Asymmetric Catalysis with Chiral Ligands

Asymmetric catalysis with chiral ligands exploits the three-dimensional architecture of tailored ligands to induce enantioselectivity in a wide range of chemical transformations. By coordinating to a central metal or acting as organocatalysts, these ligands create a chiral environment that differentiates enantiotopic faces of substrates, offering precise control over stereochemistry. The field encompasses diverse ligand classes – including phosphines, N-oxides, oxazolines and atropisomeric scaffolds – each designed to optimise electronic and steric interactions in the catalytic cycle. Advances in ligand design have enabled highly enantioselective hydrogenations, cross-couplings, cycloadditions and carbon–carbon bond-forming reactions, finding applications in pharmaceutical synthesis, agrochemicals and materials science. Mechanistic understanding, supported by computational studies, has guided the rational development of next-generation ligands with enhanced activity, selectivity and sustainability.

Research from Nature Portfolio

Recent studies have shown that bespoke C1-symmetric tridentate ligands, combining imidazoline and pyrroloimidazolone motifs, enable highly enantioselective dearomative [3+2] annulations of indoles with donor–acceptor cyclopropanes under nickel catalysis. Fine-tuning of ligand configuration revealed that a cis-arrangement affords superior diastereo- and enantioselectivity, while mechanistic investigations using density functional theory elucidated dual activation pathways involving metal coordination and hydrogen-bonding interactions. Building on these insights, foundational work on BINAP-derived rhodium complexes continues to set benchmarks in asymmetric hydrogenation, demonstrating turnover numbers and enantiomeric excesses that inform industrial catalyst design and underscore the enduring impact of classical chiral phosphine ligands.

Asymmetric Catalysis with Chiral Ligands publication trend

The graph below shows the total number of articles in asymmetric catalysis with chiral ligands across all publications each year (not limited to Nature Index journals).

Technical terms

Enantioselectivity: Preference of a catalyst to form one enantiomer over its mirror image in an asymmetric transformation.

Chiral ligand: A ligand bearing a non-superimposable mirror-image structure that induces asymmetry when bound to a metal centre or in organocatalysis.

Atropisomerism: Stereoisomerism resulting from restricted rotation around a single bond, creating isolable chiral conformers.

Cis-trans configuration: Spatial arrangement describing whether substituents on a ligand framework lie on the same (cis) or opposite (trans) side of a reference plane.

N-oxide: A nitrogen-oxygen functional group in heteroaromatic compounds that can serve as a Lewis base or organocatalyst to activate substrates via electron donation.

References

1. Design of C1-symmetric tridentate ligands for enantioselective dearomative [3 + 2] annulation of indoles with aminocyclopropanes. Nature Communications (2023).
2. Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review. Molecules (2020).
3. 1,1′-Biisoquinolines—Neglected Ligands in the Heterocyclic Diimine Family That Provoke Stereochemical Reflections. Molecules (2021).