Substrate NOBINAc ligand affinity for PdII-catalyzed enantioselective C–H activation over reactive β-C–H bonds in ferrocenyl amines

Abstract

Ferrocenyl amines as directing groups for C–H activation have limitations as they are prone to undergo oxidation, allylic deamination, and β-hydride elimination. The fundamental challenge observed here is the competition between the desired C–H activation versus the vulnerable β-C–H bond activation of amines and fine-tuning of a suitable oxidant which avoids the oxidation of the β-C–H bond and ferrocene. Herein, the potential of an axially chiral NOBINAc ligand is revealed to implement the enantioselective Pd^II-catalyzed C–H activation process of ferrocenyl amines. Mechanistically, the affinity between the NOBINAc ligand and sulfonate group of amine facilitated by the Cs⁺ cation plays an impressive role in the desired reaction outcome via an enhanced substrate ligand affinity. This approach resulted in a Pd-catalyzed enantioselective C–H activation, the first intermolecular annulation, and alkenylation of ferrocenyl amines with allenes and olefins, leading to ferrocene fused tetrahydropyridines and alkenylated ferrocenyl amines with up to 70% yields and 99 : 1 er.