P en ta bu tylen e Glycol 6. The procedure for the formation
of 3 was followed using 1.1 g (2.9 mmol, 1 equiv) of 5. Column
chromatography (70% hexane/acetone) afforded 1.0 g (91%) of 6
as an oil that solidified upon standing: TLC Rf ) 0.18 (80%
EtOAc/hexane); mp 33-34 °C; 1H NMR (CDCl3, 400 MHz) δ 3.64
(dt, 4H, J ) 8.4, 5.2 Hz), 3.44 (m, 16H) 2.53 (t, 2H, J ) 5.4 Hz),
1.65 (m, 20 H); 13C NMR (CDCl3, 100 MHz) δ 70.87, 70.85, 70.65,
70.55, 62.8, 30.4, 26.91, 26.54, 26.48 26.47; IR (thin film) ν 3400
(br), 2939, 2858, 1447, 1368, 1126, 750 cm-1; HRMS (FAB) calcd
Exp er im en ta l Section
Unless otherwise specified, all starting materials were ob-
tained from commercially available sources and used without
further purification. All air- or moisture-sensitive reactions were
performed under an atmosphere of dry argon, utilizing standard
Schlenk line techniques. Benzene was distilled from sodium
metal, pyridine and CH2Cl2 were distilled from calcium hydride,
THF was distilled from sodium benzophenone ketyl, and MeOH
was distilled from magnesium dust. Analytical TLC visualization
was accomplished with UV light, ceric ammonium molybdate,
p-anisaldehyde, I2, or KMnO4.
+
for C20H42O6 (MH+) 379.3060, found 379.3060.
Ben zyloxyp r op yl Tosyla te 10.14 To a solution of 3-benzyl-
oxypropanol15 (664 mg, 4.00 mmol, 1 equiv) in pyridine (3.3 mL)
at -10 °C was added a solution of TsCl (920 mg, 4.80 mmol,
1.2 equiv) in 1.7 mL of pyridine dropwise over 5 min. The
mixture was allowed to warm to 23 °C and continued to react
for 3 h. The reaction was quenched upon addition of 30 mL of
ice water. The aqueous solution was extracted with Et2O, and
the combined organic layers were washed with 5% aqueous HCl.
The organic layer was dried over anhydrous MgSO4 and con-
centrated in vacuo. Flash chromatography on silica gel (1:1 Et2O/
hexane) afforded 1.18 g (93%) of 10 as a colorless oil: TLC Rf )
Bisa ceta l 2. To a solution of 1 (0.50 mL, 3.9 mmol, 1.0 equiv)
and 1,4-butane diol (3.0 mL, 34 mmol, 8.7 equiv) in 50 mL of
CH2Cl2 was added TsOH (40 mg 0.2 mmol, 0.05 equiv). The
reaction mixture was heated to 40 °C for 20 h, then the reaction
quenched with 50 mL of saturated aqueous NaHCO3. The
organic layer was washed with saturated aqueous NaCl and
concentrated in vacuo. Purification of the oily solid by filtration
through silica gel (8:1 hexane/acetone) afforded 625 mg (70%)
of 2 as a white crystalline solid: TLC Rf ) 0.47 (3:1 hexane/
1
1
0.70 (1:1 EtOAc/hexane); H NMR (CDCl3, 400 MHz) δ 7.79 (d,
acetone); mp 49-50 °C; H NMR (CDCl3, 400 MHz) δ 4.68 (m,
2H), 3.87 (m, 4H), 3.62 (m, 4H), 1.71-1.64 (m, 12H); 13C NMR
(CDCl3, 400 MHz) δ 102.4, 65.7, 29.7, 29.3; IR (thin film) ν 2939
(m), 2872 (m), 1461, 1368, 1291, 1135 (s), 1062, 986 cm-1; HRMS
2H, J ) 8.4 Hz), 7.32 (d, 2H, J ) 8.4 Hz), 7.22-7.37 (m, 5H),
4.40 (s, 2H), 4.17 (t, 2H, J ) 6.0 Hz), 3.50 (t, 2H, J ) 6.0 Hz),
2.42 (s, 3H), 1.94 (app qn, 2H, J ) 6.0 Hz).
+
(FAB) calcd for C12H23O4 (MH+) 231.1596, found 231.1596.
