Conversion of Levoglucosenone into Isolevoglucosenone
597
(CDCl3, 500 MHz) 5.29 (d, J 3.4, 1H), 4.81 (t, J 4.9, 1H), 3.99 (d,
J 6.9, 1H), 3.78 (m, 2H), 3.55 (m, 1H), 3.33 (m, 1H), 2.34 (d, J
9.0, 1H). dC (CDCl3, 125 MHz) 97.8 (CH), 71.7 (CH), 66.5
(CH), 63.9 (CH2), 57.3 (CH), 50.2 (CH). m/z (ESI, þve) 167
(100 %, [M þ Na]þ. m/z (HRMS ESI (þve)) 167.0320; [M þ
Na]þ requires 167.0320.
Concentration of fraction B (RF 0.4 in 6 : 3 : 1 v/v/v ethyl
acetate/hexane/methanol) gave compound 9[13] (466 mg, 56 %)
as a white, crystalline solid, mp 158–1608C. [a]D ꢁ1298 (c 0.5
in methanol). nmax (KBr)/cmꢁ1 3386, 2973, 2907, 1489, 1414,
1084, 1053, 974, 948, 874, 808, 468. dH (CDCl3, 500 MHz) 5.32
(m, 1H), 4.73 (d, J 3.9, 1H), 4.05 (d, J 7.3, 1H), 3.87–3.83
(complex m, 2H), 3.13 (d, J 3.9, 1H), 3.00 (m, 1H), 2.36 (d, J 9.0,
1H). dC (CDCl3, 125 MHz) 99.1 (CH), 69.8 (CH), 67.3 (CH2),
65.0 (CH), 51.0 (CH), 50.0 (CH). m/z (ESI, þve) 167 (100 %,
[M þ Na]þ. m/z (HRMS ESI (þve)) 167.0320; [M þ Na]þ
requires 167.0320.
Compound 11: A magnetically stirred solution of compound
8 (166 mg, 1.30 mmol) in pyridine (5 mL) maintained at 188C
was treated with acetic anhydride (Ac2O; 500 mL, 5.29 mmol)
and 4-dimethylaminopyridine (DMAP; 20 mg, 0.164 mmol).
After 18 h, the reaction mixture was concentrated under reduced
pressure and the resulting light yellow oil was subjected to flash
chromatography (silica, 1 : 1 v/v ethyl acetate/hexane elution).
Concentration of the appropriate fractions (RF 0.5 in 4 : 2.5 : 5.5
v/v/v ethyl acetate/dichloromethane/hexane) afforded com-
pound 11[15] (198 mg, 90 %) as a clear, colourless oil. [a]D
ꢁ608 (c 0.4 in methanol). nmax (KBr)/cmꢁ1 2965, 2891, 1732,
1372, 1237, 1125, 1043, 983, 900, 884. dH (CDCl3, 500 MHz)
6.19 (m, 1H), 5.62 (m, 2H), 5.50 (s, 1H), 4.68 (m, 1H), 3.97 (d, J
6.4, 1H), 3.79 (m, 1H), 2.12 (s, 3H). dC (CDCl3, 125 MHz) 170.7
(C), 132.4 (CH), 124.7 (CH), 99.1 (CH), 71.6 (CH), 71.4 (CH2),
71.3 (CH), 21.0 (CH3). m/z (ESI, þve) 193 (100 %, [M þ Na]þ).
m/z (HRMS ESI (þve)) 193.0470; [M þ Na]þ requires
193.0477.
ethyl acetate/dichloromethane/hexane) afforded compound 9
(168 mg, 96 %) as a white, crystalline solid that was identical,
in all aspects, to the material obtained from the conversion 8 -
9 þ 10.
Compound 3: A solution of compound 9 (466 mg,
3.23 mmol) in dichloromethane (40 mL) was treated with pyri-
dine (2.6 mL, 32.14 mmol) then with DMP (2.06 g, 4.86 mmol)
and the resulting solution stirred at 188C for 18 h before being
concentrated under reduced pressure. Subjection of the resulting
light yellow oil to flash chromatography (silica, 5 : 4 : 0.5 v/v/v
ethyl acetate//hexane/methanol elution) afforded, after concen-
tration of the appropriate fractions (RF 0.5 in 7 : 2 : 1 v/v/v ethyl
acetate/hexane/methanol), compound 3[17] (449 mg, 98 %) as a
white, crystalline solid, mp 95–968C. [a]D ꢁ1938 (c 0.5 in
methanol). nmax (KBr)/cmꢁ1 2971, 2905, 1744, 1407, 1350,
1140, 1103, 1083, 973, 951, 878, 809. dH (CDCl3, 500 MHz)
5.17 (d, J 1.9, 1H), 4.99 (m, 1H), 4.04 (d, J 7.3, 1H), 3.89 (m,
1H), 3.51 (m, 1H), 3.30 (m, 1H). dC (CDCl3, 125 MHz) 192.0
(C), 99.8 (CH), 70.2 (CH), 65.1 (CH2), 49.9 (CH), 49.1 (CH).
m/z (EI, 70eV) 141 (3%, [Mꢁ Hꢂ]þ), 114 (12), 101 (23), 85
(23), 84 (31), 72 (63), 71 (56), 69 (48), 68 (57), 57 (100). m/z
(HRMS ESI (þve)) 141.0188; [Mꢁ Hꢂ]þ requires 141.0188.
Compounds 13 and 14: A magnetically stirred solution of
compound 3 (122 mg, 0.86 mmol) in methanol (10 mL) main-
tained at 188C was treated dropwise with hydrazine (3.4 mL of a
1.0 M THF solution, 3.40 mmol) and after 1 h with acetic acid
(250 mL, 4.37 mmol). The ensuing mixture was stirred at 188C
for 24 h then concentrated under reduced pressure and the light
yellow oil thus obtained was subjected to flash chromatography
(silica, 1 : 1 v/v ethyl acetate/hexane - 6 : 3 : 0.4 v/v/v ethyl
acetate/hexane/methanol gradient elution) and thereby afford-
ing two fractions, A and B.
Concentration of fraction A (RF 0.5 in 5 : 4 : 1 v/v/v ethyl
acetate/hexane/methanol) gave compound 14[9] (23 mg, 21 %)
as a white, crystalline solid, mp 59–608C. [a]D þ2098 (c 0.6 in
methanol). nmax (KBr)/cmꢁ1 3390, 2977, 2896, 1640, 1385,
1171, 1096, 1052, 1011, 988, 960, 934, 898, 864, 738, 709. dH
((CD3)2CO, 500 MHz) 6.05 (m, 1H), 5.85 (m, 1H), 5.50 (d, J 3.4,
1H), 4.65 (m, 1H), 3.95 (m, 1H), 3.65 (m, 1H), 3.45 (m, 1H),
2.20 (broad s, 1H). dC ((CD3)2CO, 125 MHz) 130.4 (CH), 127.7
(CH), 96.0 (CH), 77.8 (CH), 67.8 (CH), 63.4 (CH2). m/z (ESI,
þve) 151 (100 %, [M þ Na]þ). m/z (HRMS ESI (þve))
151.0372; [M þ Na]þ requires 151.0371.
Compound 12: A magnetically stirred solution of compound
11 (186 mg, 1.09 mmol) in dichloromethane (20 mL) was trea-
ted with m-CPBA (980 mg of material of 77 % purity,
4.37 mmol) and anhydrous NaHCO3 (735 mg, 8.75 mmol).
After stirring at 188C for 120 h, the reaction mixture was filtered
through a short pad of CeliteTM and the filtrate concentrated
under reduced pressure. The light yellow residue thus obtained
was subjected to flash chromatography (silica, 2 : 1 v/v ethyl
acetate/hexane elution) to afford, after concentration of the
appropriate fractions (RF 0.4 in 8 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane), compound 12[15] (149 mg, 73 %) as a
white, crystalline solid, mp 65–678C (lit. 688C[15]). [a]D ꢁ1428
(c 0.5 in methanol). nmax (KBr)/cmꢁ1 2969, 2899, 1740, 1435,
1372, 1234, 1142, 1055, 981, 904, 882, 821, 802. dH (CDCl3,
500 MHz) 5.44 (m, 1H), 4.86 (m, 1H), 4.75 (d, J 4.4, 1H), 4.13
(d, J 6.3, 1H), 3.89 (m, 1H), 3.16 (m, 1H), 3.01 (m, 1H), 2.15 (s,
3H). dC (CDCl3, 125 MHz) 169.8 (C), 97.0 (CH), 69.8 (CH),
67.4 (CH2), 67.1 (CH), 49.7 (CH), 49.2 (CH), 20.8 (CH3). m/z
(ESI, þve) 209 (100 %, [M þ Na]þ). m/z (HRMS ESI (þve))
209.0426; [M þ Na]þ requires 209.0426.
Concentration of fraction B (RF 0.4 in 5 : 4 : 1 v/v/v ethyl
acetate/hexane/methanol) gave compound 13[18] (27 mg, 24 %)
as a white, crystalline solid, mp 46–498C. [a]D ꢁ1218 (c 0.6
in methanol). nmax (KBr)/cmꢁ1 3413, 2953, 2894, 1449, 1338,
1179, 1097, 985, 896, 866. dH ((CD3)2CO , 500 MHz) 5.37 (s,
1H), 4.35 (m, 1H), 3.82 (m, 2H), 3.63 (m, 1H), 3.58 (broad s,
1H), 1.98–1.83 (complex m, 2H), 1.54–1.48 (complex m, 1H),
1.43–1.37 (complex m, 1H). dC ((CD3)2CO, 125 MHz) 102.1
(CH), 78.3 (CH), 67.2 (CH), 66.8 (CH2), 28.4 (CH2), 24.2
(CH2). m/z (ESI, þve) 153 (100 %, [M þ Na]þ). m/z (HRMS
ESI (þve)) 153.0529; [M þ Na]þ requires 153.0528.
Compound 14: A magnetically stirred solution of compound
3 (178 mg, 1.25 mmol) in methanol (18 mL) was treated drop-
wise with hydrazine (5 mL of a 1.0 M solution in THF,
5.00 mmol) and after 1 h with acetic acid (430 mL, 7.51 mmol).
After a further 2 h, the reaction mixture was concentrated under
reduced pressure and the light brown residue subjected to flash
chromatography (silica, 2 : 1 v/v ethyl acetate/hexane elution).
Concentration of the appropriate fractions (RF 0.5 in 5 : 4 : 1
v/v/v ethyl acetate/hexane/methanol) then gave compound 14
Compound 9: A solution of compound 12 (226 mg,
1.21 mmol) in methanol (10 mL) maintained at 188C was treated
with anhydrous K2CO3 (503 mg, 3.64 mmol) and the ensuing
mixture stirred magnetically for 2 h then filtered through a short
pad of CeliteTM. The filtrate was concentrated under reduced
pressure and the residue subjected to flash chromatography
(silica, 2 : 1 v/v ethyl acetate/hexane elution). Concentration
of the appropriate fractions (RF 0.4 in 8 : 2.5 : 5.5 v/v/v