Kumada Cross-coupling Reaction

23 Feb

What is Kumada Cross-coupling Reaction?

The Kumada cross-coupling reaction uses a palladium or nickel catalyst to couple an organohalide and a Grignard or organolithium reagent. The mechanism follows the expected oxidative addition-reductive elimination cycle.

Reaction Summary:

Reagents: Catalytic Palladium or Nickel
Reactant: Organohalide, Organomagnesium or Organolithium
Product: Coupled Product
Type of Reaction: C-C Cross-Coupling

Mechanism

The reaction proceeds through three key steps:

Oxidative Addition of the organohalide to the metal catalyst.
Transmetalation with the Grignard or organolithium reagent.
Reductive Elimination to form the desired C–C bond and regenerate the catalyst.

Lab Tips

Organolithium reagents are highly versatile as they can be prepared in multiple ways, including the direct lithiation of hydrocarbons.
Fast addition of the organolithium produces α-bromo alkenyllithiums that undergo rearrangement to give lithium acetylides, lowering yields.
No reagents should be added in excess and the Pd⁽⁰⁾ catalyst should be clean to facilitate good yields.
Base-sensitive functional groups are not tolerated as they will react with the Grignard or organolithium reagent. Tolerance is improved with the Negishi cross-coupling, which uses organozinc reagents instead.

_{Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and detailed mechanisms. Burlington, MA: Elsevier Academic Press.}

Top Citations

Nickel-Catalyzed Kumada Cross-Coupling Reactions of Tertiary Alkylmagnesium Halides and Aryl Bromides/Triflates. J. Am. Chem. Soc. 2011, 133 (22), 8478–8481.

Radical Catalysis of Kumada Cross-Coupling Reactions Using Functionalized Grignard Reagents. Angewandte Chemie International Edition 2009, 48 (1), 205–209.

Room-Temperature Kumada Cross-Coupling of Unactivated Aryl Chlorides Catalyzed by N-Heterocylic Carbene-Based Nickel(II) Complexes. J. Org. Chem. 2008,73 (10), 3954–3957.

Original Paper

Tamao, K.; Sumitani, K.; Kumada, M. Selective Carbon-Carbon Bond Formation by Cross-Coupling of Grignard Reagents with Organic Halides. Catalysis by Nickel-Phosphine Complexes. J. Am. Chem. Soc. 1972, 94 (12), 4374–4376.

Related Reactions

Grignard Reaction
Negishi Cross-coupling
Suzuki Cross-coupling
Stille Cross-coupling

Related Compounds Available from J&K

Why It Matters

The Kumada reaction is foundational in organic synthesis, enabling scalable C–C bond construction in pharmaceuticals, materials, and fine chemicals. Its cost-effective catalysts and mild conditions make it a preferred route for industrial applications.

February 23, 2021 By Olica Xu

Olica Xu