G. Mehta et al.
FULL PAPER
gradually from a syringe at 5 108C under N2 atmosphere, during which
time the reaction mixture turned from pale yellow to dark brown. The
reaction mixture was stirred at room temperature for further 2 h, before
diluting with diethyl ether (20 mL) and pouring into ice-cold water
(20 mL). The ether layer was separated and the aqueous layer was
extracted with diethyl ether (3 Â 30 mL). The combined organic extracts
were washed with 10% HCl (2 Â 10 mL), water (10 mL), brine (10 mL),
dried over anhydrous Na2SO4, and concentrated under reduced pressure to
furnish the crude product (530 mg), which on chromatography over neutral
alumina column (5% ethyl acetate/hexane) gave the crystalline trans-diene
layer was extracted with CH2Cl2 (3 Â 30 mL). The combined organic layer
was washed with saturated aqueous NaHCO3 (2 Â 10 mL), brine (10 mL),
and dried over anhydrous Na2SO4. The solvent was removed under reduced
pressure to give a solid residue, which by TLC examination was found to be
a mixture of two compounds. The residue was subjected to silica gel column
chromatography (5% ethyl acetate/hexane) to furnish epoxides 13
(295 mg, 66%) and 14 (31 mg, 7%), along with recovered starting material
5 (80 mg), in an overall yield of 73%. Compound 13: IR (thin film): nÄ
1733 cmÀ1
;
1H NMR (300 MHz, CDCl3): d 6.13 (1³2ABq, J 9.4, 3.7 Hz,
1
1H), 6.08 (d of ³2ABq, J 9.4, 3.7 Hz, 1H), 4.23 (d, J 3.7 Hz, 1H), 3.33
(brs, 1H), 2.89 (d, J 14.2 Hz, 1H), 2.41 (d, J 14.2 Hz, 1H), 2.23 2.09
(m, 1H), 2.02 (s, 3H), 2.00 (s, 3H), 1.84 1.75 (m, 1H), 1.52 1.25 (m, 4H);
5
(516 mg, 52%). M.p. 140 1418C; IR (KBr): nÄ 3052, 1731 cmÀ1
;
1H NMR (300 MHz, CDCl3): d 6.09 (m, 2H), 5.91 (m, 2H), 2.56 (s,
1H), 2.51 (s, 1H), 2.03 1.83 (m, 2H), 1.97 (s, 6H), 1.77 1.43 (m, 4H);
13C NMR (75 MHz, CDCl3): d 169.2 (2C), 130.8 (2C), 124.1 (2C), 78.8
13C NMR (75 MHz, CDCl3): d 169.3, 168.7, 134.7, 126.2, 80.7 (2C), 55.9,
46.7, 28.5, 25.5, 22.0, 21.7, 20.1, 19.7; MS (EI, 70 eV): m/z (%): 207 [M
À
(2C), 26.7 (2C), 21.6 (2C), 20.2 (2C); MS (EI, 70 eV): m/z: 251 [M H];
OAc]; elemental analysis calcd (%) for C14H18O5 (266.2): C 63.15, H 6.81;
found: C 62.85, H 6.90.
elemental analysis calcd (%) for C14H18O4 (250): C 67.18, H 7.25; found: C,
66.90, H, 7.52.
Compound 14: IR (KBr): nÄ 1738 cmÀ1; 1H NMR (300 MHz, CDCl3): d
6.15 (d, J 9.4 Hz, 1H), 5.95 (d, J 9.4 Hz, 1H), 3.41 (d, J 3.3 Hz, 1H),
3.28 (d, J 3.3 Hz, 1H), 2.92 (d, J 13.6 Hz, 1H), 2.50 (d, J 13.6 Hz, 1H),
2.02 (s, 6H), 1.81 1.25 (m, 6H); 13C NMR (75 MHz, CDCl3): d 168.8,
168.7, 138.2, 124.4, 78.4, 77.7, 54.4, 47.6, 28.3, 27.2, 21.6, 21.2, 20.3, 20.0; MS
Compound 12: Pyridiniumbromide perbromide (8.22 g, 0.025 mmol) was
added to a solution of the known[10] trans-diol 11 (3.6 g, 0.023 mol) in dry
CH2Cl2 (50 mL), and the reaction mixture was stirred at 08C under N2
atmosphere. After consumption of the starting material (monitored by
TLC), the reaction mixture was diluted with CH2Cl2 (50 mL) and poured
into ice-cold water (100 mL). The organic layer was separated and the
aqueous layer was extracted with CH2Cl2 (3 Â 30 mL). The combined
organic extracts were washed successively with saturated aqueous Na2S2O5
solution (2 Â 20 mL), water (20 mL), brine (20 mL), and dried over
anhydrous Na2SO4. Concentration of the solvent and purification of the
resultant solid residue by silica gel chromatography afforded the dibro-
(70 eV, EI): m/z (%): 267 [M H]; elemental analysis calcd (%) for
C14H18O5 (266.2): C 63.15, H 6.81; found: C 62.92, H 6.95.
