C=O methylenation mediated by organo-alkali metal reagents: metal identity and ligand effects

C=O 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 C=O 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.