Metal-Free tert-Butyl Hydrogenperoxide (TBHP) Mediated Radical Alkylation of Enol Acetates with Alcohols: A New Route to β-Hydroxy Ketones

Abstract

A metal-free TBHP-mediated radical alkylation of enol acetates with alcohols is described. This method provides a new route to a variety of β-hydroxy-ketones in moderate to good yields.

Key words

metal-free - radical alkylation - enol acetates - alcohols - β-hydroxyketones

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• 9 General Procedure for the Synthesis of Substituted β-Hydroxy Ketones A Schlenk-type tube (with a Teflon high pressure valve) equipped with a magnetic stir bar was charged with enol acetates 1 (0.3 mmol), alcohols 2 (2 mL), and TBHP (1.2 mmol, 70% aq solution). The reaction tube was then sealed and placed in an oil bath at 100 °C. After the reaction mixture was stirred for 10 h, it was allowed to cool to ambient temperature. The solvent was then removed under reduced pressure, and the residue was purified by column chromatography (EtOAc–PE) to afford the desired products. 1-(4-Fluorophenyl)-3-hydroxy-3-methylbutan-1-one (3c) Pale yellow oil; yield 62%. ¹H NMR (500 MHz, CDCl₃): δ = 8.02–7.97 (m, 2 H), 7.19–7.12 (m, 2 H), 4.06 (s, 1 H), 3.13 (s, 2 H), 1.36 (s, 6 H). ¹³C NMR (125 MHz, CDCl₃): δ = 199.9, 166.1 (d, J = 253.7 Hz), 133.7 (d, J = 3.0 Hz), 130.81 (d, J = 9.4 Hz), 115.8 (d, J = 21.3 Hz), 69.9, 48.5, 29.5. ESI-HRMS: m/z calcd for C₁₁H₁₄FO₂ [M + H]⁺: 197.0978; found: 197.0975.