Design and synthesis of Indol-PHOX: a new class of modular phosphine–oxazoline ligands for palladium-catalyzed enantioselective decarboxylative allylation

Abstract

A novel class of chiral and modular P,N-ligands featuring an indolizine core (Indol-PHOX) has been developed, successfully enabling the highly efficient and enantioselective palladium-catalyzed decarboxylative allylation of various α-fluoro-β-ketoesters to access valuable α-allyl-α-fluoro ketones with yields up to 99% and 96% ee. This process exhibits a broad substrate scope, demonstrating good tolerance for both electron-withdrawing and electron-donating groups, as well as substitution patterns of the substrates. The reaction is scalable to the gram level, and subsequent post-functionalization reactions proceed successfully without erosion of enantiopurity.