A research team led by Professors Zhou Qianghui and Cheng Honggang from the College of Chemistry and Molecular Sciences at Wuhan University has achieved a significant breakthrough in the synthesis of planar-chiral ferrocenes.

Their pioneering work has been published online in the Journal of the American Chemical Society under the title "DeNovo Construction of Planar-Chiral Ferrocenes via Palladium/Chiral Norbornene Cooperative Catalysis".

This innovative research introduces a new platform technology for the modular synthesis of planar-chiral molecules. The team employs a palladium/chiral norbornene (Pd/NBE*) cooperative catalysis strategy to construct planar-chiral ferrocenes from readily available iodoferrocene.

Planar-chiral ferrocenes are highly valued in fields such as asymmetric catalysis, functional materials, and drug development due to their unique stereochemistry and properties.

Traditional synthesis methods often rely on pre-installed chiral auxiliaries or stoichiometric chiral bases, which can limit functional group compatibility and atomic economy.

While transition metal-catalyzed asymmetric C–H functionalization presents an effective strategy, existing methods require pre-installed directing groups and are limited to single functionalization.

The study presents a "de novo" strategy for constructing planar-chiral ferrocenes. It uses palladium/chiral norbornene (NBE*) cooperative catalysis, where a sterically hindered (C1, C4)-bridged chiral norbornene serves as both co-catalyst and chiral source.

Starting from simple and accessible iodoferrocene, the method constructs two chemical bonds in one step, synthesizing a series of planar-chiral phthalimidine-type ferrocenes. This approach features mild reaction conditions, broad substrate applicability, excellent functional group tolerance, and high step economy.

Mechanistic studies and density functional theory (DFT) calculations reveal that ortho C–H bond activation is the enantioselectivity-determining step. The reductive elimination from a Pd(IV) intermediate not only serves as the rate-determining step but also amplifies enantioselectivity differences, ensuring high optical purity of the products.

The research also highlights the application potential of these planar-chiral ferrocene products. In just three steps, they can be converted into novel planar-chiral coenzymes of the NAD(P)H type, which demonstrate superior catalytic activity and stereocontrol in the challenging asymmetric hydrogenation of tetrasubstituted alkenes compared to existing coenzymes.