Heck reaction is an organic chemical reaction in which an unsaturated halide reacts with an alkene in the presence of a palladium catalyst and a base. The reaction yields a substituted alkene and is considered to be a coupling reaction.
Table of Contents
- What is Heck Reaction?
- Heck Reaction Mechanism
- Catalyst and substrates used
- Variations
- Stereoselectivity
- Frequently Asked Questions -FAQ
What is Heck Reaction?
This reaction is also called the Mizoroki-Heck reaction, named after the chemists Tsutomu Mizoroki and Richard F. Heck. For his discovery of this reaction, Richard Heck was awarded the 2010 Nobel Prize in Chemistry, which was shared with Ei-ichi Negishi and Akira Suzuki.
The Heck reaction became the first example of a reaction that formed a carbon-carbon bond following a Palladium(0)/Palladium(II) cycle. The reaction is often employed to obtain substituted alkenes. An example of such a reaction is illustrated below.
The reaction starts with the oxidative addition of the unsaturated halide to the palladium. Now, a migratory insertion of the alkene to the palladium occurs. This is followed by the beta-hydride elimination of the alkene and the subsequent addition of the base to the palladium catalyst to regenerate the starting catalyst and end the cycle.
Heck Reaction Mechanism
The Heck reaction mechanism involves organic palladium compound intermediates. It can be broken down into the following steps:
- An oxidative addition where the palladium is inserted into the aryl-bromide bond, forming a palladium pi complex with the alkene.
- The alkene is inserted in the carbon-palladium bond on the same side of the double/triple bond which is known as syn addition.
- A beta-hydride elimination step takes place, resulting in the formation of another palladium-alkene pi complex.
- Now, the new palladium-alkene pi complex is destroyed and the palladium(0) compound is then regenerated via a reductive elimination of palladium(II) compound with the help of potassium carbonate.
An illustration describing the mechanism of the Heck reaction is provided below.
Thus, the required substituted alkene is formed.
Catalyst and substrates used
The reaction catalyzation is carried out by palladium salts. Typical precatalysts and catalysts incorporate tetrakis (triphenylphosphine) palladium (0), palladium (II) acetate, and palladium chloride. The ligands such as triphenylphosphine, BINAP, and PHOX are the supporting ligands. Triethylamine, sodium acetate, and potassium carbonate are typical bases.
The aryl electrophile can be a triflate or a halide (Br, Cl) as well as vinyl or benzyl halides. It is necessary for alkanes to consist of at least an sp2-C-H bond. Acrylates are ideal because the reaction is enhanced by electron-withdrawing substituents.
Variations
The Heck reaction has been modified into the following variations:
- Ionic liquid Heck reaction: In this variation, the reaction is executed in the presence of an ionic liquid in order to avoid phosphorus ligands. This variation allows the reaction to proceed in water and makes the catalyst reusable.
- Heck oxyarylation observes the displacement of the palladium substituent by a hydroxyl group in the syn addition intermediate. This variation yields a product with a dihydrofuran ring
- Amino-Heck reaction is a variation of the heck reaction where a nitrogen-carbon bond is formed. The catalyst used here is tetrakis(triphenylphosphine)palladium(0) and the base used here is triethylamine.
Stereoselectivity
The coupling reaction is stereoselectively accompanied by a propensity for trans coupling because, in the rotation step sequence, the bulky organic residue and the palladium halide group move away from each other. The Heck reaction is widely used in the production of sunscreen component octyl methoxycinnamate and naproxen. The naproxen synthesis comprises a coupling between ethylene and a brominated naphthalene compound.
Frequently asked questions
What is meant by Heck coupling?
Heck coupling is Heck reaction. It is another term used for Heck reaction.
What is the product of Heck reaction?
Substituted alkene.
Which catalysts are used for Suzuki coupling?
Palladium catalysts.
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