Iron-Catalyzed Aerobic Oxidation of (Alkyl)(aryl)azinylmethanes

Published as part of the Cluster Catalytic Aerobic Oxidations

Abstract

An iron-catalyzed aerobic oxidation of (alkyl)(aryl)azinylmethanes has been developed leading to tertiary alcohols in moderate to good yields. Hock rearrangement was identified as a major side reaction leading to a complex mixture of undesired products. Addition of thiourea sometimes allows inhibiting this side reaction and steers the reaction towards the desired products.

Key words

aerobic oxidation - iron - catalysis - tertiary alcohols - Hock

• References and Notes


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• 16 Typical Procedure for Fe-Catalyzed Aerobic C–H Oxygenation of 1a A 10 mL vial was charged with FeCl₂·4H₂O (9.94 mg, 0.050 mmol), 2-(1-phenylethyl)pyridine (1a) (0.092 g, 0.5 mmol), salicylic acid (0.069 g, 0.500 mmol), and DMSO (1 mL). The vial was flushed for 10 s with O₂, capped with an aluminum crimp cap with septum and stirred at 100 °C for 24 h with an O₂ balloon through the septum. After cooling down to r.t., the content of the vial was transferred into a separation funnel and the vial was rinsed with CH₂Cl₂ (20 mL). Aqueous sat. NaHCO₃ (10 mL) was added, and the organic phase was separated. The aqueous phase was extracted twice with CH₂Cl₂ (10 mL). The combined organic fractions were washed with brine (20 mL), dried on MgSO₄, and filtered. Further purification was achieved by automated column chromatography (heptane–EtOAc) to give 1-phenyl-1-(pyridin-2-yl)ethanol (2a) in 88% yield. Characterization Data for 2a Colorless oil. ESI–HRMS: m/z calcd for C₁₃H₁₄NO [M + H]⁺: 200.1070; found: 200.1080. ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, 1 H, J = 4.6 Hz), 7.62 (dt, 1 H, J = 7.8, 1.4 Hz), 7.47 (d, 2 H, J = 7.4 Hz), 7.34–7.25 (m, 3 H), 7.25–7.11 (m, 2 H), 5.80 (s, 1 H), 1.92 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.8 (C], 147.4 (CH), 147.2 (C), 136.9 (CH), 128.2 (CH), 127.0 (CH), 125.9 (CH), 122.0 (CH), 120.3 (CH), 75.1 (C), 29.3 (CH₃). Characterization Data for 2m Colorless viscous oil. ESI–HRMS: m/z calcd for C₂₂H₂₀NO₅ [M + H]⁺: 378.1336; found: 378.1342. ¹H NMR (400 MHz, CDCl₃): δ = 8.58 (d, 1 H, J = 4.5 Hz), 7.65 (dt, 1 H, J = 7.7, 1.3 Hz), 7.29 (d, 4 H, J = 8.6 Hz), 7.26–7.21 (m, 1 H), 7.12 (d, 1 H, J = 7.9 Hz), 7.02 (d, 4 H, J = 8.6 Hz), 6.29 (br s, 1 H), 2.28 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.3 (C), 162.7 (C), 150.0 (C), 147.8 (CH), 143.4 (C), 136.6 (CH), 129.3 (CH), 122.9 (CH), 122.6 (CH), 121.0 (CH), 80.2 (C), 21.2 (CH₃).