Novel Intramolecular Allylindination of Terminal Alkynes in Aqueous Media

Abstract

The intramolecular cyclisation of tethered allyl bromides onto terminal alkynes mediated by metallic indium proceeds smoothly and cleanly in an mixture of THF and water to give unsaturated carbocycles and heterocycles in good yield. The reaction does not proceed efficiently under rigorously anhydrous conditions.

Key words

indium - enyne - intramolecular - cyclisation - aqueous

References

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16

General Experimental Procedure. To a well-stirred solution of (E)-2-(4-bromobut-2-enyl)-(2-prop-2-ynyl)-malonic acid dimethyl ester 4f (451 mg, 1.5 mmol) in dry THF (1 mL) and distilled water (1 mL) at room temperature, was added indium powder (Aldrich, 99.99%, 171 mg, 1.5 mmol, 1 equiv). The mixture was stirred for a further 18 hours and then the reaction mixture was poured onto a mixture of Et₂O and dilute HCl (5% v/v). The aqueous layer was extracted with Et₂O (2 × 25 mL) and the combined organic layers were washed with water (2 × 25 mL), saturated aqueous NaCl (1 × 25 mL) and dried (MgSO₄). Filtration and removal of solvent gave a residue which was purified by chromatography (SiO₂, hexane/EtOAc, 5:1) to give the cyclised product 5f (249 mg, 74%) as a clear colourless oil (R_f = 0.52). ¹H NMR (360.13 MHz, CDCl₃)
δ_H = 2.01 (1 H, dd, J = 11 Hz, 13 Hz), 2.57 (1 H, dd, J = 8 Hz, 13 Hz), 2.95 (1 H, ddd, J = 3 Hz, 6 Hz, 18 Hz), 3.08 (1 H, br d, J = 18 Hz), 3.17 (1 H, m), 3.82 (1 H, s with allylic coupling), 4.98 (1 H, s with allylic coupling), 5.05 (1 H, br s), 5.08 (1 H, m), 5.64 (1 H, ddd, J = 8 Hz, 10.5 Hz, 13 Hz) ppm. ¹³C NMR (100.62 MHz, CDCl₃) δ_C = 40.70, 48.08, 53.20, 53.26, 58.91, 108.55, 116.51, 139.44, 150.76, 172.40, 172.59 ppm. IR (thin film): 3660, 3471, 3078, 2953, 1731, 1714, 1659, 1642, 1453, 1433, 1267, 1199, 1167, 1072, 917, 891, 821, 766, 718, 690, 666 cm^-1. MS (FAB): m/z (%) = 225 (73.2) [MH⁺], 193 (36.5), 165 (65.1), 154 (74.3), 137 (68.1), 136 (61.7), 105 (100), 91 (49.7), 77 (49.1).

17

All compounds described gave ¹H, ¹³C, IR and MS data consistent with the structures reported.