Chiral Bidentate Boryl Ligand-Enabled Iridium-Catalyzed Enantioselective Dual C-H Borylation of Ferrocenes: Reaction Development and Mechanistic Insights

Ferrocenes with planar chirality are an important class of privileged scaffolds for diverse chiral ligands and organocatalysts. The development of efficient catalytic asymmetric methods under mild reaction conditions is a long-sought goal in this field. Though many transition-metal-catalyzed asymmetric C-H activation methods have been recorded during the last decade, most of them are related to C-C bond-forming reactions. Owing to the useful attribute of the C-B bond, we herein report an amide-directed iridium-catalyzed enantioselective dual C-H borylation of ferrocenes. The key to the success of this transformation relies on a chiral bidentate boryl ligand and a judicious choice of a directing group. The current reaction could tolerate a vast array of functionalities, affording a variety of chiral borylated ferrocenes with good to excellent enantioselectivities (35 examples, up to 98% enantiomeric excess). We also demonstrated the synthetic utility by preparative-scale reaction and transformations of a borylated product. Finally, on the basis of the observed experimental data, we performed DFT calculations to understand its reaction pathway and chiral induction, which reveals that methyl C(sp(3))-H borylation is crucial to conferring high enantioselectivity through an amplified steric effect caused by an interacted B-O fragment in the transition state.

Automated summary

Ferrocenes with planar chirality are important for various chiral ligands and organocatalysts. This study reports an iridium-catalyzed enantioselective dual C-H borylation of ferrocenes using an amide directing group. The reaction showed high enantioselectivity and tolerance towards different functional groups.