Herein we introduce the recent developments of a new strategy based on deacylativealkylation (DaA) reactions for the generation of quaternary stereocenters based on the in situ preparation and functionalization of enolates under very mild reaction conditions. Palladium‐catalyzed deacylativeallylation and benzylation reactions of carbon nucleophiles are performed with the corresponding alcohols. This methodology has been applied to the synthesis of the calcium ion chanel blocker verapamil, the antiviral (+)hamigeran B, several oxindole precursors of esermethole, horsfiline, physostigmine, phenserine,meso‐folicanthine, meso‐chinonanthineand the dimer cyclotriptamine alkaloids. Base‐promoted deacylative reactions allow the functionalization of 2‐oxindole enolates at the 3‐position with alkyl halides and electrophilic alkenes. In the presence of oxygen or air, 3‐hydroxy‐2‐oxindoles are prepared by deacylative oxidation. Detrifluoroacylative reactions are promoted by a base generating fluoroenolates, which can participate in aldol, Mannich and Michael reactions for the preparation of important fluorinated intermediates. Finally, palladium‐catalyzed deacylative cross‐coupling of acetyldiazoacetates and phosphonates with aryl iodides let to the formation of aryldiazoacetates and phosphonates, respectively. The same process, with 2‐iodoazoarenes and 2‐iodoaryltriazenes, gives 2H‐indazoles, which are important pharmacophores.