Manganese(III) Acetate-mediated Alkylation of 1,3-Dicarbonyls to Form Tricarbonyl Compounds Bearing a Quaternary Carbon Centre

Abstract

1,3-Dicarbonyl compounds including ethyl 2-methylacetoacetate can be efficiently alkylated with enol ethers or enol esters in the presence of manganese(III) acetate. These intermolecular radical addition reactions can be used to form sterically congested quaternary carbon centres in excellent yield (81-97%).

Key words

aldehydes - alkylations - ketones - manganese - radical reactions

References

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19

Copper(II) acetate is often added as a co-oxidant in manganese(III) acetate-mediated radical reactions (see ref. [1] ).

20

All new compounds exhibited satisfactory spectral and analytical (high-resolution mass) data. Some of the 1,4-dicarbonyl products underwent slow decomposition (e.g. aerial oxidation) and so these types of compounds should be stored appropriately or used immediately.

21

Typical Experimental Procedure: To ethyl 2-methyl-acetoacetate 11 (0.2 g, 1.38 mmol) in degassed dichloro-methane (10 cm³) was added butyl vinyl ether (0.77 g, 6 equiv, 8.32 mmol) followed by manganese(III) acetate dihydrate (0.86 g, 2.3 equiv, 3.19 mmol) and copper(II) acetate monohydrate (0.09 g, 0.3 equiv, 0.41 mmol). The solution was heated to reflux overnight (typically 18 h). Dichloromethane (40 cm³) was then added and the resulting suspension removed by filtration. The solution was washed with water (10 cm³), dried (MgSO₄) and following evaporation in vacuo the crude product was purified using column chromatography(silica) to give ethyl 2-methyl-2-(oxoethyl)acetoacetate 12 (0.24 g, 92%) as a colourless oil; R_f = 0.45 (7:3 dichloromethane:ethyl acetate); IR (CHCl₃): ν_max = 3060 (w, br), 2985 (w, br), 1716 (s, br), 1723 (s, sh), 1461 (m, sh), 1277 (s, br) cm^-1; ¹H NMR (300 MHz, CDCl₃): δ = 9.63 (1 H, s, HC=O), 4.14 (2 H, q, J = 7 Hz, O-CH ₂-CH₃), 2.93 and 2.83 (2 H, 2 × d, J = 19 Hz, O=CH-CH ₂-C), 2.18 (3 H, s, CH₃-C=O), 1.44 (3 H, s, CH₃-C-C=O), 1.19 (3 H, t, J = 7.0 Hz, O-CH₂-CH ₃); ¹³C NMR (75 MHz, CDCl₃): δ = 203.7 (CH₃-C=O), 198.2 (H-C=O), 170.6 (O=C-O), 60.9 (O-CH₂-CH₃), 56.0 (O=C-C-CH₃), 47.6 (O=CH-CH₂-C), 25.0 (CH₃-C=O), 19.4 (CH₃-C-C=O), 12.9 (O-CH₂-CH₃); MS: m/z (%)= (CI, NH₃) 203(100) [M⁺ - 1 + NH₄ ⁺], 187(82) [M + H⁺], 185(62), 169(43) (Found: [M + H⁺] 187.0967. C₉H₁₅O₄ requires for [M + H⁺] 187.0970).