An　efficient　approach　for　the　direct　synthesis　of　alkylated　4-hydroxycoumarin　derivatives　via　a　Cu-catalyzed　cascade　dehydrogenation/conjugate　addition　sequence　starting　from　simple　saturated　ketones　and　4-hydroxycoumarins　has　been　developed.　This　protocol　features　excellent　functional-group　tolerance,　easy　scale-up,　and　a　broad　substrate　scope　including　bioactive　molecules.　More　importantly,　a　series　of　marketed　drugs,　such　as　warfarin,　acenocoumarol,　coumachlor,　and　coumafuryl,　can　be　obtained　by　this　method.　©　2023　The　Royal　Society　of　Chemistry.