Y. Altun et al. / Tetrahedron xxx (2014) 1e7
5
rel-(3aS,4S,7R,7aS)-2-Oxooctahydrobenzofuran-4,7-diyl diacetate
(10) was isolated as the second fraction, colorless crystals (450 mg,
21%) from ethanol/hexane, 151e152 ꢀC. 1H NMR (400 MHz, CDCl3)
cooled to 0 ꢀC, then the resulting solution was extracted with
ether (3ꢁ100 mL). The combined extracts were washed with
saturated NaHCO3 solution (50 mL) and then with water (50 mL).
The organic phase was dried (Na2SO4) and then removed by rotary
evaporator to give colorless crystals from ethyl acetate/n-hexane
d
5.11e5.07 (m, 2H, H-4 and H-7), 4.65 (t, J¼4.8 Hz, 1H, H-7a), 2.91
(quintet, J¼5.9 Hz, 1H, H-3a), 2.53 (dd, A-part of AB-system, J¼17.3
and 6.2 Hz, 1H, H-3), 2.48 (dd, B-part of AB-system, J¼17.3 and
7.6 Hz,1H, H-30), 2.09 (s, COCH3), 2.06 (s, COCH3), 2.0e1.9 (m, 2H, H-
5 or H-6), 1.72e1.6 (m, 2H, H-5 or H-6). 13C NMR (100 MHz, CDCl3)
(1.1 g, 62%), mp 32e34 ꢀC.23b 1H NMR (400 MHz, CDCl3)
d 5.86 (dd,
A-part of AB-system, J¼9.9 and 2.8 Hz, 1H), 5.73 (dd, B-part of AB-
system, J¼9.9 and 2.3 Hz), 5.32e5.35 (m, 2H), 5.18e5.14 (m, 1H),
2.02e1.98 (m, 2H), 2.0 (s, 9H, COCH3). 13C NMR (100 MHz, CDCl3)
d 170.3, 170.2, 170.0, 128.9, 128.7, 70.0, 68.6, 66.2, 31.0, 21.1, 21.0,
20.9.
d
175.7, 169.9 (2C), 76.8, 68.9, 68.2, 38.5, 31.7, 23.8, 20.9, 20.8 (2C). IR
(KBr, cmꢂ1) 2963,1783,1729,1377,1213. Anal. Calcd for C12H16O6: C,
56.24; H, 6.29. Found: C, 56.04; H, 6.19.
4.5. rel-(1R,2R,3R,4S)-3-(2-Acetoxyethyl)cyclohexane-1,2,4-
triyl triacetate (12)
4.8. Reaction of rel-(1R,2R,4R)-cyclohex-5-ene-1,2,4-triyl tri-
acetate (17) with Mn(OAc)3$2H2O in CH3COOH
To a slurry of LiAlH4 (300 mg, 7.9 mmol) in 30 mL of dry THF,
cooled to 0 ꢀC, was added a solution of lactone 9 (500 mg,
1.95 mmol) in dry THF (25 mL) under nitrogen dropwise over
a period of 3 h. The reaction mixture was stirred for an additional
hour at room temperature and then 10 g silica gel and ether were
added. The mixture was stirred overnight. For completion of the
hydrolysis 35 mL methanol was added and filtered. The solvent was
removed by rotary evaporator at 50 ꢀC to give the crude product
(285 mg, 83%). The residue was dissolved in 5 mL of pyridine and
800 mg of acetic anhydride was added. The reaction mixture was
stirred magnetically for 6 h at room temperature. After completion
of the reaction, the reaction mixture was poured into a HCl solution
(1 N, 200 mL) cooled to 0 ꢀC. The mixture was extracted with ether
(3ꢁ100 mL). The organic phase was washed with saturated 35 mL
NaHCO3 solution and then with 20 mL of water. The combined
organic phase was dried over Na2SO4 and the solvent was removed
by rotary evaporator (40 ꢀC) to give colorless liquid (485 mg, 87%).
