2508 J . Org. Chem., Vol. 66, No. 7, 2001
Notes
4-Ben zyloxy-3-m eth yl bu t-2-en -1-ol (7). Under argon, 11.6
mL (11.6 mmol) of 1 M DIBAL in n-hexane was added to a
solution of 6 (320 mg, 1.45 mmol) in THF (10 mL) at -78 °C.
The reaction was stirred for 5 h at the same temperature, and
then the mixture was warmed to 0 °C over 1 h. After addition
of MeOH (5 mL) and H2O (5 mL), the white suspension was
vigorously stirred for 10 min at room temperature. Then, Et2O
(15 mL) was added to the slurry solution and the resulting
mixture was filtered through a thin layer of silica. The clear
filtrate was evaporated to dryness at reduced pressure, and the
residue was purified by a SiO2 column (10 g, n-hexane/ethyl
acetate 80:20) to give 7 (oil, 257 mg, 92%). 1H NMR (CDCl3, 300
MHz) δ 1.62 (s, 3H), 3.83 (s, 2H), 4.10 (d, J ) 6.8 Hz, 2H), 4.39
(s, 2H), 5.59 (t, J ) 6.8 Hz, 1H), 7.21-7.35 (bs, 5H); 13C NMR
(CDCl3, 300 MHz) δ 14.1 (C-5), 58.9 (C-4), 71.9 (C-1), 75.3 (Bn),
126.2 (C-3), 127.5 (Bn), 127.6 (Bn), 128.3 (Bn), 135.4 (C-2), 138.2
(Bn); IR (film) 3455; CIMS (NH3) 210 (40, M+NH4+), 192 (15,
M+), 91 (100).
(2R,3R)-4-Ben zyloxy-2,3-ep oxy-3-m eth yl bu ta n -1-ol (8).
Under argon atmosphere, 497 mg (2.41 mmol) of (-)-diethyl
tatrate (DET) was dissolved in 4 mL of dry CH2Cl2 in a flask
dried in oven. Through a septum, neat Ti(IV) isopropoxide (533
mg, 1.88 mmol) was added to the solution at -23 °C. After the
resulting mixture was stirred for 10 min at the same temper-
ature, 7 (239 mg, 1.24 mmol) in dry CH2Cl2 (4 mL) was added.
The reaction mixture was stirred for another 10 min at -23 °C
prior the addition of 0.83 M t-BuOOH in nonane (763 µL, 4.02
mmol). The resulting mixture was stirred at the same temper-
ature for 1h and then kept in the freezer (-20 °C) for 14 h
without stirring. The reaction was quenched with 3 mL of
MeOH. After stirring at -23 °C for 45 min, the mixture was
treated with 15% NaOH (4 mL) and stirred at room temperature
for another 45 min. The resulting suspension was partitioned
between CH2CL12 and brine, dried (Na2SO4), and evaporated.
The residue was purified by column chromatography (SiO2,
128.5, 135.6 (d, J CP ) 5.2 Hz), 137.7; 31P NMR (CDCl3, 300 MHz)
δ -0.39 (s); CIMS (NH3) m/z 469 (38, M + H+), 108; HRCIMS
m/z 469.1782 (C26H30O6P, calcd 469.1780).