1-Ben zyloxy-3-(3-ben zyloxy-p r op oxy) P r op a n e. To a mix-
ture of 3-benzyloxy propanol (332 mg, 2.00 mmol, 1 equiv), 10
(768 mg, 2.00 mmol, 1.2 equiv), and Bu4NHSO4 (339 mg,
1.00 mmol, 0.5 equiv) was added 50% (wt/wt) aqueous NaOH
(3.9 mL) and benzene (4.7 mL). The mixture was stirred at 65
°C for 12 h. After the mixture had cooled to 23 °C, 10 mL of
H2O was added and the organic material was extracted with
Et2O. The combined organic layers were dried over anhydrous
MgSO4 and concentrated in vacuo. Flash chromatography on
silica gel (1:10 EtOAc/hexane) afforded 480 mg (76%) of the
triether product as a colorless oil: TLC Rf ) 0.65 (1:4 EtOAc/
hexane); 1H NMR (CDCl3, 400 MHz) δ 7.24-7.36 (m, 10 H), 4.50
(s, 4H), 3.55 (t, 4H, J ) 6.4 Hz), 3.52 (t, 4H, J ) 6.4 Hz), 1.87
(app qn, 4H, J ) 6.4 Hz); 13C NMR (CDCl3, 100 MHz) δ 138.5,
128.3, 127.6, 127.5, 73.0, 67.8, 67.4, 30.1; IR (neat) ν 3063, 3030,
2924, 2863, 1275, 1110 cm-1; HRMS (FAB) calcd for C20H27O3
(MH+) 315.1960, found 315.1959.
Tr ibu tylen e Glycol 3. To a solution of 2 (2.0 g, 8.7 mmol,
1 equiv) in 90 mL of THF at 0 °C was added BH3-THF (1.0 M
in THF, 22 mL, 22 mmol, 2.5 equiv) dropwise. The solution was
stirred at 0 °C for 20 min and then warmed to 23 °C. The flask
was equipped with a reflux condenser, and the solution was
heated to 90 °C. After 48 h at reflux, the solution was cooled to
0 °C and quenched by the dropwise addition of 10 mL of MeOH.
The solution was then concentrated in vacuo to give 1.95 g (96%)
1
of 3 as a colorless oil: TLC Rf ) 0.18 (80% EtOAc/hexane); H
NMR (400 MHz, CDCl3) δ 3.65 (t, 4H, J ) 6 Hz), 3.47 (t, 8H, J
) 6 Hz), 2.72 (br s, 2H), 1.68 (m, 12H); 13C NMR (100 MHz,
CDCl3) δ 70.9, 70.7, 2.7, 30.4, 27.0, 26.3; IR (thin film) ν 3364
(s), 2941, 2865, 1372, 1112, 738 cm-1; HRMS (FAB) calcd for
+
C12H27O4 (MH+) 235.1909, found 235.1909.
Dia ld eh yd e 4. A solution of 3 (530 mg, 2.62 mmol, 1 equiv)
and IBX (4.4 g, 16 mmol, 7.0 equiv) in 10 mL of EtOAc was
heated to 80 °C open to the atmosphere. After the solution was
stirred vigorously for 2 h, it was cooled to 23 °C and filtered
through a medium fritted funnel.12 The filtrate was concentrated
in vacuo to yield 492 mg (94%) of 413 as an oil: TLC Rf ) 0.44
(2:1 EtOAc/hexane); 1H NMR (CDCl3, 400 MHz) δ 9.76 (t, 2H, J
) 1.6 Hz), 3.44-3.38 (m, 8H), 2.51 (td, 4H, J ) 7.2, 1.6 Hz),
1.90 (m, 4H), 1.59 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 202.4,
70.6, 69.6, 41.0, 26.4, 22.6; IR (thin film) ν 2861, 1724 (s),
Eth er Diol 7.9 To a solution of 1-benzyloxy-3-(3-benzyloxy-
propoxy) propane (456 mg, 1.45 mmol, 1 equiv) in MeOH
(20 mL) was added Pd/C (200 mg, 10 wt % Pd). The atmosphere
was replaced with H2, and the mixture was stirred under 1 atm
H2 for 5 h. The Pd/C was filtered off, and the filtrate was
concentrated in vacuo. Flash chromatography (1:10 MeOH/
EtOAc) afforded 194 mg (100%) of 7 as a colorless oil: TLC Rf
) 0.57 (1:5 MeOH/EtOAc); 1H NMR (CDCl3, 400 MHz) δ 3.76
(t, 4H, J ) 6.0 Hz), 3.62 (t, 4H, J ) 6.0 Hz), 2.45 (s, 2H), 1.83
(app qn, 4H, J ) 6.0 Hz); 13C NMR (CDCl3, 100 MHz) δ 69.8,
61.4, 32.0; MS (EI) 135 (MH+), 117 (7), 89 (38), 75(66), 59 (100).
