KF-Alumina-Mediated Selective Double Michael Additions of Aryl Methyl Ketones: A Facile Entry to the Synthesis of Functionalized Pimelate Esters and Derivatives

Abstract

Here we describe simple and efficient double Michael additions of aromatic and aliphatic methyl ketones to electron deficient alkenes promoted on a surface of KF-alumina. This one-pot procedure provides an easy access to a host of functionalized pimelate esters, which can be subsequently converted in to 3-acylcyclohexanones.

Key words

double Michael additions - acetophenone - KF-alu­mina - pimelate esters - cyclohexanones

References

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9

Representative Experimental Procedure: A mixture of 4-methoxyacetophenone (300 mg, 2 mmol) and ethyl acrylate (600 mg, 6 mmol) was added in one portion to dry preformed KF-alumina (2 g) and the solid mixture was stirred at 60 °C for 10 h. TLC was checked and the mixture was packed on a column of silica gel and eluted with petroleum ether-EtOAc (9:1) to afford diethyl (4-methoxybenzoyl) heptanedioate as colorless viscous oil (553 mg, 79%). IR (neat): 1735, 1680, 1588 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.22 (t, 6 H, J = 7.1 Hz, 2 OCH₂CH ₃ ), 1.80-1.88 (m, 2 H, 2 CHCH₂CO), 2.05-2.12 (m, 2 H, 2 CHCH₂CO), 2.19-2.41 (m, 4 H, 2 CH₂CH ₂CO), 3.56-3.63 (m, 1 H, COCHCH₂), 3.87 (s, 3 H, OCH ₃ ), 4.10 (q, 4 H, J = 7.1 Hz, 2 OCH ₂ CH₃), 6.95 (d, 2 H, J = 8.8 Hz, ArH), 7.99 (d, 2 H, J = 8.8 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 26.9, 31.5, 43.2, 55.3, 60.2, 113.8, 129.9, 130.6, 163.6, 172.9, 201.2.