A. trans-2-(2-Propenyl)cyclopentanol. A 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, reflux condenser with a stopcock, and a 250-mL addition funnel is charged with 18.3 g (750 mmol) of magnesium turnings (Note 1). The system is evacuated and placed under argon, then 100 mL of ethyl ether (Note 2) is added to the system via cannula. The system is placed in an ice–water bath, and 2 mL of allyl bromide (Note 3) is added via syringe to the magnesium suspension to initiate Grignard formation. The addition funnel is charged with 45.5 g (375 mmol) of allyl bromide and 30 mL of ethyl ether. Another 100 mL of ethyl ether is added to the reaction flask. Stirring is begun, and the allyl bromide–ethyl ether mixture is added dropwise to the cooled reaction flask over a period of about 2 hr. After the addition is complete, the dark-gray solution is stirred for several hours at ambient temperature (Note 4). Meanwhile, a 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, a reflux condenser with a stopcock, and a 60-mL addition funnel is evacuated and placed under argon. The Grignard solution is transferred, via a cannula, into the flask, and 16.8 g (200 mmol) of cyclopentene oxide (Note 5) is placed in the addition funnel. While the solution is stirred, the epoxide is added dropwise to the Grignard reagent at a rate sufficient to maintain a mild reflux. After the solution is stirred for several hours or overnight, the flask containing the dark gray reaction mixture is placed in an ice–water bath, and excess Grignard reagent is hydrolyzed with 40 mL of a saturated aqueous ammonium chloride solution. The fine white precipitate is allowed to settle (Note 6), and the liquid is decanted into a 500-mL separatory funnel. The precipitate is washed with ethyl ether (4 × 50 mL) (Note 7), and all the ethyl ether solutions are combined, washed with saturated aqueous sodium bicarbonate solution (3 × 20 mL), then with saturated aqueous sodium chloride (2 × 20 mL). The aqueous layers are combined and washed with ethyl ether (2 × 20 mL). The ether layers are combined and dried over anhydrous potassium carbonate. The desiccant is removed by gravity filtration, and the solvent removed under reduced pressure to give 24.1–26.4 g (96–105%) of a yellow oil. Distillation (43°C, 0.250 mm) yields 1 (19.8–23.0 g, 78–91%) as a clear, colorless oil (Note 8).

B. cis-2-(2-Propenyl)cyclopentylamine. A 1000-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, two addition funnels, and a stopcock is charged with 41.5 g (158 mmol) of triphenylphosphine (Note 9) and 23.3 g (158 mmol) of phthalimide (Note 10). The system is evacuated and placed under argon. To one addition funnel, 20.0 g (158 mmol) of trans-2-(2-propenyl)cyclopentanol is added; 27.5 g (158 mmol) of diethyl azodicarboxylate (Note 11) is added to the other. Tetrahydrofuran, 500 mL (Note 12), is added to the flask via cannula, and stirring is begun. The substrate and diethyl azodicarboxylate are simultaneously added dropwise, slowly over about 30 min (Note 13), with stirring; the solution turns clear and yellow (Note 14). The reaction is permitted to proceed for 2 days at room temperature; the solution is then transferred to a 1000-mL, one-neck, round-bottomed flask, and the solvent is removed under reduced pressure, to leave a yellow–white semisolid. A magnetic stirring bar is added to the flask and the semisolid is taken up in 250 mL of reagent-grade methyl alcohol. To this, 10.1 g (316 mmol) of hydrazine (Note 15) is added. A reflux condenser is attached to the flask, stirring is begun, and the system is brought to reflux (Note 16). A large amount of clumpy white solid forms in a yellow-to-orange solution. After 4 hr at reflux, the solution is allowed to cool to room temperature; a mixture of 20 mL of hydrochloric acid (Note 17) and 65 mL of methyl alcohol is added, and the system is refluxed overnight. The resulting reaction mixture is filtered to remove the precipitate, and the solvent is removed under reduced pressure to yield a white-to-pink solid, which is taken up in 800 mL of water and 28 mL of hydrochloric acid. The solution is filtered, and the solid washed with water (2 × 200 mL) and hydrochloric acid (20 mL). The liquids are combined, placed in a 2000-mL separatory funnel, and washed with chloroform (3 × 250 mL), and ethyl ether (1 × 250 mL). The aqueous layer is transferred to a 2000-mL Erlenmeyer flask and cooled in an ice–water bath. A saturated aqueous sodium hydroxide solution is used to make the solution basic, to approximately pH 14, whereupon the solution turns dark olive green. The basic solution is extracted with ethyl ether (10 × 250 mL or by continuous extraction overnight) and the combined organic layers are dried over a mixture of anhydrous sodium sulfate and anhydrous potassium carbonate. Filtration and solvent removal at atmospheric pressure yields a green–yellow oil. Distillation (52–58°C, 8–11 mm) gives 2 (11.8–12.5 g, 60–63%) as a clear, colorless oil (Note 18).

