Synthesis of (+)-Grandisol
and the solvent was evaporated, affording 194 mg (97% yield)
of 2m e as a white solid: mp 134-6 °C (EtOAc/hexane); IR
(KBr) 3114, 2959, 2910, 1757, 1257, 1159, 1096, 906 cm-1; 1H
NMR (d6-acetone) δ 7.83 (dd, J ) 5.9, 1.5 Hz, 1H), 6.22 (dd, J
) 5.9, 1.8 Hz, 1H), 5.23 (m, 1H), 4.21(d, J ) 4.4 Hz, 1H), 0.17
(s, 9H); 13C NMR (d6-acetone) δ 172.8, 156.6, 122.8, 84.0, 75.5,
0.5; MS (CI) m/z 388 (MNH4+, 100), 371 (MH+, 27). Anal. Calcd
for C16H26Si2O6: C, 51.86; H 7.07. Found: C, 52.13; H, 6.85.
[R]D ) +200 (c 0.5, CHCl3).
(5S,5′S)-5,5′-[(1R,2R)-1,2-Dih yd r oxyeth a n e-1,2-d iyl]bis-
[2(5H)-fu r a n on e] (2id ). Following the general procedure for
the preparation of the bis(butenolides), bis(epoxide) 3ic (668
mg, 3.6 mmol) afforded a crude material which, when purified
by repeated washings with CHCl3 and MeOH, furnished 583
mg (72% yield) of 2id 1b as a white solid.
P h otocycloa d d ition of Eth ylen e to 2m a . Following the
general procedure, a solution of 2m a (80 mg, 0.28 mmol) in
acetone was irradiated in the presence of ethylene for 6 h.
Purification of the reaction crude by flash chromatography
(EtOAc/hexane, 1/3) afforded 79 mg of a white solid which
analyzed by 1H NMR and GC-MS (Cross-linked 5% PH ME
Siloxane, 12 m × 0.2 mm × 0.22 µm, T1 ) 100 °C, t1 ) 1 min,
T2 ) 240 °C, rate ) 10 °C/min) showed a 1/3/3/1 mixture of
(1S,1′S,2R,2′R,4S,4′S,5R,5′R)-4,4′-bis[2-methyl-3,6-dioxabicyclo-
[3.2.1]octan-7-one], 9a, (1S,2R,4S,5R)-4-{(1R)-(ethoxy)-[(1S,4R,
5R)-2-oxo-3-oxabicyclo[3.2.0]hept-4-yl]methyl}-2-methyl-3,6-
dioxabicyclo[3.2.1]octan-7-one, 10a , (1S,1′S,4R,4′R,5R,5′R)-,
6a, and (1S,1′R,4R,4′R,5R,5′S)-4,4′-[(1R,2R)-1,2-diethoxyethane-
1,2-diyl]bis(3-oxabicyclo[3.2.0]heptan-2-one), 7a . 6a : MS (CI)
m/z 356 (MNH4+, 100), 339 (MH+, 17); (data extracted from
an enriched sample) 1H NMR (CDCl3) δ 4.30 (s, 1H), 3.66 (dq,
J ) 8.8, 7.3 Hz, 1H), 3.53 (dq, J ) 8.8, 7.3 Hz, 1H), 3.44 (s,
1H), 3.09 (complex abs., 2H), 2.57-2.00 (complex abs., 4H),
(5S,5′S)-5,5′-[(1R,2R)-1,2-Bis(tr im eth ylsilyloxy)eth a n e-
1,2-d iyl]bis[2(5H)-fu r a n on e] (2ie). To a solution of 2id (200
mg, 0.9 mmol) in anhydrous THF (10 mL) under nitrogen was
added TMSIm (1.3 mL, 8.9 mmol), and the mixture was stirred
at room temperature for 4 h. The reaction mixture was diluted
with ether (60 mL) and washed with water (3 × 60 mL). The
organic phase was dried and the solvent evaporated, affording
321 mg (98% yield) of 2ie1b as an oil, which can be crystallized
in EtOAc/hexane (1/9).
1.11 (t, J ) 7.3 Hz, 3H); 13C NMR (CDCl3) δ 180.1, 84.8, 80.6,
+
69.2, 39.2, 35.2, 24.7, 23.7, 15.6. 7a : MS (CI) m/z 356 (MNH4
,
100), 339 (MH+, 7); (data extracted from an enriched sample):
1H NMR (CDCl3, observable signals) δ 4.39 (dd, J ) 9.5, 5.8
Hz, 1H). 9a : see below. 10a : MS (CI) m/z 328 (MNH4+, 100),
311 (MH+, 2); (data extracted from an enriched sample): 1H
NMR (CDCl3, observable signals) δ 4.67 (d, J ) 5.1 Hz, 1H),
4.49 (m, 1H), 3.95 (q, J ) 6.6 Hz, 1H), 3.85 (d, J ) 3.6 Hz,
1H).
