Organic Syntheses, Vol. 78, 239-248
Checked by Jan W. Thuring and Andrew B. Holmes.
1. Procedure
A. 1,2:5,6-Bis-O-(1-methylethylidene)-O-phenyl
carbonothioate-α-D-glucofuranose
(
1). All glassware is oven-dried. A
250-mL, two-necked, round-bottomed
flask is fitted with a
magnetic stirring bar and
an
argon inlet. Under a gentle flow of argon, the
flask
is charged with
100 mL of anhydrous dichloromethane
(CH2Cl2) (Note
1) and
12.6 g (48.2 mmol) of 1,2:5,6-di-O-isopropylidene-D-glucose
(Note
2). The
flask is immersed in an
ice bath, stirring is started, and
7.34
mL (53.1 mmol) of phenyl chlorothionoformate
(Note
3) and
4.63 mL
(57.9 mmol) of pyridine (Note
4)
are added by
syringe. After 30 min, the
ice bath
is removed, and the resulting mixture is stirred at room temperature for 14 hr. Then,
in order to destroy the excess
phenyl chlorothionoformate,
5 mL of anhydrous methanol
(MeOH) (Note
5) is added via
syringe,
and the mixture is stirred at room temperature for 15 min. The resulting solution
is washed with
100 mL of aqueous hydrochloric
acid (HCl) (1 N) and
100 mL
of brine, dried over
anhydrous sodium
sulfate (Na2SO4), filtered, and concentrated
under reduced pressure. The crude product (
20.5
g; yellow oil) is triturated by the addition of
hexane
(50 mL), scratched with a
spatula
and stirred for 30 min at 0°C. The cream-colored solid is collected by filtration
of the cold suspension and washed with a minimal amount
(5-10
mL) of hexane to give
15.2 g of
1. Recrystallization from
hexane
(50 mL) affords the product as white crystals (
13.9 g;
74%).
The mother liquors are combined and evaporated to dryness to give a residue that is
recrystallized from
hexane (10
mL) to give a second crop of
1 (
1.50 g;
8%)
(Notes
6,
7
and
8).
B. 3-Deoxy-1,2:5,6-bis-O-(1-methylethylidene)-α-D-ribo-hexofuranose
(
2). All glassware is oven-dried. A
250-mL, two-necked, round-bottomed
flask is fitted with a
magnetic stirring bar and
a
reflux condenser with an
argon inlet.
Under a gentle flow of
argon,
the flask is charged with
15 mL of anhydrous
benzene (Note
9) and
13.0 g (32.7 mmol) of 1.
To this mixture are added via
cannula a solution of
0.620 mL (1.21 mmol) of bis(tributyltin)
oxide [(Bu3Sn)2O] (Note
10),
0.800 g (4.90 mmol) of 2,2'-azobis(isobutyronitrile)
(AIBN) (Note
11),
9.81
g (164 mmol) of poly(methylhydrosiloxane)
(PMHS) (Note
12), and
16.4
mL (180 mmol) of 1-butanol
(Note
13) in
20 mL
of anhydrous benzene. The resulting mixture is heated
at reflux for 3 hr, after which time a solution of
0.620
mL (1.21 mmol) of (Bu3Sn)2O
and
0.800 g (4.90 mmol) of AIBN
in
9 mL of anhydrous benzene
is added via
cannula. The reaction mixture is heated at reflux
for an additional 3 hr. The solution is allowed to cool to room temperature, and then
transferred to a
1-L, one-necked, round-bottomed flask.
Benzene and excess
1-butanol
are removed under
water pump vacuum, and the resulting residue
is redissolved in
100 mL of THF (Note 14). To this solution is added SLOWLY (Note
15)
400 mL of aqueous sodium hydroxide
(NaOH) (2 N). The resulting mixture is stirred at room temperature for
15 hr. The layers are separated, and the aqueous layer is extracted twice with
100 mL of diethyl ether.
The combined organic layers are washed with
100 mL
of aqueous HCl (1 N) and
100 mL
of brine, dried over anhydrous
Na2SO4,
filtered, and concentrated under reduced pressure. The resulting residue is purified
by
chromatography (Note
16) to give
6.2-6.4 g (
76-80%)
of
2 as a pale-yellow oil (Notes
17
and
18).
