A novel synthesis of chiral cyclopentyl- and cyclohexyl-amines

Abstract

A new route to multifunctionalised chiral cyclopentyl- and cyclohexyl-amines was developed by means of a new reaction involving the ring opening of a 2-azabicyclo-[2.2.1] or -[2.2.2] structure in high yields.

References

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9. Representative spectroscopic and analytical data. (1R,3S)-1-Tosylamino-3-vinylcyclopentane (4). Magnesium metal (3.0 g, 123 mmol) was placed in a 50 mL two-neck round-bottom flask loaded with a magnetic bar. To one neck a condenser was adapted and to the other a septum. The system was evacuated and placed under argon, after which the magnesium was suspended in dry THF (3 mL). The stirring suspension was then set to reflux and a solution of compound 3(6.0 g, 17 mmol) in dry THF (20 mL) was added in one portion via syringe. After stirring for 15 min a small amount of 1,2-dibromoethane was added to activate the magnesium and the mixture was heated at reflux for 24 h. The reaction was then cooled to 0 °C and quenched by addition of saturated NH₄Cl solution. After separation of the phases and extraction of the water phase with CH₂Cl₂, the combined organic layers were dried with magnesium sulfate. Solvent evaporation afforded a residue that was purified by flash chromatography to yield compound 4(4.1 g, 15 mmol, 90%) as a white solid; mp 65–66 °C; R_f 0.11 (silica gel, pentane–ether: 80 : 20); [α]²⁴_D=–8.9 (c= 1.0, CH₂Cl₂); v(CH₂Cl₂)/cm^–1 3623, 3369, 2870, 1641, 1599, 1345, 1092, and 1047; δ_H(CDCl₃, 400 MHz) 1.14–1.24 (1H, m), 1.38–1.45 (2H, m), 1.62–1.79 (1H, m), 1.80–1.90 (1H, m), 1.99–2.10 (1H, m), 2.34–2.42 (1H, m), 2.41 (3H, s), 3.57–3.63 (1H, m), 4.83–4.94 (2H, m), 5.65–5.75 (1H, m), 7.28 (2H, app. d, J 8.0), and 7.76 (2H, app. d, J 8.0); δ_C(CDCl₃, 100 MHz) 21.5, 29.9, 32.6, 40.2, 41.8, 54.5, 113.1, 127.1, 129.6, 137.8, 141.9, and 143.2; m/z(EI)(rel. intensity) 264 (M⁺, < 1%), 236 (25), 210 (13), 172 (14), 155 (62), 133 (44), 132 (36), 110 (41), 106 (17), 97 (12), 96 (43), 94 (13), 93 (25), 92 (35), 91 (100), 80 (21), 79 (17), and 65 (20)(Anal. Calcd. for C₁₄H₁₉NO₂S: C, 63.37; H, 7.22; N, 5.28. Found: C, 63.10; H, 7.07; N, 5.20%). The relative stereochemistry of this compound was determined by means of NOESY experiments.