Copper-Catalyzed Asymmetric Synthesis of Organoboron Compounds

Organoboron compounds, characterised by carbon–boron linkages, have emerged as indispensable building blocks in pharmaceuticals, agrochemicals and materials science. Copper catalysts offer a cost-effective, low-toxicity route to asymmetric borylation under mild conditions, enabling high levels of enantio- and diastereocontrol across a range of unsaturated substrates such as alkenes, allenes and enones. The key to these transformations lies in the formation of copper–boryl intermediates that undergo element-cupration, followed by electrophilic trapping or tandem sequences such as borylation–cyclisation cascades. Chiral ligands, often based on N-heterocyclic carbenes or phosphines, organise substrate–catalyst interactions in well-defined transition states to dictate stereochemical outcomes. Advances in mechanistic understanding, supported by density functional theory, have shed light on noncovalent interactions that govern selectivity. As a result, copper-catalysed asymmetric synthesis of organoboron compounds now encompasses multi-component couplings, enantioselective cyclisations and remote boryl migrations, creating densely functionalised architectures with high atom economy. These methods have been adopted in the synthesis of complex natural products, fine chemicals and enantioenriched intermediates, underscoring their global significance for sustainable and scalable synthesis.

Research from Nature Portfolio

Recent studies have demonstrated the power of copper catalysis in orchestrating asymmetric borylation and cyclisation within a single operation. One report detailed an enantioselective Cu(I)-catalysed β-borylation/Michael addition on enone-tethered cyclohexadienones, effecting desymmetrisation to furnish bicyclic enones with four contiguous stereocentres in excellent yield and stereopurity. A subsequent one-pot protocol combined borylation, intramolecular cyclisation and oxidation to access chiral alcohols without loss of enantiomeric integrity. Gram-scale reactions and downstream chemoselective modifications showcased the scalability and utility of this sequence. Computational studies rationalised the crucial role of base in forming a reactive lithium-enolate complex and delineated a chair-like transition state that delivers the observed stereochemical outcome.

Copper-Catalyzed Asymmetric Synthesis of Organoboron Compounds publication trend

The graph below shows the total number of articles in copper-catalyzed asymmetric synthesis of organoboron compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Organoboron compounds: Molecules containing carbon–boron bonds that serve as versatile synthetic intermediates.

Copper–boryl intermediate: A reactive species in which a copper centre is bonded to a boryl group, enabling element-cupration of unsaturated substrates.

Enantioselectivity: The preferential formation of one enantiomer over its mirror image in a chiral product.

Diastereoselectivity: The selective formation of one diastereomer among multiple stereocentres in a single molecule.

Element-cupration: The addition of a copper-containing fragment across an unsaturated bond, often preceding electrophilic trapping.

Michael addition: A nucleophilic addition to an α,β-unsaturated carbonyl compound, frequently used in borylation–cyclisation sequences.

Density functional theory (DFT): A computational approach to modelling electronic structure and reaction pathways in catalytic systems.

References

1. Remote 1,4‐Carbon‐to‐Carbon Boryl Migration: From a Mechanistic Challenge to a Valuable Synthetic Application of Bicycles. Advanced Science (2024).
2. Copper-Catalyzed Enantioselective Borylative Allyl–Allyl Coupling of Allenes and Allylic gem-Dichlorides. ACS Catalysis (2023).
3. Copper-boryl mediated organic synthesis. Chemical Society Reviews (2018).
4. Enantioselective Cu(I)-catalyzed borylative cyclization of enone-tethered cyclohexadienones and mechanistic insights. Nature Communications (2022).