Unexpected course of a Williamson ether synthesis

Abstract

The Williamson ether synthesis between the sodium salt of methyl mandelate and methyl α-bromophenylacetate was reinvestigated. In addition to the expected ether product cis-dimethyl 2,3-diphenyloxirane-2,3-dicarboxylate, methyl phenylacetate and methyl phenylglyoxylate were obtained. Their formation is explained by an initial α-elimination producing an α-oxo-carbene from the α-bromoester. This is followed by a hydride transfer from the sodium salt of methyl mandelate to the carbenic intermediate furnishing the enolate of methyl phenylacetate as reduction product and methyl phenylglyoxylate as oxidation product. Finally, the methyl phenylglyoxylate reacts with the enolate of the α-bromoester in a diastereospecific Darzens condensation to the cis-oxirane (cis-conformation confirmed by single crystal structure analysis). In this series of parallel and sequential reactions, the sodium salt of methyl mandelate displays 3 modes of action: nucleophile (ether synthesis), base (α-elimination) and hydride donor (redox process).