COUPLING REACTIONS USING TRANSITION METALS
DEEPSHIKHA
DEPARTMENT OF CHEMISTRY
The term coupling reaction refers to the class of organic reactions that involves the joining of two hydrocarbon fragments which are coupled with the help of a metal catalyst. Transition metal catalysts are used because they increase the reaction rate without affecting the heat of the reaction. During the reaction, transmetalation occurs in which an alkyl group is transferred from one metal to another. The energy is transferred from the reactants’ side to the product’s side.
COUPLING REACTIONS
What happens in a coupling reaction?
Types of coupling reaction:
Coupling reactions can be divided into two main classes, cross-couplings and homocoupling.�
Cross-coupling: In this type of reaction, two different molecules react to form one new molecule. It is also known as hetero coupling reactions.
Examples: Grignard reagent reaction, Suzuki reaction, Negishi coupling, and hiyama coupling.
Homocoupling: In this type of reaction, two similar molecules are coupled together to form a new molecule.
Example: Wurtz reaction, Ullman reaction ,Glaser coupling,Pinacol coupling
Homocoupling Reactions:
The Ullmann reaction (also known as Ullmann coupling) is an organic named reaction that involves the coupling of two aryl halides in the presence of copper to yield a biaryl as the product. Ullmann coupling reaction is named after the German chemist Fritz Ullmann.
Ullmann reaction
Also known as: Ullmann coupling or Ullmann biaryl synthesis
�
The proposed mechanism begins with oxidative addition of the copper to the aryl halide followed by a SET to form an organocuprate reagent. The organocuprate performs another oxidative addition on an aryl halide and after reductive elimination results in the final biaryl product.�
Mechanism involving an aryl intermediate
. Although bromides and chlorides have also been utilized, aryl iodides are the most common substrate for the reaction. The aryl bromides and chlorides often do not participate in the reaction if there is no electron-withdrawing group present at the ortho and or para to the halogen atom.
Therefore, ArI > ArBr > ArCl is the sequence of reactivity and the prerequisite for the reactivity of aryl bromide or chloride in the presence of nitro or carbonyl group etc. at the ortho or para position.
Ullmann Reaction Application
Withthe latest modifications and latest green technologies, the Ullmann reaction can be used to synthesize heterocycles, drug-like molecules, natural products, chiral auxiliaries, and other compounds. Some of the most common applications of the Ullmann reaction are:
The Glaser coupling is a type of coupling reaction. It is by far the oldest acetylenic coupling and is based on cuprous salts like copper(I) chloride or copper(I) bromide and an additional oxidant like oxygen. The base in its original scope is ammonia. The solvent is water or an alcohol. The reaction was first reported by Carl Andreas Glaser in 1869
An advantage of the Glaser coupling is the formation of a C(sp)–C(sp) bond, which makes it very suitable for the formation of conjugated carbon structures.
�
Glaser Coupling Reaction
Glaser coupling it is the oxidative homo-coupling of terminal alkynes using copper catalyst in the presence of oxygen.
Sonogashira reaction
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vinyl halide.
The palladium cataly-zed mechanism begins with oxidative addition of the organohalide to the Pd(0) to form a Pd(II) complex. Transmetalation with the organocopper reagent, formed from the terminal alkyne and the copper catalyst, then follows. The alkynyl anion replaces the halide on the palladium complex and regenerates the copper halide catalyst. Reductive elimination then gives the final coupled product, regenerates the palladium catalyst, and the catalytic cycle can begin again.[1]
The palladium cataly-zed mechanism begins with oxidative addition of the organohalide to the Pd(0) to form a Pd(II) complex. Transmetalation with the organocopper reagent, formed from the terminal alkyne and the copper catalyst, then follows. The alkynyl anion replaces the halide on the palladium complex and regenerates the copper halide catalyst. Reductive elimination then gives the final coupled product, regenerates the palladium catalyst, and the catalytic cycle can begin again.
Sonogashira reaction
Mechanism
Example
Sonogashira Coupling is important in a wide variety of areas and has become essential in the synthesis of compounds with application in material science pharmaceuticals, nanomaterials and natural product chemistry.
A simple example of the Sonogashira Coupling reaction is tazarotene synthesising in a treatment of acne and psoriasis, also called as Altinicline.
Suzuki cross-coupling
Also known as: Suzuki-Miyaura cross-coupling
The Suzuki cross-coupling reaction is the organic reaction of an organohalide with an organoborane to give the coupled product using a palladium catalyst and base. The mechanism begins with oxidative addition of the organohalide to the Pd(0) to form a Pd(II) complex. A molecule of the hydroxide or alkoxide base then replaces the halide on the palladium complex, while another adds to the organoborane to form a borate regent making its R group more nucleophilic. Transmetalation with the borate then follows where its R group replaces the halide anion on the palladium complex. Reductive elimination then gives the final coupled product, regenerates the palladium catalyst, and the catalytic cycle can begin again.[
Suzuki reaction can conjoin a variety of aryl halides and alkenyl halides with alkenylboranes and arylboronic acids and is thus an essential method of synthesizing many styrenes, alkenes, and biphenyls. It is very cost-effective for use in the synthesis of intermediates for pharmaceuticals or fine chemicals
Applications of Suzuki Reaction
THANKS