J. Gagnepain et al. / Tetrahedron 63 (2007) 6493–6505
6503
3481, 2972, 2927, 1719, 1681, 1448, 1361 cmꢀ1; 1H NMR
(CDCl3, 400 MHz) d 0.56 (d, J¼6.6 Hz, 3H), 0.81 (d,
J¼6.8 Hz, 3H), 0.84 (d, J¼7.1 Hz, 3H), 0.95 (d, J¼6.6 Hz,
3H), 1.50–1.65 (m, 1H), 1.60 (s, 3H), 1.76 (sept,
J¼6.8 Hz, 1H), 1.95 (s, 3H), 2.36 (br s, 1H), 3.08 (d,
J¼7.3 Hz, 1H), 3.16 (s, 1H), 3.26 (d, J¼8.3 Hz, 1H), 3.29
(d, J¼6.6 Hz, 1H), 3.79 (s, 1H), 5.82 (d, J¼6.1 Hz, 1H),
5.97 (s, 1H); 13C NMR (CDCl3, 100 MHz) d 214.8, 201.8,
155.9, 135.7, 126.6, 125.3, 78.1, 77.8, 57.2, 47.1, 41.8,
37.2, 37.1, 32.5, 22.1, 21.3, 16.7, 16.6, 16.3, 16.0; ESIMS
(MeOH) m/z 333 [MH+].
50.6, 48.9, 45.8, 38.5, 36.1; EIMS m/z (rel intensity) 424
(M+, 2), 409 (2), 393 (17), 365 (17), 306 (7), 212 (6), 174
(100); HRMS (ESI) calcd for C20H24O10Na 447.1267, found
447.1286.
5.3.2. 4,11-Bis(30,30-dimethyl-10,40-dioxaspirocyclopen-
tan-2-one)pentacyclo[6.4.0.02,7.03,10.06,9]dodeca-5,12-di-
one (4k). Photoannelation of 3,10-bis(30,30-dimethyl-10,40-
dioxaspirocyclopentan-2-one)tricyclo[6.2.2.02,7]dodeca-
5,11-diene-4,9-dione21b (3k, 9 mg, 0.023 mmol) in CH2Cl2
(2 mL) was carried out over 20 h according to the general
procedure. The reaction mixture was then evaporated to fur-
nish 4k as a white solid (9 mg, quantitative yield). Recrystal-
lization from hexanes–CH2Cl2 afforded pure 4k as colorless
prisms: mp 310–313 ꢁC; IR (NaCl) 2921, 1806, 1738,
5.2.3. 3,10-Dihydroxy-3,12-di-iso-propyl-6,10-dimethyl-
tricyclo[6.2.2.02,7]dodeca-5,11-diene-4,9-dione (3s0).
SIBX-mediated oxidation of a 1:1 mixture of carvacrol
(1a, 150 mg, 1 mmol) and thymol (150 mg, 1 mmol) was
carried out according to the general procedure to give, after
purification by column chromatography, eluting with hex-
anes–acetone (10:1), three fractions: one black and two yel-
low solids. Submission of the black solid residue (90 mg) to
column chromatography, eluting with hexanes–Et2O (4:1),
afforded pure catechol 5 as a brown oil (40 mg, 24%) and
pure thymol-based cyclodimer 3s as a white solid (40 mg,
12%). Recrystallization at low temperature from hexanes–
CH2Cl2 of the two yellow solids identified as the carvacrol-
based cyclodimer 3a and the cyclodimer 3s0, respectively,
furnished pure cyclodimers 3a (68 mg, 21%) and 3s0
(31 mg, 9%) as white needles.
1
1177 cmꢀ1; H NMR (CDCl3, 300 MHz) d 1.49 (s, 6H),
1.52 (s, 6H), 2.86 (s, 2H), 3.36 (s, 6H); 13C NMR (CDCl3,
75.5 MHz) d 201.8, 174.0, 98.7, 78.8, 45.0, 41.2, 35.9,
35.6, 27.0, 25.0; CIMS (NH3) 406 (MNH+4); HRMS (ESI)
calcd for C20H21O8 389.1236, found 389.1219; CCDC
637238.
5.3.3. 4,11-Dihydroxy-7,8-di-iso-propyl-4,11-dimethyl-
pentacyclo[6.4.0.02,7.03,10.06,9]dodeca-5,12-dione (4a).