C. cis-1-N-Tosyl-2-(2-propenyl)cyclopentylamine. A 100-mL, one-necked, round-bottomed flask equipped with a sidearm, a magnetic stirring bat, stopcock, and a serum cap on the sidearm, is charged with 8.00 g (64 mmol) of cis-2-(2-propenyl)cyclopentylamine. The system is evacuated and placed under argon. Via cannula, 50 mL of pyridine (Note 19) is added. The flask is cooled in an ice–water bath, the stopcock removed, 12.58 g (66 mmol) of p-toluenesulfonyl chloride (Note 20) is added to the reaction mixture, and the stopcock replaced. The reaction mixture immediately turns orange; it is allowed to stir at 0°C overnight, during which time the reaction mixture turns deep purple. The reaction mixture is then poured into a separatory funnel, 60 mL of distilled technical grade ethyl acetate is added, and the solution is washed with 100-mL portions of 1 : 1 2 N HCl: saturated aqueous sodium chloride until the washings are acidic. The organic layer is washed with saturated aqueous sodium chloride (2 × 60 mL), and dried over anhydrous magnesium sulfate. Gravity filtration and solvent removal under reduced pressure yield a dark red–brown solid. This is purified by recrystallization from 250 mL of ethyl alcohol: water (4 : 1); crystallization is completed in the refrigerator to give 3 (12.7–13.9 g, 71–78%) as off-white plates, mp 109–110°C (Note 21).

D. cis-N-Tosyl-3-methyl-2-azabicyclo[3.3.0]oct-3-ene. A 500-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar and reflux condenser is charged with 5.159 g (18.49 mmol) of cis-1-N-tosyl-2-(2-propenyl)cyclopentylamine, 1.998 g (18.49 mmol) of p-benzoquinone (Note 22), 0.096 g (0.370 mmol, 2 mol%) of PdCl₂ (CH₃CN)₂ (Note 23), 3.920 g (92.46 mmol, 500 mol%) of lithium chloride (Note 24), and 1.960 g (18.49 mmol) of sodium carbonate (Note 25). Tetrahydrofuran (100 mL) (Note 12) is added and stirring is begun. The yellow–orange solution is heated at reflux until thin-layer chromatography (3 : 1 hexane : ethyl acetate, SiO₂) shows that no starting material remains (about 3–4 hr); it is then poured into a 500-mL separatory funnel and 100 mL of ethyl acetate is added. This is washed with 100-mL portions of 1 : 1 saturated aqueous sodium chloride : sodium hydroxide (1%) until the aqueous layer is clear; then the yellow–green organic layer is washed with saturated aqueous sodium chloride (2 × 50 mL). The organic layer is dried over anhydrous magnesium sulfate, filtered by gravity, and passed through a short column (approximately 5 cm) of neutral alumina, and the column is washed with 100 mL of ethyl acetate. The combined solvents are removed under reduced pressure to give 4.9–5.1 g (94–99%) of a tan solid. The product is recrystallized from 100 mL of methyl alcohol : water (4 : 1) to yield 4 (3.9–4.45 g, 76–87%) as white needles, mp 91–92°C (Note 26) and (Note 27).