Compounds 15 and 16: A solution of epoxide 13 (250 mg, 0.94 mmol) in
THF (5 mL) was treated with 10% AcOH (2 mL), and the resulting
mixture was stirred at 508C for 16 h. Upon completion of the reaction
(monitored by TLC), the mixture was cooled and neutralized by the
addition of solid NaHCO3, followed by extraction with ethyl acetate (3 Â
30 mL). The combined organic extracts were washed with saturated
aqueous NaHCO3 (2 Â 10 mL), brine (10 mL), dried over anhydrous
modiol (4.7 g, 66%). m.p. 1068C; IR (thin film): nÄ 3531, 3457 cmÀ1
;
1H NMR (300 MHz, CDCl3): d 4.89 (s, 2H), 2.87 (d, J 16Hz, 2H), 2.47
(s, 2H), 2.28 (d, J 15.6 Hz, 2H), 1.86 1.80 (m, 4H), 1.62 (br s, 2H);
13C NMR (75 MHz, CDCl3): d 80.0 (2C), 50.1 (2C), 35.8 (2C), 33.3 (2C),
Na2SO4, and concentrated under reduced pressure to give
a solid.
Purification of the residue by column chromatography over silica gel
(30% ethyl acetate/hexane) gave 15 (160 mg, 60%) and 16 (53 mg, 20%) as
colorless crystalline solids in 80% overall yield. Compound 15: m.p. 198
18.9 (2C); MS (70 eV, EI): m/z (%): 314 [M ]. The dibromodiol was
dissolved in acetic anhydride (10 mL) and BF3 ¥ Et2O (100 mL) was added at
08C and stirred at the same temperature for 1 h under N2. On complete
consumption of the starting material (monitored by TLC), the reaction
mixture was quenched by the careful addition of ice-cold water (50 mL)
and diluted with CH2Cl2 (30 mL). The aqueous layer was extracted with
CH2Cl2 (3 Â 30 mL) and the combined organic extracts were washed
carefully with saturated aqueous NaHCO3 (2 Â 20 mL), brine (20 mL), and
dried over anhydrous Na2SO4. The residue obtained after concentration at
reduced pressure was purified by silica gel chromatography to furnish the
dibromodiacetate 12 (5.3 g, 89%) as a colorless crystalline solid. M.p.
1998C; IR (KBr): nÄ 3478, 1735 cmÀ1
;
1H NMR (300 MHz, CDCl3): d
5.98 (ddd, J 10.2, 4.6, 2.2 Hz, 1H), 5.55 (dd, J 10.3, 1.3 Hz, 1H), 5.42 (d,
J 1.3 Hz, 1H), 4.68 (dd, J 11.1, 4.6 Hz, 1H), 3.14 (d, J 11.1 Hz, 1H),
2.72 (d, J 14.7 Hz, 1H), 2.45 (s, 1H), 2.26 2.05 (m, 1H), 2.16 (s, 3H), 2.04
(s, 3H), 1.67 1.56 (m, 4H); 13C NMR (75 MHz, CDCl3): d 170.1, 169.3,
129.2, 124.6, 83.1 (2C), 73.6, 72.9, 64.8, 31.7, 24.5, 22.2, 21.0, 20.3; MS (70 eV,
EI): m/z (%): 285 [M H]; elemental analysis calcd (%) for C14H20O6
(284): C 59.14, H 7.09; found: C 59.08, H 7.04.
Compound 16: m.p. 162 1638C; IR (KBr): nÄ 3402, 1737, 1723 cmÀ1
;
127.38C; IR (thin film): nÄ 1742 cmÀ1
;
1H NMR (300 MHz, CDCl3): d
1H NMR (300 MHz, CDCl3): d 6.21 (d, J 10 Hz, 1H), 5.91 (dd, J 10,
3.3 Hz, 1H), 5.54 (d, J 8.4 Hz, 1H), 4.29 (brs, 1H), 3.04 (d, J 9.6 Hz,
1H), 2.61 (d, J 11.1 Hz, 1H), 2.21 2.09 (m, 2H), 2.04 (s, 3H), 2.00 (s,
3H), 1.87 1.78 (m, 2H), 1.66 1.22 (m, 4H); 13C NMR (75 MHz, CDCl3):
d 169.8, 167.7, 130.1, 129.7, 80.5, 79.9, 73.5, 70.5, 27.7, 24.5, 22.2, 21.8, 20.2,
4.76 (s, 2H), 3.20 (brs, 1H), 3.14 (brs, 1H), 2.69 (d, J 3.9 Hz, 1H), 2.64 (d,
J 3.9 Hz, 1H), 2.57 2.53 (m, 2H), 2.01 (s, 6H), 1.8 1.6 (m, 4H);
13C NMR (75 MHz, CDCl3): d 170.1 (2C), 86.7 (2C), 48.2 (2C), 30.7
(2C), 27.4 (2C), 23.3 (2C), 18.4; MS (70 eV, EI): m/z (%): 317 [M À BrÀ
H], 319 [M À BrH].
