Ligand-Free Nickel-Catalyzed Reductive Allylic Defluorinative Cross-Coupling of α-Trifluoromethyl Alkenes with Epoxides

Abstract

We report a reductive allylic defluorinative reaction of α-trifluoromethyl alkenes with terminal epoxides, which consists of an iodide-mediated regioselective ring opening and a nickel-catalyzed radical-type cross-coupling, providing diverse tertiary gem-difluorobishomoallylic alcohols in moderate to high yields. Notably, this reaction is conducted under mild conditions and requires no external ligand or proton donor.

Key words

nickel catalysis - epoxides - difluoroalkenes - defluorination - ring opening

Publication History

Received: 05 May 2020

Accepted: 01 June 2020

Article published online:
01 July 2020

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• 11 4-Aryl-5,5-difluoropent-4-en-1-ols (3aa–la, 3ab–am); General Procedure A Schlenk tube equipped with a stirrer bar was charged with NiI₂ (8.8 mg, 0.04 mmol, 10 mol %), NaI (30 mg, 0.2 mmol, 0.5 equiv), and Zn (78 mg, 1.2 mmol, 3 equiv). The tube was then evacuated and filled with N₂ (three cycles). DMA (1.0 mL) was added under N₂, followed by the appropriate trifluoromethyl alkene 1 (0.4 mmol, 1.0 equiv) and epoxide 2 (0.8 mmol, 2.0 equiv). The mixture was stirred at rt for 24 h, and then the reaction was quenched by addition of H₂O. The aqueous phase was extracted with EtOAc (3 × 20 mL) and the combined organic phases were washed with brine, dried (Na₂SO₄), filtered, and concentrated in vacuo. The crude material was purified by column chromatography (silica gel, PE–EtOAc). 7,7-Difluoro-1,6-bis(4-methoxyphenyl)-3-methylhept-6-en-3-ol (3aa) Colorless oil; yield: 126 mg (84%). ¹H NMR (400 MHz, CDCl₃): δ = 7.24 (d, J = 7.9 Hz, 2 H), 7.08 (d, J = 8.6 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 6.82 (d, J = 8.6 Hz, 2 H), 3.80 (s, 3 H), 3.77 (s, 3 H), 2.60–2.53 (m, 2 H), 2.49–2.42 (m, 2 H), 1.77–1.68 (m, 2 H), 1.59–1.53 (m, 2 H), 1.23 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 158.7, 157.8, 153.2 (dd, J = 289.1, 286.2 Hz), 134.3, 129.3 (t, J = 3.4 Hz, 2 C), 129.2 (2 C), 125.7 (t, J = 2.8 Hz), 114.0 (2 C), 113.9 (2 C), 91.9 (dd, J = 20.6, 14.3 Hz), 72.4, 55.3 (2 C), 43.9, 39.9 (t, J = 2.3 Hz), 29.4, 26.7, 22.5. ¹⁹F NMR (376 MHz, CDCl₃): δ = –92.39 (d, J = 46.6 Hz, 1 F), –92.58 (d, J = 46.7 Hz, 1 F). HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₆F₂NaO₃: 399.1742; found: 399.1741.