212
Vol. 54, No. 2
8d: Yellow powder (AcOEt), mp 240 °C. IR (KBr) cmꢃ1: 1648, 1613, 787,
760. H-NMR (CDCl3) d: 4.01 (6H, s, OMeꢄ2), 6.92 (1H, s, H-7), 7.48—
with eluted acetone–hexane (2 : 1) was evaporated in in vacuo to give 5a
(20 mg, 75%). b) To a solution of 6b (28 mg, 0.086 mmol) in THF (3 ml)
was added 1 mol/THF TBAF (0.43 ml, 0.43 mmol) and the reaction solution
was stirred at 30 °C for 2 h. The reaction mixture was treated as described
above to gave 5b (15 mg, 83%).
1
7.55 (2H, m, H-10, 2 or 3), 7.76 (1H, dd, Jꢀ7.7, 8.0 Hz, H-2 or 3), 8.12 (1H,
d, Jꢀ8.0 Hz, H-1), 8.52 (1H, d, Jꢀ7.7 Hz, H-4), 11.54—11.61 (1H, br s,
NH). 13C-NMR (CDCl3) d: 56.15, 56.34, 99.39, 104.43, 111.09, 121.43,
124.57, 126.57, 128.24, 131.06, 132.64, 134.95, 145.73, 151.22, 163.06. MS
m/z: 255 (Mꢂ). HR-MS m/z: Calcd for C15H13NO3, 255.0895. Found:
255.0894.
Calculation of Activation Energy Structures of the initial and the tran-
sition states (TS) were optimized using Gaussian 03 at HF/6-31G(d) level.15)
The solvent effect was not considered. We assumed that the diene and the
dienophile were far apart in the initial state. We calculated the activation en-
ergy as the difference in energy between the TS and the initial state. After
optimizing the TS structure, vibrational calculation was performed to con-
firm that the TS had only one imaginary vibrational frequency. Iintrinsic re-
action coordinate calculation was also carried out to ensure that the TS con-
nected the initial and the intended final state.
Methylation of 5a a) To a suspention of cesium carbonate (391 mg,
1.2 mmol) and 5a (65 mg, 0.3 mmol) in THF (4 ml) was added MeI (175 mg,
1.2 mmol) at room temperature under N2. The mixture was refluxed for 2 h.
The reaction mixture was concentrated in vacuo, quenched with H2O (10 ml)
and extacted with ethyl acetate. The organic layer was washed with saturated
aqueous NaCl and dried over MgSO4. The ethyl acetate was evaporated in
vacuo and the residue was chromatographed on a column of silica gel. The
solvent of first fraction eluted with ethyl acetate–hexane (1 : 1) was evapo-
rated to give 7a (63 mg, 88%). b) A DME solution of 5a (50 mg, 0.22 mmol)
and TFA (0.09 ml, 0.12 mmol) was heated at 180 °C for 3 d in a sealed tube.
The reaction mixture was concentrated in vacuo and the resulting residue
was purified by silica gel column chromatography. The first fraction eluted
with ethyl acetate–hexane (1 : 1) was concentrated to give 7a (5 mg, 8%).
The second fraction gave 5a (30 mg, 60%).
References and Notes
Typical Procedure for DA Reaction of 1a with 2d a) A solution of 1a
(100 mg, 0.49 mmol) and 2d (0.30 ml, 2.45 mmol) in DME (3 ml) was
heated at 180 °C for 3 d in a sealed tube. The reaction mixture was then con-
centrated in vacuo, and the resulting residue was purified by silica gel col-
umn chromatography. The first fraction that was eluted using
acetone–hexane (1 : 2) was evaporated to give 8a (50 mg, 36%). The second
fraction that was eluted using acetone–hexane (1 : 2) gave 1a (59 mg, 59%).
8a: Yellow powder (CHCl3), mp 170 °C. IR (KBr) cmꢃ1: 1645, 1610, 771,
1) Tomisawa H., Fujita R., Chem. Pharm. Bull., 21, 2585—2589 (1973).
2) Horning D. E., Lacassf G., Muchowski J. M., Can. J. Chem., 49,
2785—2796 (1971), and references cited therein.
3) Dyke S. F., Sainsbury M., Brown D. W., Clipperton R. D. J., Tetrahe-
dron, 26, 5969—5980 (1970).
4) For biological properties of phenanthridine alkaloids, see: Rigby J. H.,
Holsworth D. D., James K., J. Org. Chem., 54, 4019—4020 (1989).
5) For biological properties of phenanthridine alkaloids, see: Narasimhan
N. S., Chandrachood P. S., Tetrahedron, 37, 825—827 (1981).
6) For biological properties of phenanthridine alkaloids, see: Okamoto T.,
Torri Y., Isogai Y., Chem. Pharm. Bull., 16, 1860—1864 (1968).
7) For biological properties of phenanthridine alkaloids, see: Mondon A.,
Krohn K., Chem. Ber., 108, 445—468 (1975).
8) Weltin D., Picard V., Aupeix K., Varn M., Oth D., Marchal J., Dufour
P., Bischoff P., Int. J. Immunopharmc., 17, 265—271 (1995).
9) Snders G. M., van Dijk M., den Hertog H. J., Recueil J. Royal Nether-
lands Chemical Society, 93, 298—300 (1974).
10) Harayama T., Akiyama T., Nakano Y., Nishioka H., Abe H., Takeuchi
Y., Chem. Pharm. Bull., 50, 519—522 (2002).
