Remote Editing of Stacked Aromatic Assemblies for Heteroannular C-H Functionalization by a Palladium Switch between Aromatic Rings

An approach allowing remote editing of stacked aromatic assemblies for heteroannular C-H functionalization would represent a transformative chemical toolbox that may make the diversification of complex molecules in a straightforward manner. However, such a C-H activation is usually less kinetically and thermodynamically favorable than homoannular ortho C-H activation and remains a fundamental challenge. Herein we disclose an engineer's approach, using a transient ligand as an interim bridge between two aryl rings (analogues to mountaintops) to anchor the metal center on the remote heteroannular C-H bond. As a proof-of-concept, we present the palladium-catalyzed heteroannular C-H olefination of stacked aromatic assemblies with olefins and allylation with vinyl acetates using L-tert-leucine acid as a transient ligand. Mechanistic investigations suggest an unusual olefin coordination-promoted interannular palladium migration process determinative for reversal of the site-selectivity.

Automated summary

In this study, we present a new approach allowing remote editing of stacked aromatic assemblies through the use of a transient ligand as a bridge. Our results demonstrate the successful heteroannular C-H functionalization and uncover a unique reaction mechanism involving olefin coordination.