R. Bittman et al. / Tetrahedron 57 62001) 4277±4282
4281
in 50mL of THF was added KH 3260mg, 6.60mmol).
After the evolution of hydrogen ceased, MeI 31.25 g,
8.80mmol) was added. After the solution was stirred at
room temperature for 2 h, MeOH was added to destroy
the excess KH. The solution was diluted with 100 mL of
Et2O and washed with saturated aqueous NH4Cl solution
and water. Evaporation of the solvents gave a residue that
was dissolved in 50mL of MeOH. The resulting solution
was treated with p-TsOH 382 mg, 0.44 mmol) overnight at
room temperature. The solution was neutralized with
concentrated aqueous NH4OH solution. The solvent was
evaporated, leaving a residue that was puri®ed by ¯ash
chromatography 3elution with hexane/EtOAc 9:1) to give
J6.80Hz, 3H), 1.25 3s, 26H), 2.03 3q, J6.96 Hz,
6.80Hz, 2H), 3.46 3s, 3H), 3.47±3.57 3m, 3H), 3.82 3s,
3H), 3.76±3.87 3m, 2H), 4.31±4.36 3m, 1H), 4.48 3s, 2H),
5.92 3d, J6.16 Hz, 1H), 6.87 3d, J8.64 Hz, 2H), 7.26 3d,
J8.48 Hz, 2H); 13C NMR 3CDCl3) d 159.2, 145.0, 129.3,
113.8, 107.4, 79.3, 77.3, 73.6, 71.6, 68.9, 58.2, 55.3, 31.9,
29.8, 29.7, 29.6, 29.4, 29.3, 28.9, 23.9, 22.7, 14.1. FAB
HRMS calcd for C30H52O4 3M)1 m/z 476.3866, found
476.3853.
3.1.4. 1-O-*10-*Z)-Octadecenyl)-2-O-methyl-sn-glycerol
*11). Twenty milliliters of liquid NH3 was collected in a
three-neck round-bottom ¯ask by using a Dewar trap at
2788C. Sodium 3100 mg, 4.35 mmol) was added, and the
mixture was stirred for 1 h. A solution of O-alkenyl ether 10
31.0g, 2.10mmol) in 20mL of THF was added dropwise
over a 3-min period. The reaction mixture was stirred for 1 h
and warmed slowly to room temperature. MeOH was added
to destroy the excess sodium. After the solution was diluted
with 100 mL of Et2O, water was added slowly, and the
ammonia was removed by separation of the aqueous layer.
The organic layer was dried 3Na2SO4), and the solvents were
evaporated. The residue was puri®ed by ¯ash chroma-
tography 3elution with hexane/EtOAc 3:1 with 1% NEt3
by volume) to give 670mg 390%) of alcohol 11 as a light
yellow solid with a low melting point. 1H NMR 3CDCl3) d
0.88 3t, J6.78 Hz, 3H), 1.25 3s, 26H), 2.05 3q, J6.56 Hz,
6.28 Hz, 2H), 3.49 3s, 3H), 3.45±3.49 3m, 1H), 3.62 3ABq,
J5.66 Hz, Dn10.24 Hz, 1H), 3.76 3ABq, J3.77 Hz,
Dn11.03 Hz, 1H), 3.77±3.84 3m, 2H), 4.35±4.40 3m,
1H), 5.91, 5.93 3dt, J1.32 Hz, 6.12 Hz, 1H, the Z vinyl
proton), and a trace of E vinyl proton at d 6.20; 13C
NMR 3CDCl3) d 144.7, 107.8, 80.1, 71.2, 62.0, 58.1, 31.9,
29.7, 29.7, 29.7, 29.5, 29.4, 29.3, 23.9, 22.7, 14.1. FAB
HRMS calcd for C22H45O3 3M1H)1 m/z 357.3369, found
357.3372.
1
900 mg 390%) of product 8 as a colorless oil. H NMR
3CDCl3) d 2.27 3s, 1H), 3.45 3s, 3H), 3.43±3.47 3m, 1H),
3.54±3.55 3m, 2H), 3.63 3ABq, J5.45 Hz, Dn10.24 Hz,
1H), 3.74 3ABq, J4.01 Hz, Dn10.92 Hz, 1H), 3.80 3s,
3H), 4.47 3s, 2H), 6.88 3d, J8.60Hz, 2H), 7.25 3d,
J8.59 Hz, 2H); 13C NMR 3CDCl3) d 159.2, 129.9, 129.3,
113.8, 80.0, 73.1, 69.2, 62.4, 57.7, 55.2. FAB HRMS calcd
for C12H18O4 3M)1 m/z 226.1205, found 226.1199.
3.1.2. 1-O-*10-Octadecynyl)-2-O-methyl-3-O-*40-methoxy-
benzyl)-sn-glycerol *9). A solution of diether glycerol
derivative 8 3700 mg, 3.10 mmol) in 10 mL of THF was
treated with KH 3273 mg, 6.81 mmol) for 1 h. After the
reaction mixture was cooled to 2428C, trichloroethylene
3448 mg, 3.41 mmol) was added. The solution was warmed
slowly to room temperature and stirred for 2 h. The resulting
dark brown solution was cooled to 2788C, and treated with
2.8 mL 37.0mmol) of n-BuLi 3a 2.5 M solution in hexane).
