Direct Propargylation of ortho-Quinone Methides with Alkynyl Zinc Reagents: An Application to the One-Pot Synthesis of 2,3-Disubstituted Benzofurans

Manman Sun; Jinyu Song; Lei Wang; Wenguang Yin; Maozhong Miao; Hongjun Ren

doi:10.1055/s-0039-1691739

Synlett, Table of Contents

Synlett 2020; 31(08): 818-822
DOI: 10.1055/s-0039-1691739

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Direct Propargylation of ortho-Quinone Methides with Alkynyl Zinc Reagents: An Application to the One-Pot Synthesis of 2,3-Disubstituted Benzofurans

Manman Sun

^aAdvanced Research Institute and Department of Chemistry, Taizhou University, 1139 Shifu Avenue, Taizhou 318000, P. R. of China Email: renhj@tzc.edu.cn

,

Jinyu Song

^aAdvanced Research Institute and Department of Chemistry, Taizhou University, 1139 Shifu Avenue, Taizhou 318000, P. R. of China Email: renhj@tzc.edu.cn

,

Lei Wang

^bDepartment of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China

,

Wenguang Yin

^bDepartment of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China

,

Maozhong Miao

^bDepartment of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China

,

Hongjun Ren ∗

^aAdvanced Research Institute and Department of Chemistry, Taizhou University, 1139 Shifu Avenue, Taizhou 318000, P. R. of China Email: renhj@tzc.edu.cn

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Abstract

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Abstract

A transition-metal-free propargylation of ortho-quinone methides (o-QMs) with alkynyl zinc reagents was achieved. A conjugate alkynylation of an o-QM and subsequent cyclization sequence in the presence of KOt-Bu for the synthesis of 2,3-disubstituted benzofurans in one pot was developed. This efficient strategy exhibits good functional-group compatibility and gives moderate to good yields. The present reaction might serve as an attractive method for the synthesis of polysubstituted benzofurans.

Key words

propargylation - ortho-quinone methides - alkynyl zinc reagents - benzofurans

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References

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13 4-Fluoro-2-[1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-yl]phenol (2b); Typical ProcedureA 2.5 M solution of BuLi in hexanes (1.5 mmol) was added dropwise to a solution of ethynylbenzene (1.5 mmol) in anhyd THF (2 mL) at –20 °C under N₂, and the mixture was stirred for 30 min at –20 °C. A 1.0 M solution of ZnBr₂ in THF (1.5 mL) was added, and the resulting mixture was stirred for about 15 min at 0 °C. 4-fluoro-2-((4-methoxyphenyl)(tosyl)methyl)phenol 1b (193 mg, 0.5 mmol) was then added, and the mixture was stirred at rt for 15 h until the reaction was complete. The reaction was then quenched by adding sat. aq NH₄Cl (5 mL) and the mixture was extracted with EtOAc (3 × 10 mL). The combined organic phase was washed with H₂O (3 × 10 mL), dried (Na₂SO₄), concentrated in vacuo, and purified by flash chromatography (silica gel, petroleum ether/EtOAc = 5:1) to give a yellow solid; yield: 140 mg (84%); mp 89–90 °C (PE–EtOAc); R_f = 0.66 (PE–EtOAc, 3:1). IR (neat): 3380, 2221, 1605, 1512, 1234, 1182, 1024 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.48–7.46 (m, 2 H), 7.37 (d, J = 8.8 Hz, 2 H), 7.32–7.30 (m, 3 H), 7.14–7.11 (m, 1 H), 6.89–6.82 (m, 3 H), 6.76–6.73 (m, 1 H), 5.37 (s, 1 H), 5.29 (s, 1 H), 3.79 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.6 (d, J_C _–F = 40 Hz), 156.0, 149.1, 131.7, 131.6, 129.4, 129.3, 128.8, 128.3, 128.2, 122.7, 117.4 (d, J_C _–F = 7.9 Hz), 115.7 (d, J_C _–F = 24 Hz), 114.7 (d, J_C-F = 22.8 Hz), 114.2, 88.5, 85.4, 55.3, 37.7. HRMS (ES⁺-TOF): m/z [M + H]⁺ calcd for C₂₂H₁₈FO₂: 333.1291; found: 333.1288.

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