Reductive O-alkylation of methanol by ketones using a heterogeneous palladium catalyst under continuous flow conditions†

A mild and efficient continuous-flow catalytic process for the reductive alkylation of methanol by various linear, cyclic, saturated, and unsaturated aliphatic ketones has been developed. This reaction, conducted at 130 °C using a Pd/C cartridge (5 wt%) under 1 bar of hydrogen, yields secondary O-methyl ethers in high yields. This innovative continuous process offers a new route for the synthesis of CPME, as a versatile eco-friendly solvent. Starting from arylic ketones, the same process furnished the corresponding tolyl derivatives via a reductive alkylation/hydrogenolysis sequence. A mechanism is proposed to explain these results.