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(sp3)-H
borylation is crucial to conferring high enantioselectivity through
an amplified steric effect caused by an interacted B–O fragment
in the transition state.