Pd-catalyzed direct acylation reaction of iodoacetanilides/iodophenyl acetates with aldehydes is presented. Simple, bench-top aldehydes were used as non-toxic acylating agents. This protocol comprises direct coupling with aldehydes without activating the carbonyl group and without directing group assistance. The strategy was applied to a domino one-pot synthesis of 2-quinolinones through acylation and intramolecular aldol condensation. Significantly, the strategy was extended to the domino one-pot synthesis of drugs and bioactive compounds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim