Catalysis

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

Authors

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 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.

Content

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Supplementary material

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