Organic Syntheses, Vol. 76, 178
Checked by Kazuya Matsunaga and Rick L. Danheiser.
1. Procedure
B. 3-(tert-Butyldimethylsilyl)-2-propyn-1-ol. An oven-dried,
250-mL, three-necked, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar is sealed under
argon with three rubber septa, one of which contains a
needle adapter to an argon-filled balloon. The flask is charged with
19.5 g (139 mmol) of 2-propargyloxytetrahydropyran and
140 mL of tetrahydrofuran (THF) (Note
6) and cooled to −78°C in a dry
ice-acetone bath. To the well-stirred solution,
13.9 mL (139 mmol) of a 10.0 M solution of butyllithium in hexanes (Note
7) is added slowly via syringe over 15 min. The resulting yellow solution is stirred for 5 min at −78°C, after which time the dry ice-acetone bath is removed and replaced with an ice-water bath, and the reaction mixture is stirred for 15 min at 0°C. One of the septa is removed,
22.0 g (146 mmol) of solid tert-butyldimethylsilyl chloride (Note
8) is added to the reaction mixture in one portion, and the reaction flask is sealed again with a rubber septum. After an additional 2 min at 0°C, the ice-water bath is removed. Within 15 min an exotherm is observed (up to 40°C), followed by a slow return to room temperature (Note
9). The orange-red reaction mixture is poured into a
1-L separatory funnel containing
250 mL of aqueous 10% sodium chloride solution and
250 mL of hexanes. The layers are mixed vigorously and separated. The aqueous layer is extracted with two
125-mL portions of hexanes, and the combined organic extracts are dried over anhydrous
sodium sulfate, filtered, and concentrated under reduced pressure. The residue is transferred to a
1-L round-bottomed flask equipped with a Teflon-coated magnetic stirring bar. To this flask,
500 mL of anhydrous methanol (Note
10) is added, followed by
0.530 g (2.79 mmol) of p-toluenesulfonic acid monohydrate (Note
11). The flask is sealed with a rubber septum containing a needle adapter to an argon-filled balloon. The reaction mixture is stirred at 23°C for 2 hr and then quenched by the addition of
100 mL of an aqueous saturated sodium bicarbonate solution. The resulting suspension is stirred for an additional 10 min, after which time the mixture is concentrated under reduced pressure to remove most of the
methanol. The residue is transferred to a 1-L separatory funnel containing
250 mL of an aqueous 10% sodium chloride solution, and the mixture is extracted with three
200-mL portions of 1:1 hexanes-ethyl acetate. The combined organic extracts are dried over anhydrous
sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by distillation at reduced pressure (1.5 mm) using a 15-cm Vigreux column to afford
22.0 g (
93%) of
3-(tert-butyldimethylsilyl)-2-propyn-1-ol as a colorless oil that solidifies on standing at 23 °C (Note
12).
2. Notes
3. Extraction with bicarbonate removes residual acid and ensures that no hydrolysis of the acetal product takes place during concentration and distillation.
4. Rotary evaporation (at 22 mm) was conducted at or below 23°C to prevent evaporative loss of the product.
5. The product exhibits the following properties: bp
69-70°C/13 mm (lit.
2 63-65°C/9 mm); TLC R
f = 0.53 (
25% ethyl acetate-hexanes); IR (neat, cm
−1): 3290, 2943, 1442, 1220, 1120, 1029, 901, 870;
1H NMR (300 MHz, CDCl
3) δ: 1.50-1.88 (m, 6 H), 2.41 (t, 1 H, J = 2.4), 3.51-3.58 (m, 1 H), 3.80-3.88 (m, 1 H), 4.22 (dd, 1 H, J = 15.6, 2.4), 4.28 (dd, 1 H, J = 15.6, 2.4), 4.82 (t, 1 H, J = 3.0);
13C NMR (75 MHz, CDCl
3) δ: 18.8, 25.2, 30.0, 53.8, 61.8, 74.0, 79.6, 96.6.
6.
Tetrahydrofuran was obtained from EM Science and distilled from
sodium benzophenone ketyl under an atmosphere of
argon.
10. Anhydrous
methanol was obtained from J. T. Baker Inc., and used without further purification.