19.8; MS (70 eV, EI): m/z (%): 242 [M À AcH]; elemental analysis calcd
(3aR*,7aR*)-2,3,3a,7a-Tetrahydro-1H-3a,7a-indenediol (6): Dibromodia-
cetate 12 (1 g, 2.51 mmol) was dissolved in dry DMSO (5 mL) and DBU
(0.75 mL, 5.02 mmol) was added dropwise at 5 108C from a syringe under
N2 atmosphere, during which time the reaction turned dark brown. The
reaction mixture was stirred at room temperature for further 2 h, before
diluting with diethyl ether (30 mL) and pouring into ice-cold water
(10 mL). The organic layer was separated and the aqueous layer was
extracted with diethyl ether (3 Â 50 mL). The combined organic extracts
were washed with 10% HCl (2 Â 20 mL), water (20 mL), brine (15 mL),
dried over anhydrous Na2SO4, and concentrated under reduced pressure.
The resultant solid residue was purified by chromatography over neutral
alumina (5% ethyl acetate/hexane) to furnish crystalline trans-diene 6
(%) for C14H20O6 (284.3): C 59.14, H 7.09; found: C 58.91, H 7.07.
Crystal data for compound 15: Structure was solved by direct methods
(SIR92). Refinement was by full-matrixleast-squares procedures on F2 by
using SHELXL-97. Crystal system: rhombohedral-hexagonal, space group:
R3c, cell parameters: a 27.761(2), b 27.761(2), c 9.956(10) ä, g
120(6)8, V 6645.19 ä3, Z 18, 1calcd 1.279 gcmÀ3, F(000) 2736, m
0.10mmÀ1, l 0.71 ä. R1 0.0491 for Fo > 2s(Fo) and 0.0499 for all
2111 data. wR2 0.1392, GOF 1.097. There are four independent mole-
cules in the asymmetric unit. An ORTEP drawing of compound 15 with
50% ellipsoidal probability level is shown in Figure 1.
Compound 17: OsO4 (2 mg, 1 mol%) and 50% aqueous N-methylmorpho-
line N-oxide (NMMO) (130 mL, 0.56 mmol) were added to a solution of
diol 15 (155 mg, 0.545 mmol) in acetone/water (4:1, 5 mL) at 08C, and the
resulting pale yellow reaction mixture was stirred at room temperature for
2 h, before quenching with solid NaHSO3. The resulting mixture was
diluted with ethyl acetate (10 mL), filtered through Celite, and the filtrate
was concentrated under reduced pressure. The residue was subjected to
column chromatography over silica gel (80% ethyl acetate/hexane) to
afford the tetrol 17 (152 mg, 88%). IR (KBr): nÄ 3391, 1727 cmÀ1; 1H NMR
(300 MHz, D2O): d 5.19 (d, J 10.2 Hz, 1H), 5.56 (d, J 2.5 Hz, 1H),
4.10 (dd, J 10.2, 4 Hz, 1H), 4.04 (dd, J 4, 2.5 Hz, 1H), 2.28 (d, J
(319 mg, 54%). M.p. 139.58C; IR (KBr): nÄ 1724 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d 6.43 (d, J 10.2 Hz, 2H), 5.90 (d, J 10.2 Hz,
2H), 2.41 2.35 (m, 2H), 2.09 1.99 (m, 2H), 1.94 1.84 (m, 2H), 1.94 (s,
6H); 13C NMR (75 MHz, CDCl3): d 169.6 (2C), 128.9 (2C), 125.6 (2C),
87.2 (2C), 28.4 (2C), 21.7 (2C), 21.2; MS (70 eV, EI): m/z (%): 152 [M
2Ac2].
À
Compounds 13 and 14: mCPBA (70%, 493 mg, 2 mmol) was added at 08C
to a solution of 5 (500 mg, 2 mmol) in dry CH2Cl2 (10 mL), and the reaction
mixture was stirred at room temperature for 5 h before quenching with
10% Na2SO3 (5 mL). The organic layer was separated and the aqueous
2268
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2003, 9, 2264 2272