12396
J.-C. Legeay et al. / Tetrahedron 61 (2005) 12386–12397
ethyl 3-aminocrotonate 10b (188 mg, 1.45 mmol, 1 equiv)
and 5,5-dimethyl-1,3-cyclohexanedione 15 (204 mg,
4.7.3. Methyl 4-[4-(methoxycarbonyl)phenyl]-2,7,7-tri-
methyl-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carb-
oxylate (17a). The product 17a was prepared from 1-[2-[4-
[3-(methoxycarbonyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinolin-4-yl]benzoyloxy]ethyl]pyridinium hexa-
fluorophosphate (16a) according to the experimental
procedure used for the preparation of 12a. YieldZ85%.
Yellow needles. MpZ228–230 8C. IR (KBr): 1227, 1282,
1
.45 mmol, 1 equiv) was placed in a cylindrical quartz
reactor (ØZ1.8 cm). Then, the reactor was then introduced
into a Synthewave 402 Prolabo microwave reactor. The
w
stirred mixture was stirred mechanically and was irradiated
at 120 8C (Power level: 50%, 150 W) for 10 min. After
microwave dielectric heating, the crude reaction mixture
was allowed to cool down at room temperature and acetone
K1
1
1489, 1600, 1647, 1687, 1719, 2952, 3078, 3204 cm . H
NMR (CDCl , 300 MHz) dZ0.83 (s, 3H, gem-CH3), 1.00
(
10 ml) was added in the cylindrical quartz reactor. The
3
resulting solution was concentrated by rotary evaporation
under reduced pressure. The desired 3,4-DHP 11 was
purified by washing with diethylether (2!10 ml) or flash
chromatography (column: ØZ1 cm, HZ4 cm) on neutral
alumina oxide 90 gel (Merck) with CH Cl –MeOH (9/1) as
(s, 3H, gem-CH3), 2.06–2.27 (m, 4H, H-8, H-6), 2.32 (s, 3H,
CH ), 3.58 (s, 3H, CO CH ), 3.85 (s, 3H, OCH ), 5.10 (s,
3
2
3
3
0
0
1H, H-4), 7.37 (d, 2H, JZ8.2 Hz, H-2 , H-6 ), 7.54 (br s,
0
0
13
1H, NH), 7.87 (d, 2H, JZ8.2 Hz, H-3 , H-6 ); C NMR
(CDCl , 75 MHz) dZ19.18 (CH ), 26.91–29.57 (gem-
CH3), 32.65 (C-7), 36.91 (C-4), 40.66 (C-8), 50.78 (C-6),
2
2
3
3
eluent. The expected compounds 16(a,b) were further dried
under high vacuum (10 Torr) at 25 8C for 3 h. The pure
K2
51.09 (OCH ), 52.08 (OCH ), 104.84 (C-3), 111.08 (C-4a),
3
3
1 13
products 16(a,b) were characterized by H, C NMR, IR
and HRMS.
0
0
0
0
0
145.03 (C-1 ), 149.82 (C-2), 152.51 (C-8a), 167.46 (ArCO),
127.82 (C-4 ), 128.02 (C-2 , C-6 ), 129.49 (C-3 , C-6 ),
0
67.77 (CO), 195.83 (CO, C-5). HRMS, m/z: 383.1744
1
C
4.7.1. 1-[2-[4-[(3-(Methoxycarbonyl)-2,7,7-trimethyl-5-
oxo-1,4,5,6,7,8-hexahydroquinolin-4-yl]benzoyloxy]
found (calculated for C22H25NO , M requires 383.1733).
5
ethyl]pyridinium hexafluorophosphate (16a). YieldZ
4.7.4. Ethyl 4-[4-(methoxycarbonyl)phenyl]-2,7,7-tri-
methyl-5-oxo-1,4,5,6,7,8-hexahydroquinolin-3-carb-
oxylate (17b). The product 17a was prepared from 1-[2-[4-
[3-(ethoxycarbonyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
hydroquinolin-4-yl]benzoyloxy]ethyl]pyridinium hexa-
fluorophosphate (16b) according to the experimental
procedure used for the preparation of 12a. YieldZ80%.
