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 catalysis. Detailed optimization of 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 distinction results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments.


Supplementary material

Supporting Info
Experimental procedures and details, copies of NMR spectra, and X-ray crystal structure data tables
2ba CIF
Crystallographic Information File for compound 2ba
NMR Data
Original NMR data in MNova format