Dib en zyl (2S,3R)-1-b en zyloxy-2-C-m et h yler yt h r it ol-4-
p h osp h a te (10). Perchloric acid (20 µL) in 800 µL of distilled
water was added to a solution of 9 (95 mg, 0.195 mmol) in 1.2
mL DMSO at 0 °C over 5 min. The reaction mixture was stirred
at room temperature overnight, and then neutralized with a
saturated solution (2.6 mL) of NaHCO3. The aqueous solution
was frozen and freeze-dried. The resulting residue was fraction-
ated by column chromatography (SiO2, CHCl3/acetone 95:5) to
give 10 (57 mg, 64%) as a colorless oil, [R]20° +2.8° (c 2.7,
D
1
CHCl3). H NMR (CDCl3, 300 MHz) δ 1.09 (s, 3H), 3.31 (d, J )
9.1 Hz, 1H), 3.56 (d, J ) 9.1 Hz, 1H), 3.80 (bm, 1H), 4.03 (m,
1H), 4.25 (ddd, J ) 10.7, 10.7 and 2.2 Hz, 1H), 4.52 (s, 2H), 5.05
(d, J ) 8.5 Hz, 4H), 7.30-7.35 (m, 15H); 13C NMR (CDCl3, 300
MHz) δ 19.6 (C-5), 69.5 (bs), 72.6 (C-2), 73.5 (C-1), 74.3 (d, J CP
) 4.9 Hz, C-4), 74.7 (C-3), 121.7, 127.9, 128.0, 128.2, 128.5, 128.6,
135.6 (d, J CP ) 6.3 Hz), 137.6; 31P NMR (CDCl3, 300 MHz) δ
1.00 (s); FAB+ MS (glycerol) m/z 509 (28, M+Na+), 487 (38, M
+ H+); FAB + HRMS m/z 487.1881 (C26H32O7P, calcd 487.1885).
2-C-Meth yler yth r itol 4-p h osp h a te (1). A solution of 10 (28
mg, 0.058 mol) in 1.5 mL of 50% MeOH in water was hydroge-
nated by H2 and catalytic 10% Pd/C at room temperature
overnight. The catalyst was filtered off, and the filtrate was
evaporated to dryness to give 12 mg (0.056 mmol, 96%) of 1 as
an amorphous solid, [R]20°D +13.4° (c 0.8, H2O) [lit.17 [R]20°D +6.4°
1
(c 0.1, H2O)]. H NMR (D2O, 300 MHz) δ 1.13 (s, 3H), 3.47 (d, J
) 11.8 Hz, 1H), 3.59 (d, J ) 11.8 Hz, 1H), 3.80 (dd, J ) 8.2 and
2.4 Hz, 1H), 3.90 (m, 1H), 4.13 (m, 1H); 13C NMR (D2O + 1 drop
DMSO-d6, 300 MHz) δ 19.4 (C-5), 67.5 (C-4 and C-1), 74.6 (d,
J CP ) 8.9 Hz, C-3), 75.1 (C-2); 1H NMR (D2O + 1 drop DCl, 300
MHz) δ 1.06 (s, 3H), 3.40 (d, J ) 11.8 Hz, 1H), 3.53 (d, J ) 11.8
Hz, 1H), 3.76 (dd, J ) 8.2 and 2.4 Hz, 1H), 3.91 (m, 1H), 4.16
(m, 1H); 31P NMR (D2O + 1 drop DCl, 300 MHz) δ 1.11 (s)
(phosphoric acid as internal standard, δ ) 0.00).
hexane/EtOAc 80:20) to give 8 (240 mg, 93%) as a colorless oil,
1
[R]20° +0.21° (c 10, CHCl3). H NMR (CDCl3, 300 MHz) δ 1.37
P r ep a r a tion of th e Mon o-(R)-MTP A Der iva tive of 10.
Under dry conditions, (S)-MTPA Cl (Chiraselect, Fluka) (10.8
mg, 8 µL) was added to a solution of 10 (3.5 mg) and a catalytic
amount DMAP in 400 µL of CH2Cl2. The reaction mixture was
stirred at room temperature overnight and then evaporated to
dryness. The oil residue was dissolved in CHCl3 and purified
by column chromatography (SiO2, CHCl3/acetone 95:5) to give
quantitatively the mono MTPA ester of 10. 1H NMR (CDCl3, 300
MHz) δ 0.99 (s, 3H, minor isomer), 1.09 (s, 3H, major isomer),
3.07 (d, J ) 9.4 Hz, 1H, minor isomer), 3.15 (d, J ) 9.4 Hz, 1H,
minor isomer), 3.19 (d, J ) 9.4 Hz, 1H, major isomer), 3.30 (d,
J ) 9.4 Hz, 1H, major isomer), 3.47 (bs, 3H, MTPA, minor
compound), 3.51 (bs, 3H, MTPA, major compound), 4.07 (m), 4.56
(m), 4.98 (m), 5.49 (dd, J ) 8.3 and 2.5 Hz, 1H, major isomer),
5.52 (dd, J ) 8.3 and 2.5 Hz, 1H, minor isomer), 7.15-7.65 (m).
