Palladium-Catalyzed ortho-C–H Alkoxycarbonylation of Aromatic Aldehydes via a Transient Directing Group Strategy

Abstract

Transient directing groups (TDGs) can be a powerful strategy for directly functionalizing C–H bonds of aldehydes. We report a palladium-catalyzed o-C–H alkoxycarbonylation of benzaldehydes using a catalytic amount of aromatic amine to form a transient imine that plays the role of a monodentate TDG. The reaction conditions were applied to a broad range of aldehydes, and the corresponding 2-formyl benzoates were used as direct precursors for the synthesis of phthalides and 1-isoindolinones.

C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

“…Very recently, our team (Prévost) disclosed a palladium‐catalyzed C−H alkoxycarbonylation of aromatic aldehydes, using potassium oxalate monoesters as ester provider, to efficiently deliver 2‐formyl benzoates (Scheme 5). [15] 4‐Fluoro‐3‐(trifluoromethyl)aniline was able to form efficiently a monodentate TDG and corresponding esters 13 were isolated in very good yields from ortho ‐substituted benzaldehydes. The reaction conditions were reoptimized for non‐ ortho ‐substituted aldehydes to avoid difunctionalization and another aniline as well as a 2‐pyridone ligand L 1 were necessary to obtain expected esters 15 in moderate yield.…”