Darzens Reaction Rate Enhancement Using Aqueous Media Leading to a High Level of Kinetically Controlled Diastereoselective Synthesis of Steroidal Epoxyketones

Abstract

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.

Stereospecific, High-Yielding, and Green Synthesis of β-Glycosyl Esters

“…22,23 Various carbonates including lithium, sodium, potassium, and cesium were used; the PTC was Aliquat 336 or TBAB, the amount of water was varied from 10 to 310 equiv, and the reaction temperature ranged from 25 to 80°C. For all reaction combinations, the desired product, β-glucosyl ester, was contaminated with a substantial amount of the partially hydrolyzed products.…”

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

“…Because researchers are still developing new chiral organocatalysts, the substitute scope of the highly enantioselective asymmetric Darzens reaction is expanding [47]. Moreover, shorter reaction times were achieved by using aqueous media in the presence of a Li + -containing base, a phase-transfer catalyst and granular polytetrafluoroethylene under mechanical stirring [48]. These developments make the Darzens reaction a promising method for the synthesis of natural products in an efficient and green way.…”

Synthesis of 1-(2,4-Dinitrophenyl)-3,5-diphenyl-1H-pyrazol-4-ol via trans-1,3-Diphenyl-2,3-epoxy-1-propanone

“…Chalcone epoxides are produced through Darzens reaction of α-halo carbonyl with aldehydes in a basic condition such as sodium hydroxide, lithium hydroxide, lithium carbonate, potassium carbonate, potassium hydroxide, sodium ethoxide, sodium amide, sodium tert-butoxide (Tanaka and Shiraishi 2001, Li and Li 2014, Preveena et al 2015, Mphahlele et al 2019. They are useful synthons in the synthesis of organic compounds through ring opening to produce C-C bond.…”