(3a R,4R,5S,6R,6a S)-5,6-Bis(tr im eth ylsilyloxy)-3a ,5,6,-
6a-tetr ah ydr ospir o[cyclopen ta[b]fu r o-4(5H),2′(5′H)-fu r an ]-
2(3H),5′-d ion e (I). Compound I was eventually detected as a
byproduct of the former reaction. An analytical sample of I
could be isolated by flash chromatography (EtOAc/hexane, 2/1)
of a 1:1 mixture of 2ie and I, followed by crystallization. I:
mp 215-7 °C (EtOAc/hexane); IR (KBr) 3535, 3350, 3100,
P h otocycloa d d ition of Eth ylen e to 2m b. Following the
general procedure, a solution of 2m b (152 mg, 0.37 mmol) in
acetone was irradiated in the presence of ethylene for 6 h.
Purification of the reaction crude by flash chromatography
(EtOAc/hexane, 1/4) afforded 120 mg of a white solid which
analyzed by 1H NMR showed a 1/10/5 mixture of (1S,1′S,4R,4′R,
5R,5′R)-4,4′-[(1R,2R)-1,2-dibenzyloxyethane-1,2-diyl]bis(3-oxa-
bicyclo[3.2.0]heptan-2-one), 6b, (1S,1′S,2R,2′R,4S,4′S,5R,5′R)-
4,4′-bis[2-phenyl-3,6-dioxabicyclo[3.2.1]octan-7-one], 9b, and
(1S,2R,4S,5R)-4-{(1R)-(benzyloxy)-[(1S,4R,5R)-2-oxo-3-oxa-
bicyclo[3.2.0]hept-4-yl]methyl}-2-phenyl-3,6-dioxabicyclo[3.2.1]-
octan-7-one, 10b. 6b: (data extracted from an enriched
sample): 1H NMR (CDCl3, observable signals) δ 4.40 (s, 1H),
3.70 (s, 1H). 9b: see below. 10b: (data extracted from an
enriched sample): 1H NMR (CDCl3, observable signals) δ
4.70-4.50 (complex abs., 4H), 4.05 (d, J ) 4.1 Hz, 1H), 3.77
(t, J ) 4.1 Hz, 1H).
1
2938, 1792, 1750, 1187, 1110, 1039 cm-1; H NMR (CDCl3) δ
7.18 (d, J ) 5.5 Hz, 1H), 6.17 (d, J ) 5.5 Hz, 1H), 4.66 (dd, J
) 8.8, 2.9 Hz, 1H), 4.25 (dd, J ) 6.4, 2.9 Hz, 1H), 3.97 (d, J )
6.4 Hz, 1H), 3.13 (ddd, J ) 9.8, 8.8, 3.5 Hz, 1H), 2.51 (dd, J )
18.5, 9.8 Hz, 1H), 2.37 (dd, J ) 18.5, 3.5 Hz, 1H), 0.17 (s, 9H),
0.05 (s, 9H); 13C NMR (CDCl3) δ 174.8, 170.8, 153.9, 123.5,
92.5, 86.1, 81.6, 79.7, 39.9, 27.9, 0.1, -0.1; MS m/z 370 (M+,
1), 215 (20), 129 (42), 73 (100). Anal. Calcd for C16H26Si2O6:
C, 51.86; H 7.07. Found: C, 52.04; H, 6.70. [R]D ) -20 (c 0.7,
THF).
P h otocycloa d d ition of Eth ylen e to 2m c: Gen er a l P r o-
ced u r e for th e Ir r a d ia tion of th e Bis(bu ten olid es) in th e
P r esen ce of Eth ylen e. A solution of 2m c (96 mg, 0.36 mmol)
in freshly distilled acetone (60 mL) was placed in a photo-
chemical reactor. The reactor was immersed in a cooling bath
at -78 °C, and a stream of MeOH at -20 °C was circulated
throughout the refrigeration jacket. The solution was saturated
with ethylene by bubbling it through and then the reactor was
connected to a gas buret filled with ethylene. The reaction
P h otocycloa d d ition of Eth ylen e to 2m d . Following the
general procedure, a solution of 2m d (86 mg, 0.38 mmol) in
acetone was irradiated in the presence of ethylene for 7 h.