2. Notes
1.
Laboratory grade dichloromethane
was first distilled and then was further purified and dried by distillation from
calcium hydride. The submitters used
solvent supplied by EM Science.
5.
Methanol was used
as supplied by Merck & Company, Inc. or Mallinckrodt
Inc.
6. Both crops were pure as judged by elemental analysis. The combined
yield ranged from
15.4-17.3 g
(
82-90%). The checkers found
the recrystallization procedure to be more convenient (albeit in slightly lower yield)
than isolation by chromatography. The residue can alternatively be purified by flash
column chromatography with
30 g of silica (Merck
9385 Kieselgel 60, 230-400 ASTM) per g of residue, eluting with a gradient
of 0

50%
EtOAc/hexane
to afford
18.0 g (
94%; the checkers obtained
91% on half scale) of
1 as a colorless solid,
mp 108-110°C (Notes
7 and
8).
7. TLC analyses (R
f = 0.47, in
EtOAc/hexane
7:3; the submitters observed R
f = 0.49 in
EtOAc/hexane
4:1) were performed on 0.25-mm Merck 60 F
254 silica gel plates
(the submitters used 0.25-mm silica gel 60 plates supplied by EM Reagents) that were
stained with a solution of
phosphomolybdic acid
in
95% ethanol.
8. Compound
1 ([α]D18
−44.9° (CHCl3, c 0.6), lit.
2 [α]D18
−43° (CHCl3)) has the following spectral data:
1H NMR (250 MHz, CDCl
3)
δ: 1.35 (s, 3 H), 1.38 (s, 3 H), 1.45 (s, 3
H), 1.56 (s, 3 H), 4.04-4.15 (m, 2 H), 4.31
(m, 2 H), 4.78 (d, 1 H, J = 4), 5.65 (d, 1 H, J = 2),
5.97 (d, 1 H, J = 4), 7.12 (d, 2 H, J = 8), 7.31 (t,
1 H, J = 8), 7.44 (t, 2 H, J = 7);
13C NMR (62.5 MHz, CDCl
3) δ:
25.7, 26.7, 27.1, 27.3, 67.5,
72.7, 80.1, 83.3, 85.5, 105.4,
109.9, 112.9, 122.1, 127.2, 130.0,
153.7, 194.1; IR
(KBr pellet) cm
−1: 2987, 1164, 1082,
948, 917. HRMS
(FAB) m/z Calcd for C
19H
24O
7S: 396.1243.
Found: 396.1243. Anal. Calcd for C
19H
24O
7S:
C, 57.6; H, 6.1. Found: C, 57.5; H, 6.1.
9.
Benzene (Aldrich
Chemical Company, Inc. or EM Science) was
purified by distillation from
sodium benzophenone
ketyl.
CAUTION: Benzene
is harmful as a vapor and by skin absorption, and it should always be handled in a
well-ventilated hood. Chronic exposure may cause fatal blood disease.
10.
(Bu3Sn)2O (Aldrich
Chemical Company, Inc. or Gelest) was distilled [bp
140-142°C (0.1 mm)] before its use.
12.
Poly(methylhydrosiloxane)
(Fluka Chemical, Corp.) was degassed overnight under
full vacuum at 25°C (≈0.1 mm) prior to use.
13.
Anhydrous 1-butanol
(99.8%; Aldrich Chemical Company, Inc.)
was used without purification.
15. The addition of base should be slow, as the aqueous NaOH (2 N)
cleaves the siloxanes and ionizes the
phenol
that is generated in the reaction. The reaction is vigorous.
16. Flash column chromatography is performed with
30
g of silica (Merck 9385 Kieselgel 60, 230-400 ASTM) per gram of
residue, eluting with a gradient of 0

50%
EtOAc/hexane.
17. TLC analyses (R
f = 0.32, in
hexane:EtOAc
7:3; the submitters observed R
f = 0.33 in
hexane:EtOAc
4:1) were performed on 0.25-mm Merck 60 F
254 silica gel plates (the submitters
used 0.25-mm silica gel 60 plates supplied by EM Reagents) that were stained with
a solution of
phosphomolybdic acid
in
95% ethanol.
