Checked by Robert J. Ross and Leo A. Paquette.
1. Procedure
A.
1-Iodo-3-trimethylsilylpropane. In a dry,
100-mL, two-necked, round-bottomed flask equipped with a
magnetic stirring bar, a
reflux condenser, and a
rubber septum is placed
15.0 g (0.10 mol) of sodium iodide. A
nitrogen inlet tube is connected to the top of the reflux condenser and all the apparatus is kept under
nitrogen. To this vessel are added
50 mL of acetone and
11.5 mL (10 g, 0.066 mol) of 1-chloro-3-trimethylsilylpropane (Note
1) with a
hypodermic syringe through the septum; the resulting white suspension is stirred under reflux for 24 hr. The condenser is replaced with a
Claisen head, and the bulk of the solvent is removed under ordinary pressure (Note
2) to give a white slurry. To this is added
60 mL of hexane and the inorganic salts are filtered off by suction. The filter cake is washed with five
10-mL portions of hexane. The
hexane is distilled off from the combined organic portions at atmospheric pressure. The residual oil is transferred to a
50-mL, round-bottomed flask fitted with a stirring bar and a Claisen head, and is distilled under reduced pressure to afford
1-iodo-3-trimethylsilylpropane 1 (
11.5–13.1 g,
72–81%), bp
84–86°C (25 mm), as a clear liquid (Note
3) and (Note
4).
B.
2-Methyl-2-vinylcyclopentanone. A
300-mL, two-necked, round-bottomed flask fitted with a magnetic stirring bar, a nitrogen inlet tube, and a rubber septum is kept under dry
nitrogen. To this flask are introduced
8.3 mL (5.99 g, 0.0591 mol) of diisopropylamine and
120 mL of tetrahydrofuran (Note
5) with a syringe through the septum. The flask is cooled in a
dry ice–hexane bath. To the solution is slowly added
38.7 mL of butyllithium (1.53 M in hexane, 0.0592 mol) with a syringe and the mixture is kept at 0°C (in an
ice bath) for 10 min. The resulting solution of
lithium diisopropylamide is again cooled in a dry ice–hexane bath (−78°C), and
11.2 mL (11.57 g, 0.0645 mol) of N,N'-dimethylpropyleneurea (DMPU) (Note
6) is added. After stirring for 30 min,
6.47 mL (6.15 g, 0.0539 mol) of methyl tiglate is injected drop by drop at −78°C. After the solution is stirred for an additional 20 min,
13.0 g (0.0537 mol) of 1-iodo-3-trimethylsilylpropane 1 is added with a syringe and the dry ice–hexane bath is replaced with an ice bath. The solution is stirred at about 0°C for 1 hr and then poured onto
150 mL of ice-cooled 3 N hydrochloric acid covered with
150 mL of hexane. The organic layer is separated and the aqueous layer is extracted with two
80-mL portions of hexane. The combined organic layers are washed successively with
50 mL of 3 N hydrochloric acid and
50 mL of saturated sodium bicarbonate solution and dried over anhydrous
magnesium sulfate. The solvent is removed on a
rotary evaporator to afford the crude ester
2 (ca. 13 g) (Note
7), which is sufficiently pure for the next operation.
In a two-necked, round-bottomed flask equipped with a magnetic stirring bar, a rubber septum, and a reflux condenser, the top of which is fitted with a nitrogen inlet tube, is placed
7.3 g (ca. 0.13 mol) of 85% pure potassium hydroxide. To the flask are added 4 mL of water and an
ethanol solution (60 mL) of the crude ester
2 (ca. 13 g) with a syringe; the mixture is refluxed for 1 hr. The reflux condenser is replaced with a Claisen head and the bulk of the solvent is distilled off over 30 min (Note
8). The residue is cooled in an ice bath and
80 mL of 6 N hydrochloric acid is cautiously introduced. The mixture is extracted with
150 mL of hexane and the organic layer is separated. To the aqueous layer is added
40 mL of concentrated hydrochloric acid and the solution is again extracted with two
100-mL portions of hexane. The combined organic extracts are dried over anhydrous
magnesium sulfate and concentrated under reduced pressure to afford the
crude acid 3 (
10.6–12.0 g) as a dark-colored oil (Note
9).