Purification of the reaction crude by flash chromatography
(EtOAc) afforded 95 mg (90% yield) of a white solid which
analyzed by 1H NMR showed a 49/42/9 mixture of (1S,1′S,4R,
4′R,5R,5′R)-, 6d , (1S,1′R,4R,4′R,5R,5′S)-, 7d , and (1R,1′R,4R,
4′R,5S,5′S)-4,4′-[(1R,2R)-1,2-dihydroxyethane-1,2-diyl]bis(3-
oxabicyclo[3.2.0]heptan-2-one), 8d . 6d + 7d + 8d : IR (KBr)
3360, 2952, 2860, 1778, 1764, 1335, 1166, 1068 cm-1; MS m/z
283 (MH+, 4), 111 (100), 83 (38), 55 (33). Anal. Calcd for
C14H18O6: C, 59.57; H 6.43. Found: C, 59.30; H, 6.47. 6d : (data
1
mixture was irradiated, following the reaction progress by H
NMR analysis of aliquot samples. After a 4 h irradiation, the
solvent was removed and the residue was purified by flash
chromatography (CHCl3/hexane, 2/1), giving 75 mg (65% yield)
of a white solid identified as a 77/23 mixture of (1S,1′S,4R,
4′R,5R,5′R)-, 6c, and (1S,1′R,4R,4′R,5R,5′S)-4,4′-[(1R,2R)-1,2-
di-O-isoprolylidendioxyethane-1,2-diyl]bis(3-oxabicyclo[3.2.0]-
heptan-2-one), 7c. 6c + 7c: IR (KBr) 2987, 2938, 1771, 1384,
1321, 1236, 1166, 1103, 1068 cm-1; MS m/z 307 (15), 211 (28),
111 (100), 55 (30); MS (CI) m/z 340 (MNH4+, 100), 323 (MH+,
44). Anal. Calcd for C17H22O6: C, 63.34; H 6.88. Found: C,
63.22; H, 6.86. 6c (data extracted from an enriched sample):
1H NMR (400 MHz, CDCl3) δ 4.40 (m, 1H), 3.78 (dd, J ) 3.4,
1.5 Hz, 1H), 3.09 (complex abs., 2H), 2.59-2.00 (complex abs.,
4H), 1.33 (s, 3H); 13C NMR (CDCl3) δ 179.6, 110.8, 85.0, 78.7,
38.4, 35.5, 26.8, 24.6, 23.6. 7c (data extracted from an enriched
sample): 1H NMR (400 MHz, CDCl3, observable signals) δ 4.58
(br d, J ) 2.4 Hz, 1H), 4.34 (dd, J ) 9.1, 6.1 Hz, 1H), 4.27 (dd,
J ) 6.7, 2.4 Hz, 1H), 3.30 (m, 1H), 1.36 (s, 3H), 1.29 (s, 3H);
13C NMR (CDCl3, observable signals) δ 84.0, 81.7, 81.2, 74.0,
39.4, 39.3, 37.2, 34.7, 23.7, 23.2, 19.5.
1
extracted from an enriched sample) H NMR (CDCl3, observ-
able signals) δ 4.35 (d, J ) 6.6 Hz, 1H), 3.61 (d, J ) 6.6 Hz,
1H), 3.25 (m, 1H), 3.12 (m, 1H), 2.68 (d, J ) 7.3 Hz, 1H), 2.56-
2.13 (complex abs., 4H); 13C NMR (d6-DMSO) δ 183.0, 87.3,
71.9, 40.0, 37.1. 25.7, 24.5. 7d : (data extracted from an
enriched sample) 1H NMR (CDCl3, observable signals) δ 4.47-
4.37 (complex abs., 2H), 3.86 (dd, J ) 10.4, 1.8 Hz, 1H), 3.70
(dd, J ) 7.0, 1.8 Hz, 1H); 13C NMR (d6-DMSO, observable
signals) δ 87.2, 80.0, 72.5, 69.0, 41.4, 40.0, 38.4, 23.9, 20.5.
8d : (data extracted from an enriched sample) 1H NMR (CDCl3,
observable signals) δ 4.50 (dd, J ) 9.7, 6.2 Hz, 1H), 4.00 (d, J
) 9.7 Hz, 1H).
P h otocycloa d d ition of Eth ylen e to 2m e. Following the
general procedure, a solution of 2m e (196 mg, 0.53 mmol) in
acetone was irradiated in the presence of ethylene for 6 h.
Purification of the reaction crude by flash chromatography
J . Org. Chem, Vol. 68, No. 6, 2003 2445