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A. Błonska et al. / Tetrahedron: Asymmetry 20 (2009) 2728–2732
were dried, concentrated, and the product was purified by column
chromatography (hexane–ethyl acetate, 98:2) to afford 11 as an
amorphous solid (430 mg, 70%).
[a]
D = +55.6; 1H NMR d: 5.48 (m, H-3), 5.03 (dd, J2,3 3.0, J1,2 11.7,
H-2), 4.31–4.78 (8H, 4 Â OCH2Ph), 4.02 (m, H-7), 3.93 (dd, J8,9 1.5,
J1,9 6.2, H-9), 3.90 (dd, J7,8 4.8, H-8), 3.26 (dd, J 4.1, Jgem 9.1, one
of CH2OBn), 3.15 (dd, J 6.0, one of CH2OBn), 2.75 (ddd, J1,6 13.4,
H-1), 2.26 (m, H-5), 2.05 (3H, s, CH3), 1.99 (m, one of H-4), 1.89
(3H, s, CH3), 1.71 (ddd, J6,7 3.8, J5,6 11.4, H-6), 1.50 (m, one of H-
4); 13C NMR d: 170.40, 170.16 (2 Â CH3CO), 138.93, 138.38,
138.08, 138.02 (4 Â Cipso), 88.29 (C-8), 81.31 (C-9), 77.53 (C-7),
73.71, 73.08, 72.24, 72.10, 71.29 (4 Â OCH2Ph and CH2OBn),
71.53 (C-2), 69.18 (C-3), 45.10 (C-6), 41.65 (C-1), 32.78 (C-4),
31.21 (C-5), 21.13 and 20.90 (2 Â CH3). NOE: H1–H9, H1–H5,
H2–H3, H2–H6, H6–H7, H6–H8, H7–H8.
HRMS m/z: 583.28072 [C38H40O4Na (M+Na+) requires
583.28188]; [a]
D = +62.9; 1H NMR d: 5.91 (dd, J1,2 2.1, J2,3 10.0, H-
2), 5.67 (m, H-3), 4.33–4.69 (8H, 4 Â OCH2Ph), 3.99 (dd, J 2.9, 6.8,
H-8), 3.86 (dd, J 4.5, Jgem 9.3, one of CH2OBn), 3.70–3.74 (2H, m,
H-7 and H-9), 3.33 (ꢀt, J 9.3, one of CH2OBn), 2.48 (m, one of H-
4), 2.13 (m, H-1), 2.05 (m, H-5), 1.87 (m, one of H-4), 1.82 (m, H-
6); 13C NMR d: 138.77, 138.28, 138.16, 138.15 (4 Â Cipso), 127.39–
128.47 (Ar, C-3), 126.97 (C-2), 87.23 and 80.68 (C-7, C-9), 81.60
(C-8), 73.92 (CH2OBn), 73.00, 72.17, 72.02, 71.59 (4 Â OCH2Ph),
45.04 (C-6), 44.19 (C-1), 39.69 (C-5), 31.50 (C-4). NOE: H1–H2,
H1–H5, H1–H8, H2–H3.
