Transition Metal-Catalyzed Alkylation of C-H bonds with Organoboron Reagents

New ways to produce drug leads - Part II

The Situation: Current methods for selective introduction of functional groups to organic molecules are costly, inefficient, environmentally unfriendly, and restrictive against further synthetic manipulations.

Our Solution: We developed a novel strategy for direct functionalization of pyridyl- and pyrazole-substituted aromatic compounds. This technology is highly efficient for C−C bond formation; it allows a remarkable range of functional group tolerance; and it uses environmentally-friendly coupling partners such as organoboron as reagents.


The controlled functionalization of C−H bonds in organic molecules is one of the most challenging and rewarding processes in chemistry, generally requiring either a stoichiometeric amount of a heavy-metal salt or a catalyst containing a transition metal. Currently, such catalytic procedures are costly due to the many lengthy steps involved; use of toxic or environmental-unfriendly chemicals; low efficiency caused by the thermodynamic and homocoupling properties of organometallic reagents; and lack of versatility for further synthetic manipulations. In order to produce a new class of compounds useful as drug leads for bio-pharmaceutical research, developments of novel and synthetically practical procedures for C−H functionalization are greatly in need.


  1. To customize or modify pharmacologically important molecules with desired functional groups.
  2. To generate previously unattainable compounds as candidates for drug screening (creating new combinational libraries).


  • Offers a one-pot procedure for the coupling of C−H bonds with nontoxic and readily available reagents.
  • The direct coupling of aryl C−H bonds and alkyl C−H bonds with organoboron reagents is a highly efficient process for C−C bonds formation.
  • This technology allows a remarkable range of functional group tolerance, including substrates incorporating double bond moieties.
  • Functionalized products obtained by this technology can be used as building blocks for further synthetic transformations to yield biologically active small molecules.


Figure 1

Figure 2

This invention provides a one-pot procedure for the direct functionalization of pyridyl- and pyrazole-substituted aromatic compounds. Using transition metal-containing catalysts, alkylation of sp2 and sp3-hybridized C−H bonds can be obtained with nontoxic reagents such as organo-boroxines and organo-boronic acids via a C−H activation/C−C coupling sequence. The success of this unprecedented approach satisfies the increasingly strict environmental constraints that are in great demand by the pharmaceutical and chemical industries. In addition, this technology will allow the production of a novel class of compounds that are becoming targets of bio-pharmaceutical research. Currently, functionalized pyridine moieties are used extensively as intermediates in the synthesis of drugs, herbicides, and agrochemicals. Therefore, this technology is readily adaptable with existing manufacturing procedures and hence will become tremendously valuable for the pharmaceutical and fine chemical industries in the near future.

Patent Status

  • Patent pending in United States


Jin-Quan Yu

To discuss this technology with a licensing officer, please call Irene Abrams at (781)-736-2176 or email and ask about record ID: 2006-0601.