MCAT-53™: A Green Ruthenium Catalyst for Cross-Coupling & C–H Activation

Introduction

Modern catalytic functionalization reactions are continuously advancing the synthesis of valuable heterocyclic molecules, and in parallel, it is vital to ensure the environment is not taxed for the progress. Traditional aryl-coupling and C–H bonds activation methods (such as Suzuki-Miyaura and Stille cross-coupling reactions) are accomplished by tedious preparation of unstable, toxic organometallic reagents and the reactions are routinely run in harsh organic solvents (such as DMF, NMP, DMSO and toluene)1.

Palladium-based catalysts, which often demand the use of phosphine-ligand systems, have dominated the realm of modern catalytic cross-coupling. Recently, the Chicago Discovery Solutions developed MCAT-53™: a recyclable, ligand-free ruthenium catalyst for C–H activation reactions and concomitant C–C bond formation in the presence of water.

MCAT-53™ structure

Reactions using MCAT-53™ negate the necessity for undesirable toxicity and disposal costs2. After the reaction is complete and worked up, the ruthenium catalyst is easily recovered in aqueous medium to continue generating new diversely functionalized entities.

Advantages

  • MCAT-53™ achieves C–H-activated C–C coupling in aqueous conditions
  • Unlike Pd-catalysts, MCAT-53™ requires no ligands, acids or oxidants such as Cu(II) and Ag(I) salts
  • Ruthenium-catalyst is recyclable
  • Bench- and air-stable

Representative Application

The catalyst is tailor made to work in water and there is no need to add acid, co-solvent, surfactant, or perform additional steps for activation for the catalyst. By simply combing an aryl halide with an aromatic coupling partner in the presence MCAT-53™ and a base (such as K2CO3), a safe and cost effective alternative to some of the very expensive Pd-catalysts and precatalysts3 is now available.

Bromides, chlorides and halide structures

Bromides, chlorides and heavily substituted halides can work smoothly under the catalytic conditions.

Pyridine derivatives structures

A variety of pyridine derivatives can serve as excellent directing groups, and the reactions produces ortho- products. Other nitrogen-based directing groups, including imines, oxime ethers, azobenzene derivatives, and nitrogen heterocycles (e.g., pyrazoles and isoxazolines) can be used. Furthermore, amides, which contain relatively basic oxygen atoms, could be used to direct these reactions.

See the MCAT-53™ Protocol

Materials

     
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