18. Compound
2 (
[α]D20
−8.1° (CHCl3, c 2.4), lit.
3
[α]D18 −8.5°
(CHCl3, c 1.5)) has the following spectral data:
1H NMR (250 MHz, CDCl
3)
δ: 1.32 (s, 3 H), 1.36 (s, 3 H), 1.43 (s, 3
H), 1.51 (s, 3 H), 1.77 (m, 1 H), 2.19 (dd,
1 H, J = 4, 14), 3.82 (m, 1 H), 4.12 (m, 3 H), 4.75
(t, 1 H, J = 4), 5.81 (d, 1 H, J = 4);
13C NMR (62.5 MHz, CDCl
3) δ:
25.5, 26.5, 26.8, 27.1, 35.6,
67.6, 77.2, 79.0, 80.8, 106.0,
110.0, 111.7; IR
(neat) cm
−1: 1064, 957, 941.
HRMS (FAB) m/z Calcd for C
12H
20O
5:
244.1311. Found: 244.1312. Anal. Calcd for C
12H
20O
5:
C, 59.0; H, 8.2. Found: C, 59.0; H, 8.3.
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The Barton-McCombie protocol for the deoxygenation of alcohols
4,5
is an extremely useful method that has found widespread application in synthetic organic
chemistry.
6
This radical-mediated process typically employs 1.5-3 equiv of Bu
3SnH
7 as the reducing agent.
Because some tributyltin-containing compounds are toxic,
8 and product isolation from
large quantities of organotin residues can be difficult,
9 the development of alternative reducing
agents to Bu
3SnH has been an active area of investigation. Indeed, it has
been established that silicon hydrides
10
and dialkyl phosphites
11
can serve as substitutes for Bu
3SnH in many instances. Despite these facts,
Bu
3SnH continues to be the reagent most commonly used for effecting this
reduction.
12
Additional applications of this method to the deoxygenation of secondary alcohols
are provided in the Table.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Tributylstannane: Stannane, tributyl-
(8,9); (688-73-3)
3-Deoxy-1,2:5,6-bis-O-(methylethylidene)-α-D-ribo-hexofuranose:
D-ribo-Hexofuranose, 3-deoxy-1,2:5,6-bis-O-isopropylidene, α-
(8); α-D-ribo-Hexofuranose, 3-deoxy-1,2:5,6-bis-O-(1-methylethylidene)-
(9); (4613-62-1)
1,2:5,6-Bis-O-(1-methylethylidene)-, O-phenyl carbonothioate-α-D-glucofuranose:
Glucofuranose, 1,2:5,6-di-O-isopropylidene, O-phenyl thiocarbonate, α-D-
(8); α-D-Glucofuranose, 1,2:5,6-bis-O-(1-methylethylidene)-,
O-phenyl thiocarbonate (9); (19189-62-9)
1,2:5,6-Di-O-isopropylidene-D-glucose: Glucofuranose
1,2:5,6-di-O-isopropylidene-α-D- (8); α-D-Glucofuranose,
1,2:5,6-bis-O-(1-methylethylidene)- (9); (582-52-5)
Phenyl chlorothionoformate: Formic acid,
chlorothio-, O-phenyl ester (8); Carbonochloridothioic acid,
O-phenyl ester (9); (1005-56-7)
Pyridine (8,9); (110-86-1)
Benzene: CANCER SUSPECT AGENT
(8,9); (71-43-2)
Bis(tributyltin) oxide: Distannoxane, hexabutyl-
(8,9); (56-35-9)
Azobisisobutyronitrile: Propionitrile, 2,2'-azobis[2-methyl-
(8); Propanenitrile, 2,2'-azobis[2-methyl- (9); (78-67-1)
Poly(methylhydrosiloxane): PMHS: Poly[oxy(methylsilylene)]
(8,9); (9004-73-3)
1-Butanol: Butyl alcohol (8);
1-Butanol (9); (71-36-3)
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved