This Nobel Prize-winning (2010) palladium-catalyzed cross-coupling reaction between organohalides and organoboron compounds is a versatile four-step process, creating carbon-carbon sigma bonds:
(i) Oxidative addition of the organohalide to the Pd(0) catalyst, creating a halide-Pd(II)-alkyl complex
(ii) Replacement of the halide attached to the complex with the anion of the base (metathesis)
(iii) The organoboron compound and base form a tetracoordinate borate anion, which increases the nucleophilicity of its alkyl group to exchange with the attached anion of the base, forming a Pd(II) complex with two alkyl groups (transmetallation)
(iv) Reductive elimination facilitates the formation of a single bond between the alkyl groups, regenerating the Pd(0) catalyst.
- Reagents:Catalytic Palladium, Base (NaOH, Ba(OH2), Na2CO3, K3PO4, etc.)
- Reactant: Organic Electrophile (Organohalide/Triflate, etc.), Organoboron Compound (Alkyl-, Allyl-, Alkenyl-, Alkynyl-, Aryl-Borane, Boronic Acid, or Boronic (Boronate) Ester)
- Product: Coupled Product
- Type of Reaction: Cross-Coupling
- Bond Formation: C-C
Lab Tips
- Nickel [1] or nanocatalysts [2] can also be used for this reaction. Moreover, transition-metal-free biaryl coupling has been carried out in water with tetrabutylammonium bromide (TBAB) as an additive. [3]
- The R group of the organic electrophile may be an alkenyl, aryl, or alkyl. Possible electrophile groups include Cl, Br, I, OTf, and OPO(OR)2 (enol phosphate). [4][4] , but improvements to the protocol have been developed. [5,6]
- Organotrifluoroborates are an alternative to boronic acids, boronate esters, and organoboranes. [7]
- This coupling reaction is highly stereo- and regioselective. [4][4]
- Many organic compounds are base-sensitive; choosing the right base and solvent system reduces side reactions and improves yields. [8][8][8]
2. Fihri, A. et al, Nanocatalysts for Suzuki cross-coupling reactions. J. Chem. Soc. Rev. 2011, 40(10), 5181-5203.
3. Leadbeater, N. E., Marco, M. Transition-metal-free Suzuki-type coupling reactions. Angew. Chem. Int. Ed. 2003, 42(12).
4. Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and Detailed Mechanisms. Burlington, MA: Elsevier Academic Press.
5. Littke, A. F., Fu, G. C. A convenient and general method for Pd-catalyzed Suzuki cross-couplings of aryl chlorides and arylboronic acids. Angew. Chem. Int. Ed. Engl. 1999, 37, 3387-3388.
6. Wolfe, J. P., Singer, R. A., Yang, B. H., Buchwald, S. L. Highly active palladium catalysts for Suzuki coupling reactions. J. Am. Chem. Soc. 1999, 121, 9550-9561.
7. Molander, G. A., Ellis, N. Organotrifluoroborates: Protected boronic acids that expand the versatility of the Suzuki coupling reaction. Acc. Chem. Res. 2007, 40, 4, 275-286.
8. Suzuki, Akira. Cross-coupling reactions of organoboranes: an easy way to construct C-C bonds (Nobel Lecture). Angew. Chem. Int. Ed. 2011, 50, 6722-6737.
Mechanism
Original Paper
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Related Reactions
- Hiyama Coupling
- Kuamada Cross-Coupling
- Miyaura Borylation Reaction
- Negishi Cross-Coupling
- Stille Cross-Coupling
Related Compounds
- Palladium Catalyst
- Base
- Organohalide
- Organoborane
