Darzens reaction rate enhancement using aqueous media leading to a high level of kinetically controlled diastereoselective synthesis of steroidal epoxyketones

Article abstract of DOI:10.1021/jo501500v

Darzens reactions between halocarbonyls and aldehydes have been carried out in water in the presence of a Li⁺-containing base, a phase-transfer catalyst, and granular polytetrafluoroethylene under mechanical stirring. Reactions using both aromatic and aliphatic aldehydes produced epoxides stereoselectively in good to excellent yields. This is the first time that aliphatic aldehydes with α-H have been used in aqueous Darzens reactions. The Darzens reactions were much faster in water than in organic solvents. This aqueous rate enhancement occurred for Darzens reactions between enantiopure steroidal haloketones and aldehydes, yielding enantiopure spiroepoxides with a high level of kinetically controlled diastereoselectivity. Chromatography was avoided in the purifications of the steroidal spiroepoxides. This is an example of preparing enantiopure epoxyketones via aqueous Darzens reaction using chiral α-haloketone substrates.