T. Okujima et al. / Tetrahedron 64 (2008) 2405e2411
2409
for 4 days in an autoclave. The solvent was removed under re-
duced pressure. The residue was washed with ether to give 9
(9.88 g, 79%). White powder; mp 172.0e173.1 ꢀC; MS
(FAB) m/z (relative intensity) 417 (Mþþ1, 59%); IR (KBr
disk) nmax 3066, 2972, 2935, 2870, 1446, 1306, 1217, 1147,
was washed with water, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel with CHCl3 to give 10b
(250 mg, 71%). Colorless crystals; mp >90 ꢀC (decomp.); MS
(70 eV) m/z (relative intensity) 173 (Mþ, 3%) and 117 (100);
IR (KBr disk) nmax 3365 (NeH), 3039, 2964, 2929, 2861,
1602, 1508, 1428, 1340, 1288, 1255, 1197, 1155, 1122, 1089,
1
and 1084 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.95 (m, 2H,
C-20,60), 7.83 (m, 2H, C-20,60), 7.64e7.70 (m, 2H, C-40), 7.58
(m, 2H, C-30,50), 7.56 (m, 2H, C-30,50), 6.29 (dd, 1H, J¼7.3,
6.5 Hz, H-3), 6.20 (dd, 1H, J¼7.3, 6.5 Hz, H-2), 4.37 (dd,
1H, J¼6.3, 2.0 Hz, H-7), 3.67 (ddd, 1H, J¼6.3, 2.4, 2.0 Hz,
H-8), 3.12 (m, 1H, H-1), 2.57 (d, 1H, J¼6.5 Hz, H-4), 2.16
(dd, 1H, J¼13.7, 2.0 Hz, H-6), 1.15 (s, 3H, 5-Me), 1.00 (ddd,
1H, J¼13.7, 2.4, 2.0 Hz, H-6), and 0.86 (s, 3H, 5-Me); 13C
NMR (100 MHz, CDCl3) d 139.60 (C-10), 138.84 (C-10),
134.77 (C-3), 133.79 (C-40), 133.75 (C-40), 130.22 (C-2),
129.12 (C-30,50), 129.06 (C-30,50), 128.49 (C-20,60), 128.48
(C-20,60), 63.76 (C-8), 62.35 (C-7), 44.08 (C-4), 34.09 (C-70),
33.87 (C-6), 33.24 (C-1), 31.56 (5-Me), and 26.83 (5-Me).
Anal. Calcd for C22H24O4S2: C, 63.43; H, 5.81. Found: C,
63.21; H, 5.78.
1
1047 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.46 (br s, 1H,
NH), 6.54 (m, 1H, H-6), 6.48 (m, 1H, H-5), 6.47 (m, 1H, H-1
or H-3), 6.41 (m, 1H, H-1 or H-3), 3.70 (m, 1H, H-4), 3.22 (d,
1H, J¼5.9 Hz, H-7), 1.41 (dd, 1H, J¼11.5, 2.7 Hz, H-9), 1.24
(dd, 1H, J¼11.5, 2.7 Hz, H-9), 1.04 (s, 3H, 8-Me), and 0.72
(s, 3H, 8-Me); 13C NMR (100 MHz, CDCl3) d 136.97, 135.23,
128.65, 127.87, 110.28, 107.67, 46.03, 44.32, 37.39, 34.52,
31.00, and 30.73. Anal. Calcd for C12H15N: C, 83.19; H, 8.73;
N, 8.08. Found: C, 82.97; H, 8.55; N, 8.04.
4.1.4. Tetrakis(dimethylBCOD)porphyrin 3a
Route A: to a solution of 10a (487 mg, 1.99 mmol) in dry
THF (30 ml), LiAlH4 (352 mg, 9.27 mmol) was added at
0 ꢀC under an Ar atmosphere. The resulting mixture was stirred
at the same temperature for 2 h. The reaction mixture was
poured into water, filtrated with Celite, and extracted with ethyl
acetate. The organic layer was washed with water and brine,
dried over Na2SO4, and concentrated under reduced pressure.
The residue was diluted with CHCl3 (400 ml) and
p-TsOH$H2O (30 mg) was added. After stirring at room tem-
perature for 1 day, p-chloranil (291 mg, 1.18 mmol) was added.
The resulting mixture was stirred at the same temperature for 1
day. The mixture was poured into water. The organic layer was
washed with satd aqueous NaHCO3, water, and brine, dried
over Na2SO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on alumina
with CHCl3, column chromatography on silica gel with
CHCl3 and EtOAc/CHCl3, and recrystallization from metha-
nol/CHCl3 to give 3a (207 mg, 57%) and 3b (56 mg, 15%).
Route B: 10b (173 mg, 0.999 mmol) and paraformaldehyde
(36 mg) were dissolved in CHCl3 (200 ml) in a shaded vessel.
After stirring at room temperature for 10 min under an Ar
atmosphere, p-TsOH$H2O (34 mg) was added. The resulting
mixture was stirred at the same temperature for 24 h. After ad-
dition of p-chloranil (100 mg, 0.407 mmol), the mixture was
stirred for 2 h and poured into satd aqueous NaHCO3. The or-
ganic layer was washed with water and brine, dried over
Na2SO4, and concentrated under reduced pressure. The residue
was purified by column chromatography on alumina with
CHCl3 and on silica gel with CHCl3 to give 3a (8 mg, 4%)
and 3b (53 mg, 29%).
4.1.2. Ethyl 4,7-dihydro-8,8-dimethyl-4,7-ethano-2H-
isoindole-1-carboxylate (10a)
To a stirred solution of 9 (16.66 g, 40.00 mmol) and ethyl
isocyanoacetate (5.6 ml) in dry THF (190 ml) was added drop-
wise a solution of potassium tert-butoxide (13.61 g) in dry THF
(120 ml) at 0 ꢀC under an Ar atmosphere. The resulting mixture
was stirred at room temperature under an Ar atmosphere for 1
day. The reaction mixture was poured into 1 M HCl (10 ml),
evaporated, and extracted with CHCl3. The organic layer was
washed with water, satd aqueous NaHCO3, and brine, dried
over Na2SO4, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel
with CHCl3 to give 10a (8.285 g, 84%). Colorless crystals;
mp 127.2e128.0 ꢀC; MS (70 eV) m/z (relative intensity) 245
(Mþ, 0.1%), 189 (100); IR (KBr disk) nmax 3309 (NeH),
3051, 2974, 2929, 2859, 1685 (C]O), 1608, 1587, 1494,
1458, 1427, 1369, 1315, 1259, 1211, 1155, 1116, and
1
1033 cmꢁ1; H NMR (400 MHz, CDCl3) d 8.50 (br s, 1H,
NH), 6.55 (d, 1H, J¼2.7 Hz, H-3), 6.47e6.56 (m, 2H,
H-5,6), 4.36 (dq, 1H, J¼10.7, 7.1 Hz, 1-CO2Et), 4.27 (dq,
1H, J¼10.7, 7.1 Hz, 1-CO2Et), 3.81 (d, 1H, J¼5.9 Hz, H-7),
3.73 (m, 1H, H-4), 1.40 (m, 1H, H-9), 1.36 (t, 3H, J¼7.1 Hz,
1-CO2Et), 1.22 (dd, 1H, J¼11.7, 2.7 Hz, H-9), 1.07 (s, 3H,
8-Me), and 0.70 (s, 3H, 8-Me); 13C NMR (100 MHz, CDCl3)
d 161.63 (1-CO2Et), 136.49 (C-7a), 135.96 (C-6), 135.22
(C-5), 130.02 (C-3a), 116.20 (C-1), 112.67 (C-3), 59.73
(1-CO2Et), 46.42 (C-7), 43.82 (C-9), 37.77 (C-8), 34.61
(C-4), 30.82 (8-Me), 30.29(8-Me), and 14.63 (1-CO2Et).
Anal. Calcd for C15H19NO2: C, 73.44; H, 7.81; N, 5.71. Found:
C, 73.53; H, 7.82; N, 5.67.
Porphyrin 3a: purple crystals; mp >200 ꢀC (decomp.); MS
(FAB) m/z (relative intensity) 736 (Mþþ2, 12%) and 511
(100); HRMS calcd for C52H55N4 735.4427, found 735.4425;
1
UVevis (CHCl3) lmax, nm: 385, 496, 527, 564, and 616; H
4.1.3. 4,7-Dihydro-8,8-dimethyl-4,7-ethano-2H-isoindole (10b)
A solution of 10a (496 mg, 2.02 mmol) and NaOH (617 mg)
in ethyleneglycol (35 ml) was heated at 170 ꢀC for 80 min under
an Ar atmosphere in a shaded vessel. The reaction mixture was
poured into water and extracted with CHCl3. The organic layer
NMR (400 MHz, CDCl3) d 10.27 (s, 4H, meso-H), 7.16 (m,
8H, olefin), 5.62 (m, 4H, bridge head), 5.12 (d, 1H,
J¼5.9 Hz, bridge head), 2.09 (dd, 4H, J¼11.7, 2.4 Hz, bridge
CH2), 1.84 (m, 4H, bridge CH2), 1.56 (s, 12H, Me), 0.75 (s,
12H, Me), and ꢁ4.66 (br s, 2H, NH). Porphyrin 3b: purple