Palladium-catalyzed Carboxylate-directed Functionalization of C-H Bonds

New ways to produce drug leads - Part I

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 C−H activation/C−C coupling directed by synthetically useful groups, providing advantageous alternatives to conventional procedures for selective functionalization of organic molecules. This technology allows remarkable short-cuts and versatility for organic synthesis of pharmacologically important compounds, and will revolutionize pharmaceutical manufacturing in the near future.


Selective 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).


  • First technology available for carboxyl-directed Pd-insertion into sp3 β-C−H bonds in simple aliphatic acids.
  • Offers unconventional short-cuts in synthetic processes, hence dramatically cuts cost in manufacturing pharmaceuticals and other fine chemicals.
  • Cheap and readily available substrates are used.
  • Functionalized products obtained by this technology can be used as building blocks for further synthetic transformations to yield biologically active small molecules.



This invention provides procedures for the direct functionalization (e.g. C−heteroatom bond formation) and coupling (e.g. C−C bond formation) of sp2 and sp3-hybridized C−H bonds with readily available reagents (e.g. organoboroates, organo-boronic acids, arylhalides) utilizing a carboxylate moiety or an O-(lower alkyl)hydroxamic acid moiety as a directing group. Using palladium-containing catalysts, alkylation and arylation of ortho-C−H bonds and β-C−H bonds can be achieved via a C−H activation/C−C coupling sequence. The success of this unprecedented approach opens up a great opportunity to make C−heteroatom and C−C bounds directly from unactivated C−H bonds, thereby greatly decreasing the costs for manufacturing pharmaceuticals and other fine chemicals, and also allowing versatility for further manipulation of synthesized compounds.

Patent Status

  • Patent pending in United States


Jin-Quan Yu, Ramesh Giri, Nathan Maugel, Jiao-Jie Li, Dong-Hui Wang, Stephen Breazzano and Lindsey Saunders.

To discuss this technology with a licensing officer, please call Irene Abrams at (781)-736-2176 or email and ask about record ID: 2007-0107.