Mapping Ambiphile Reactivity Trends in the <i>Anti</i>‐(Hetero)annulation of Non‐Conjugated Alkenes via Pd<sup>II</sup>/Pd<sup>IV</sup> Catalysis
Hui‐Qi Ni, Phillippa Cooper, Shouliang Yang, Fen Wang, Neal W. Sach, Pranali G. Bedekar, Joyann S. Donaldson, Michelle Tran‐Dubé, Indrawan McAlpine, Keary M. Engle
Abstract
Abstract 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.