D
(s, 3H), 3.13 (dd, J ) 6.5 and 4.3 Hz, 1H), 3.47 (d, J ) 10.9 Hz,
1H), 3.52 (d, J ) 10.9 Hz, 1H), 3.70 (dd, J ) 12.2 and 6.8 Hz,
1H), 3.82 (dd, J ) 12.2 and 4.4 Hz, 1H), 4.54 (d, J ) 12.0 Hz,
1H), 4.59 (d, J ) 12.0 Hz, 1H), 7.30-7.35 (bs, 5H); 13C NMR
(CDCl3, 300 MHz) δ 14.5 (C-5), 60.0 (C-2), 60.3 (C-3), 60.9 (C-4),
73.2 (C-1), 74.1 (Bn), 127.7 (Bn), 127.8 (Bn), 128.4 (Bn), 137.8
(Bn); IR (film) 3455; CIMS (NH3) 226 (30, M+NH4+), 210 (10),
91 (100).
Diben zyl (2R,3R)-4-Ben zyloxy-2,3-ep oxy-3-m eth yl-bu t-
1-yl p h osp h a te (9). To a solution of tribenzyl phosphite (715
mg, 2.03 mmol) in dry CH2Cl2 (18 mL) was added iodine (469
mg, 1.84 mmol) at 0 °C in an argon atmosphere. The resulting
mixture was cooled to -78 °C, and treated with 8 (192 mg, 0.92
mmol) and dry pyridine (588 µL). The reaction mixture was
stirred at the same temperature for 20 min and then warmed
to room temperature over 2 h. When the starting material was
not detectable any longer by TLC, the mixture was washed
subsequently by 0.6 M potassium hydrogen sulfate, sat. NaH-
CO3, and brine. The organic layers were dried (Na2SO4) and
evaporated. The resulting oil was purified by column chroma-
tography (SiO2, CH2Cl2/acetone 97.5:2.5) to give 9 (410 mg, 95%)
Ack n ow led gm en t. This work would not have been
realizable without the support and valuable suggestions
of Prof. Raymond Andersen (University of British
Columbia, Vancouver). MS and NMR spectra were
recorded at the Department of Chemistry of UBC. Staffs
of both services are acknowledged.
as a colorless oil, [R]20° +0.19° (c 3, CHCl3). 1H NMR (CDCl3,
D
300 MHz) δ 1.30 (s, 3H), 3.14 (dd, J ) 6.1 and 5.0 Hz, 1H), 3.40
(d, J ) 11.1 Hz, 1H), 3.49 (d, J ) 11.1 Hz, 1H), 4.11 (m, 2H),
4.51 (d, J ) 12.0 Hz, 1H), 4.55 (d, J ) 12.0 Hz, 1H), 5.06 (d, J
) 12.2 Hz, 6H), 7.31-7.33 (m, 15H); 13C NMR (CDCl3, 300 MHz)
δ 14.3 (C-5), 57.5 (d, J CP ) 8.6 Hz, C-3), 59.7 (C-2), 65.9 (d, J CP
) 5.2 Hz, C-4), 69.4 (m, J CP ) 2.8 Hz), 73.1, 73.4 (C-1), 127.6-
Su p p or tin g In for m a tion Ava ila ble: Data about identi-
fication (1H and 13C NMR) for newly synthesized compounds
(1, 5-10) are available free of charge via the Internet at
http://pubs.acs.org.
J O005732O