The invention relates to the development of new ligands for transition metals. These ligated transition metal complexes can provide a new and/or improved catalytic platform for various carbon-carbon and carbon-heteroatom bond forming reactions. For example, a new approach of transition-metal-catalyzed cross-electrophile coupling has been realized using these ligands.
Figure (1) X-ray structure of Ligand 3; (2) X-ray structure of Precatalyst 11
Despite advances in transition metal catalysis, existing methods for carbon–carbon and carbon–heteroatom bond formation face key limitations such as poor availability and reactivity of nucleophilic carbon reagents, instability of organoboron compounds, and stringent reaction conditions. Moreover, reliance on expensive catalysts and generation of metal waste hinder large-scale, sustainable use. This calls for innovative ligand systems to enhance catalytic performance under milder, more practical conditions.
- Tailored Ligand Design: Introduces novel ligands (L1–L3) with customizable alkyl, cycloalkyl, and aryl substituents that tune electronic and steric properties to optimize catalysis.
- Synthetic Versatility: The ligands are synthesized using a scalable, modular approach involving metal-catalyzed reactions and strategic functional group transformations.
- Effective Precatalysts: Ligands form stable phosphino palladacyclic complexes that act as highly efficient precatalysts in cross-Ullmann, Suzuki-Miyaura, and C–N coupling reactions.
- Enhanced Reactivity: The dimethylamino-substituted ligand architecture improves catalyst stability, efficiency, and functional group tolerance under ambient or photothermal conditions.
The prototype comprises a series of novel phosphino ligands (L1, L2, and L3) synthesized through multi-step procedures involving aromatic substitution, methylation, and phosphination. These ligands are complexed with palladium to form stable palladacyclic precatalysts, including compounds such as precatalyst 11, which have been structurally characterized by X-ray crystallography. The catalytic activity of these systems has been validated under laboratory conditions for a range of bond-forming reactions, including cross- Ullmann couplings, Suzuki-Miyaura couplings, and C–N couplings. The ligands and precatalysts were tested using glove box and Schlenk line techniques under thermal or photochemical conditions. Reactions demonstrated high efficiency, functional group tolerance, and excellent yields, confirming the practical performance of the catalytic system in real-world synthetic applications.
The technology has achieved Technology Readiness Level (TRL) 9, indicating that the ligand and palladium precatalyst systems have been fully developed, tested, and are ready for deployment in real-world applications. The ligand systems have been successfully implemented in synthetic laboratories, demonstrating efficiency in various C–C and C–X bond-forming reactions, particularly in cross-Ullmann coupling, Suzuki-Miyaura coupling, and C–N coupling. The system's performance and yield have been validated under standard reaction protocols.
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Ligand-driven catalytic advancements contribute significantly to improved healthcare by enabling the development of new medicines and therapies that address unmet medical needs. The adoption of greener catalytic processes also supports environmental conservation by reducing waste, conserving resources, and minimizing pollution. Furthermore, by making drug synthesis more efficient and cost-effective, this technology helps promote global health equity through the increased accessibility and affordability of essential medicines.
- Pharmaceutical Industry: Ligand-enabled catalytic systems are extensively used in pharmaceutical synthesis, enabling the efficient production of drug candidates and active pharmaceutical ingredients (APIs).
- Agrochemicals and Crop Protection: Ligand-driven catalysis plays a crucial role in the synthesis of agrochemicals, pesticides, and herbicides, supporting crop protection and agricultural productivity.
- Fine Chemicals and Specialty Materials: Industries manufacturing fine chemicals, specialty materials, and high-value intermediates utilize ligand-based catalytic processes for the production of specialty chemicals, functional materials, and advanced polymers.
- Biotechnology and Biopharmaceuticals: Ligand-enabled catalytic systems are employed in biotechnology and biopharmaceutical manufacturing for the synthesis of biomolecules, peptide-based drugs, and bioactive compounds.
Geography of IP
Type of IP
202321010040
505111