Triacetate 17 (1.28 g, 5 mmol), Mn(OAc)3$2H2O (7.75 g,
28 mmol) KOAc (3.2 g, 32.6 mmol) were dissolved in 160 mL of
acetic acid and the resulting mixture was refluxed until the re-
action mixture turned to white (4 days). After cooling to room
temperature, the mixture was washed with CH2Cl2 (3ꢁ100 mL).
The CH2Cl2 phase was washed with saturated NaHCO3 solution
and then with water. The combined organic phase was dried over
MgSO4 and the solvent was removed by rotary evaporator. The
yield of crude product was 60% for four isomers. The analysis of
the 1H NMR spectrum showed the formation of an isomeric
mixture consisting of 18, 19, 20, and 21, in the following ratio
46:31:15:8, respectively. Chromatography of the residue on silica
with ethyl acetate/hexane 65:35 gave a mixture of 18 and 19 as the
first fraction. Crystallization of this mixture from ethanol/n-hex-
ane gave pure 18.
4.8.1. (3aS,4S,5S,7S,7aS)-2-Oxooctahydrobenzofuran-4,5,7-triyl tri-
1H NMR (400 MHz, CDCl3)
d
5.08 (dd, J¼4.8 and 3.8 Hz, 1H, H-2),
acetate (18). White crystalline product from n-hexane/EtOAc, mp
4.85e4.79 (m, 2H, H-1 and H-4), 4.06 (dd, A-part of AB-system,
J¼11.1, 6.8 Hz, 1H, OCH2), 3.01 (dd, B-part of AB-system, J¼11.1,
6.6 Hz, 1H, OCH2), 2.13e2.05 (m, 1H, H-3), 2.02 (s, COCH3), 2.01 (s,
COCH3), 2.008 (s, COCH3), 1.97 (s, COCH3), 1.84e1.76 (m, 3H),
130e132 ꢀC. 1H NMR (400 MHz, CDCl3)
d 5.22e5.17 (m, 3H, H-4, H-
5, and H-7), 4.67 (t, J¼6.9 Hz, 1H, H-7a), 2.95e2.87 (m, 1H, H-3a),
2.67 (dd, A-part of AB-system, J¼17.3 and 8.3 Hz, 1H, H-3), 2.45 (dd,
B-part of AB-system, J¼17.3 and 10.5 Hz, 1H, H-30), 2.2e2.12 (m, 1H,
H-6), 2.13 (s, 3H, COCH3), 2.12 (s, 3H, COCH3), 2.07 (s, 3H, COCH3),
1.70e1.51 (m, 3H). 13C NMR (100 MHz, CDCl3)
d 170.8, 170.3, 169.6,
169.7, 72.0, 71.1, 68.1, 62.5, 38.1, 26.1, 25.1, 24.0, 21.2, 21.0, 20.9, 20.8.
IR (KBr, cmꢂ1) 2957,1737,1369,1233,1027. Anal. Calcd for C16H24O8:
C, 55.81; H, 7.02. Found: C, 55.49; H, 6.74.
2.05e1.98 (m, 1H, H-60). 13C NMR (100 MHz, CDCl3)
d 173.4, 169.9,
169.7, 169.4, 79.1, 71.5, 67.8, 67.5, 39.8, 31.4, 29.8, 20.9, 20.8, 20.7. IR
(KBr, cmꢂ1) 2944, 1787, 1733, 1430, 1235, 1051, 1015. Anal. Calcd for
C14H18O8: C, 53.50; H, 5.77. Found: C, 52.58; H, 5.60.
4.6. rel-(1R,2R,3R,4S)3-(2-Hydroxyethyl)cyclohexane-1,2,4-
triol (11)
4.8.2. rel-(3aR,4S,5S,7S,7aR)-2-Oxooctahydrobenzofuran-4,5,7-triyl
triacetate (19). After repeated crystallization of a mixture consist-
ing of 18 and 19, the second isomer 19 was isolated as colorless
crystals from n-hexane/EtOAc, mp 150e152 ꢀC. 1H NMR (400 MHz,
Tetraacetate 12 (250 mg, 0.73 mmol) was dissolved in 50 mL of
methanol and dry NH3 gas was passed through solution for 2 h.
