Abstract
<jats:p>Herein, we report a quinoline-based photocatalyst that enables the highly important yet challenging metallaphotoredox methylation with high efficiency and generality, accommodating diverse coupling partners, including derivatives from carboxylic acids, alcohols, amines, halides and arenes. Central to this breakthrough lies the rational design of a hydroxylated diarylquinoline as a non-innocent ligand, thus in situ evolving photocatalytically active aluminium complexes. Such a distinct paradigm not only formulates a dynamic platform uniquely suited to produce and tailor the otherwise elusive methyl radical for downstream cross couplings, but also establishes a privileged photocatalytic scaffold that could expand the synthetic repertoire of less explored main-group elements. Of equal importance, our diversity-oriented strategy demonstrates broad translational utility in drug discovery by late-stage methylation of pharmaceutically relevant compounds. These efforts eventually culminated in a methylated analogue with potent antitumour activity in vitro and in vivo, which remained unknown in the current literature and was synthetically challenging using existing methods.</jats:p>