Mapping Ambiphile Reactivity Trends in the Anti-(Hetero)annulation of Non-Conjugated Alkenes via PdII/PdIV 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.

Automated summary

In this study, we evaluated different ambiphilic organohalides for their participation in anti-selective carbocyclic or heterocyclic annulation with non-conjugated alkenyl amides under Pd-II/Pd-IV catalysis. By optimizing the reaction conditions, we developed protocols for the synthesis of various carbocyclic or heterocyclic compounds. We also demonstrated the reactivity of otherwise unreactive ambiphilic haloketones through Pd-II/amine co-catalysis. This method proceeds via a distinct Pd-II/Pd-IV mechanism, resulting in unique reactivity and selectivity patterns.