl ):δ -73.4 [q, 6J = 2.2 Hz, C(O)CF ], -75.2 (q, 6J = 2.2 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 600.1604; found: 600.1582.
32 24 6 4
Found: C, 63.82; H, 3.85; N, 2.27; F, 18.74. Calc. for C H F NO (599.53): C, 64.11; H, 3.87; N, 2.34;
32 23 6 4
F, 19.01.
7 6
6a
8 5
11 4a 4
9 10aN O
Me 10 1 CF3
i
2 3 12
13
p o i' o'
m O 14 CF3 m'
p'
2,2,2-Trifluoro-1-[10-methyl-1-phenyl-3-(phenylethynyl)-3-(trifluoromethyl)-3H,4aH-
[1,3]oxazino[3,2-a]quinolin-2-yl]ethanone (3j). Analogously, from quinoline 1e (0.036 g, 0.25 mmol)
and acetylene 2a (0.099 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 204 h) 1,3-oxazinoquinoline 3j was
obtained as pale yellow crystals, 0.074 g, 87%, mp 177-179 °C (hexane). Eluent was mixture of
hexane/dichloromethane. Mixture of three isomers, ratio is 26:53:21 (19F NMR). Initial acetylene 2a was
recovered (0.037 g, conversion was 62%).
H
H
H
N O
N O
CF N O
Me 3 CF
Me 3 CF
Me 3
Ph
O CF
3 O CF
3 O CF
3
Ph
(3S*,4aS*)-diastereomer, (3S*,4aS*)-diastereomer, (3R*,4aS*)-diastereomer
atropomerA atropomerB
(3S*,4aS*)-3j(A): 1H NMR (400.1 MHz, CDCl ): δ 7.47 (m, 2H, H from Ph), 7.40-7.30 (m, 8H,
3 o
H from Ph), 7.01 (m, 1H, H-7), 6.99 (m, 1H, H-8), 6.81 (dd, 3J = 9.4 Hz, 1H, H-6), 6.72 (m,
o’,m,m’,p,p’ 5,6
1H, H-9), 6.18 (dd, 3J = 4.1 Hz, 3J = 9.0 Hz, 1H, H-5), 5.73 (d, 3J = 4.1 Hz, 1H, H-4a), 1.87 (s,
4a,5 5,6 4a,5
3H, Me) ppm.
S9
13C NMR (100.6 MHz, CDCl ): δ 183.2 (q, 2J = 35.8 Hz, C-14), 157.2 (C-1), 134.6 (C-10a), 133.1 (C
3 CF p
from Ph), 133.0 (C from Ph), 132.1 (C from Ph), 132.0 (C-9), 130.9 (C from Ph), 130.1 (C-6), 129.7
i o’ m’
(C-2), 129.5 (C from Ph), 128.2 (C from Ph), 126.7 (C from Ph), 125.3 (C-10), 124.4 (C-7), 123.3 (C-
p’ m o
8), 122.5 (q, 1J = 291.2 Hz, CF ), 122.4 (C-6a), 120.7 (C from Ph), 117.6 (C-5), 115.0 [q, 1J = 292.7
CF 3 i’ CF
Hz, C(O)CF ], 88.9 (C-13), 81.1 (C-4a), 80.6 (C-12), 74.8 (q, 2J = 34.3 Hz, C-3), 21.2 (Me) ppm.
3 CF
19F NMR (376.3 MHz, CDCl ):δ -73.4 [s, C(O)CF ], -75.3 (s, CF ) ppm.
3 3 3
(3S*,4aS*)-3j(B): 1H NMR (400.1 MHz, CDCl ): δ 7.30 (m, 2H, H from Ph), 7.40-7.30 (m, 6H, H
3 o o’,m’,p,p’
from Ph), 7.10 (t, 3J = 7.1 Hz, 3J = 7.1 Hz, 1H, H-8), 7.01 (m, 1H, H-7), 6.92 (m, 2H, H from Ph),
7,8 8,9 m
6.71 (m, 1H, H-6), 6.61 (d, 3J = 7.1 Hz, 1H, H-9), 6.14 (dd, 3J = 4.3 Hz, 3J = 9.9 Hz, 1H, H-5),
8,9 4a,5 5,6
5.73 (d, 3J = 4.3 Hz, 1H, H-4a), 1.67 (s, 3H, Me) ppm.
4a,5
13C NMR (100.6 MHz, CDCl ): δ 185.0 (q, 2J = 36.5 Hz, C-14), 161.2 (C-1), 134.8 (C-10a), 133.5 (C
3 CF p
from Ph), 133.4 (C from Ph), 132.1 (C from Ph, C-9), 130.8 (C from Ph), 129.9 (C-6), 129.5 (C-2),
i o’ m’
129.1 (C from Ph), 128.3 (C from Ph), 126.2 (C from Ph), 126.1 (C-10), 124.4 (C-7), 123.3 (C-8),
p’ m o
122.8 (q, 1J = 187.7 Hz, CF ), 122.4 (C-6a), 120.7 (C from Ph), 117.6 (C-5), 114.7 [q, 1J = 291.9 Hz,
CF 3 i’ CF
C(O)CF ], 89.7 (C-13), 81.4 (C-4a), 81.1 (C-12), 74.3 (q, 2J = 32.8 Hz, C-3), 20.8 (Me) ppm.
