C1 benzylated isoquinoline derivatives constitute the core of benzylisoquinoline alkaloids (BIAs). However, their C4 congeners remain elusive. Here, we describe a diastereoselective, catalytic, and modular C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds of readily affordable vicinally functionalized dihydroisoquinolones are replaced by sp³ C–benzyl bonds. The method provides expedient access to C4 quaternary and homobenzylic dihydroisoquinolones, which are attractive fragments for potential drug discovery.