A
200-mL, two-necked, round-bottomed flask fitted with a magnetic stirring bar, a reflux condenser, and a rubber septum is flushed with
nitrogen. To this flask is introduced a dry
benzene solution (50 mL) of crude acid
3 through the septum. Then
8.9 mL (12.9 g, 0.101 mol) of oxalyl chloride is slowly added with stirring at room temperature. After the evolution of gas ceases, the solution is further heated in an
oil bath maintained at 70°C for 30 min. The solvent, together with excess
oxalyl chloride, is removed at room temperature first on a rotary evaporator and finally with a
vacuum pump to leave the crude acid chloride of
3 as a dark-colored oil (Note
10).
In a
300-mL, three-necked, round-bottomed flask fitted with an nitrogen inlet tube, a
dropping funnel, and a rubber septum are placed
7.45 g (0.0559 mol) of powdered aluminum chloride and a magnetic stirring bar. After
100 mL of dichloromethane (Note
11) is introduced, the crude acid chloride, dissolved in
50 mL of dichloromethane, is added via the dropping funnel to the stirred suspension of
aluminum chloride at 0°C over 5 min, whereupon most of the
aluminum chloride dissolves. After further stirring at 0°C for 15 min and at room temperature for 15 min, the flask is recooled in an ice bath and
100 mL of 3 N hydrochloric acid is cautiously added through the dropping funnel. The organic phase is separated and the aqueous layer is extracted 3 times with
50-mL portions of dichloromethane. The combined organic layers are successively washed with
30 mL of 3 N hydrochloric acid and
50 mL of saturated sodium bicarbonate solution, and dried over anhydrous
magnesium sulfate. The solvent is removed under ordinary pressure and the residue is distilled under reduced pressure to give
2-methyl-2-vinylcyclopentanone as a clear liquid (
3.74–5.6 g,
56–84% yield based on the
methyl tiglate), bp
104–124°C (110 mm) (Note
12), ca. 95% pure by GLC (Note
13).
2. Notes
2. About 40 mL of distillate is collected.
3.
1-Iodo-3-trimethylsilylpropane has the following spectral properties:
1H NMR (CCl
4, 3% benzene (δ 7.24) as an internal standard) δ: −0.03 (s, 9 H, (CH
3)
3Si), 0.34–0.74 (m, 2 H, CH
2Si), 1.47–2.04 (m, 2 H, CH
2), 3.07 (t, 2 H,
J = 7, CH
2I); IR (neat) cm
−1: 2950, 1250, 860, 830.
7. Alkylation of
methyl tiglate was carried out according to a reported procedure.
4
8. About 50 mL of distillate was collected.
9. Crude
3 exhibited the following spectral properties, which are virtually identical to those of an analytically pure sample:
1H NMR (CCl
4, 3% benzene (δ 7.24) as an internal standard) δ: 0.16 (s, 9 H, (CH
3)
3Si), 0.44–0.77 (m, 2 H, CH
2Si), 1.1–2.0 (m, 4 H, CH
2CH
2), 1.41 (s, 3 H, CH
3), 4.91–5.31 (m, 2 H, C=CH
2), 6.04 (d of d, 1 H,
J = 10 and 18, CH=CH
2), 11.34 (s, 1 H, CO
2H); IR (neat) cm
−1: 2950, 1700, 1400, 1250, 1180, 920, 840, 740, 680.
10. Conversion of the carboxylic acid to the acid chloride was based on a reported method.
5
12.
2-Methyl-2-vinylcyclopentanone showed the following spectral properties:
1H NMR (CCl
4) δ: 0.73 (s, 3 H, CH
3), 1.6–2.3 (m, 6 H, (CH
2)
3), 4.67–5.07 (m, 2 H, C=CH
2), 5.62 (d of d, 1 H,
J = 8 and 18, CH=CH
2); IR (neat) cm
−1: 3070, 2950, 1730, 1640, 1450, 1400, 1150, 1060, 1040, 1000, 920.
13. Vapor-phase chromatography was performed on an OV 101, fused silica, 20-m capillary column.
3. Discussion
Cyclopentanones are widely found in natural products and are also useful intermediates in organic synthesis. Thus a facile construction of cyclopentanones from easily available acyclic precursors is particularly desirable. This method of preparation is based on an intramolecular acylation of 5-trimethylsilylalkanoyl chlorides previously reported by us.
2 The starting materials are generally prepared by alkylation of carboxylic acids with 3-trimethylsilylalkyl halides followed by their conversion to the corresponding acid chlorides. The cyclization of the acid chlorides proceeds cleanly with
aluminum chloride. An acyl cation generated from the acid chloride and
aluminum chloride is trapped with the alkyl–silicon bond in the same molecule to yield a cyclopentanone selectively:
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