Fe(III)-Catalyzed Intermolecular C(sp^²)-C(sp^³) Dehydration Coupling Reaction of Ketene Dithioacetals and Propargyl Alcohols: Synthesis of Novel gem-Dialkylthiopenten-4-ynes and Further Conversion into Methyl Pent-4-ynoates

Abstract

We report an iron(III)-catalyzed intermolecular C(sp^²)-C(sp^³) dehydration coupling reaction between ketene dithioacetals and propargyl alcohols, leading to the synthesis of gem-dialkylthiopenten-4-ynes in high efficiency. The products could be transformed into methyl pent-4-ynoates in high yields.

iron - dehydration - coupling reactions - alkynes - thioacetals

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Synthesis of gem-dialkylthiopenten-4-ynes (3); Typical procedure with 3a: To a solution of 1-(1,3-dithiolan-2-ylidene)propan-2-one (1a; 160 mg, 1.0 mmol) and 1,3-diphenylprop-2-yn-1-ol (2a; 250 mg, 1.2 mmol) in MeCN (2.0 mL), FeBr₃ (88 mg, 0.3 mmol) was added, and the mixture was stirred at r.t. for 20 min. After completion of the reaction (progress monitored by TLC), the mixture was poured into ice-water and extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were dried with MgSO₄, filtered, evaporated in vacuum, and the residue was purified by column chromatography (petroleum ether-diethylether = 10:1) to give product 3a (308 mg, 88% yield) as a white solid. Mp 170-171 ˚C. ^¹H NMR (CDCl₃, 500 Hz): δ = 2.17 (s, 3 H), 3.63-3.40 (m, 2 H), 3.42-3.45 (m, 2 H), 5.68 (s, 1 H), 7.25-7.31 (m, 1 H), 7.32-7.37 (m, 5 H), 7.49-7.53 (m, 4 H). ^¹³C NMR (CDCl₃, 125 Hz): δ = 28.4, 35.9, 39.32, 41.9, 85.6, 87.3, 123.1, 124.2, 126.8, 127.0, 128.2, 128.3, 128.6, 131.6, 138.5, 163.8, 194.7. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₁H₁₉OS₂: 351.0877; found: 351.0833

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