Reactivity in Chemistry

Oxidative Addition & Reductive Elimination

OA.6. Coupling Reactions in Organic Synthesis

Oxidative addition and reductive elimination are key steps in industrial catalysis. For example, both steps are featured in palladium-catalyzed cross-coupling reactions, the subject of the 2010 Nobel Prize in Chemistry. The prize was awarded to Richard Heck of the University of Delaware, Ei-Ichi Negishi of Purdue University and Akira Suzuki of Hokkaido University. With these reactions, workers in a variety of fields can make molecules that otherwise would be quite difficult to make. These molecules in turn may be important pharmaceuticals or useful compounds for electronic displays in computers and other devices, to name just a couple.

The Negishi reaction involves catalytic addition of alkylzinc nucleophiles to vinyl halides.

Figure OA6.1.  The Negishi cross-coupling reaction.

The catalytic cycle believed to operate for this reaction involves the crucial oxidative addition of the vinyl halide to the metal.  The alkylzinc probably delivers the alkyl nucleophile to the metal via more conventional nucleophilic substitution.  Once both pieces are both on the metal, they can reductively eliminate together.

Figure OA6.2.  Catalytic cycle for the Negishi cross-coupling reaction.

Problem OA6.1.

Explain why the vinyl halide pictured in the example above would not react directly with the alkylzinc reagent.

Problem OA6.2.

Label each step of the catalytic cycle for the Negishi reaction with the appropriate term (oxidative addition, etc).

Problem OA6.3.

Draw the mechanism for the Negishi reaction using curved arrow notation.

There are many other examples of coupling reactions in organic synthesis.  The Suzuki reaction is somewhat similar to the Negishi reaction.

Figure OA6.4.  The Suzuki reaction.

The Heck reaction involves activation of a vinylic or aryl C-H bond.

Figure OA6.5.  The Heck reaction.

Problem OA6.4.

By analogy with the Negishi reaction, propose a catalytic cycle for the Suzuki reaction.

Problem OA6.5.

Propose a catalytic cycle for the Heck reaction.

Problem OA6.6.

Problem OA6.7.

Problem OA6.8.

 

Read more about these Nobel Prize-winning reactions at the Nobel Prize website.

 

This site is written and maintained by Chris P. Schaller, Ph.D., College of Saint Benedict / Saint John's University (with contributions from other authors as noted).  It is freely available for educational use.

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Structure & Reactivity in Organic, Biological and Inorganic Chemistry by Chris Schaller is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License

Send corrections to cschaller@csbsju.edu

This material is based upon work supported by the National Science Foundation under Grant No. 1043566.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

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