Suzuki Coupling

Definition:

Palladium-catalyzed cross coupling of organic halides or perfluorinated sulfonates with organoboron derivatives proceeding with high stereo- and regioselectivity:

Frequency of appearance:

        This bar graph represents all of the online articles that were found to contain this specific name reaction in the title of the article. Tetrahedron letters, Tetrahedron, Synthetic letters, Synthesis, Journal of Organic Chemistry and Journal of the American Chemical Society are represented here. This table by no means represents the periodicity of the name reaction found in the literature.

Original References:

1. N. Miyaura et al., Tetrahedron Letters, 3437 (1979).

Recent academic references: Click here for more references

2. Fabrication of Hollow Palladium Spheres and Their Successful Application to the Recyclable Heterogeneous Catalyst for Suzuki Coupling Reactions

• Kim, S., J. Am. Chem. Soc., 124, 762-7643 (2002).

3. Suzuki reactions with b-allyl-9-borabicyclo[3.3.1]nonane (b-allyl-9-bbn)

• Fürstner, A.* Seidel, G. SynLett, 161-162 (1998).

4. Synthesis of 2-Substituted Dihydropyran 3-O-Carbamates via Combined Metalation-Suzuki-Miyaura Cross-Coupling Reactions

• Bower, J.F.; Guillaneux, D.; Nguyen, T.; Wong, P.L.; Snieckus, V.* J. Org. Chem., 63, 1514-1518 (1998).

5. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds

• Miyaura, N.; Suzuki, A. Chem. Rev., 95, 2457 (1995).

6. http://www.chem.ufl.edu/~reynolds/term01/cardola.pdf
7. http://www.iecb-polytechnique.u-bordeaux.fr/publis/2001/cjc20011827.pdf

Recent process papers:

8. Multikilogram-Scale Synthesis of a Biphenyl Carboxylic Acid Derivative Using a Pd/C-Mediated Suzuki Coupling Approach

• Ennis, D. S.; McManus, J.; Wood-Kaczmar, W.; Richardson, J.; Smith, G. E.; Carstairs, A.; Org. Process Res. Dev.; 1999; 3(4); 248-252.

9. Suzuki Reaction of a Diarylborinic Acid: One-Pot Preparation and Cross-Coupling of Bis(3,5-dimethylphenyl)borinic Acid

• Winkle, D. D.; Schaab, K. M.; Org. Process Res. Dev.; 2001; 5(4); 450-451.  

 

Mechanism:

Scope and Limitations:

• Boron species = B(OH)₂, 9-BBN, B(CHCH₃CH(CH₃)₂)₂
• Leaving groups = I > OTf > Br >>Cl
• Boronic esters = aryl, alkenyl, alkyl
• Boronic halides = aryl, alkenyl, alkynyl, benzyl, allyl, alkyl
• Bases = Na₂CO₃, NaOCH₂CH₃, TIOH, N(CH₂CH₃)₃, K₃PO₄
• Palladium catalysts = Pd(PPh₃)₄, Pd(dppf)Cl₂

• Most frequently used catalyst for the reaction is Pd(PPh₃)₄

             Has the advantage that its chemistry is well understood and is controllable

            Is versatile, being used in a range of metal-mediated reactions

• There are disadvantages using Pd(PPh₃)₄:

  Only aryl bromides and iodides can be used as chlorides react slowly, if at all

  Not particularly amenable to aqueous-phase catalysis 

  By products often formed

• Suzuki reactions generally employ organic solvents such as tetrahydrofuran and ethers as well as complex palladium catalysts which are soluble in these solvents
• Boronic acid is thermally stable and inert to air and water (allowing for easy handling without special precautions).

Synonyms: