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Universal palladium precursor for catalyst preparation

Universal Palladium Precatalyst for Efficient Chemical Synthesis for in situ cross-coupling catalyst preparation

Palladium Molecule

Background

Cross-coupling reactions have become widely used in organic molecule synthesis for forming carbon-carbon and carbon-element bonds. Approximately 10-25% of chemical reactions carried out in pharmaceutical R&D require palladium(Pd)-based precatalysts. They are also used in agrochemical and fine chemical industries. However, Pd(0)-dba complexes can produce inconsistent catalytic results, degrade rapidly in solution, and the dba released after activation can interfere with catalysis. While Pd(II)-based precatalysts exist, they require basic conditions to be activated and a pre-installation step of a phosphine ligand. Therefore, each precatalyst is specific to the substrates being coupled. There is a need for a universal Pd source that is easy to handle, stable, reliable, cost-effective, reproducible, and usable for many Pd-catalyzed transformations. It also needs to be scalable from microscale to large-scale manufacturers.

Overview

Dr. David Leitch and his team at the University of Victoria have developed a novel, versatile Pd(0) precursor, (DMP)DAB-Pd-MAH, for in situ cross-coupling catalyst preparation. It is also an excellent platform for single-component precatalyst synthesis. This Pd(0) complex was designed by stabilizing the Pd(0) source with a chelating diazabutadiene (DAB) ligand and maleic anhydride (MAH) as an electron deficient alkene. This multifunctional Pd(0) source is optimized for cross-coupling reaction screening and scale-up.

Benefits

  • Good solubility in a range of organic solvents. 
  • Excellent solid-state and solution stability.
  • Reactions proceed to well-defined Pd(0) products that are easily isolated, providing a way to generate air-stable single component Pd(0) precatalysts when desired. 
  • Rapid ligand substitution of the chelating DAB with various phosphines relevant to cross-coupling. 
  • More cost-effective than alternative catalysts.

Applications

  • High-throughput reaction screening
  • Preparative-scale synthesis

Opportunity

  • Industrial use and research partnerships (exclusive)
  • Licensing for R&D (non‑exclusive)

Patent Status: