W.H. Kim et al. / Tetrahedron 66 (2010) 1706–1715
1711
added diisobutylaluminum hydride (Dibal-H, 71.53 mL, 71.53 mmol,
1.0 M solution in hexanes) at ꢀ78 ꢁC, and the reaction mixture was
stirred for 30 min at the same temperature. MeOH (71.50 mL) was
added and the resulting mixture was stirred overnight, allowing it to
reach room temperature. The gel generated was filtered off through
a pad of Celite, and the filtrate collected was concentrated under
reduced pressure. The residue was purified by silica gel column
LRMS(FABþ) m/z 491 (MþH)þ; HRMS(FABþ) m/z C30H39O4Si
(MþH)þ calcd 491.2618, obsd 491.2629.
5.1.7. (þ)-((1R,2S)-2-((tert-Butyldiphenylsilyloxy)methyl)-1-((4-me-
thoxybenzyloxy)methyl)cyclopropyl)methyl benzoate (12). To a stir-
red solution of 11 (5.03 g, 10.25 mmol) and DMAP (0.13 g,
1.02 mmol) in methylene chloride (70 mL) and pyridine (4.14 mL,
51.24 mmol) was treated dropwise benzoyl chloride (1.31 mL,
12.81 mmol) at 0 ꢁC and the reaction mixture was stirred at room
temperature for 8 h. After being evaporated under reduced pres-
sure, the reaction mixture was extracted with ethyl acetate, washed
with 0.5 M HCl solution and a saturated NaHCO3 solution, dried
over MgSO4 and filtered. The filtrate was concentrated under
reduced pressure to give an oil, which was purified by silica gel
chromatography using hexane and ethyl acetate (1.8:1) to give lactol
25
9 (8.53 g, 95%) as a colorless oil: [
n
a
]
þ4.45 (c 1.34, CHCl3); IR (neat):
D
3387, 3085 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
7.22 (d, 2H, J¼8.8 Hz,
Ar), 6.85 (d, 2H, J¼8.4 Hz, Ar), 5.25 (d,1H, J¼5.6 Hz, anomeric H), 4.48
(d,1H, J¼11.6 Hz, PMPCHH), 4.44 (d,1H, J¼11.6 Hz, PMPCHH), 4.32 (d,
1H, J¼5.6 Hz, OH), 4.04 (dd, 1H, J¼2.8, 7.6 Hz, 4-HH), 3.77 (s, 3H,
OCH3), 3.72–3.68 (m, 2H, 4-HH, CHHOPMB), 3.61 (d, 1H, J¼10.4 Hz,
CHHOPMB), 1.58–1.54 (m, 1H, 5-H), 0.66 (dd, 1H, J¼4.8, 8.0 Hz,
6-HH), 0.56 (t, 1H, J¼4.4 Hz, 6-HH); 13C NMR (100 MHz, CDCl3)
column chromatography using hexane and ethyl acetate (15:1) to
25
give compound 12 (5.79 g, 95%) as a colorless oil: [
1.17, CHCl3); IR (neat):
3086, 1724 cmꢀ1
CDCl3)
7.97–7.29 (m,15H, 3ꢂPh), 7.22 (d, 2H, J¼8.4 Hz, Ar), 6.79 (d,
a
]
þ17.30 (c
D
d
159.5, 129.9, 129.7, 114.1, 99.5, 73.0, 70.2, 67.5, 55.5, 32.6, 20.4, 13.3;
n
;
1H NMR (400 MHz,
LRMS(FABþ) m/z 251 (MþH)þ; HRMS(FABþ) m/z C14H19O4 (MþH)þ
d
calcd 251.1283, obsd 251.1290.
2H, J¼8.8 Hz, Ar), 4.60 (d, 1H, J¼11.6 Hz, CHHOBz), 4.50 (d, 1H,
J¼11.6 Hz, PMPCHH), 4.46 (d, 1H, J¼11.6 Hz, PMPCHH), 4.35 (d, 1H,
J¼11.6 Hz, CHHOBz), 3.84 (dd, 1H, J¼6.0, 11.6 Hz, TBDPSOCHH), 3.73
(s, 3H, OCH3), 3.72 (dd, 1H, J¼7.2, 11.2 Hz, TBDPSOCHH), 3.43 (d, 1H,
J¼10.0 Hz, CHHOPMB), 3.38 (d, 1H, J¼10.4 Hz, CHHOPMB), 1.26–1.15
(m, 1H, 2-H), 0.99 (s, 9H, tert-butyl), 0.72 (dd, 1H, J¼5.6, 14.0 Hz,
3-HH), 0.55 (t, 1H, J¼5.6 Hz, 3-HH); 13C NMR (100 MHz, CDCl3)
5.1.5. (þ)-(1R,2S)-2-((tert-Butyldiphenylsilyloxy)methyl)-1-((4-me-
thoxybenzyloxy) methyl)cyclopropanecarbaldehyde (10). To a solu-
tion of lactol
9 (8.53 g, 34.07 mmol) and imidazole (4.87 g,
71.56 mmol) in anhydrous methylene chloride (150 mL) was added
tert-butyldiphenylsilylchloride (9.30 mL, 39.19 mmol) dropwise at
0 ꢁC. After being stirred at room temperature for 3 h, the reaction
mixture was extracted with methylene chloride. The organic layer
was dried over anhydrous MgSO4, filtered, and evaporated under
reduced pressure. The residue was purified by silica gel column
d
166.8, 159.3, 135.8, 133.9, 133.8, 132.9, 130.7, 130.6, 129.9, 129.4,
128.5, 127.9, 127.8, 113.9, 74.2, 72.4, 65.4, 63.5, 55.4, 27.0, 24.5, 24.3,
19.4, 13.5; LRMS(FABþ) m/z 595 (MþH)þ; HRMS(FABþ) m/z
C37H43O5Si (MþH)þ calcd 595.2880, obsd 595.2874.