3 CF
19F NMR (376.3 MHz, CDCl ):δ -73.4 [s, C(O)CF ], -76.8 (s, CF ) ppm.
3 3 3
(3R*,4aS*)-3j: 1H NMR (400.1 MHz, CDCl ): δ 7.47 (m, 2H, H from Ph), 7.40-7.30 (m, 8H, H
3 o o’,m,m’,p,p’
from Ph), 7.10 (t, 3J = 8.0 Hz, 3J = 8.0 Hz, 1H, H-8), 7.01 (m, 1H, H-7), 6.71 (m, 1H, H-6), 6.60 (d,
7,8 8,9
3J = 8.0 Hz, 1H, H-9), 6.38 (dd, 3J = 1.3 Hz, 3J = 9.4 Hz, 1H, H-5), 5.81 (br s, 1H, H-4a), 1.72 (s,
8,9 4a,5 5,6
3H, Me) ppm.
13C NMR (100.6 MHz, CDCl ): δ 185.3 (q, 2J = 36.5 Hz, C-14), 151.9 (C-1), 134.3 (C-10a), 133.9 (C
3 CF i
from Ph), 132.9 (C from Ph), 132.1 (C from Ph), 131.9 (C-9), 130.9 (C from Ph), 130.3 (C-6), 129.3
p o’ m’
(C-2), 129.2 (C from Ph), 128.2 (C from Ph), 127.5 (C from Ph), 125.8 (C-10), 124.4 (C-7), 123.6 (C-
p’ m o
6a), 123.4 (C-8), 122.9 (q, 1J = 285.6 Hz, CF ), 120.7 (C from Ph), 117.7 (C-5), 115.3 [q, 1J = 285.6
CF 3 i’ CF
Hz, C(O)CF ], 85.9 (C-13), 81.9 (C-12), 80.6 (C-4a), 73.3 (q, 2J = 35.0 Hz, C-3), 18.3 (Me) ppm.
3 CF
19F NMR (376.3 MHz, CDCl ):δ -74.5 [q, 6J = 2.0 Hz, C(O)CF ], -76.4 (q, 6J = 2.0 Hz, CF ) ppm.
3 F,F 3 F,F 3
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C H F NO +: 540.1393; found: 540.1393.
30 20 6 2
CN
7 6
6a
8 5
11 4a
9 10aN O4
10 CF
1 3
i
2 3 12
13
p o i' o'
m O 14 CF3 m'
p'
1-Phenyl-3-(phenylethynyl)-2-(trifluoroacetyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-
a]quinoline-7-carbonitrile (3k). Analogously, from quinoline 1d (0.0385 g, 0.25 mmol) and acetylene
2a (0.099 g, 0.5 mmol) in 0.2 ml MeCN (20-24 oC, 24 h) 1,3-oxazinoquinoline 3k was obtained as pale
yellow crystals, 0.124 g, 90%, mp 107-109 °C (hexane), (3S*,4aS*):(3R*,4aS*)-isomers ratio is 41:59
(19F NMR). Eluent was mixture of hexane/dichloromethane.
(3S*,4aS*)-3k: 1H NMR (400.1 MHz, CDCl ): δ 7.60-7.30 (m, 11H, H from Ph, H-8), 7.24 (d,
3 o,o’,m,m’,p,p’
3J = 7.6 Hz, 1H, H-6), 6.95 (t, 3J = 8.1 Hz, 3J = 8.1 Hz, 1H, H-9), 6.60 (d, 3J = 8.1 Hz, 1H, H-
5,6 8,9 9,10 9,10
10), 6.43 (dd, 3J = 10.0 Hz, 3J = 4.4 Hz, 1H, H-5), 5.79 (d, 3J = 4.4 Hz, 1H, H-4a) ppm.
5,6 4a,5 4a,5
13C NMR (100.6 MHz, CDCl ): δ 184.4 (q, 2J = 36.7 Hz, C-14), 156.0 (C-1), 135.6 (C-10a), 133.0 (C
3 CF p
from Ph), 132.8 (C from Ph), 132.0 (C from Ph), 130.1 (C from Ph), 129.8 (C-2), 129.5 (C-9), 128.9
i o’ o,m
(C from Ph), 128.2 (C from Ph), 126.4 (C-8), 126.1 (C-6), 123.8 (C-6a), 121.7 (q, 1J = 286.0 Hz,
p’ m’ CF
CF ), 121.4 (C-5, C-10), 120.9 (C from Ph), 116.6 (CN), 115.0 [q, 1J = 293.4 Hz, C(O)CF ], 111.0 (C-
3 i’ CF 3
7), 90.2 (C-13), 80.7 (C-12), 79.1 (C-4a), 74.8 (q, 2J = 34.8 Hz, C-3) ppm.
CF
19F NMR (376.3 MHz, CDCl ):δ -74.1 [s, C(O)CF ], -78.6 (s, CF ) ppm.
3 3 3
S10