LETTER
W.; Blaskovich, M. A.; Evindar, G.; Wilkinson, S.; Luo, Y.
Swern Oxidation of Alcohols
2703
to give 6-(methylthio)hexyl p-toluenesulfonate (95% yield)
–
1 1
Org. Synth. 2002, 79, 216. (g) Pichlmair, S.; Margues, M.
M. B.; Green, M. P.; Martin, H. J.; Mulzer, J. Org. Lett.
as an oil. IR (neat): 1360, 1175 cm ; H NMR (400 MHz,
CDCl ): d = 1.31–1.37 (m, 4 H), 1.51–1.68 (m, 4 H), 2.07
3
2
003, 5, 4657. (h) Ahmad, N. M. Name Reactions for
(s, 3 H), 2.44 (t, J = 7.3 Hz, 2 H), 2.45 (s, 3 H), 4.02 (t,
J = 6.5 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2 H), 7.79 (d,
Functional Group Transformations; Li, J. J.; Corey, E. J.,
Eds.; Wiley: New York, 2007, 291.
1
3
J = 8.1 Hz, 2 H); C NMR (100 MHz, CDCl ): d = 15.39,
3
(
(
3) Liu, Y.; Vederas, J. C. J. Org. Chem. 1996, 61, 7856.
4) (a) Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001, 123,
21.52, 24.89, 27.92, 28.60, 28.72, 33.93, 70.41, 127.75,
129.72, 133.05, 144.60.
7
449. (b) Crich, D.; Neelamkavil, S. Tetrahedron 2002, 58,
(d) Preparation of 1-Methyl-3-[6¢-(methylthio)hexyl]-
1H-imidazol-3-ium p-Toluenesulfonate (Ion-Supported
Methyl Sulfide): 1-Methylimidazole (33 mmol) was added
to a solution of 6-(methylthio)hexyl p-toluenesulfonate (30
mmol) in MeCN (30 mL) at r.t., and the mixture was stirred
at 60 °C for 48 h. The reaction mixture was concentrated in
3865.
(
5) (a) Nishide, K.; Ohsugi, S.; Fudesaka, M.; Kodama, S.;
Node, M. Tetrahedron Lett. 2002, 43, 5177. (b) Ohsugi, S.;
Nishide, K.; Ohno, K.; Okuyama, K.; Fudesaka, M.;
Kodama, S.; Node, M. Tetrahedron 2003, 59, 8393.
6) (a) Harris, J. M.; Liu, Y.; Chai, S.; Andrews, M. D.; Vederas,
J. C. J. Org. Chem. 1998, 63, 2407. (b) Choi, M. K. W.;
Toy, P. H. Tetrahedron 2003, 59, 7171.
(
(
vacuo, and the residue was washed with Et O (3 × 100 mL)
2
to give ion-supported methyl sulfide (99% yield) as an oil.
–
1 1
IR (neat): 1191, 1034 cm ; H NMR (400 MHz, CDCl ):
3
7) (a) Akiike, J.; Yamamoto, Y.; Togo, H. H. Synlett 2007,
d = 1.19–1.38 (m, 4 H), 1.48–1.56 (m, 2 H), 1.73–1.81 (m,
2 H), 2.07 (s, 3 H), 2.34 (s, 3 H), 2.43 (t, J = 7.3 Hz, 2 H),
3.93 (s, 3 H), 4.14 (t, J = 7.6 Hz, 2 H), 7.15 (d, J = 7.8 Hz,
2 H), 7.31 (t, J = 1.8 Hz, 1 H), 7.41 (t, J = 1.8 Hz, 1 H), 7.74
2168. (b) Ishiwata, Y.; Togo, H. Tetrahedron Lett. 2009, 50,
5354. (c) Kawano, Y.; Togo, H. Tetrahedron 2009, 65,
6251.
1
3
(8) (a) Imura, Y.; Shimojuh, N.; Togo, H. Tetrahedron 2010, 66,
421. (b) Shimojuh, N.; Imura, Y.; Moriyama, K.; Togo, H.
(d, J = 7.8 Hz, 2 H), 9.59 (s, 1 H); C NMR (100 MHz,
3
CDCl ): d = 15.41, 21.20, 25.64, 27.87, 28.62, 29.95, 33.89,
3
Tetrahedron 2011, 67, 951.
36.25, 49.63, 121.81, 123.52, 125.71, 128.61, 137.51,
139.36, 143.56.
(
9) (a) Preparation of 6-mercaptohexan-1-ol: Thiourea (270
mmol) and KI (90 mmol) were added to a solution of 6-
chlorohexan-1-ol (180 mmol) in EtOH (150 mL) at r.t., and
the mixture was heated at reflux for 14 h. Then, aq NaOH
(e) Preparation of 3-Methyl-1-[6¢-(methylsulfinyl)-
hexyl]-1H-imidazolium p-Toluenesulfonate (Ion-
Supported Methyl Sulfoxide): H O (30% in H O, 1.47
2
2
2
(
2.7 M, 270 mmol, 100 mL) was added to the mixture, which
mL, 48 mmol) was added dropwise to a solution of ion-
supported methyl sulfide {1-methyl-3-[6¢-(methylthio)hexyl]-
1H-imidazol-3-ium p-toluenesulfonate; 7.69 g, 20 mmol} in
AcOH–THF (2:1, 45 mL) at 0 °C, and the mixture was
stirred at r.t. for 2 h. The reaction mixture was quenched with
aq sat. Na SO , and concentrated in vacuo. The obtained
was then heated at reflux for 3 h. The reaction mixture was
cooled to r.t., and neutralized with aq HCl (1 M, 200 mL).