The solution was stirred for 1 h, then warmed to 2428C and
stirred for 1 h. A solution of n-hexadecyl iodide 31.31 g,
3.72 mmol) in 10mL of HMPA was added, and the reaction
mixture was warmed to room temperature and stirred for
2 h. Methanol was then added to destroy excess KH and
n-BuLi. The solution was diluted with 100 mL of Et2O,
washed with water 33£50mL), and dried 3Na 2SO4).
Evaporation of the solvents gave a brown residue that was
puri®ed by ¯ash chromatography 3elution with hexane/
EtOAc 15:1 in the presence of 1% Et3N by volume) to
3.1.5. 1-O-*10-*Z)-Octadecenyl)-2-O-methyl-sn-glycero-3-
O-phosphocholine *4). A solution of glycerol derivative 11
3200 mg, 0.561 mmol), pyridine 3118 mg, 0.841 mmol), and
2-chloro-2-oxo-1,3,2-dioxaphospholane 3104 mg, 0.73 mmol)
in 8 mL of benzene was stirred overnight at 48C. The solution
was decanted to another ¯ask and cooled to solidify. Lyo-
philization from benzene gave the cyclic phospholane inter-
mediate as a white solid, which was immediately transferred
to a pressure tube with 2 mL of benzene. After addition of
6 mL of MeCN, the solution was cooled to 2208C and 2 mL
of NMe3 were collected. The contents in the capped pressure
tube were heated at 658C for 48 h. The cooled solution was
transferred onto a silica gel column, which was eluted with a
gradient of CHCl3/MeOH/H2O 3100:0:0, 80:20:0, 65:25:4) to
give 200 mg 368%) of product 4 after lyophilization from
benzene and ®ltration through a Cameo ®lter 3Fisher Scienti®c
Co.) to remove suspended silica gel; Rf 0.7 3CHCl3/MeOH/
H2O 65:25:4); [a]25D-1.978 3c 0.64, CHCl3); 1H NMR 3CDCl3)
d 5.92 3d, J6.20Hz, 1H), 4.30±4.35 3m, 3H), 3.82±3.95 3m,
5H), 3.76 3ABq, J6.10Hz, Dn9.25 Hz, 1H), 3.51±3.57
3m, 1H), 3.44 3s, 3H), 3.39 3s, 9H), 2.02 3q, J6.76 Hz,
6.84 Hz, 2H), 1.25 3s, 28H), 0.88 3t, J6.44 Hz, 3H); 13C
NMR 3CDCl3) d 144.9, 107.4, 79.5 3d, JC±P8.0Hz), 71.7,
66.3 3d, JC±P6.0Hz), 64.2 3d, JC±P5.0Hz, 59.4 3d,
JC±P3.0Hz), 58.1, 54.4, 31.9, 29.9, 29.7, 29.7, 29.7, 29.4,
29.4, 24.0, 22.7, 14.1. Anal. calcd for C27H56O6NP´2.5H2O: C,
1
give 1.01 g 369%) of alkyne 9 as a light yellow oil. H
NMR 3CDCl3) d 0.88 3t, J6.72 Hz, 3H), 1.25 3s, 26H),
1.40±1.47 3m, 2H), 2.09 3t, J6.94 Hz, 2H), 3.46 3s, 3H),
3.49 3ABq, J5.27 Hz, Dn9.29 Hz, 1H), 3.54 3q,
J4.90Hz, 9.93 Hz, 1H), 3.63±3.67 3m, 1H), 3.81 3s,
3H), 4.03 3ABq, J5.95 Hz, Dn8.82 Hz, 1H), 4.09
3ABq, J4.11 Hz, Dn9.80Hz, 1H), 4.48 3s, 2 H), 6.88
3d, J8.56 Hz, 2H), 7.25 3d, J8.16 Hz, 2H). 13C NMR
3CDCl3) d 159.3, 130.0, 129.3, 113.8, 89.5, 77.9, 77.5,
73.2, 68.3, 58.2, 55.3, 37.3, 31.9, 29.7, 29.7, 29.6, 29.4,
29.2, 28. 9, 22.7, 17.2, 14.1. FAB HRMS calcd for
C30H49O4 3M±H)1 m/z 473.3631, found 473.3683.
3.1.3. 1-O-*10-*Z)-Octadecenyl)-2-O-methyl-3-O-PMB-sn-
glycerol *10). A solution of alkyne 9 31.00 g, 2.11 mmol),
Lindlar catalyst 3100 mg), and quinoline 350 mL,
0.42 mmol) in 60 mL of hexane/EtOAc 1:1 was stirred
under H2 at 1 atm for 2 h. The solid was ®ltered through a
silica gel pad that was washed with hexane/EtOAc 1:1. The
®ltrate was concentrated to give 1.00 g 3100%) of O-alkenyl
1
ether 10 as a light yellow oil. H NMR 3CDCl3) d 0.88 3t,