Metal-Free Synthesis of 1,3-Dioxane Derivatives from Aromatic Alkynes and Paraformaldehyde

Abstract

Here we report the efficient synthesis of a series of 1,3-dioxane derivatives from aromatic alkynes, paraformaldehyde, and a Lewis acid catalyzed reaction at room temperature. This reaction is metal-free and atom-economic. Single crystals of two typical 1,3-dioxane derivatives are obtained. A mechanism that the reaction proceeds through a six- or eight-membered ring intermediate is proposed.

Key words

metal-free - 1,3-dioxane derivatives - aromatic alkynes - Lewis acid catalyzed - paraformaldehyde

• References and Notes

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• 13 ¹H NMR, ¹³C NMR spectra were recorded on a Bruker DMX400 NMR spectrometer. The solvent signal of CDCl₃ was referenced at δ = 7.26 ppm. Coupling constants (J values) are reported in Hz. ¹H NMR data were recorded in the order as follows: chemical shift value, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad), number of protons that gave rise to the signal and coupling constant where applicable. ¹³C spectra were proton-decoupled and recorded on Bruker ACF400 (400 MHz). The solvent, CDCl₃, was referenced at δ = 77 ppm. CDCl₃ (99.8% deuterated) was purchased from Aldrich and used without further purification. High-resolution mass spectra (HRMS) were recorded on a Thermo Fisher Scientific Exactive^TM spectrometer. CCDC: 2047024 for 2a; CCDC: 2047025 for 2b; CCDC: 2131310 for 2d and 2d′. Synthesis of 2a To a solution of 1,2-diphenylethyne (1a, 0.5 mmol) in CH₂Cl₂ (10 mL) were sequentially added 100 mol% of BF₃·Et₂O and 3.0 equiv of (CH₂O) _n . Then the reaction mixture was allowed to stir at room temperature for 6 h. The mixture was poured into ice water, and the product was extracted with CH₂Cl₂. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over Na₂SO₄, filtered, and the solvents were removed under reduced pressure. The residue was purified by flash column chromatography (silica gel, PE/EtOAc = 6:1) to give the 2a. Characterization Data of 2a–i Compound 2a: yield 91%; 122 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.45–7.38 (m, 6 H), 7.30–7.26 (m, 4 H), 4.96 (d, J = 5.9 Hz, 1 H), 4.85 (d, J = 6.0 Hz, 1 H), 4.70 (d, J = 11.5 Hz, 2 H), 4.21 (d, J = 11.6 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 200.71, 137.36, 136.82, 131.97, 129.48, 128.73, 128.30, 128.11, 126.59, 94.08, 77.33, 77.22, 77.02, 76.70, 72.89, 53.88. HRMS: m/z calcd for C₁₇H₁₆O₃ [M + H]⁺: 269.1178; found: 269.1183. Compound 2b: yield 82%; 112 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.41–7.19 (m, 7 H), 7.06 (d, J = 8.0 Hz, 2 H), 4.92 (d, J = 5.9 Hz, 1 H), 4.85 (d, J = 5.9 Hz, 1 H), 4.65 (d, J = 11.5 Hz, 2 H), 4.24 (d, J = 11.5 Hz, 2 H), 2.30 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 200.01, 142.84, 137.92, 133.85, 130.21, 129.42, 129.11, 129.00, 128.92, 128.73, 128.28, 127.98, 126.70, 126.39, 94.06, 77.42, 77.11, 76.79, 73.05, 53.75. HRMS: m/z calcd for C₁₈H₁₈O₃ [M + H]⁺: 283.1334; found: 283.1349. Compound 2c: yield 71%; 106 mg; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.51 (d, J = 9.0 Hz, 2 H), 7.48–7.37 (m, 4 H), 6.99 (d, J = 9.0 Hz, 1 H), 6.76 (d, J = 9.0 Hz, 2 H), 4.91 (d, J = 6.9 Hz, 2 H), 4.62 (d, J = 11.6 Hz, 2 H), 4.29 (d, J = 11.6 Hz, 2 H), 3.78 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 198.49, 162.65, 138.39, 131.51, 131.13, 129.38, 128.79, 127.87, 127.05, 126.81, 126.73, 