Gallium(III) Chloride Catalyzed Stereoselective Synthesis of E-Configured α,β-Unsaturated Ketones [1]

Abstract

A simple and highly stereoselective method has been developed for the synthesis of E-configured α,β-unsaturated ketones using gallium(III) chloride as a novel catalyst. This new procedure offers significant advantages such as high conversions, short reaction times and enhanced E-selectivity together with mild reaction conditions.

activated alkynes - gallium(III) chloride - ynones - α,β-unsaturated ketones

References and Notes

1

IICT Communication No. 061125.

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14

General Procedure.
To the reaction mixture containing substrate 1 (1.0 mmol), CH₂Cl₂ (10 mL) and alkynone 2 (1.5 mmol) was added a catalytic amount of GaCl₃ (0.1 mmol). The resulting mixture was stirred at r.t. for the appropriate time (Table [1] ). After completion of the reaction as indicated by TLC, EtOAc (20 mL) and H₂O (10 mL) were added to the reaction mixture and further stirred at r.t. for additional 10 min. Then, the EtOAc layer was separated and aqueous phase was extracted again with EtOAc (2 × 10 mL). The combined extracts were washed with brine, dried over anhyd Na₂SO₄ and concentrated in vacuo. The resulting crude product was purified by column chromatography on silica gel (Merck, 60-120 mesh, EtOAc-hexane, 2:8) to afford a pure product.
Spectral Data for Selected Products:
Compound 3a: IR (KBr): ν_max = 2924, 2856, 1732, 1556, 1458, 1337, 1234, 1172, 1103, 768, 744, 588 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.40 (d, J = 16.4 Hz, 1 H), 7.25 (s, 1 H), 7.12-7.05 (m, 1 H), 6.83 (d, J = 8.6 Hz, 1 H), 6.56 (d, J = 16.4 Hz, 1 H), 3.91 (s, 6 H), 2.34 (s, 3 H). MS (EI): m/z (%) = 206 (75) [M⁺], 191 (100), 163 (15), 149 (18), 107 (20), 77 (18), 43 (70).
Compound 3b: IR (KBr): ν_max = 3414, 3136, 2925, 1732, 1629, 1591, 1512, 1412, 1364, 1258, 1115, 1008, 962, 829, 711, 539 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.41-7.24 (m, 3 H), 6.76 (d, J = 8.3 Hz, 1 H), 6.58 (d, J = 15.8 Hz, 1 H), 5.28 (s, 1 H), 2.38 (s, 3 H), 2.27 (s, 3 H). MS (EI): m/z (%) = 176 (38) [M⁺], 161 (100), 149 (12), 141 (8), 133 (35), 105 (12), 79 (7), 77 (15), 55 (10), 43 (50).
Compound 3g: IR (KBr): ν_max = 3414, 3131, 2929, 1730, 1625, 1512, 1412, 1362, 960 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.43 (d, J = 16.0 Hz, 1 H), 7.30-7.22 (m, 2 H), 6.74 (d, J = 8.3 Hz, 1 H), 6.55 (d, J = 16.0 Hz, 1 H), 5.78 (s, 1 H), 2.60 (t, J = 7.3 Hz, 2 H), 2.58 (s, 3 H), 1.71-1.62 (m, 2 H), 1.37-1.28 (m, 4 H), 0.91 (t, J = 6.7 Hz, 3 H). MS (EI): m/z (%) = 232 (5) [M⁺], 176 (25), 161 (100), 133 (25), 105 (10), 77 (30), 43 (60).
Compound 3l: IR (KBr): ν_max = 3124, 3002, 2922, 2853, 1663, 1612, 1552, 1474, 1425, 1359, 1254, 1202, 1107, 969, 748, 585 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.46 (d, J = 1.5 Hz, 1 H), 7.23 (d, J = 15.6 Hz, 1 H), 6.63-6.44 (m, 3 H), 2.30 (s, 3 H). ESI-MS: m/z = 157.1 [M + Na]⁺, 134.9 [M]⁺, 121.