4.4.2. (1S,2S,3R,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 15 (18%)
This product was characterized as the diacetate 15-Ac: HRMS
m/z: 701.31159 [C42H46O8Na (M+Na+) requires 701.30849];
4.3. (1R,2R,5R,6R,7R,8R,9R)-2-Hydroxy-7,8,9-tri-O-benzyl-5-
benzyloxymethyl-bicyclo[4.3.0]non-3-ene 18
[a]
D = +10.3; 1H NMR d: 5.28–5.22 (2H, m, H-2, H-3), 4.40–4.90
To a solution of diphenyldiselenide (70 mg, 0.23 mmol) in anhy-
drous ethanol (6 mL), sodium borohydride was added in portions
(17 mg, 0.46 mmol) and the mixture was stirred for 1 h until the
yellow color disappeared. Then a solution of the epoxide 1310
(130 mg, 0.23 mmol) in THF (2 mL) was added and the mixture
was heated at reflux for 5 h. After cooling to 5 °C (ice bath) hydro-
gen peroxide (30% in water, 0.75 mL) was added, the mixture was
stirred for 24 h at rt, and quenched with saturated sodium carbon-
ate (6 mL). Water (20 mL) was added, and the product was ex-
tracted with diethyl ether (3 Â 15 mL). The organic phase was
washed with brine, dried, concentrated, and the product was iso-
lated by HPLC (hexane–ethyl acetate, 84:16) to give allylic alcohol
18 (48 mg; 37%) as an oil. HRMS m/z: 599.27974 [C38H40O5Na
(8H, 4 Â OCH2Ph), 3.93–3.97 (3H, H-7, H-8, H-9), 3.52 (dd, J 7.7,
Jgem 9.1, one of CH2OBn), 3.33 (dd, J 5.9, one of CH2OBn), 2.43 (m,
H-6), 2.30 (m, H-1), 2.20 (m, H-5), 2.08 (m, one of H-4), 2.02 (3H,
s, CH3), 2.00 (3H, s, CH3), 1.72 (m, one of H-4); 13C NMR d:
170.27, 170.17 (2 Â CH3CO), 138.70, 138.44, 138.42, 138.37
(4 Â Cipso), 87.54, 87.22, 82.07 (C-7, C-8, C-9), 74.13 (CH2OBn),
73.43, 72.93, 72.49, 71.98 (4 Â OCH2Ph), 72.70 (C-2), 79.17 (C-3),
41.80 (C-1), 39.30 (C-6), 32.26 (C-5), 29.19 (C-4), 21.17 and 21.07
(2 Â CH3).
1H NMR (C6D6) d: 1H NMR d: 5.66 (dd, J2,3 3.1, J1,2 9.0, H-2), 5.52
(m, H-3), 4.30–4.79 (8H, 4 Â OCH2Ph), 4.18 (ꢀt, H-9), 3.90 (ꢀt,
J7,8 ꢀ J8,9 4.6, H-8), 3.71 (ꢀt, J6,7 ꢀ J7,8 4.4, H-7), 3.44 (dd, J 7.0, Jgem
9.0, one of CH2OBn), 3.31 (dd, J 5.9, one of CH2OBn), 2.50 (ddd, J1,9
4.2, J1,2 ꢀ J1,6 ꢀ 8.9, H-1), 2.44 (m, H-6), 2.27 (m, H-5), 2.04 (ddd,
J3,4eq 4.1, J4eq,5 10.0, Jgem 14.2, Heq-4), 1.81 (dd, J3,4ax 7.0, Hax-4),
1.77 (3H, s, CH3), 1.70 (3H, s, CH3); 13C NMR (C6D6) d: 169.73,
169.51 (2 Â CH3CO), 139.28, 139.27, 139.21, 139.08 (4 Â Cipso),
87.62 (C-9), 87.13 (C-8), 82.42 (C-7), 74.27 (CH2OBn), 73.49,
73.04, 72.67, 72.20 (4 Â OCH2Ph), 72.70 (C-2), 69.17 (C-3), 42.95
(C-1), 39.55 (C-6), 32.95 (C-5), 29.53 (C-4), 20.81 and 20.78
(2 Â CH3); NOE: H1–H2, H1–H5, H1–H9, H2–H3, H2–H9, H3–H5,
H6–H7, H6–H8, H7–H8.
(M+Na+) requires 599.2768]; [
a
]
D = À29.6; 1H NMR d: 5.91 (ddd,
J2,3 5.2, J3,5 2.5, J3,4 9.9, H-3), 5.83 (dd, J4,5 1.8, H-4), 4.47–4.79
(8H, 4 Â OCH2Ph), 4.48 (m, H-2), 4.43 (dd, J8,9 5.8, J1,9 9.7, H-9),
4.15 (ꢀt, H-7), 3.96 (dd, J7,8 3.5, H-8), 3.40 (2H, m, CH2OBn), 2.77
(m, H-5), 2.38 (ddd, J1,2 2.9, J1,6 13.2, H-1), 2.17 (ddd, J6,7 2.8, J5,6
10.5, H-6); 13C NMR d: 139.04, 138.42, 137.97, 137.83 (4 Â Cipso),
132.57 (C-4), 128.85 (C-3), 90.93 (C-8), 84.65 (C-9), 76.55 (C-7),
72.23–73.34 (4 Â OCH2Ph), 64.59 (C-2), 43.40 (C-1), 38.44 (C-6),
38.05 (C-5). NOE: H1–H9, H1–H2, H1–H5, H2–H3, H3–H4, H4–
H5, H6–H7, H6–H8, H7–H8.
