A Facile and Efficient Synthesis of Six-Membered Enol Carbocyclic Compounds

Abstract

A facile and efficient method for the synthesis of six-membered enol carbocyclic compounds was realized by intermolecular cyclization reaction of 3-aryllidenepentane-2,4-diones with t-BuOK in CH₂Cl₂. The reaction is conducted under mild conditions and shows good functional group tolerance.

Key words

Michael addition - enol - dicarbonyl compounds - synthesis

• References and Notes

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• 11 General Procedure: To a solution of α,β-unsaturated ketone derivatives 1a (1 mmol) in CH₂Cl₂ (5.0 mL), t-BuOK (1.3 mmol) was added at room temperature. Upon completion, the reaction was quenched with H₂O, the mixture was extracted with EtOAc (3 × 15 mL), and the combined organic extract was washed with H₂O, saturated brine, dried over Na₂SO₄, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel to afford the corresponding enolate of 2a. Data for 2a: ¹H NMR (400 MHz, CDCl₃): δ = 7.38 (t, J = 7.2 Hz, 2 H), 7.31 (dd, J = 14.6, 7.2 Hz, 2 H), 7.28–7.24 (m, 2 H), 7.23 (d, J = 4.8 Hz, 2 H), 7.19 (t, J = 6.5 Hz, 2 H), 4.69 (s, 1 H), 3.88 (t, J = 8.9 Hz, 1 H), 3.01 (d, J = 8.7 Hz, 2 H), 2.44 (s, 3 H), 1.95 (s, 3 H), 1.15 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 208.7, 205.8, 200.2, 180.2, 140.3, 139.0, 130.0, 129.2, 129.0, 128.3, 128.1, 127.0, 108.6, 71.8, 48.3, 39.2, 36.9, 30.3, 30.0, 25.6. IR (neat): 3060, 2918, 2850, 1724, 1683, 1496, 1414, 1350, 768 cm^–1. HRMS (ESI): m/z [M – H] calcd for C₂₄H₂₃O₄: 375.1597; found: 375.1603. Data for 2b: ¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, J = 8.4 Hz, 2 H), 7.21 (d, J = 8.5 Hz, 2 H), 7.16 (d, J = 8.5 Hz, 2 H), 7.13 (d, J = 8.7 Hz, 2 H), 4.66 (s, 1 H), 3.75 (t, J = 9.0 Hz, 1 H), 2.95 (d, J = 9.0 Hz, 2 H), 2.41 (s, 3 H), 1.95 (s, 3 H), 1.28 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 207.3, 205.4, 200.1, 180.0, 138.4, 137.5, 134.4, 133.1, 131.1, 130.8, 129.2, 128.5, 108.4, 72.0, 47.4, 38.9, 36.6, 30.5, 29.9, 25.6. IR (neat): 3076, 2919, 2850, 1720, 1689, 1490, 1413, 1352, 775 cm^–1. HRMS (ESI): m/z [M – H] calcd for C₂₄H₂₁Cl₂O₄: 443.0817; found: 443.0825.