Then, the reaction flask was closed and stirred for 3 d at room
temperature. When the reaction was complete the solvent was
removed by rotary evaporator (55 ꢀC) to give 11 as colorless liquid,
CDCl3)
d
5.35 (dt, J¼5.8 and 4.2 Hz, 1H, H-7) 5.19 (dt, J¼4.0 and
8.8 Hz, 1H, H-5), 5.00 (t, J¼7.7 Hz, 1H, H-4), 4.51 (t, J¼5.1 Hz, 1H, H-
7a), 2.83 (quintet, J¼5.9 Hz, 1H), 2.70 (dd, A-part of AB-system,
J¼17.4 and 6.6 Hz, 1H, H-3), 2.65 (dd, B-part of AB-system, J¼17.4
and 5.5 Hz, H-30), 2.16 (s, 3H, COCH3), 2.6e2.1 (m, 1H, H-6), 2.11 (s,
3H, COCH3), 2.09 (s, 3H COCH3), 2.06e2.02 (m, 1H, H-30). 13C NMR
123 mg, 96%. 1H NMR (400 MHz, D2O)
d
3.74e3.72 (m, 1H),
3.68e3.64 (m, 1H), 3.63e3.54 (m, 3H), 1.77e1.47 (m, 7H). 13C NMR
(100 MHz, D2O) d 71.7, 69.4, 68.9, 60.1, 41.0, 29.0, 27.2, 25.6. IR (KBr,
cmꢂ1) 3339, 2938, 1287, 1054, 1010. HRMS Calcd for C8H16O4Na:
199.0946; found: 199.0939.
(100 MHz, CDCl3) d 173.7, 169.8, 169.77, 169.4, 78.2, 71.2, 68.6, 67.6,
39.5, 33.5, 29.3, 20.9, 20.8, 20.7. IR (KBr, cmꢂ1) 2958, 1787, 1744,
1377, 1234, 1158, 1054. Anal. Calcd for C14H18O8: C, 53.50; H, 5.77.
Found: C, 53.22; H, 5.65.
4.7. rel-(1R,2R,4R)-Cyclohex-5-ene-1,2,4-triyl triacetate (17)
Bicyclic endoperoxide (14)23b (1.0 g, 6.94 mmol) was dissolved
in 50 mL of methanol and 1.06 g (13.9 mmol) thiourea was added.
The reaction was stirred magnetically for 2 h at room temperature.
The mixture was filtrated and the solvent was removed by a rotary
evaporator. The residue was dissolved in 10 mL of pyridine and
2.0 g of acetic anhydride was added. The reaction mixture was
stirred magnetically for 6 h at room temperature. The reaction
mixture was poured into a 200 mL of 1 N HCl solution, which was
4.8.3. rel-(3aS,4S,5S,7S,7aS)-2-Oxooctahydrobenzofuran-4,5,7-triyl
triacetate (20). Lactone 20 was isolated as the second fraction as
a viscous liquid. 1H NMR (400 MHz, CDCl3)
d
5.24 (dt, J¼9.8 and
3.9 Hz, 1H, H-7), 5.11 (dt, J¼6.1 and 2.7 Hz, 1H, H-5), 5.05 (t,
J¼5.8 Hz, 1H, H-4), 4.66 (t, J¼4.7 Hz, 1H, H-7a), 3.02 (quintet,
J¼5.7 Hz,1H, H-3a) 2.46 (dd, A-part of AB-system, J¼17.2 and 7.8 Hz,
H-3), 2.41 (dd, B-part of AB-system, J¼17.2 and 5.5 Hz, H-30), 2.19
(ddd, J¼14.2, 9.8, and 2.8 Hz, 1H, H-6) 2.04 (s, 3H, COCH3), 2.01