Cross-Diels-Alder Reactions of 2-Pyridones
In the case of Danishefsky’s diene 4f (95 µL, 0.5 mmol) and
pyridone 1b (62 mg, 0.2 mmol), the purification was as follows:
After decompression, the solvent was evaporated under reduced
pressure, and the excess diene was eliminated by bulb-to-bulb
distillation under reduced pressure (50 °C/0.1 bar). The residue was
then stirred overnight in methanol (2 mL) in the presence of silica
(100 mg) to hydrolyze the silyl enol ether moiety. After filtration
on celite and concentration under reduced pressure, the oily material
was purified by flash chromatography on silica (cyclohexane/ethyl
acetate 2:1 followed by 1:1) to sequentially give 16p (34 mg, 42%),
17p (15 mg, 19%), and 19p (15 mg, 13%).
55.94; H, 6.43; N, 2.42; S, 5.53. Found: C, 55.74; H, 6.59; N,
2.41; S, 5.31.
Representative Procedure for Cycloadditions under Lewis
Acid Activation. To a stirring solution of pyridone 1b (307 mg, 1
mmol) in dry toluene (3 mL) placed in a pressure tube was added
a 1 M solution of diethylzinc in diethyl ether (100 µL, 0.1 mmol)
under inert atmosphere. The mixture was stirred for 1 h at room
temperature, and freshly distilled dimethylbutadiene (564 µL, 5
mmol) was added. The resultant solution was heated at 140 °C for
72 h. After evaporation of the volatiles, the residue was purified
by flash chromatography on silica (cyclohexane/ethyl acetate 5:1)
to yield 10a (194 mg, 50%).3
Representative Procedures for cycloaddition Reactions under
Microwave Activation. To a stirring solution of pyridone 1b (154
mg, 0.5 mmol) in dry THF (1 mL) was added freshly distilled
cyclopentadiene (206 µL, 2.5 mmol). The solution was submitted
to microwave irradiation in a sealed tube at 130 °C for 1 h. The
resultant mixture was concentrated under reduced pressure, and the
residue was purified by flash chromatography on silica (cyclo-
hexane/ethyl acetate 2:1) to give 12d (111 mg, 60%).
Methyl 8-Aza-9-[(4-methylphenyl)sulfonyl]-9-oxo-tricyclo-
[51.7.21.7.21.7.02.6]undec-3,10-diene-11-carboxylate (12d). Colorless
solid (mp 160 °C). 1H NMR δ 1.82 (m, 1H), 2.40 (s, 3H), 2.42 (m,
1H), 3.13 (m, 1H), 3.35 (m, 1H), 3.59 (dd, 1H, J ) 6.4, 2.6 Hz),
3.80 (s, 3H), 5.40 (m, 1H), 5.58 (m, 1H), 5.84 (m, 1H), 7.02 (dd,
1H, J ) 6.4, 2.3 Hz), 7.27 (d, 2H, J ) 8.3 Hz), 7.82 (d, 2H, J )
8.3 Hz). 13C NMR δ 21.6, 35.3, 42.0, 48.1, 50.4, 52.3, 56.5, 127.9
(2C), 129.0, 129.5 (2C), 133.5, 134.4, 135.5, 141.3, 145.1, 163.5,
169.6. IR (KBr) ν 3098, 3053, 2947, 2921, 2860, 1717, 1542, 1438,
1368, 1287, 1264, 1236, 1181, 1089, 1021, 918, 731 cm-1. MS
(CI, C4H10) m/z (relative intensity) 374 (100) [M + H]+, 273 (75).
HRMS. Calcd for C19H20NO5S: (MH+) 374.1062. Found: 374.1075.
The same compound was also obtained under high-pressure
activation, following the above representative procedure. The
residue was purified by flash chromatography on silica (CH2Cl2/
ethyl acetate 99.5/0.5) to yield 12d (60 mg, 80%).
(4aR*,5R*,8aS*)-Methyl5-Methoxy-2,7-dioxo-1-[(4-methylphen-
yl)sulfonyl]-1,2,4a,5,6,7,8,8a-octahydroquinoline-4a-carboxylate
1
(16p). Colorless solid (mp 199-201 °C). H NMR δ 2.24-2.33
(m, 1H), 2.41 (s, 3H), 2.60 (dd, 1H, J ) 15.1, 12.1 Hz), 2.84-
2.93 (m, 2H), 3.35 (s, 3H), 3.65 (s, 3H), 3.98 (dd, 1H, J ) 12.1,
4.3 Hz), 5.22 (ddd, 1H, J ) 11.7, 5.7, 1.9 Hz), 6.18 (d, 1H, J )
9.8 Hz), 6.96 (dd, 1H, J ) 9.8, 1.9 Hz), 7.30 (d, 2H, J ) 8.3 Hz),
7.87 (d, 2H, J ) 8.3 Hz). 13C NMR δ 21.6, 42.4, 44.5, 53.6, 54.6,
55.8, 57.7, 78.3, 127.6, 129.0 (2C), 129.3 (2C), 135.5, 139.5, 145.3,
160.6, 171.5, 201.6. IR (KBr) ν 3058, 2952, 2840, 1731, 1695,
1597, 1434, 1381, 1353, 1242, 1169, 1094, 1029, 984, 917, 822,
735, 663 cm-1. MS (EI) m/z (relative intensity) 343 (85), 311 (65),
244 (100), 91 (95). Anal. Calcd for C19H21NO7S: C, 56.01; H,
5.20; N, 3.44; S, 7.87. Found: C, 56.05; H, 5.34; N, 3.48; S, 7.78.
(4aR*,5S*,8aS*)-Methyl 5-Methoxy-2,7-dioxo-1-[(4-methylphen-
yl)sulfonyl]-1,2,4a,5,6,7,8,8a-octahydroquinoline-4a-carboxylate
(17p). Colorless solid (mp 214-216 °C). 1H NMR δ 2.42 (s, 3H),
2.35-2.50 (m, 1H), 2.55 (dd, 1H, J ) 14.7, 11.3 Hz), 2.84 (ddd,
1H, J ) 15.0, 3.8, 2.3 Hz), 3.05 (ddd, 1H, J ) 14.7, 6.4, 2.3 Hz),
3.33 (s, 3H), 3.74 (s. 3H), 4.25 (dd, 1H, J ) 3.8, 2.3 Hz), 5.75
(ddd, 1H, J ) 11.3, 6.4, 1.9 Hz), 6.05 (d, 1H, J ) 9.8 Hz), 6.53
(dd, 1H, J ) 9.8, 1.9 Hz), 7.31 (d, 2H, 8.3), 8.04 (d, 2H, J ) 8.3
Hz). 13C NMR δ 21.6, 39.6, 44.6, 52.3, 53.0, 54.1, 56.9, 81.2, 126.7,
129.0 (2C), 129.5 (2C), 135.6, 139.6, 145.3, 160.1, 168.8, 202.3.
IR (KBr) ν 3058, 2963, 2931, 1732, 1687, 1389, 1345, 1258, 1238,
1168, 1088, 907, 732 cm-1. MS (CI, C4H10) m/z (relative intensity)
408 (100) [M + H]+. HRMS. Calcd for C19H22NO7S: (MH+)
408.1117. Found: 408.1108.
Acknowledgment. We are indebted to Drs. P. George and
M. Sevrin (Sanofi-Aventis R&D) for fruitful discussions and
suggestions. We warmly thank Sanofi-Aventis R&D for finan-
cial support. The “Re´gion Haute-Normandie” and Novelect are
gratefully acknowledged for support allowing the purchase of
the hyperbaric reactors.
Methyl 9-Aza-6-methoxy-11-[(E)-2-methoxyvinyl]-11-trimethyl-
silyloxy-9-[(4-methylphenyl)sulfonyl]-4,10-dioxo-tricyclo-
[61.8.21.8.21.8.02.7]dodecane-7-carboxylate (19p). Colorless solid (mp
180 °C). 1H NMR δ 0.00 (s, 9H), 1.96 (dd, 1H, J ) 15.1, 3.8 Hz),
2.14-2.43 (m, 5H), 2.44 (s, 3H), 2.95 (dd, 1H, J ) 18.8, 6.0 Hz),
3.20 (s, 3H), 3.26 (ddd, 1H, J ) 13.6, 6.0, 2.6 Hz), 3.46 (s, 3H),
3.74 (s, 3H), 4.05 (dd, 1H, J ) 11.7, 6.0 Hz), 4.43 (d, 1H, J )
13.2 Hz), 5.29 (dd, 1H, J ) 3.8, 2.3 Hz), 5.81 (d, 1H, J ) 13.2
Hz), 7.32 (d, 2H, J ) 8.2 Hz), 7.92 (d, 2H, J ) 8.2 Hz). 13C NMR
δ 2.1 (3C), 21.6, 31.2, 40.0, 40.4, 42.1, 52.4, 53.1, 53.8, 55.6, 57.4,
59.5, 72.2, 75.5, 108.4, 128.3 (2C), 129.4 (2C), 135.3, 145.4, 149.0,
169.4, 171.4, 206.5. IR (KBr) ν 2956, 2837, 1723, 1648, 1435,
Supporting Information Available: Procedures for compounds
1c and 1d, as well as for the thermal Cope rearrangement of 12b
into 10b; analytical data for compounds 1c,d, 3c,d, 10b,c, 12b,
12e-i, 12k-n, 13j,k, 13m,n, 14a,b, 16j,k, 16n-r, 17j,k, 17m,
17p-r, 18n, and 19n-q, as well as 1H NMR and 13C NMR spectra
of compounds 1b-d, 3b, 10a, 10c, 12d, 12f-i, 12k, 12m,n, 13k,
13m,n, 16n, 16r, 17p, 17r, and 19m. This material is available
1354, 1259, 1212, 1170, 1101, 1075, 1049, 982, 842, 718, 672 cm-1
.
MS (EI) m/z (relative intensity) 579 (88) [M]+, 564 (100), 548 (7),
424 (32), 392 (20), 91 (72). Anal. Calcd for C27H37NO9SSi: C,
JO062186B
J. Org. Chem, Vol. 72, No. 7, 2007 2373