Catalytic Methylation Using Methanol as C1 Source

The development of 3d metal-catalyzed molecular transformations has been a key focus of research in recent decades. One significant advancement is the discovery of the homogenous iron, cobalt, and manganese-catalyzed (de)hydrogenation processes. Among these redox transformations, the “Borrowing Hydrogen” (BH) principle, also known as hydrogen auto-transfer, stands out as an elegant and eco-friendly method that facilitates the self-transfer of hydrogen between reaction molecules and intermediates, eliminating the need for external hydrogen donors or acceptors. This concept allows for the eco-friendly use of alcohols, such as methanol, as environmentally benign C1 synthons for the alkylation of organic molecules, including pharmaceutically relevant candidates. In this context, the methyl group represents one of the most prevalent carbon fragments in small-molecule drugs. In this book chapter, we summarize the discovery and recent advancements in the use of 3d metal complexes for (multi)methylation of organic compounds using methanol via the hydrogen borrowing methodology. Additionally, we discuss current limitations, challenges, and the future prospects of this field.