CO methylenation mediated by organo-alkali metal reagents: metal identity and ligand effects

Abstract

CO methylenation mediated by α-silyl organo-alkali metal reagents, namely Peterson methylenation, is a textbook organic reaction that has been widely employed in synthetic chemistry for over 50 years. The process is performed over two steps, by isolating the β-silyl alcohol intermediate generated via nucleophilic addition and then subjecting it to elimination. The choices of alkali metal and external Lewis base ligand play a critical role in the elimination step, but the reasons remain poorly understood. In this work, we have systematically investigated the metal identity and ligand effects in CO methylenation reactions mediated by MCH₂SiMe₃ (M = Li; Na; K). We observed pronounced alkali metal cation and ligand effects on the methylenation performance, with K⁺ and tetrahydrofuran (THF) being optimal. Based upon these learnings, a straightforward new methylenation method has been designed involving carbonyl addition with LiCH₂SiMe₃, followed by in situ addition of KOtBu in THF, facilitating facile transmetallation-enabled elimination. This strategy enables the methylenation to be achieved in one pot, whilst circumventing the use of KCH₂SiMe₃. Excellent yields have been achieved for a range of ketones (including enolizable examples) and aldehydes. The method uses commercial solvents and reagents, and can be performed without any requirement for stringent drying or deoxygenation.