Hypervalent-Iodine-Mediated Base-Free Oxidative Olefination of Benzylic Amines to Access α,β-Unsaturated Ketones

Abstract

We report a one-pot base-free protocol for the oxidative olefination of benzylic amines promoted by a hypervalent iodine reagent for the synthesis of α,β-unsaturated ketones. Mechanistically, (diacetoxyiodo)benzene oxidizes the benzylic amine to the corresponding imine, which, on reaction with a phenacyl(triphenyl)phosphonium bromide salt and an in situ generated acetoxy anion leads to an α,β-unsaturated ketone. A wide range of α,β-unsaturated ketones were easily accessed through direct oxidative olefination of substituted benzylic amines in good to excellent yields and with high E-selectivity.

Key words

hypervalent iodine - benzylic amines - enones - oxidation - olefination

• References and Notes

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• 15 α,β-Unsaturated Ketones 3a–o and 4a–m; General Procedure PhI(OAc)₂ (1.2 mmol) was added to a solution of the appropriate benzylic amine (1.0 mmol) in EtOH (5 mL) at rt. The appropriate phenacyl(triphenyl)phosphonium bromide salt (1.2 mmol) was then added, and the resulting mixture was refluxed at 70 °C for 4 h until the reaction was complete (TLC). Ice was added and the mixture was concentrated under reduced pressure to remove EtOH. CH₂Cl₂ was then added and the reaction was quenched with sat. aq NaHCO₃ (5 mL). The mixture was extracted with CH₂Cl₂ (10 mL), and the organic layers were combined, washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel (100–200 mesh), 5–20% EtOAc–PE]. (2E)-3-(2-Methoxyphenyl)-1-phenylprop-2-en-1-one (3c) White solid; yield: 188 mg (79%); mp 58 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.13 (d, J = 15.9 Hz, 1 H), 8.05-8.00 (m, 2 H), 7.66-7.61 (m, 2 H), 7.59-7.55 (m, 1 H), 7.50 (ddd, J = 8.3, 6.7, 1.3 Hz, 2 H), 7.38 (ddd, J = 8.3, 7.4, 1.7 Hz, 1 H), 7.00 (td, J = 7.5, 1.0 Hz, 1 H), 6.94 (dd, J = 8.4, 1.0 Hz, 1 H), 3.91 (s, 3 H). ¹³C {¹H} NMR (126 MHz, CDCl₃): δ = 191.2, 158.9, 140.4, 138.6, 132.6, 131.8, 129.3, 128.6, 128.6, 123.9, 122.9, 120.8, 111.3, 55.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₅O₂: 239.1067; found: 239.1056.