Radical-Mediated Hetaryl Functionalization of Nonactivated Alkenes through Distal ipso-Migration of O- or S-Hetaryls

Dedicated to Ilhyong Ryu on the occasion of his 70^th birthday

Abstract

A radical-mediated hetaryl functionalization of nonactivated alkenes through distal ipso-migration of O- or S-containing hetaryls was developed. Furyl, benzofuryl, thienyl, and benzothienyl groups showed satisfactory migratory abilities. A variety of heteroatom-centered radicals, including azido, trifluoromethylsulfanyl, and silyl radicals readily trigger the migration cascade, and a new C–heteroatom and C–C bond are concomitantly constructed in the reaction. This method provides an efficient approach to the synthesis of high-valued complex O- or S-hetaryl compounds.

Key words

hetaryl compounds - alkene difunctionalization - functional-group migration - radical reaction - radicals - rearrangement

Publikationsverlauf

Eingereicht: 15. August 2020

Angenommen nach Revision: 21. September 2020

Artikel online veröffentlicht:
30. Oktober 2020

• References and Notes


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• 12 5-Azido-4-(1-benzofuran-2-yl)-1-phenylpentan-1-one (2a); Typical Procedure Tertiary alcohol 1a (0.2 mmol, 1.0 equiv), PIDA (0.4 mmol, 2.0 equiv) were loaded into a flame-dried reaction vial that was subjected to three cycles of evacuation and flushing with N₂. CH₃CN (2.0 mL) was added to the mixture from a syringe, and TMSN₃ (0.8 mmol, 4.0 equiv) was added dropwise. The mixture was then stirred at 25 °C until the starting material was consumed (TLC). The mixture was extracted with EtOAc (3 × 10 mL), and the organic solvent was removed under vacuum. The residue was purified by flash column chromatography [silica gel, EtOAc–PE (30:1)] to give a yellow oil; yield: 39.7 mg (62%). FTIR: 3063, 2925, 2854, 1717, 1521, 1455, 1353, 1254, 1225 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.92–7.84 (m, 2 H), 7.57–7.49 (m, 2 H), 7.47–7.38 (m, 3 H), 7.28–7.19 (m, 2 H), 6.57 (s, 1 H), 3.76–3.68 (m, 1 H), 3.67–3.58 (m, 1 H), 3.29–3.19 (m, 1 H), 3.00 (t, J = 7.2 Hz, 2 H), 2.34–2.14 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.2, 157.3, 154.8, 136.7, 133.2, 128.6, 128.3, 128.0, 124.0, 122.8, 120.7, 111.1, 104.4, 54.5, 39.2, 35.7, 25.3. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₇N₃NaO₂: 342.1213; found: 342.1213.

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• 14 4-(1-Benzofuran-2-yl)-1-phenyl-5-[(trifluoromethyl)sulfanyl]pentan-1-one (3a); Typical Procedure Tertiary alcohol 1a (0.2 mmol, 1.0 equiv), AgSCF₃ (0.3mmol, 1.5 equiv), and Na₂S₂O₈ (0.6 mmol, 3.0 equiv) were loaded into a flame-dried reaction vial that was subjected to three cycles of evacuation and flushing with N₂. DMF (2.0 mL) was added to the mixture from a syringe, and the mixture was stirred at 25 °C until the starting material was consumed (TLC). The mixture was then extracted with EtOAc (3 × 10 mL), and the combined organic extracts were washed with brine, dried (MgSO₄), filtered, and concentrated. The residue was purified by flash column chromatography [silica gel, EtOAc–PE (30:1)] to give a white solid; yield: 78.7 mg (87%); mp 93–94 °C. FTIR: 3676, 2988, 2970, 1792, 1671, 1636, 1522, 1436, 1374 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.91–7.81 (m, 2 H), 7.57–7.49 (m, 2 H), 7.47–7.37 (m, 3 H), 7.29–7.20 (m, 2 H), 6.55 (d, J = 0.8 Hz, 1 H), 3.38–3.26 (m, 3 H), 2.98 (t, J = 7.2 Hz, 2 H), 2.42–2.33 (m, 1 H), 2.27–2.17 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.9, 157.0, 154.9, 136.6, 133.2, 131.0 (q, J _C–F = 304.3 Hz), 128.6, 128.1, 128.0, 124.1, 122.9, 120.8, 111.1, 104.8, 39.3, 35.8, 33.7 (q, J _C–F = 1.9 Hz), 27.1. ¹⁹F NMR (376 MHz, CDCl₃): δ = –41.2 (s). HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₇F₃NaO₂S; 401.0794; found: 401.0793.

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• 17 4-(1-Benzofuran-2-yl)-1-phenyl-5-(triphenylsilyl)pentan-1-one (4a); Typical Procedure Tertiary alcohol 1a (0.2 mmol, 1.0 equiv), Ph₃SiH (1.0 mmol, 5.0 equiv), tert-butyl peroxyacetate (0.8 mmol, 4.0 equiv, 50 wt.% in mineral spirit), CuO (0.02 mmol, 10 mol%), and DMAP (0.05 mmol, 0.25 equiv) were loaded into a sealed tube which was subjected to three cycles of evacuation and flushing with N₂. Benzene (2 mL) was added to the mixture, the tube was sealed, and the mixture was stirred at 130 °C until the starting material was consumed (TLC). The organic solvent was removed under vacuum, and the residue was purified by flash column chromatography [silica gel, EtOAc–PE (30:1)] to give a colorless oil; yield: 62.5 mg (59%). FTIR: 3068, 3011, 2922, 1772, 1684, 1455, 1428, 1363, 1253, 1219 m^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.80–7.72 (m, 2 H), 7.51–7.45 (m, 7 H), 7.38–7.34 (m, 2 H), 7.34–7.28 (m, 5 H), 7.26–7.22 (m, 6 H), 7.19–7.10 (m, 2 H), 6.10 (s, 1 H), 3.28–3.16 (m, 1 H), 2.84–2.70 (m, 2 H), 2.25–2.05 (m, 3 H), 1.91–1.83 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.7, 160.9, 154.4, 136.9, 135.6, 134.6, 132.9, 129.4, 128.5, 128.5, 128.0, 127.8, 123.1, 122.3, 120.3, 110.9, 103.0, 36.4, 34.9, 32.1, 19.4. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₇H₃₂NaO₂Si: 559.2064; found: 559.2068.
• 18 Detailed mechanistic pathways for each reaction are presented in the Supporting Information (Figures S1–S3).
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