Oxidative coupling of sinapic acid

Abstract

Oxidative coupling of phenolic compounds is an important method used by synthetic organic chemists for the synthesis of various lignans. It has also been implicated in lignan biosynthesis. Recently, it was discovered that sinapic acid in a basic buffer in the presence of oxygen was quantitatively converted to the lignan, thomasidioic acid. This interesting reaction formed the basis for several studies described in this thesis. The scope of the oxidation reaction described above was studied by applying t e same reaction conditions to other 4-hydroxycinnamic acids (ferulic, caffeic and coumaric acids). The efficient oxidative coupling/cyclization appears to be limited to only sinapic acid. Oxidation of sinapic acid in more strongly basic solution (0.1 N KOH) unexpectedly produced 6-hydroxy-5,7-dimethoxy-2-naphthoic acid. The formation of this compound appeared to involve the secondary oxidation of thomasidioic acid. As well as studying the synthetic scope of the oxidative coupling of para-hydroxycinnamic acids, the details of the mechanism of this interesting reaction were also studied. Various aspects of the reaction were studied, including the nature of the intermediates involved and stoichiometry of the reaction. Oxidizing agents other than oxygen were also used in order to provide more insight into the mechanism of the oxidative coupling. The oxidative coupling of esters of sinapic acid has also been studied. For the reaction of methyl sinapate, some of the expected dimethyl thomasidioate was formed in a mixture with a diarylbutadiene diester in a 1:2 ratio. For the reaction of (methyl (R)-mandelyl) sinapate in basic buffer, the products were a mixture of isomers of the diaryl butadiene product. These results indicate that the direct asymmetric synthesis of aryltetralins by oxidative coupling of chiral cinnamate esters is probably not feasible.