Diels-Alder Reaction Mechanism

Introduction

The Diels-Alder reaction mechanism continues via suprafacial (same face presence of the isolated orbital or the π system that exists in the process) interaction between a 4π with a 2π electron system. Diels-Alder reaction involves the cycloaddition reactions that result in the creation of a new ring from two reactants.


In the Diels-Alder reaction, the 4π electron system is referred to as the diene structure, whereas the 2π electron system is known as the dienophile structure. Now, this interaction leads to a transition state without any external energy barrier from the orbital symmetry imposition.


What is the Diels-Alder Reaction?

The Diels-Alder reaction is an essential organic chemical reaction where the reactants include a conjugated diene and a substituted alkene. Commonly, this substituted alkene is referred to as a dienophile, and this reaction gives rise to a substituted derivative of cyclohexene. The Diels-Alder reaction is such a good example of pericyclic reactions that proceed through the concerted mechanisms (it means, all bond breakage and bond formation occurs at a single step).


This reaction was discovered in 1928 by the German chemists’, Kurt Alder and Otto Diels, and for which they are awarded the Nobel Prize in Chemistry in 1950. The Diels-Alder reaction can be used to produce six-membered rings since there is a simultaneous construction of two new carbon-carbon bonds.


An illustration of the reaction between Diene and Dienophile is given below.


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From the above illustration, if we observed clearly, two pi bonds were converted into two sigma bonds. This happens because of the concerted bonding of two independent pi-electron systems. Also, the Diels-Alder reaction involves the shift of four pi electrons of diene and two pi electrons of dienophile.


This reaction is used to produce vitamin B6. The reverse reaction (also known as a retro-Diels-Alder reaction) is used to produce cyclopentadiene on an industrial scale.


Mechanism of Diels-Alder Reaction

The simple mechanism of the Diels-Alder reaction is explained below.

Since the pi bonds are converted into stronger sigma bonds, thermodynamically, the reaction is favourable. The Diels-Alder reaction is favoured by the electrophilic dienophiles with electron-withdrawing groups that are attached to them. In addition, it is favoured by the nucleophilic dienes with electron-donating groups present in them. A few examples are given below for good dienes and dienophiles for the Diels-Alder reaction.


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Because the Diels-Alder reaction mechanism is concerted, the reaction follows in a single step cycloaddition reaction. Here, two unsaturated molecules combine to produce a cyclic adduct. There is also a net reduction in bond multiplicity. All the bond formations and bond breakages occur simultaneously.


An example is given below on an illustration of the simple reaction mechanism.


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Therefore, the diene and dienophile react to each other to form a cyclohexene derivative. It can be observed from the mechanism representation where three carbon-carbon pi bonds break, but it forms only one pi bond, and two sigma bonds are formed thereby.


Stereoselectivity of Diels-Alder Reaction

The stereoselectivity of the Diels-Alder reaction has several modifications. Where some of them are mentioned below. The stereoselectivity is also known as variations.

  1. The Hetero Diels-Alder Variation

  • These reactions involve either one or more heteroatoms (any atom other than hydrogen or carbon). 

  • When carbonyl groups react with dienes, dihydropyran products are produced.

  • The aza Diels-Alder reaction includes the use of imines as dienophile or diene substituents. The resultant product formed in this reaction is an N-heterocyclic compound.

  • If a nitroso compound is used as a dienophile, the reaction resulting from the diene yields oxazines.

  1. Usage of Lewis Acids

  • A Lewis acid can be used as a catalyst in this variation.

  • The Lewis acids examples that can be used in these reactions include boron trifluoride, aluminium chloride, zinc chloride, and tin tetrachloride.

  • The electrophilicity of the dienophile complex is increased by the Lewis acid in these reactions.

  • The advantages of this variation are increased reaction rates and improved regioselectivity and stereoselectivity. These types of Diels-Alder reactions can proceed at relatively low temperatures.

  1. The Asymmetric Variation

In this reaction, there exist many variations that influence its stereoselectivity. The use of a chiral auxiliary is one such example. Organocatalysts with relatively small molecules can often be used to modify the stereoselectivity of this reaction.


Some significant applications of the Diels-Alder reaction include its role in the formation of vitamin B6 and its reverse-reaction role in the production of cyclopentadiene on an industrial scale.

  1. Hexa Dehydro Diels-Alder

In this Hexa dehydro Diels-Alder reaction, diynes and alkynes are used instead of dienes and alkenes, forming an unstable benzyne intermediate, which then can be caught to produce an aromatic product. This reaction also allows the formation of heavily-functionalized aromatic rings in one single step.


Application of Diels-Alder reaction

The retro Diels-Alder reaction is used for the industrial production of cyclopentadiene. Cyclopentadiene is a precursor to many norbornenes, which are common monomers. Also, the Diels-Alder reaction is employed in vitamin B6 production.


A typical route for the production of ethylidene norbornene from cyclopentadiene via vinyl norbornene is represented below.


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FAQ (Frequently Asked Questions)

1. Mention the Objectives of the Diels Alder Reaction?

We can’t say that reactions have “objectives,” perhaps unless they are part of a planned synthesis. Consider the below reaction given.


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If the Diels-Alder reaction has reactants, a diene and an alkene (also called dienophile), then the product is a cyclohexene derivative.


The “A” group represented here is typically an electron-withdrawing group like -CN or -COOR. The “A” group is strictly not necessary, but it helps to lower the activation energy of the reaction vis-a-vis ethylene itself.


Now, an “objective” on Diels-Alder reactions can include the mechanism that we know. A typical Diels-Alder reaction happens via a concerted reaction with an “aromatic” which is so-called a transition state because it has six electrons that move cyclically and lower activation energy than expected otherwise as would be, as in a benzene ring. Diels-Alder reactions are called 4+2 cycloadditions, with the 4 indicates the reacting diene ‘pi,’ and the 2 indicates the reacting dienophile ‘pi’ electrons.

2. Was the Diels-Alder Reaction ever Important in Biochemistry?

It is obviously Yes. But mostly in the biosynthesis of secondary microbial metabolites like Spinosyn A, Thiomuracin, or Leporine. For such compounds, the Diels-Alder reaction is simply not a key for biosynthesis but can be examined in detail if we want to generate derivatives of these compounds for drug testing.


If a thermodynamically favourable reaction mechanism is prevented sterically by the enzyme in favour of the product-generating mechanism (as an example, Endo vs. Exo DA products), a simple point mutation can be employed to allow the reaction to proceed thermodynamically, generating an analogue thereby to our natural compound.