General and selective homogeneous Ru-catalyzed transfer hydrogenation, deuteration, and methylation of functional compounds using methanol

Abstract

Catalytic valorization of methanol in organic synthesis and energy technologies is interesting and important for both fundamental research and industrial applications. In particular, its utilization as hydrogen, deuterium and methyl sources for selective reduction and deuteration reactions as well as to access N-methylated products is highly desirable and can be considered as a potential methodology for the amplification of transfer hydrogenation and C1 chemistry. Here, we report homogeneous Ru-MACHO complex catalyzed transfer hydrogenation of different functionalized compounds such as ketones, aldehydes, alkynes, alkenes, imines, azobenzenes, and nitro compounds as well as deoxygenation of N-oxide derivatives employing methanol as an affordable hydrogen donor and solvent. This Ru-based strategy has been proven to be very convenient for the deuteration process to synthesize advanced deuterium-labelled compounds, including the gram-scale synthesis of deuterated pharmaceuticals such as d-Cloperastine, d-Buclizine, d-Diphendyarmine, d-Modafinil, and d-Adrafinil using CD3OD. In addition, the application of methanol as a C1 source for the preparation of N-methylated products is showcased. Finally, kinetic and mechanistic investigations for this Ru-catalyzed transfer hydrogenation and deuteration protocols have been performed.