chromatography using hexane and ethyl acetate (12:1) to give silyl
25
ether 10 (14.70 g, 97%) as a colorless oil: [
a
]
þ17.49 (c 1.22, CHCl3);
5.1.8. (þ)-((1R,2S)-2-(Hydroxymethyl)-1-((4-methoxybenzyloxy)-
methyl)cyclopropyl)methyl benzoate (13) and (þ)-((1S,2S)-2-(hy-
droxymethyl)-2-((4-methoxybenzyloxy)methyl)cyclopropyl)methyl
benzoate (14). To a stirred solution of 12 (5.66 g, 9.51 mmol) in THF
(60 mL) and acetic acid (0.65 mL, 11.41 mmol) was added n-tetra-
butylammonium fluoride (11.4 mL, 11.4 mmol, 1 M solution in THF).
And the reaction mixture was stirred at room temperature for 7 h.
After the reaction mixture was evaporated under reduced pressure,
the reaction mixture was extracted with ethyl acetate and washed
with brine. The organic layer was dried over anhydrous MgSO4,
filtered, and evaporated under reduced pressure. The residue was
purified by silica gel column chromatography using hexane and
D
IR (neat): ; d 9.49 (s,
n
3089, 1737 cmꢀ1 1H NMR (500 MHz, CDCl3)
1H, CHO), 7.68–7.37 (m, 10H, 2ꢂPh), 7.27 (d, 2H, J¼8.5 Hz, Ar), 6.89
(d, 2H, J¼9.0 Hz, Ar), 4.51 (s, 2H, PMPCH2), 4.00 (dd, 1H, J¼6.0,
12.0 Hz, TBDPSOCHH), 3.91 (d, 1H, J¼10.0 Hz, CHHOPMB), 3.82
(s, 3H, OCH3), 3.66 (dd, 1H, J¼8.5, 11.5 Hz, TBDPSOCHH), 3.49 (d, 1H,
J¼10.5 Hz, CHHOPMB), 1.79–1.73 (m, 1H, 2-H), 1.44 (dd, 1H, J¼5.5,
7.0 Hz, 3-HH), 1.23 (dd, 1H, J¼5.5, 9.0 Hz, 3-HH), 1.04 (s, 9H, tert-
butyl); 13C NMR (100 MHz, CDCl3)
d 201.0, 159.4, 135.8, 133.8, 133.5,
130.5, 129.9, 129.5, 128.0, 127.9, 114.0, 72.8, 70.8, 61.7, 55.5, 36.53,
31.2, 27.0, 19.4, 17.6; LRMS(FABþ) m/z 489 (MþH)þ; HRMS(FABþ)
m/z C30H37O4Si (MþH)þ calcd 489.2461, obsd 489.2457.
ethyl acetate (2:1) to give 13 (3.62 g, 100%) as a colorless oil:
25
5.1.6. (-)-((1S,2S)-2-((tert-Butyldiphenylsilyloxy)methyl)-1-((4-me-
thoxybenzyloxy) methyl)cyclopropyl)methanol (11). To a stirred so-
lution of 10 (14.70 g, 30.08 mmol) in MeOH (100 mL) was added
sodium borohydride (0.57 g, 15.04 mmol) at 0 ꢁC and the reaction
mixture was stirred at 0 ꢁC for 10 min. After being evaporated
under reduced pressure, the reaction mixture was extracted be-
tween ethyl acetate and H2O, and washed with brine. The organic
layer was dried over anhydrous Na2SO4, filtered, and evaporated
under reduced pressure. The resulting residue was purified by
compound 13: [
a
]
þ15.56 (c 0.91, CHCl3); IR (neat):
n
3376, 3100,
D
1726 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.95–7.38 (m, 5H, Ph), 7.21
(d, 2H, J¼8.8 Hz, Ar), 6.79 (d, 2H, J¼8.8 Hz, Ar), 4.78 (d, 1H,
J¼11.6 Hz, CHHOBz), 4.47 (d, 1H, J¼11.6 Hz, PMPCHH), 4.42
(d, 1H, J¼12.0 Hz, PMPCHH), 4.17 (d, 1H, J¼11.6 Hz, CHHOBz), 3.85
(dd, 1H, J¼5.6, 12.0 Hz, HOCHH), 3.71 (s, 3H, OCH3), 3.58 (d, 1H,
J¼9.6 Hz, CHHOPMB), 3.51 (dd, 1H, J¼9.2, 11.6 Hz, HOCHH), 3.17
(d, 1H, J¼10.0 Hz, CHHOPMB), 2.08 (br s, 1H, OH), 1.32–1.24 (m, 1H,
2-H), 0.85 (dd, 1H, J¼5.2, 8.8 Hz, 3-HH), 0.55 (t, 1H, J¼6.0 Hz, 3-HH);
silica gel column chromatography using hexane and ethyl acetate
13C NMR (100 MHz, CDCl3)
d 166.8, 159.3, 133.3 130.4, 130.2, 129.8,
25
(5:1) to give alcohol 11 (14.09 g, 95%) as a colorless oil: [
(c 0.58, CHCl3); IR (neat):
3392, 3086 cmꢀ1
CDCl3)
7.68–7.35 (m, 10H, 2ꢂPh), 7.26 (d, 2H, J¼8.8 Hz, Ar), 6.87
a
]
ꢀ5.51
129.5, 128.7, 113.9, 79.9, 72.8, 65.4, 62.7, 55.4, 24.7, 24.3, 13.9;
D
n
;
1H NMR (400 MHz,
LRMS(FABþ) m/z 357 (MþH)þ; HRMS(FABþ) m/z C21H25O5 (MþH)þ
d
calcd 357.1702, obsd 357.1698. Compound 14 (benzoyl-migrating
25
(d, 2H, J¼8.4 Hz, Ar), 4.53 (d, 1H, J¼11.6 Hz, PMPCHH), 4.44 (d, 1H,
J¼11.6 Hz, PMPCHH), 4.08 (t, 1H, J¼11.2 Hz, OH), 4.01 (dd, 1H,
J¼5.6, 11.6 Hz, TBDPSOCHH), 3.99 (d, 1H, J¼10.8 Hz, TBDPSOCHH),
3.79 (s, 3H, OCH3), 3.42 (t, 1H, J¼11.2 Hz, CHHOH), 3.42 (dd, 1H,
J¼1.6, 10.4 Hz, CHHOH), 3.37 (dd, 1H, J¼1.6, 10.4 Hz, CHHOPMB),
2.93 (d, 1H, J¼9.6 Hz, CHHOPMB), 1.03 (s, 9H, tert-butyl), 1.03
(m, 1H, 2-H, overlapped by tert-butyl), 0.70 (dd, 1H, J¼5.6, 8.4 Hz,
3-HH), 0.37 (t, 1H, J¼5.2 Hz, 3-HH); 13C NMR (100 MHz, CDCl3)
compound, generated in the absence of acetic acid): [
1.95, CHCl3); IR (neat):
CDCl3)
8.05–7.42 (m, 5H, Ph), 7.24 (d, 2H, J¼8.5 Hz, Ar), 6.87 (d, 2H,
a
]
þ15.48 (c
D
n
3384, 3088, 1731 cmꢀ1; 1H NMR (500 MHz,
d
J¼8.5 Hz, Ar), 4.61 (dd, 1H, J¼6.5, 11.5 Hz, CHHOBz), 4.50 (d, 1H,
J¼11.5 Hz, PMPCHH), 4.46 (d, 1H, J¼11.5 Hz, PMPCHH), 4.28 (dd, 1H,
J¼8.5, 12.0 Hz, CHHOBz), 3.98 (dd, 1H, J¼6.0, 12.0 Hz, CHHOH), 3.81
(s, 3H, OCH3), 3.63 (dd, 1H, J¼5.0, 11.5 Hz, CHHOH), 3.50 (d, 1H,
J¼10.0 Hz, CHHOPMB), 3.40 (d, 1H, J¼10.0 Hz, CHHOPMB), 2.70
(t, 1H, J¼6.0 Hz, OH) 1.40–1.34 (m, 1H, 2-H), 0.82 (dd, 1H, J¼5.5,
8.5 Hz, 3-HH), 0.61 (t, 1H, J¼5.0 Hz, 3-HH); 13C NMR (100 MHz,
d
159.3, 135.8, 135.7, 133.2, 133.1, 130.8, 130.1, 130.1, 129.4, 128.1,
128.0, 114.0, 75.0, 72.9, 65.0, 64.2, 55.5, 28.2, 27.0, 22.6, 19.3, 14.6;