Asymmetric Michael addition of 5 H-oxazol-4-ones to vinyl sulfones : stereoselective synthesis of monofluorinated analogs of 2-tertiary hydroxyl-3-methyl-substituted carboxylic acidl derivatives

Abstract

An asymmetric Michael addition of 5H-oxazol-4-ones to vinyl sulfones has been developed. In the presence of 10 mol % of quinine-based benzyl-substituted thiourea as catalyst at 0 °C, the products could be obtained with excellent enantio- and diastereoselectivity (up to>99 % ee and>20:1 dr). 1.0 mol % of catalyst also produced the corresponding adducts with similar stereoselective results when the temperature was increased to 25 °C. The obtained adducts have been demonstrated as significant synthetic fragments to conveniently access the monofluorinated analogs of biologically important 2-tertiary hydroxyl-3-methyl-substituted carboxylic acid derivatives.