A Novel Catalytic Cycle for the Synthesis of Epoxides Using Sulfur Ylides

Abstract

A novel, neutral catalytic cycle for the synthesis of epoxides from carbonyl compounds and diazo compounds using catalytic quantities of transition metal salts and sulfides has been developed. In this catalytic cycle, the diazo compound is decomposed by the transition metal salt to give a metallocarbene, and this is picked up by the sulfide to give a sulfur ylide, which then reacts with the aldehyde to give an epoxide and returns the sulfide back into the catalytic cycle. To obtain good yields of epoxides it is necessary to maintain a low concentration of the diazo compound (by slow addition), otherwise dimerisation of the diazo compound is the dominant reaction. Factors affecting the outcome of the reaction were studied. The reactions are relatively insensitive to solvent, but are sensitive to the structure of the sulfide, the metal salt and the concentration. Unhindered sulfides give good yields of epoxides with any metal salt, but with hindered sulfides higher yields are obtained with Cu(acac)₂ than with Rh₂(OAc)₄. The yields of epoxides are sensitive to sulfide concentration especially when using substoichiometric amounts of sulfides. Higher concentration leads to faster rates of formation and subsequent reaction of the sulfur ylides, and consequently to higher yields. This novel catalytic cycle has also been applied to base‐sensitive aldehydes. We found that our new catalytic cycle for epoxidation gives much improved yields of epoxides compared to those obtained by traditional sulfur ylide chemistry and is tolerant to a wide variety of sensitive functional groups. Ketones also participate in the catalytic cycle, although they give reduced yields of epoxides compared to aldehydes and require a slightly elevated temperature.