Mapping Ambiphile Reactivity Trends in the Anti ‐(Hetero)annulation of Non‐Conjugated Alkenes via Pd ^II /Pd ^IV Catalysis

In this study, we systematically evaluate different ambiphilic organohalides for their ability to participate in anti ‐selective carbo‐ or heteroannulation with non‐conjugated alkenyl amides under Pd II /Pd IV catalysis. Detailed optimization of the reaction conditions has led to protocols for synthesizing tetrahydropyridines, tetralins, pyrrolidines, and other carbo/heterocyclic cores via [ n +2] ( n =3–5) (hetero)annulation. Expansion of scope to otherwise unreactive ambiphilic haloketones through Pd II /amine co‐catalysis is also demonstrated. Compared to other annulation processes, this method proceeds via a distinct Pd II /Pd IV mechanism involving Wacker‐type directed nucleopalladation. This difference results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments.