A Convenient Ruthenium‐Catalysed α‐Methylation of Carbonyl Compounds using Methanol

An efficient ruthenium catalyst is reported, for the first time, to catalyse the α‐methylation of ketones and esters using methanol as a green methylating agent. The in situ generated catalyst from the complexes [RuCp*Cl 2 ] 2 or [RuCp*Cl 2 ] n with dpePhos provided up to quantitative yields in the presence of only 20 mol% of lithium tert ‐butoxide (LiO‐ t‐ Bu) as a base. Regioselective mono‐ or multi‐methylation could be effectively controlled by temperature. This catalyst system was also effective for the one‐pot sequential α‐alkylation–α‐methylation of methyl ketones and conjugate reduction–α‐methylation of α,β‐unsaturated ketones to synthesise α‐branched ketones. An application of the α‐methylation of esters using the ruthenium catalyst was demonstrated for an alternative catalytic synthesis of Ketoprofen. magnified image