12. The product exhibits the following properties: bp
69-72°C/1.5 mm (lit.
4 68-70°C/0.3 mm); mp
34-37°C (lit.
4 36-38°C); TLC R
f = 0.43 (
25% ethyl acetate-hexanes); IR (CHCl
3) cm
−1: 3423, 2960, 1506, 1455, 1348, 1273, 1212, 1138, 1012, 958, 830, 715, 679;
1H NMR (300 MHz, CDCl
3) δ: 0.10 (s, 6 H), 0.93 (s, 9 H), 1.91 (bs, 1 H), 4.27 (s, 2 H);
13C NMR (75 MHz, CDCl
3) δ −4.8, 16.5, 26.0, 51.6, 88.8, 104.4.
13.
Triphenylphosphine (PPh3) and diethyl azodicarboxylate (DEAD) were obtained from Aldrich Chemical Company, Inc., and used without further purification.
14. Comparable results are obtained using either a cryobath (−15°C) or a bath containing a mixture of solid
sodium chloride and ice (−12 to −18°C) for cooling.
15. Extended stirring of
PPh3 and
DEAD can lead to precipitation of the
betaine and inferior results. Similarly, more concentrated solutions of
PPh3 and
DEAD, or cooling below −15°C, can induce precipitation. For this reason, the indicated protocol and concentrations are recommended. With other substrates, a modified order of addition, involving the addition of
DEAD to a solution of
PPh3 and substrate followed by addition of
o-nitrobenzenesulfonylhydrazine, may prove beneficial. In the present case this modified order of addition provided nearly identical results (isolated yield 68%).
16.
o-Nitrobenzenesulfonyl hydrazide (NBSH) was prepared as follows:
5 Hydrazine monohydrate (12.1 mL, 0.25 mol, 2.5 equiv) is added dropwise to a solution of
o-nitrobenzenesulfonyl chloride (22.2 g, 0.10 mol, 1 equiv) in THF (100 mL) at −30°C under an
argon atmosphere. During the addition the reaction mixture becomes brown and a white precipitate of
hydrazine hydrochloride is deposited. After stirring at −30°C for 30 min, thin-layer chromatographic (TLC) analysis indicates that the sulfonyl chloride has been consumed (2:1
ethyl acetate-
hexanes eluent).
Ethyl acetate (200 mL, 23°C) is added to the cold reaction solution, and the mixture is washed repeatedly with ice-cold aqueous
10% sodium chloride solution (5 × 150 mL); each wash involved a contact time of ≤ 1 min. The organic layer is dried over
sodium sulfate at 0°C, then added slowly to a stirring solution of
hexanes (1.2 L) at 23°C over 5 min.
o-Nitrobenzenesulfonyl hydrazide precipitates within 10 min as an off-white solid and is collected by vacuum filtration. The filter cake is washed with
hexanes (2 × 50 mL, 23°C), and dried under reduced pressure (< 1.5 mm) at 23°C for 14 hr to afford pure NBSH as an off-white powder (
17.6 g,
81%); mp
100-101°C; IR (EtOAc) cm
−1: 3100-3400, 1547, 1352, 1165;
1H NMR (300 MHz, CD
3CN) δ: 3.90 (bs, 2 H), 5.97 (bs, 1 H), 7.78-7.91 (m, 3 H), 8.03-8.17 (m, 1 H);
13C NMR (75 MHz, CD
3CN) δ: 125.8, 130.8, 133.2, 133.4, 135.5, 149.4. Anal. Calcd for C
6H
7N
3O
4S: C, 33.18; H, 3.25; N, 19.35. Found: C, 33.41; H, 3.27; N, 19.20; R
f = 0.19 (2:1
ethyl acetate-
hexanes). Because solutions of NBSH are unstable at room temperature, the solution of
NBSH in
tetrahydrofuran should be prepared just prior to addition to the reaction mixture.
17. An orange oil composed of
tetrahydrofuran and reaction by-products separates during the work-up and is removed.
18. A short
silica gel pad approximately 10 cm in length by 5 cm in diameter is recommended. Isolation of the product by distillation (bp
111-120°C, bath temperature 150°C) resulted in significant material loss presumably due to its thermal decomposition.
