Copper-Catalyzed Aerobic Oxidative Rearrangement of Tertiary Allylic Alcohols Mediated by TEMPO

Abstract

A mild method for the oxidative rearrangement of tertiary allylic alcohols to β-substituted enones using a TEMPO/CuCl₂ system, in the presence of molecular sieves, is described. Depending on the substrate, CuCl₂ was used in either a catalytic amount under an oxygen atmosphere or stoichiometrically.

copper(II) salts - oxidation - rearrangement - TEMPO

References and Notes

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<A NAME="RD08309ST-10">10</A>

Typical Procedure for Copper-Catalyzed Oxidative Rearrangement of Tertiary Allylic Alcohols Mediated by TEMPO. Method A: 3-Butylcyclohex-2-en-1-one (entry 1): To a stirred solution of 1-butylcyclohex-2-en-1-ol (0.1 g, 0.65 mmol) in acetonitrile (2.5 mL) were successively added TEMPO (0.01 g, 0.1 equiv), 4 Å molecular sieves (0.1 g) and CuCl₂˙2H₂O (0.056 g, 0.5 equiv). The brown suspension was stirred under oxygen (balloon) for 7 h, then the suspension was diluted with Et₂O, washed twice with water, dried (Na₂SO₄) and evaporated. The residue was purified by chromatography on silica gel (PE-EtOAc, 5:1) to give the enone as a liquid. ^¹H NMR (CDCl₃, 200 MHz): δ = 0.88 (t, J = 7.1 Hz, 1 H, Me), 1.2-1.53 (m, 4 H, 2 × CH₂), 1.95 (sept, J = 6.2 Hz, 2 H), 2.18 (t, J = 7.7 Hz, 2 H, CH₂), 2.29 (t, 4 H, 2 × CH₂), 5.84 (s, 1 H). ^¹³C NMR (50 MHz): δ = 13.8, 22.3, 22.8, 29.1, 29.7, 37.4, 37.8, 125.6, 166.8, 199.9. HRMS: m/z calcd for C₁₀H₁₆O: 152.1201; found: 152.1190. Method B: 2-(tert-Butyldiphenylsilyloxymethyl)-3-methylcyclohex-2-en-1-one (entry 7): To a stirred solution of 2-(tert-butyl-diphenylsilyloxymethyl)-1-methylcyclohex-2-en-1-ol (0.1 g, 0.26 mmol) in acetonitrile (2 mL) were successively added TEMPO (0.004 g, 0.1 equiv), molecular sieves (0.05 g) and CuCl₂˙2H₂O (0.089 g, 2 equiv). After stirring the reaction mixture for 10 h, work-up as described in method A gave an oil, which was purified by flash chromatography (PE-Et₂O, 6:1) to afford an oil that crystallized on standing. Mp 61-63 ˚C. IR (neat): 3049, 1667, 1634 cm^-¹. ^¹H NMR (300 MHz): δ = 1.04 (s, 9 H, Me), 1.91 (quint, J = 6.2 Hz, 2 H), 1.99 (s, 3 H, Me), 2.32-2.40 (m, 4 H, 2 × CH₂), 4.47 (s, 2 H, CH₂), 7.4 (m, 6 H), 7.7 (m, 4 H). ^¹³C NMR (75 MHz): δ = 19.5, 21.5, 22.1, 27.0 (3 × Me), 33.1, 37.6, 56.3, 127.6 (4 × CH), 129.6 (2 × CH), 134 (2 × CH), 134.5, 135.8 (4 × CH), 160.5, 197.6. HRMS: m/z [M+H]⁺ calcd for C₂₄H₃₁O₂Si: 379.2093; found: 379.2093.

For kinetic studies on TEMPO-mediated oxidation, see:

<A NAME="RD08309ST-11A">11a</A> de Nooy AEJ. Besemer AC. Van bekkum H. Tetrahedron  1995,  51:  8023 

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<A NAME="RD08309ST-12">12</A> For examples of the formation of fragmentation products, see: Alvarez FM. Van der Meer RK. Lofgren CS. Tetrahedron  1987,  43:  2897 ; see also refs. 1a, 1b and 2b