Organic Syntheses, Vol. 76, 101
Checked by Marc Renard and Léon Ghosez.
1. Procedure
A. L-Threitol 1,4-bismethanesulfonate. A dry, 1-L, round-bottomed flask equipped with a
magnetic stirring bar,
vacuum adapter,
rubber septum, and a
nitrogen line (Note
1) is charged with
2,3-O-isopropylidene-L-threitol (25.0 g, 0.154 mol) (Note
2), pumped under high vacuum for 10 min, and a
nitrogen atmosphere is introduced.
Methylene chloride (308 mL) (Note
3) and
pyridine (37.4 mL, 0.462 mol) (Note
4) are added, and the stirred solution is cooled to 0°C with an
ice-water bath.
Methanesulfonyl chloride (29.8 mL, 0.385 mol) (Note
5) is added dropwise via a 50-mL glass syringe over a period of 10 min. After an additional 30 min, the ice-water bath is removed, and the stirred solution is allowed to warm to room temperature. After an additional 6 hr a precipitate forms (
pyridinium chloride);
300 mL of an aqueous saturated solution of sodium bicarbonate (NaHCO3) is added slowly, dissolving the precipitate. The solution is stirred for a further 30 min and then transferred to a
1-L separatory funnel. The layers are separated, and the aqueous layer is extracted with
methylene chloride (3 × 100 mL). The organic layers are combined, dried with anhydrous
sodium sulfate, and the drying agent is removed by filtration. The solvent is removed by rotary evaporation to give a tan solid that can be used as such or recrystallized (Note
6) from 1:1
chloroform-diethyl ether to give the product as a crystalline white solid, mp
77-78°C,
43 g (
88% yield) (Note
7).
A
1-L, one-necked, round-bottomed flask equipped with a
heating mantle, magnetic stirring bar, and a
reflux condenser is charged with
2,3-O-isopropylidene-L-threitol 1,4-bismethanesulfonate (40 g, 0.126 mol),
95% ethanol (250 mL) (Note
8) and
methanesulfonic acid (0.204 mL, 3.14 mmol) (Note
9), and brought to a gentle reflux. The solution is refluxed for 10 hr and then cooled to 0°C with an ice-water bath resulting in the formation of crystals. The crystals are collected by suction filtration, washed with cold
ethanol (2 × 50 mL) and
diethyl ether (2 × 50 mL), and dried in a
vacuum desiccator at 60°C under full vacuum for 4 hr to give the product as white crystals, mp
101-102°C,
29.6 g, (
84% yield) (Note
10).
B. (S,S)-1,2,3,4-Diepoxybutane. A
250-mL, two-necked, round-bottomed flask equipped with a magnetic stirring bar, nitrogen line, and a
125-mL pressure-equalizing addition funnel is charged with
L-threitol 1,4-bismethanesulfonate (25.0 g, 0.0898 moles) and
diethyl ether (180 mL). The mixture is stirred vigorously to form a suspension, and a solution of
potassium hydroxide (11.6 g, 0.207 mol) (Note
11) in water (35 mL) is added dropwise via the addition funnel over a period of 15 min. The clear mixture is stirred for an additional 45 min at room temperature, and the
ether layer is decanted. The aqueous layer is transferred to a
500-mL separatory funnel and extracted with
methylene chloride (3 × 50 mL). The combined
ether and
methylene chloride extracts are dried with anhydrous
sodium sulfate, the
sodium sulfate is removed by filtration, and the solution is concentrated to approximately 50 mL total volume by rotary evaporation. The concentrate is fractionally distilled through a
13-cm Vigreux distillation column at atmospheric pressure to give the product as a clear oil, bp
138-140°C,
6.3 g (
81%) (Note
12) and (Note
13).
C. (2S,3S)-Dihydroxy-1,4-diphenylbutane. A
500-mL, one-necked, round-bottomed flask is equipped with a vacuum adapter, septum, magnetic stirring bar and an
argon line (Note
14). The flask is flame-dried under reduced pressure, an
argon atmosphere is reintroduced, and
copper iodide (CuI) (1.89 g, 9.9 mmol) (Note
15) is added. The flask with
CuI is pumped under reduced pressure for 10 min, and the
argon atmosphere is reintroduced. Then
30 mL of tetrahydrofuran (THF) (Note
16) is added to the flask, stirring is initiated, and the slurry is cooled to −30°C with a
dry ice-bromobenzene bath.
Phenylmagnesium bromide in THF (18.0 g, 0.099 mol, 99 mL of a 1 M solution in THF) (Note
17) is added via a 50-mL syringe over a period of 10 min, and the stirred slurry is aged a further 10 min.
(S,S)-1,2,3,4-Diepoxybutane (2.84 g, 0.033 mol, 11 mL of a 3 M solution in THF) is added dropwise via syringe over a period of 10 min. After an additional 10 min at −30°C, the reaction mixture is warmed to 0°C with an ice-water bath. After an additional 2.5 hr at 0°C, the reaction is quenched by the slow addition of
200 mL of an aqueous saturated ammonium chloride solution, the ice-water bath is removed, and the quenched reaction is stirred for 15 min yielding a deep blue color. The reaction mixture is transferred to a 1-L separatory funnel, and the layers are separated. The aqueous layer is extracted with
methylene chloride (4 × 50 mL), the combined organic layers are dried with
magnesium sulfate the drying agent is removed by filtration, and solvent is removed by rotary evaporation to give
7.1 g of a light yellow solid. The solid is dissolved in
225 mL of toluene with heat (heating mantle) then and cooled to 0°C with an ice-water bath resulting in the formation of fine needles. The needles are collected via suction filtration and dried in a vacuum desiccator at 40°C under full vacuum for 6 hr to yield
6.0 g of a white solid. The filtrate is evaporated to dryness via rotary evaporation to yield
1.1 g of a yellow solid. The yellow solid is flash-chromatographed on
30 g of Merck 230-400 mesh silica gel with 1:1
hexanes-ethyl acetate to give
1.0 g of a white solid (Note
18). The combined recrystallized and chromatographed product yields a total of
7.0 g of diol (
88%) (Note
19).