6
19. A suitable stain for detection of the allene (TLC analysis) is basic aqueous
potassium permanganate solution.
20. On the basis of
1H NMR analysis, the product contains
6-10% of pentane that can be removed by further rotary evaporation at 23°C, accompanied by evaporative loss of the product. The submitters obtained the product in
72% yield and report that their material contains
3-5% pentane. The allene product exhibits the following properties: TLC R
f = 0.64 (
hexanes); IR (neat, cm
−1): 2953, 2858, 1933, 1617, 1471, 1250, 1214, 827, 805, 781;
1H NMR (300 MHz, C
6D
6) δ: 0.06 (s, 6 H), 0.89 (s, 9 H), 4.26 (d, 2 H, J = 7.2), 4.86 (dd, 1 H, J = 7.2, 7.2);
13C NMR (75 MHz, C
6D
6) δ: −5.8, 17.3, 26.4, 66.9, 78.2, 213.8; high resolution mass spectrum (EI) m/z 154.1176 [(M)+ calcd for C
9H
18Si: 154.1178].
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
There are few methods for the stereodefined construction of allenes.
7,8,9,10,11,12,13 The procedure described here provides a general and practical method for the synthesis of allenes from
propargylic alcohol precursors in a single operation. The transformation involves the Mitsunobu invertive displacement of an alcohol with
o-nitrobenzenesulfonyl hydrazide (NBSH), followed by elimination of
o-nitrobenzenesulfinic acid to form a propargylic diazene intermediate that undergoes spontaneous sigmatropic elimination of dinitrogen to form an allene. The method is highly efficient and proceeds with complete stereospecificity under mild reaction conditions (neutral pH, reaction temperatures ≤23°C). The method is also well suited for the synthesis of (trialkylsilyl)allenes, including the heretofore difficultly accessible parent
(tert-butyldimethylsilyl)allene,
12,13 as illustrated here. In addition, the method is applicable for the preparation of allenes with a wide variety of sensitive functional groups.
14,15
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
(tert-Butyldimethylsilyl)allene: Silane, (1,1-dimethylethyl)dimethyl-1,2-propadienyl- (13); (176545-76-9)
2-Propargyloxytetrahydropyran: 2H-Pyran, tetrahydro-2-(2-propynyloxy)- (8,9); (6089-04-9)
(±)-Camphorsulfonic acid: Bornanesulfonic acid, 2-oxo-, (±)- (8);
Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (±)- (9); (5872-08-2)
Propargyl alcohol: 2-Propyn-1-ol (8,9); (107-19-7)
3,4-Dihydro-2H-pyran: 2H-Pyran, 3,4-dihydro- (8,9); (110-87-2)
3-(tert-Butyldimethylsilyl)-2-propyn-1-ol: 2-Propyn-1-ol, 3-[(1,1-dimethylethyl)dimethylsilyl]- (12); (120789-51-7)
Butyllithium: Lithium, butyl- (8,9); (109-72-8)
tert-Butyldimethylsilyl chloride: Silane, chloro(1,1-dimethylethyl)dimethyl- (9); (18162-48-6)
p-Toluenesulfonic acid monohydrate (8); Benzenesulfonic acid, 4-methyl-, monohydrate (9); (6192-52-5)
Triphenylphosphine: Phosphine, triphenyl- (8,9); (603-35-0)
Diethyl azodicarboxylate: Formic acid, azodi-, diethyl ester (8); Diazenedicarboxylic acid, diethyl ester (9); (1972-28-7)
o-Nitrobenzenesulfonyl hydrazide: Benzenesulfonic acid, 2-nitro-, hydrazide (9); (5906-99-0)
N-Benzylidenebenzylamine: Benzylamine, N-benzylidene- (8);
Benzenemethanamine, N-(phenylmethylene)- (9); (780-25-6)
Hydrazine HIGHLY TOXIC. CANCER SUSPECT AGENT (8,9); (302-01-2)
o-Nitrobenzenesulfonyl chloride: Benzenesulfonyl chloride, o-nitro- (8);
Benzenesulfonyl chloride, 2-nitro- (9); (1694-92-4)
Hydrazine hydrochloride CANCER SUSPECT AGENT (8,9); (14011-37-1)
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