Photoannelation of cyclodimer 3a (68 mg, 0.2 mmol) in
MeOH (5 mL) was carried out over 24 h according to the
general procedure. Purification by column chromatography,
eluting with hexanes–acetone (3:1), gave 4a as a colorless
solid (55 mg, 81%). Further recrystallization from hex-
anes–CH2Cl2 afforded pure 4a as colorless prisms: mp
238–239 ꢁC (lit.39 mp 229 ꢁC); IR (KBr) 3469, 2974,
Compound 3s0: mp 158–159 ꢁC; IR (KBr) 3451, 1724, 1676,
1157 cmꢀ1
;
1H NMR (CDCl3, 400 MHz) d 0.59 (d,
1
J¼6.6 Hz, 3H), 0.87 (d, J¼6.8 Hz, 3H), 0.90 (d, J¼6.6 Hz,
3H), 0.98 (d, J¼6.6 Hz, 3H), 1.22 (s, 3H), 1.58 (sept,
J¼6.6 Hz, 1H), 1.80–2.00 (m, 1H), 1.97 (s, 3H), 2.38 (br
s, 1H), 3.09 (d, J¼8.1 Hz, 1H), 3.25 (br s, 2H), 3.40 (d,
J¼8.6 Hz, 1H), 3.86 (br s, 1H), 5.82 (d, J¼6.6 Hz, 1H),
5.95 (s, 1H); 13C NMR (CDCl3, 100 MHz) d 213.0, 201.6,
156.4, 145.5, 126.0, 125.2, 76.7, 72.9, 55.0, 44.3, 43.9,
37.8, 36.8, 33.1, 25.9, 22.4, 20.4, 19.4, 16.7, 15.9; ESIMS
(MeOH) m/z 333 (MH+); Anal. Calcd for C20H28O4: C,
72.26; H, 8.49; O, 19.25. Found: C, 71.89; H, 8.51; CCDC
636462.
1702, 1131 cmꢀ1; H NMR (CDCl3, 300 MHz) d 0.77 (s,
6H), 1.06 (s, 6H), 1.32 (s, 6H), 2.04 (s, 2H), 2.75 (s, 2H),
2.94 (s, 4H), 2.90–3.30 (m, 2H); 13C NMR (CDCl3,
75.5 MHz) d 215.9, 73.3, 50.7, 50.2, 40.6, 36.2, 30.0,
23.2, 19.1, 18.3; EIMS m/z (rel intensity) 332 (M+, 10),
289 (30), 271 (32), 243 (63), 229 (29), 201 (58), 191 (32),
166 (56), 159 (84), 149 (66), 123 (100); HRMS (ESI)
calcd for C20H28O4Na 355.1885, found 355.1891; CCDC
636464.
5.3.4. 4,11-Dihydroxy-4,11-di-iso-propyl-7,8-dimethyl-
pentacyclo[6.4.0.02,7.03,10.06,9]dodeca-5,12-dione (4s).
Photoannelation of cyclodimer 3s (100 mg, 0.3 mmol) in
MeOH (5 mL) was carried out over 24 h according to the
general procedure. Purification by column chromatography,
eluting with hexanes–Et2O (1:1), furnished 4s as a white
solid (90 mg, 90%). Further recrystallization from hex-
anes–CH2Cl2 gave pure 4s: mp 150 ꢁC (lit.39 mp 155 ꢁC);
5.3. General procedure for [2D2] photoannelation
reaction of cyclodimers
A Pyrex tube containing a solution of cyclodimer in either
dry MeOH or dry CH2Cl2 (ca. 0.04 M) was irradiated at
room temperature using a medium-pressure mercury lamp.
The reaction mixture was then evaporated and purified by
column chromatography.
1
IR (KBr) 3507, 2974, 1710, 1154, 1017 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 0.79 (s, 6H), 0.96 (s, 6H), 1.16 (s,
6H), 1.66 (s, 2H), 2.56 (s, 2H), 2.85 (s, 4H), 3.10 (br s,
2H); 13C NMR (CDCl3, 75.5 MHz) d 215.0, 79.1, 49.2,
44.4, 40.5, 39.6, 29.0, 16.6, 16.2, 15.7; EIMS m/z (rel inten-
sity) 332 (M+, 6), 314 (5), 296 (8), 271 (8), 243 (30), 225
(18), 173 (29), 166 (41), 151 (67), 135 (38), 123 (35), 105
(62), 91 (65), 71 (100); HRMS (ESI) calcd for
C20H28O4Na 355.1885, found 355.1881.
5.3.1. 4,4,11,11-Tetramethoxy-7,8-dimethoxycarbonyl-
pentacyclo[6.4.0.02,7.03,10.06,9]dodeca-5,12-dione (4g).
Photoannelation of cyclodimer 3g (40 mg, 0.09 mmol) in
MeOH (3 mL) was carried out over 10 h according to the
general procedure. Purification by column chromatography,
eluting with cyclohexane–acetone (2:1), afforded 4g as
a pale yellow oil (22 mg, 55%): IR (NaCl) 2957, 2850,
1735, 1437, 1282, 1252, 1223, 1121, 1079, 1050 cmꢀ1; 1H
NMR (CDCl3, 300 MHz) d 2.89 (d, J¼3.9 Hz, 2H), 3.21
(s, 6H), 3.35 (s, 6H), 3.68 (d, J¼6.8 Hz, 2H), 3.72 (s, 8H);
13C NMR (CDCl3, 75.5 MHz) d 200.7, 169.4, 95.5, 52.5,
5.3.5. 4,11-Dihydroxy-4,8-di-iso-propyl-7,11-dimethyl-
pentacyclo[6.4.0.02,7.03,10.06,9]dodeca-5,12-dione (4s0).
Photoannelation of cyclodimer 3s0 (25 mg, 0.075 mmol) in
MeOH (2 mL) was carried out over 24 h according to the