Organic Chemistry: Concepts and Applications - Headley Allan D. 2020

Conjugated Systems and Pericyclic Reactions
18.2 Pericyclic Reactions

The mechanisms for most of the reactions that we have looked at so far involve intermediates and a rate-determining step leading to the formation of one of the intermediates. Some reactions are concerted reactions, that is, no intermediates are formed as the reactants proceed to products by going through only a transition state. We have seen these type reactions for the E2 and S_N2 mechanisms. Pericyclic reactions are another type of concerted reactions, where reactants proceed directly to products by going through a transition state. Pericyclic reactions have the following characteristics: (i) concerted; (ii) cyclic transition state; (iii) energy is usually supplied by heat or light; (iv) solvents have little or no effect on the reaction rate; and (v) they are stereospecific. In this section, we will examine three types of pericyclic reactions: (i) cycloaddition, (ii) electrocyclic and (iii) sigmatropic reactions.

18.2.1 Cycloaddition Reactions

For these reactions, the π electrons from two different molecules react to give a single cyclic product. These reactions involve π electrons, and the number of π electrons involved is important for these reactions. The first pericyclic cycloaddition reaction that we will examine is the reaction of two ethylene molecules to form a cyclobutane.

18.2.1.1 Cycloaddition Reactions

The simplest cycloaddition reaction is the reaction of two ethylene functionalities to form cyclobutane. The reactions of ethylene with cis and trans 2-butene are shown in Reactions (18-9) and (18-10).

(18-9)

(18-10)

Note from the reaction, that the methyl groups of cis-2-butene remain on the same side to give the product. Hence, the stereochemical outcomes of these reactions are predictable based on the stereochemistry of the reactants. These types of reactions are called stereospecific reactions.

The source of energy needed for these [2+2] reactions is light and not heat, and we will now use the molecular orbital theory to explain this requirement and also to explain the stereochemical outcome of these reactions. The energy that is needed for this reaction to proceed is light at the proper wavelength of the electromagnetic spectrum. The frontier molecular orbital method is an approach that is widely used to gain a better understanding of how pericyclic reactions proceed from reactants to give the product. For the analysis of these reactions, only the π orbitals and π electrons of the reactants are considered.

The carbons of ethylene are sp² hybridized; thus, there are two p orbitals associated with each carbon atom and each contains a single electron. In order to form the π bond, these two p atomic orbitals must form molecular orbitals. Since there are two p atomic orbitals, they form two molecular orbitals; one molecular is lower in energy (π₁) and the other orbital (π₂*) is higher in energy as illustrated in Figure 18.2.

Since the molecular orbital π₁ is the lowest in energy and each orbital can accept two electrons, this molecular orbital contains both p electrons and is called the HOMO, which means highest occupied molecular orbital. The other molecular orbital, which is higher in energy, does not contain any electrons and, as a result, is called the LUMO, which means lowest unoccupied molecular orbital. For the reaction to proceed, electrons must flow from the HOMO of one reactant to the LUMO of the other reactant. In addition, the orbitals must have the correct phase for interaction of the orbitals to occur and eventually for the reaction to proceed from reactants to product. If the orbitals do not have the correct phase, then the reaction is symmetry forbidden (as shown in Figure 18.3), and if they have the correct phase, the reaction is symmetry allowed as shown in Figure 18.4.

Figure 18.2 Molecular orbitals of ethylene molecule with its p electrons.

Figure 18.3 Illustration of incorrect phase of the orbitals of two ethylene molecules.

Figure 18.4 Illustration of correct phase of the orbitals of two ethylene molecules for the reaction to occur.

Figure 18.5 Promotion of electron from the HOMO to LUMO for light.

Under conditions without additional energy, such as light, it is obvious that the phase of HOMO of one reactant does not match the phase of LUMO of the other reactant.

In order to meet the symmetry allowed requirement as shown in Figure 18.4, an electron must be promoted from π₁ to π₂* and this electron promotion can be accomplished by light as shown in Figure 18.5. When this happens, the molecule is described as being in the excited state.

Note that this electron promotion can occur in either the ethylene or 2-butene to form a new HOMO in the excited molecule. As a result, the phase will be correct for an interaction between both orbitals, i.e. the reaction is symmetry allowed and electrons can flow from the HOMO of one reactant to the LUMO of the other reactant to form the new bonds. This reaction will not occur in heat since a specific energy is required to promote the electron from π₁ to π₂*, which comes from light.

Reaction 18-11 shows the proposed mechanism for the [2 + 2] cycloaddition of cis 2-butene and ethylene.

(18-11)

The mechanism for the trans addition is shown in Reaction 18-12

(18-12)

Based on this information, the reaction conditions can be given more specifically to indicate light and not just energy as given earlier. These reactions, with specific reaction conditions, are given in Reaction (18-13) for the reaction of ethylene with cis butene and Reaction (18-14) for the reaction of ethylene with trans-2-butene.

(18-13)

(18-14)

Problem 18.2

Give the product of the following [2+2] cycloaddition reaction.

18.2.1.2 Cycloaddition Reactions [4+2]

Let us now consider the reaction involving 1,3-butadine and ethylene as shown in Reaction (18-15).