2. Notes
1. The reaction was maintained under a positive pressure of dry
nitrogen except during the quenching process. All glassware was dried in a 150°C oven for 30 min and cooled in a desiccator prior to use.
5.
Methanesulfonyl chloride was obtained from Aldrich Chemical Company, Inc., distilled under reduced pressure and stored under
nitrogen at 0°C (freezer) until needed.
6. The tan solid is recrystallized as follows. It is dissolved in approximately
250 mL of 1:1 chloroform-diethyl ether with heat (heating mantle). Upon cooling to 0°C with an ice-water bath, a solid precipitates that is collected by suction filtration. The solid is washed twice with cold
50-mL portions of diethyl ether and dried in a vacuum desiccator at 40°C under full vacuum to give the product as a white crystalline solid.
7. This product was found to be greater than 98% pure by
1H and
13C NMR. Physical properties and spectral data are as follows:
[α]D −22.1 (
acetone,
c 1.9, ), lit.
3 [α]D −21.3 (
acetone,
c 2.0);
1H NMR (CDCl
3) δ: 1.49 (s, 6 H), 3.10 (s, 6 H), 4.20 (q, 2 H), 4.39 (q, 4 H);
13C NMR (CDCl
3) δ: 27.1, 37.9, 67.9, 75.7, 111.4.
8.
95% ethanol from Pharmco Products Inc. was used as obtained.
10. This product was found to be greater than 98% pure by
1H and
13C NMR. Physical properties and spectral data are as follows:
[α]D −5.2 (
acetone,
c 1.85), lit.
3 [α]D −5.5 (
acetone,
c 2);
1H NMR (CDCl
3 + DMSO-d
6) δ: 2.80 (s, 6 H), 3.62 (m, 2 H), 3.79 (br s, 2 H), 4.00 (m, 4 H);
13C NMR (CDCl
3 + DMSO) Δ: 36.5, 67.5, 70.1.
12. This product was found to be greater than 98% pure by
1H and
13C NMR. Physical properties and spectral data are as follows
[α]D +25.7 (CHCl
3,
c 2.1), lit.
4 [α]D +23.6 (
CHCl3,
c 2);
1H NMR (CDCl
3) δ: 2.56 (m, 2 H), 2.68 (m, 4 H);
13C NMR (CDCl
3) δ: 44.4, 51.0.
13. The product was stored in a dry, round-bottomed flask under
argon in a freezer until needed.
14. The reaction was maintained under a positive pressure of dry
argon except during the quenching process. All glassware was dried in a 150°C oven for 30 min and cooled in a desiccator prior to use.
15.
Copper iodide, from Aldrich Chemical Company, Inc., was purified by Soxhlet extraction in
THF followed by drying under full vacuum overnight.
18. The diol elutes at an R
f = 0.64, (SiO
2, 1:1,
hexanes-
ethyl acetate).
19. This product was found to be greater than 98% pure by
1H and
13C NMR. Physical properties and spectral data are as follows:
[α]D +6.2 (
chloroform,
c 1.7);
1H NMR (CDCl
3) δ: 2.07 (bd, 2 H), 2.88 (m, 4 H), 3.75 (m, 2 H), 7.23 (m, 6 H), 7.31 (m, 4 H);
13C NMR (CDCl
3) δ: 40.3, 74.0, 126.6, 128.6, 129.4, 138.0. The checkers recrystallized the product in
hexane-
ethyl acetate (1:1).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The present approach provides a general method for the preparation of optically active diols. The Table illustrates the preparation of several diols.
5 6 The procedures are simple, and there is no possibility of racemization in any of the steps. This method does not require any difficult-to-handle or disposal of metals, which makes it a good alternative to osmium-catalyzed dihydroxylation.
7 A variety of diols can be prepared from the one diepoxide substrate. The optically active epoxides and diols are highly useful in organic synthesis.
8 9 10 A variety of diols have been useful as chiral ligands in asymmetric catalyst.
11
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
(S,S)-1,2,3,4-Diepoxybutane: Butane, 1,2:3,4-diepoxy-, (2S,3S)- (8);
2,2'-Bioxirane, [S-(R,R)]- (9); (30031-64-2)
L-Threitol 1,4-methanesulfonate: 1,2,3,4-Butanetetrol, 1,4-dimethanesulfonate, [S-(R,R)]- (9); (299-75-2)
2,3-Di-O-isopropylidene-L-threitol: Aldrich: (+)-2,3-O-Isopropylidene-L-threitol: 1,3-Dioxolane-4,5-dimethanol, 2,2-dimethyl-, (4S-trans)- (9); (50622-09-8)
Pyridine (8,9); (110-86-1)
Methanesulfonyl chloride (8,9); (124-63-0)
Pyridinium chloride: Pyridinium hydrochloride (8,9); (628-13-7)
Methanesulfonic acid (8,9); (75-75-2)
(2S,3S)-Dihydroxy-1,4-diphenylbutane: 2,3-Butanediol, 1,4-diphenyl-, [S-(R,R)]- (12); (133644-99-2)
Copper iodide (8,9); (7681-65-4)
Phenylmagnesium bromide: Magnesium, bromophenyl- (8,9); (100-58-3)
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