124.61, 114.04, 113.53, 94.04, 77.34, 77.22, 77.02, 76.70, 73.19, 68.30, 68.05, 55.56, 55.37, 53.51, 45.93. HRMS: m/z calcd for C₁₈H₁₈O₄ [M + H]⁺: 299.1283; found: 299.1198. Compound 2d: yield 68%; 97 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.52–7.46 (m, 1 H), 7.46–7.33 (m, 5 H), 7.29–7.27 (m, 1 H), 7.12 (t, J = 8.7 Hz, 1 H), 6.98–6.92 (m, 1 H), 4.96 (d, J = 6.0 Hz, 1 H), 4.92 (d, J = 6.0 Hz, 1 H), 4.88 (d, J = 6.0 Hz, 1 H), 4.85 (d, J = 6.0 Hz, 1 H), 4.68 (d, J = 11.6 Hz, 1 H), 4.60 (d, J = 11.6 Hz, 1 H), 4.22 (t, J = 11.3 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 200.42, 198.97, 166.05, 163.52, 137.30, 136.48, 132.86, 132.83, 132.21, 131.53, 131.44, 129.58, 128.74, 128.61, 128.53, 128.39, 128.24, 126.51, 116.56, 116.34, 115.56, 115.35, 94.10, 94.06, 72.91, 72.89, 53.87, 53.21. HRMS: m/z calcd for C₁₇H₁₅FO₃ [M + H]⁺: 287.1083; found: 287.1091. Compound 2e: yield 67%; 102 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.45–7.36 (m, 6 H), 7.33–7.25 (m, 3 H), 4.97 (d, J = 6.0 Hz, 1 H), 4.92–4.86 (m, 1 H), 4.84 (d, J = 6.0 Hz, 1 H), 4.69 (d, J = 11.5 Hz, 1 H), 4.57 (d, J = 11.7 Hz, 1 H), 4.25 (d, J = 11.7 Hz, 1 H), 4.18 (d, J = 11.6 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 200.13, 199.46, 138.35, 137.02, 136.42, 136.30, 134.99, 134.13, 132.33, 130.22, 129.64, 129.61, 128.78, 128.63, 128.43, 128.31, 128.28, 126.47, 94.11, 94.04, 72.82, 72.77, 53.97, 53.29. HRMS: m/z calcd for C₁₇H₁₅ClO₃ [M + H]⁺: 303.0788; found: 303.0797. Compound 2f: yield 79%; 136 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.58–7.53 (m, 1 H), 7.47–7.39 (m, 3 H), 7.38–7.27 (m, 4 H), 4.97 (d, J = 6.0 Hz, 1 H), 4.89 (s, 1 H), 4.83 (d, J = 6.0 Hz, 1 H), 4.69 (d, J = 11.5 Hz, 1 H), 4.56 (d, J = 11.7 Hz, 1 H), 4.25 (d, J = 11.7 Hz, 1 H), 4.17 (d, J = 11.6 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 200.05, 199.67, 136.99, 136.26, 135.45, 132.59, 132.36, 131.61, 130.31, 129.61, 128.79, 128.61, 128.44, 128.32, 126.96, 126.46, 122.29, 94.11, 94.04, 72.78, 72.75, 53.99, 53.35. HRMS: m/z calcd for C₁₇H₁₅BrO₃ [M + H]⁺: 347.0283; found: 347.0291. Compound 2g: yield 36%; 53 mg; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.77–7.68 (m, 2 H), 7.70–7.61 (m, 2 H), 7.52–7.38 (m, 3 H), 7.30 (t, J = 7.8 Hz, 2 H), 4.97 (d, J = 6.0 Hz, 1 H), 4.84 (d, J = 6.0 Hz, 1 H), 4.43 (q, J = 11.6 Hz, 4 H). ¹³C NMR (101 MHz, CDCl₃): δ = 199.06, 144.11, 135.56, 133.01, 132.87, 128.88, 128.61, 128.17, 118.33, 111.91, 94.03, 72.74, 53.70. HRMS: m/z calcd for C₁₈H₁₅NO₃ [M + H]⁺: 294.1130; found: 294.1135. Compound 2h: yield 78%; 122 mg; yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.35–8.23 (m, 2 H), 7.83–7.68 (m, 2 H), 7.52–7.39 (m, 3 H), 7.38–7.27 (m, 2 H), 5.00 (d, J = 6.0 Hz, 1 H), 4.84 (d, J = 6.0 Hz, 1 H), 4.46 (s, 4 H). ¹³C NMR (101 MHz, CDCl₃): δ = 198.88, 147.34, 146.27, 135.41, 132.98, 128.93, 128.65, 128.44, 124.39, 94.05, 72.81, 53.70. HRMS: m/z calcd for C₁₇H₁₅NO₅ [M + H]⁺: 314.1028; found: 314.1021. Compound 2i: yield 60%; 98 mg; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.15–8.03 (m, 2 H), 7.62–7.49 (m, 2 H), 7.42 (d, J = 7.2 Hz, 3 H), 7.28 (dd, J = 6.2, 5.3 Hz, 2 H), 4.91 (s, 2 H), 4.59 (d, J = 11.7 Hz, 2 H), 4.32 (d, J = 11.7 Hz, 2 H), 3.92 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 199.81, 166.54, 143.07, 136.16, 132.42, 130.57, 129.79, 128.79, 128.44, 127.02, 94.05, 72.77, 53.90, 52.27. HRMS: m/z calcd for C₁₉H₁₈O₅ [M + H]⁺: 327.1232; found: 327.1239.