Butenolide annelation using a manganese(III) oxidation. A synthesis of chromolaenin (Laevigatin)

Abstract

A procedure was developed for the annelation of a butenolide to an aromatic ketone that highlighted a manganese(III) oxidation of an aromatic ketone. The merit of this procedure was illustrated in a synthesis of Chromolaenin (Laevigatin) (1) from 4,7-dimethyl-1-tetralone (2c). Oxidation of tetralone and indanone with manganese(III) acetate in the presence of chloro- or bromopropionic acid or their Mn(II) salts furnished a α-haloesters 3a-d. An Arbuzov reaction of haloesters with triethylphosphite and an intramolecular Horner-Watsworth-Emmons cyclization of the resulting phosphonate gave butenolide 5a, b in 77-79% yield. This methodology was also applied to 4,7-dimethyl-1-tetralone (2c), and the corresponding butenolide 6 is synthesized in 85% yield, which was then converted to Chromolaenin (1) using DIBAL-H.Key words: chromolaenin (Laevigatin), manganese(III) acetate oxidation, aromatic ketones, butenolide annelation, lactone, Horner-Watsworth-Emmons cyclization, Arbuzov reaction.