ꢁ The reaction of 11 was conducted for 40 h and afforded two
products 16 and 17 which were separated by HPLC (hexane–
ethyl acetate, 7:3).
4.4. cis-Di-hydroxylations: general procedure
The corresponding olefin 10, 11, or 18 (0.50 mmol) was dis-
solved in THF (5 mL), tert-butanol (0.5 mL), and water (0.05 mL)
to which N-methyl morpholine N-oxide (1.2 equiv, 0.60 mmol,
70 mg) and osmium tetraoxide (0.25 mL of a ca. 2% solution in
tert-BuOH) were added. The mixture was stirred at rt until the dis-
appearance of the starting material (TLC monitoring in hexane–
ethyl acetate, 2:1). Methanol (15 mL) was added followed by satu-
rated aq NaHSO3 solution. The mixture was stirred for 0.5 h, and
then partitioned between water (20 mL) and ethyl acetate
(50 mL). The organic phase was separated, washed with water
(50 mL), brine (20 mL), dried, concentrated, and the crude products
were isolated by column chromatography or HPLC.
4.4.3. (1R,2R,3S,5S,6S,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 16 (43%)
HRMS m/z: 617.28785 [C38H42O6Na (M+Na+) requires
617.28736]. This product was characterized further as the diace-
tate 16-Ac: [a]
D = +21.1; 1H NMR d: 5.62 (m, H-2), 4.86 (ddd, J2,3
2.9, J3,4eq 4.8, J3,4ax 12.3, H-3), 4.31–4.63 (8H, 4 Â OCH2Ph), 3.93
(dd, J8,9 2.7, J7,8 6.5, H-8), 3.88 (dd, J 3.9, Jgem 9.5, one of CH2OBn),
3.67 (dd, J1,9 8.8, H-9), 3.61 (dd, J6,7 10.3, H-7), 3.29 (ꢀt, J 9.3, one
of CH2OBn), 2.13 (ddd, J4eq,5 4.0, Jgem 12.8, Heq-4), 2.04 (m, H-6),
1.76 (m, H-5), 1.63 (m, H-1), 1.51 (m, Hax-4); 13C NMR d: 170.48,
170.11 (2 Â CH3CO), 138.54, 137.92, 137.86, 137.73 (4 Â Cipso),
82.22 (C-9), 81.23, 81.22 (C-7 and C-8) 71.72–73.06 (4 Â OCH2Ph
and CH2OBn), 72.11 (C-3), 67.97 (C-2), 46.90 (C-1), 40.62 (C-5),
40.34 (C-6), 29.93 (C-4), 20.93, 20.88 (2 Â CH3). NOE: H1–H2,
H1–H3, H1–H5, H1–H7, H2–H3, H5–H7, H6–H9, H7–H8.
ꢁ The reaction of 10 was conducted for 40 h and afforded two
products 14 and 15 which were separated by column chroma-
tography (hexane–ethyl acetate, 4:1).
4.4.1. (1S,2R,3S,5R,6R,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 14 (75%)
This product was characterized as the diacetate 14-Ac: HRMS
m/z: 701.30602 [C42H46O8Na (M+Na+) requires 701.30849];
4.4.4. (1R,2S,3R,5S,6S,7R,8R,9R)-2,3-Di-hydroxy-7,8,9-tri-O-
benzyl-5-benzyloxymethyl-bicyclo[4.3.0]nonane 17 (33%)
HRMS m/z: 617.28775 [C38H42O6Na (M+Na+) requires
617.28736].