Synthesis of 2-Alkynyl-1,4-cyclohexadienes via a Diels–Alder Reaction of Conjugated 2,4-Diynones

Abstract

The development and utilization of highly functionalized and reactive dienophiles in the Diels–Alder cyclization reaction is of value in producing diversely functionalized, and therefore useful, cyclic products. We have developed a Diels–Alder reaction of conjugated 2,4-diynones, promoted by Lewis acids, to produce substituted 2-alkynyl-1,4-cyclohexadiene (‘skipped’ cyclohexadiene) products in good to excellent yields. The reaction was successful with a variety of cyclic and acyclic dienes as well as with a diversity of 2,4-diynones.

Key words

diynones - Diels–Alder reaction - 1,4-cyclohexadienes - Lewis acid catalysis - cyclization

• References and Notes

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• 12 General Procedure for Diels–Alder Reaction of Diynones: To a solution of diynone 1 (1.0 equiv) and diene 2 (5.0 equiv) in CH₂Cl₂ (ca. 0.05–0.15 M) was added dimethylaluminum chloride (1.0 M in hexanes, 1.0 equiv) slowly over 10 min. The reaction mixture was stirred at r.t. for 1–5 h, quenched with dilute aq NaHCO₃, dried over anhyd MgSO₄ and filtered. The solvent was removed in vacuo and the crude product was purified by column chromatography (silica gel).
• 13 1-Benzoyl-2-[2-(trimethylsilyl)ethynyl]-4,5-dimethyl-1,4-cyclohexadiene (3a): This reaction was performed according to the general procedure (305 mg of diynone 1a and 748 μL of diene 2a). Purification by column chromatography (toluene) afforded 3a (366 mg, 88% yield) as a pale yellow oil; R_f 0.52 (toluene). ¹H NMR (500 MHz, CDCl₃): δ = 7.86–7.93 (m, 2 H), 7.50–7.55 (m, 1 H), 7.39–7.44 (m, 2 H), 2.95–3.02 (m, 2 H), 2.84–2.91 (m, 2 H), 1.67 (s, 6 H, 2 × Me), –0.17 (s, 9 H). ¹³C NMR (125 MHz, CDCl₃): δ = 198.7, 141.9, 137.2, 133.0, 129.8, 128.5, 122.2 (2 coincidental peaks), 120.5, 103.2, 101.7, 38.0, 35.0, 18.3, 18.1, –0.4. IR (cast film): 2959, 2858, 2813, 2142, 1656, 1598, 1580, 1448 cm^–1. HRMS (ESI–TOF): m/z [M + Na]⁺ calcd for C₂₀H₂₄NaOSi: 331.1494; found: 331.1490.