Advances in transition metal-catalyzed allylic substitution with unstabilized nucleophiles

Transition metal-catalyzed allylic substitution is a key reaction for forming carbon-carbon and carbon-heteroatom bonds, with broad applications in organic synthesis. While most methods rely on “soft” stabilized nucleophiles, the use of “hard” unstabilized derivatives has been less explored due to their high reactivity and challenges associated with controlling regio- and stereoselectivity. This review highlights advances in catalytic allylic substitution with unstabilized organometallic nucleophiles, focusing on aryl, alkyl, allyl, alkenyl, alkynyl, benzyl, and allenyl reagents and their direct cross-coupling with acyclic and cyclic allylic substrates. Key developments are categorized by reaction type, including achiral, racemic, stereoselective, and stereospecific processes. These advancements provide deeper insight into the reaction progress, challenges, and limitations. We anticipate a better understanding of the underlying mechanistic intricacies will further broaden their applicability in target-directed synthesis.