11) Rigby J. H., Laurent S., J. Org. Chem., 63, 6742—6744 (1998).
12) Kraatz U., Korte F., Chem. Ber., 106, 62—68 (1973).
13) Naito T., Ninomiya I., Heterocycles, 22, 1705—1708 (1984).
14) Laltha S., Rajeswari S., Pai B. R., Suguna H., Indian J. Chem., 15,
180—182 (1977).
15) Gaussian 03, Revision B.05, Frisch M. J., Trucks G. W., Schlegel H.
B., Scuseria G. E., Robb M. A., Cheeseman J. R., Montgomery J. A.,
Jr., Vreven T., Kudin K. N., Burant J. C., Millam J. M., Iyengar S. S.,
Tomasi J., Barone V., Mennucci B., Cossi M., Scalmani G., Rega N.,
Petersson G. A., Nakatsuji H., Hada M., Ehara M., Toyota K., Fukuda
R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai
H., Klene M., Li X., Knox J. E., Hratchian H. P., Cross J. B., Adamo
C., Jaramillo J., Gomperts R., Stratmann R. E., Yazyev O., Austin A.
J., Cammi R., Pomelli C., Ochterski J. W., Ayala P. Y., Morokuma K.,
Voth G. A., Salvador P., Dannenberg J. J., Zakrzewski V. G., Dapprich
S., Daniels A. D., Strain M. C., Farkas O., Malick D. K., Rabuck A.
D., Raghavachari K., Foresman J. B., Ortiz J. V., Cui Q., Baboul A. G.,
Clifford S., Cioslowski J., Stefanov B. B., Liu G., Liashenko A.,
Piskorz P., Komaromi I., Martin R. L., Fox D. J., Keith T., Al-Laham
M. A., Peng C. Y., Nanayakkara A., Challacombe M., Gill P. M. W.,
Johnson B., Chen W., Wong M. W., Gonzalez C., Pople J. A., Gauss-
ian, Inc., Pittsburgh PA, 2003.
1
719. H-NMR (CDCl3) d: 2.39 (3H, s, CMe), 2.42 (3H, s, CMe), 3.79 (3H,
s, NMe), 7.18 (1H, s, H-7), 7.53 (1H, dd, Jꢀ7.9, 7.9 Hz, H-3), 7.72 (1H,
ddd, Jꢀ1.0, 7.9, 8.1 Hz, H-2), 8.0 (1H, s, H-10), 8.23 (1H, d, Jꢀ8.1 Hz, H-
1), 8.53 (1H, dd, Jꢀ1.0, 8.1 Hz, H-4). 13C-NMR (CDCl3) d: 19.45, 20.47,
29.94, 116.01, 117.05, 121.34, 123.86, 125.32, 127.34, 128.89, 130.94,
132.23, 133.63, 136.25, 138.78, 161.69. MS m/z: 237 (Mꢂ). HR-MS m/z:
Calcd for C16H15NO, 237.1154. Found: 237.1170.
Typical Procedures for DA Reaction of 1a, b with 2e a) A solution of
1a (100 mg, 0.49 mmol) and 2e (0.32 ml, 2.45 mmol) in o-xylene (3 ml) was
heated at 180 °C for 3 d in a sealed tube. The reaction mixture was then con-
centrated in vacuo, and the resulting residue was purified by silica gel col-
umn chromatography. The first fraction that was eluted using ethyl
acetate–hexane (1 : 1) was evaporated to give 8c (38 mg, 28%). b) A solution
of 1b (100 mg, 0.526 mmol) and 2e (0.32 ml, 2.45 mmol) in DME (3 ml) was
heated at 180 °C for 5 d in a sealed tube. The reaction mixture was concen-
trated in vacuo. The residue was chromatographed on a column of silica gel.
The solvent of fraction eluted with ethyl acetate was evaporated, and the
residure diluted with chloroform (20 ml). The chloroform was washed with
saturated aqueous NaCl (10 ml) and was evaporated. The residue was
rechromatographed on a column of silica gel. The first fraction that was
eluted using ethyl acetate–hexane (1 : 2) was evaporated to give 1b (40 mg,
40%). The second fraction that was eluted using ethyl acetate–hexane (1 : 2)
was evaporated to give 8d (25 mg, 21%). c) Reaction of 1a or 1b
(0.49 mmol) with 2e (2.45 mmol) was carried out under conditions as listed
in Table 1. The products were purified as described above to give 8c or 8d,
with yields as summarized in Table 1.
8c: Pale yellow powder (CHCl3), mp 140 °C. IR (KBr) cmꢃ1: 1648, 1611,
1
771, 719. H-NMR (CDCl3) d: 3.82 (3H, s, NMe), 4.04 (6H, s, OMeꢄ2),
6.88 (1H, s, H-7), 7.53 (1H, dd, Jꢀ7.1, 7.8 Hz, H-3), 7.68 (1H, s, H-10),
7.73 (1H, ddd, Jꢀ1.0, 7.1, 8.2 Hz, H-2), 8.13 (1H, d, Jꢀ8.2 Hz, H-1), 8.54
(1H, dd, Jꢀ1.0, 7.8 Hz, H-4). 13C-NMR (CDCl3) d: 30.20, 30.91, 56.14,
98.61, 105.41, 111.96, 121.15, 124.69, 126.89, 129.05, 132.26, 133.10,
133.50, 145.18, 150.85, 161.66. MS m/z: 269 (Mꢂ). HR-MS m/z: Calcd for
C16H15NO3, 269.1052. Found: 269.1067.