Diben zyl Tetr a p r op ylen e Glycol 11. To a mixture of 7 (194
mg, 1.45 mmol, 1 equiv), 10 (1.12 g, 3.48 mmol, 2.4 equiv), and
Bu4NHSO4 (492 mg, 1.45 mmol, 1 equiv) was added 50% (wt/
wt) aqueous NaOH (3.9 mL) and benzene (4.7 mL). The mixture
was heated to 65 °C for 36 h. After the mixture had cooled to
23 °C, 10 mL of H2O was added and the organic material was
extracted with Et2O. The combined organic layers were dried
over anhydrous MgSO4 and concentrated in vacuo. Flash chro-
matography (1:10 EtOAc/hexane) afforded 500 mg (80%) of 11
+
1114 cm-1; HRMS (EI) calcd for C12H23O4 (MH+) 231.1596,
found 231.1605.
Bisa cet a l 5. To a solution of freshly prepared 4 (264 mg,
1.15 mmol, 1 equiv) and 1,4-butane diol (1.25 mL, 14.1 mmol,
12 equiv) in 100 mL of CH2Cl2 was added TsOH (11 mg,
0.057 mmol, 0.05 equiv). After 4 h, the reaction mixture was
neutralized with 100 mL of saturated aqueous NaHCO3. The
organic layer was removed and washed with saturated aqueous
NaCl and then concentrated in vacuo, and the resultant oil was
purified by column chromatography (6:1 hexane/acetone) to
afford 305 mg (71%) of 5 as an oil: TLC Rf ) 0.32 (6:1 hexane/
acetone); 1H NMR (CDCl3, 400 MHz) δ 4.68 (m, 2H), 3.87 (m,
4H), 3.62 (m, 4H), 3.41 (m, 8H), 1.64 (m 20 H); 13C NMR (CDCl3,
100 MHz) δ 102.6, 70.6, 70.5, 65.7, 31.0, 29.3, 26.5, 25.1; IR (thin
film) ν 2940, 2868, 1139, 1116, 1062, 981 cm-1; HRMS (FAB)
1
as a colorless oil: TLC Rf ) 0.55 (1:4 EtOAc/hexane); H NMR
(CDCl3, 400 MHz) δ 7.24-7.38 (m, 10H), 4.50 (s, 4H), 3.43-
3.58 (m, 16H), 1.78-1.90 (m, 8H); 13C NMR (CDCl3, 100 MHz)
δ 138.5, 128.3, 127.6, 127.5, 72.9, 67.9, 67.84, 67.79, 67.4, 30.12,
calcd for C20H39O6 (MH+) 375.2747, found 375.2747.
+
30.07; IR (neat) ν 3064, 3031, 2923, 2860, 1275, 1110 cm-1
;
HRMS (CI) calcd for C26H39O5 (MH+) 431.2799, found 431.2798.
Tetr a p r op ylen e Glycol 12. The procedure for the prepara-
tion of 7 was followed using 490 mg (1.14 mmol, 1 equiv) of 11.
(12) It is important to quench the reaction upon complete conversion
to the dialdehyde as extended reaction times lead to decomposition of
the product.
(13) Although 1H NMR indicates that the product is >95% pure,
further purification can be performed without significant decomposition
of the product by column chromatography using 2% Et3N in 2:1 EtOAc/
hexane.
(14) Gill, D. M.; Pegg, N. A.; Rayner, C. M. Tetrahedron 1996, 52,
3609.
(15) (a) Gennari, C.; Cozzi, P. G. J . Org. Chem. 1988, 53, 4015. (b)
Garc´ıa, C.; Mart´ın, T.; Mart´ın, V. S. J . Org. Chem. 2001, 66, 1420.
9168 J . Org. Chem., Vol. 68, No. 23, 2003