Yellow viscous oil. IR (KBr): 1220, 1280, 1487, 1605,
1
9
7%. Viscous oil. H NMR ((CD ) CO, 300 MHz) dZ
3
2
0
(
.86 (s, 3H, gem-CH ), 1.05 (s, 3H, gem-CH ), 2.09–2.53
3
3
00 00
m, 4H, H-8 , H-6 ), 2.38 (s, 3H, CH ), 3.56 (s, 3H, OCH ),
3 3
00
.92 (m, 2H, NCH ), 5.07 (s, 1H, H-4 ), 5.31 (t, 2H, JZ
2
4
4
2
0
0
.9 Hz, OCH ), 7.38 (d, 2H, JZ8.3 Hz, H-3 , H-5 ), 7.79 (d,
2
0
0
H, JZ8.3 Hz, H-2 , H-6 ), 8.21 (br s, 1H, NH), 8.32 (t, 2H,
JZ7.0 Hz, H-3, H-5), 8.78 (t, 1H, JZ7.8 Hz, H-4), 9.32 (d,
1
3
K1 1
2
H, JZ5.6 Hz, H-2, H-6); C NMR ((CD ) CO, 75 MHz)
1648, 1700, 1721, 2954, 3074, 3194, 3294 cm . H NMR
(CDCl , 300 MHz) dZ0.83 (s, 3H, gem-CH3), 1.00 (s, 3H,
3
2
dZ19.89 (CH ), 26.95 (gem-CH ), 29.60 (gem-CH ), 32.99
3
3
3
3
0
0
0
0
00
00
C-6 ), 61.72 (OCH ), 63.88 (NCH ), 104.35 (C-3 ), 111.15
(
(
(
C-7 ), 37.73 (C-4 ), 40.69 (C-8 ), 51.02 (OCH ), 51.24
gem-CH3), 1.15 (t, 3H, JZ7.1 Hz, CH ), 2.04–2.26 (m, 4H,
3
3
00
2
2
H-8, H-6), 2.31 (s, 3H, CH ), 3.84 (s, 3H, OCH ), 4.02 (q,
3
3
0
0
0
0
0
C-4a ), 127.57 (C-1 ), 128.98 (C-3 , C-6 ), 129.47 (C-3,
2H, JZ7.1 Hz, OCH ), 5.08 (s, 1H, H-4), 7.37 (d, 2H, JZ
2
0
47.43 (C-2, C-6), 150.26 (C-2 ), 154.45 (C-8a ), 166.13
0
0
0 0
8.2 Hz, H-2 , H-6 ), 7.50 (br s, 1H, NH), 7.86 (d, 2H, JZ
13
C-5), 130.05 (C-2 , C-6 ), 146.34 (C-4), 146.50 (C-4 ),
1
00
00
ArCO), 168.07 (CO), 195.03 (CO, C-5 ). HRMS, m/z:
0
0
8.2 Hz, H-3 , H-5 ); C NMR (CDCl , 75 MHz) dZ14.26
3
0
0
(
4
(CH ), 19.12 (CH ), 26.91–29.55 (gem-CH3), 32.62 (C-7),
37.10 (C-4), 40.65 (C-8), 50.75 (C-6), 51.04 (OCH ), 59.90
3
3
C
75.2227 found (calculated for C H N O , C requires
2
8
31
2
5
3
0
C-2 , C-6 ), 129.37 (C-3 , C-5 ), 144.73 (C-1 ), 149.74
4
75.2223).
(OCH ), 105.10 (C-3), 111.12 (C-4a), 127.74 (C-4 ), 128.20
2
(
0
(C-2), 152.68 (C-8a), 167.31 (CO), 167.46 (ArCO), 195.77
0
0
0
0
4.7.2. 1-[2-[4-[3-(Ethoxycarbonyl)-2,7,7-trimethyl-5-
oxo-1,4,5,6,7,8-hexahydroquinolin-4-yl]benzoyloxy]
ethyl]pyridinium hexafluorophosphate (16b). YieldZ
(CO, C-5). HRMS, m/z: 397.1880 found (calculated for
C
C
, M requires 397.1889).
H27NO
23
5
9
2
3
0%. Viscous oil. IR (KBr): 1220, 1273, 1488, 1717,
872, 2958, 3069, 3285 cm
K1
1
.
H NMR ((CD ) CO,
3 2
00 MHz) dZ0.87 (s, 3H, gem-CH ), 1.05 (s, 3H, gem-
3
Acknowledgements
CH ), 1.15 (t, 3H, JZ7.0 Hz, CH ), 2.09–2.53 (m, 4H,
3
3
0
OCH ), 4.91 (m, 2H, NCH ), 5.07 (s, 1H, H-4 ), 5.31 (t, 2H,
0
00
H-8 , H-6 ), 2.38 (s, 3H, CH ), 4.01 (q, 2H, JZ7.0 Hz,
One of us (J.C.L.) wishes to thank the ‘Ministere de la
`
´
3
00
2
2
Recherche et de l’Enseignement Superieur’ for a research
fellowship. We also thank Professor Jack Hamelin for
0
0
JZ4.9 Hz, OCH ), 7.40 (d, 2H, JZ8.3 Hz, H-3 , H-5 ), 7.80
d, 2H, JZ8.3 Hz, H-2 , H-6 ), 8.22 (br s, 1H, NH), 8.32 (t,
H, JZ7.2 Hz, H-3, H-5), 8.78 (t, 1H, JZ7.8 Hz, H-4), 9.32
2
0
0
(
2
(
fruitful discussions, Dr. Pierre Guenot (CRMPO) for the
´
mass spectrometry measurements and Merck Eurolab
1
3
w
Prolabo (Fr.) for providing the Synthewave 402 apparatus.
d, 2H, JZ5.6 Hz, H-2, H-6); C NMR ((CD ) CO,
3 2
7
5 MHz) dZ14.45 (CH ), 18.88 (CH ), 26.85–29.48
3 3
00
00
00
(
gem-CH ), 32.83 (C-7 ), 37.76 (C-4 ), 40.64 (C-8 ),
3
00
1.04 (C-6 ), 60.06 (OCH ), 61.34 (OCH ), 63.76
2 2
5
0
0
00
0
(
NCH ), 104.55 (C-3 ), 110.75 (C-4a ), 127.32 (C-1 ),
2
References and notes
0
45.95 (C-4), 146.46 (C-4 ), 147.17 (C-2, C-6), 150.85
0
0
0
1
1
28.99 (C-3 , C-5 ), 129.18 (C-3, C-5), 129.87 (C-2 , C-6 ),
0
1. Sucholeiki I. in High-Throughput Synthesis. Principles and
Practises; Marcel Dekker: New York, 2001.
2. Zaragoza D o¨ rwald F. in Organic Synthesis on Solid Phase;
Wiley-VCH: Weinheim, 2000.
0
95.54 (CO, C-5 ). HRMS, m/z: 489.2386 found (calculated
0
00
(
C-2 ), 154.38 (C-8a ), 166.00 (ArCO), 167.70 (CO),
0
for C H N O , C requires 489.2390).
0
1
C
2
9 33 2 5