Metal-free Direct Arylation of Dialkyl Phosphonates for the Synthesis of Mixed Alkyl Aryl Phosphonates


An invention to utilize “green chemistry” in a metal-free, mild condition to synthesize pharmaceutical agent

Inventors: Jun Yong Kang

Kang: His areas of expertise include Organic Chemistry, Asymmetric Catalysis, New Reaction Discovery, Natural Product Synthesis, Biocompatible Materials. His research interests include the development and synthesis of novel organocatalysts, new reaction discovery, synthesis of biologically active organic compounds and biocompatible biomaterials.

The Invention: 

This innovative compound, NHP-thiourea, serves as a powerful phosphorylation reagent capable of forming both phosphorus-carbon (P-C) and phosphorus-nitrogen (P-N) bonds under metal-free reaction conditions. These bonds are frequently found in pharmaceuticals and biologically active compounds. Unlike existing methods that rely on transition metal-catalyzed coupling reactions, which necessitate extra steps for metal impurity removal, NHP-thiourea has proven its efficacy as a reagent in six peer-reviewed publications for the synthesis of diverse phosphonates.


  • Metal-free, mild reaction conditions
  • Reduces number of synthetic steps
  • Cost effective
  • Environmentally friendly


  • Reagent for synthesis of various phosphonates:
    • Vinylphosphonates
    • Hydrazine phosphonates
    • α-Aminophosphonates
    • α-Hydroxyphosphonates
    • B-Aminophosphonates
    • y-Ketophosphonates

Market Opportunity: 

Reducing the number of synthetic steps and removal of impurities such as toxic metal catalysts from drugs are challenging tasks within the pharmaceutical industry, and are significantly related to price deviations. The transition-metal-free synthetic route presents a green and cost-effective method. 

Development Status

Gram quantities of the material have been prepared for characterization and testing. 15 plus different NHP-thiourea derivatives have been successfully synthesized.

Intellectual property:

Issued US Patent No. 10,633,403


Patent Information:
For Information, Contact:
John Minnick
Business Development Officer
University of Nevada, Las Vegas
Jun Yong Kang
Hai Huang
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