The mixture was extracted with Et O (2 × 300 mL) and the
combined organic layer was dried over Na SO , filtered, and
2
2
4
evaporated in vacuo. The residue was dissolved in Et O (200
2
2
3
mL) and the mixture was filtered. The filtrate was concen-
trated to give 6-mercaptohexan-1-ol as an oil. IR (neat):
mixture was dissolved in CH Cl , dried over Na SO , and
2 2 2 4
filtered. After removal of the solvent, ion-supported methyl
sulfoxide was obtained (99% yield) as an oil; IR (neat): 1034
–
1 1
3
348, 2555, 1054 cm ; H NMR (400 MHz, CDCl ):
3
–
1 1
d = 1.34–1.47 (m, 5 H), 1.54–1.67 (m, 4 H), 1.84 (s, 1 H),
cm ; H NMR (500 MHz, CDCl ): d = 1.28–1.49 (m, 4 H),
3
3
2
.54 (q, J = 7.4 Hz, 2 H), 3.64 (t, J = 6.6 Hz, 2 H); 1 C NMR
1.67–1.86 (m, 4 H), 2.34 (s, 3 H), 2.55 (s, 3 H), 2.68 (t,
J = 7.6 Hz, 2 H), 3.93 (s, 3 H), 4.19 (t, J = 7.4 Hz, 2 H), 7.15
(d, J = 7.9 Hz, 2 H), 7.36–7.38 (m, 2 H), 7.74 (d, J = 8.2 Hz,
(
100 MHz, CDCl ): d = 24.49, 25.17, 28.05, 32.53, 33.86,
3
6
2.76.
b) Preparation of 6-(methylthio)hexan-1-ol: MeI (189
mmol) was added to a solution of 6-mercaptohexan-1-ol
1
3
(
2 H), 9.63 (s, 1 H); C NMR (125 MHz, CDCl ): d = 21.21,
3
22.06, 25.37, 27.59, 29.59, 36.25, 38.30, 49.49, 53.79,
121.96, 123.38, 125.71, 128.64, 137.63, 139.48, 143.43;
HMRS (APPI): m/z [M ] calcd for C H ON S: 229.1369;
(
180 mmol) and K CO (198 mmol) in DMF (160 mL) at
2 3
+
0
°C, and the mixture was stirred for 2 h. The reaction
1
1
21
2
mixture was filtered and concentrated, then H O (150 mL)
found: 229.1357
2
was added to the residue, which was extracted with EtOAc
(10) General Procedure for the Swern Oxidation using Ion-
Supported Methyl Sulfoxide: Oxalyl chloride (0.34 mL)
was added dropwise to a solution of ion-supported methyl
sulfoxide (1.60 g, 4.0 mmol) in CH Cl (6 mL) at –70 °C and
(
3 × 200 mL). The combined organic layer was washed with
brine, dried over Na SO , filtered, and concentrated in
2
4
vacuo. Purification of the residue by distillation (85–95 °C/
2
2
1
.0 mmHg) gave 6-(methylthio)hexan-1-ol (66% yield from
the mixture was stirred for 30 min at the same temperature.
A solution of alcohol (2.0 mmol) in CH Cl (3 mL) was
–
1 1
6-chlorohexan-1-ol) as an oil. IR (neat): 3365, 1055 cm ; H
2
2
NMR (400 MHz, CDCl ): d = 1.34–1.47 (m, 4 H), 1.55–
added dropwise at –70 °C and the obtained mixture was
stirred for 30 min. Triethylamine (1.66 mL, 12 mmol) was
added dropwise at –70 °C and the mixture was stirred for
1 h at the same temperature. The resulting mixture was
warmed to –60 °C and stirred for 1.5 h at the same
temperature. The mixture was warmed to –50 °C and stirred
for 1 h at the same temperature. Finally, the mixture was
warmed to r.t. by removing the cooling bath and stirred for
2 h at the same temperature. The reaction mixture was
3
1
.67 (m, 5 H), 2.10 (s, 3 H), 2.50 (t, J = 7.4 Hz, 2 H), 3.64 (t,
1
3
J = 6.6 Hz, 2 H); C NMR (100 MHz, CDCl ): d = 15.47,
3
2
5.32, 28.49, 29.01, 32.57, 34.14, 62.76.
c) Preparation of 6-(methylthio)hexyl 4¢-methyl-
benzenesulfonate: p-TsCl (72 mmol) in CH Cl (60 mL)
(
2
2
was added to a solution of 6-(methylthio)hexan-1-ol (60
mmol), Et N (90 mmol) and Me N·HCl (6.0 mmol) in
3
3
CH Cl (60 mL) at 0 °C, and the obtained mixture was
2
2
stirred for 1 h. H O (100 mL) was added to the reaction
quenched with H O (10 mL), neutralized (pH 6–7) with aq
2
2
mixture, which was neutralized with 1 M HCl and extracted
with EtOAc (2 × 200 mL). The combined organic layer was
washed with H O, brine, dried over Na SO , and concen-
1 M HCl, and extracted with Et O (2 × 40 mL). The organic
2
layer was washed with H O (10 mL), dried over Na SO , and
2
2
4
filtered. After removal of the solvent, aldehyde or ketone
2
2
4
1
trated in vacuo. The residue was purified by column
was obtained. The purity was estimated by H NMR
chromatography on silica gel (hexane–EtOAc, 4:1; R = 0.4)
analysis.
f
Synlett 2011, No. 18, 2701–2704 © Thieme Stuttgart · New York