(18-15)

This type of reaction is also known as a [4+2] cycloaddition owing to the fact that there are two π electrons from one reactant and four π electrons from the other reactant. This type of reaction is often referred to as the Diels Alder reaction, named after the German chemists, Otto Diels and Kurt Alder, who discovered this reaction. They discovered the reaction in 1938 and received the Nobel Prize for their contribution to the advancement of chemistry in 1950. Their discovery opened up a new arena for synthesizing cyclic compounds that are of extreme value in the synthesis of important cyclic compounds. For this reaction only the π electrons participate as shown in Reaction (18-16) in which the arrow-pushing formulism is used to explain the mechanism.

(18-16)

For this reaction, the diene is the molecule with two double bonds in conjugation with each other, and the other molecule is called the dienophile, which means diene-loving. We can use the frontier molecular orbital method to analyze this reaction to determine if light or heat is required for this reaction. Shown in Figure 18.6 are the molecular orbitals for the diene (1,3-butadiene) and dienophile (ethylene). Shown in Figure 18.7 is the correct phase requirement of the orbitals of the diene (1,3-butadiene) and the dienophile (ethylene) for a reaction to occur.

For these two molecules, the HOMO and the LUMO have the correct symmetry and the electrons will flow from the HOMO from one of the reactants into the LUMO of the other reactant molecule to form the product as shown in Reaction 18-16. As a result, excitation by light is not needed for these [4+2] reactions, but they are typically carried out at elevated temperatures.

Figure 18.6 Molecular orbitals of the ground state of 1,3-butadiene and ethylene.

Figure 18.7 Illustration of the correct phase involving the HOMO of 1,3-butadiene and the LUMO of ethylene.

For these reactions, stereochemistry is conserved, as shown in Reactions (18-17) and (18-18).

(18-17)

(18-18)

For more complex molecules, the possibility exists for different products as shown in Reaction (18-19).

(18-19)

In order to determine the major product, we will have to examine the mechanism again, specifically the electronic distribution of the reactants leading to the transition states for the different products. Shown below are the resonance structures of the diene and dienophile.

It is obvious that the cycloaddition that leads to the 1,4-addition product (Reaction 18-20) is more favorable, compared to the 1,3-addition product shown in Reaction (18-21).

(18-20)

(18-21)

Reaction (18-20) is favorable since the electron-releasing methoxy group makes the adjacent carbon nucleophilic as shown in the resonance structure of the diene to the left. Regarding the dienophile, the resonance structure shows that the electrons of the double bond are delocalized into the carbonyl of the ester functionality, making the carbon furthest from the ester functionality electrophilic. This electron distribution occurs since the ester functionality is electron withdrawing. As a result, both reactant molecules in Reaction (18-20) are perfectly oriented for the nucleophilic portion of the diene to react with the electrophilic portion of the dienophile as illustrated in Reaction (18-20). On the other hand, a different orientation of the dienophile as given in Reaction (18-21) shows that the nucleophilic end of the diene and the electrophilic end of the dienophile are not oriented for an effective reaction to occur. As a result, the major product of the reaction shown in Reaction (18-19) is given below in Reaction (18-22). In general, Diels-Alder reactions are favored if electron-donating groups are bonded to the diene and electron-withdrawing groups bonded to the dienophile.

(18-22)

Problem 18.3

Give the major organic products of the following [4+2] cycloaddition reaction.

18.2.2 Electrocyclic Reactions

Another category of pericyclic reactions involves reactions in which the π electronic systems of a conjugated system are rearranged to form cyclic compounds. Examples of the reactions of two isomers of 2,4-hexadiene are shown in Reactions (18-23) and (18-24) in which each reaction is initiated by a different form of energy, heat in one case and light for the other.

(18-23)

(18-24)

Note the stereochemical outcome for each of these reactions is different depending on the type of energy used. To better visualize the electrocyclic ring closure reactions 18-23 and 18-24, the process can be viewed as the formation of a new σ-bond, which is made at the ends of the polyene as shown in Reaction 18-25.

Figure 18.8 Ground and excited states of 2,4-hexadiene.

(18-25)π

The frontier molecular orbital method can be used to explain the outcomes of these reactions. Figure 18.8 gives the molecular orbitals for the HOMO of the ground state and excited state of 2,4-hexadiene.

For the ring closure reaction of the ground state molecule, which involves the HOMO, the phase for the orbitals are correct for ring closure with a conrotatory closure as illustrated in Figure 18.9.

Let us now look at the ring closure for the excited molecule, which is shown in Figure 18.10. Note that the stereochemistry of the products is dictated by the different required rotations for these reactions as shown in Figures 18.9 and 18.10.

As you can imagine, the number of π electrons will dictate the type of ring closure and Table 18.1 gives a summary.

Figure 18.9 Conrotatory ring closure of ground state 1,3-hexadiene to give the products shown in Reactions (18-23) and (18-24).

Figure 18.10 Disrotatory ring closure of excited 1,3-hexadiene to give the products shown in Reactions (18-23) and (18-24).

Table 18.1 Relationship between number of pi (π) electrons of conjugated systems and type of ring closure for electrocyclic reactions.

Shown in Reaction (18-26) is the electrocyclic reaction of 2,4,6-octatriene.

(18-26)

Problem 18.4

Give the product of the following electrocyclic reactions, include appropriate stereochemistry where appropriate.

18.2.3 Sigmatropic Reactions

For these reactions, a sigma bond is formed and another sigma bond is broken. In the process, the π bonds are rearranged as shown in Reaction (18-27).

(18-27)σσ

As you can imagine, the transition states for these reactions are cyclic and shown in Reaction (18-28) is the sigmatropic rearrangement reaction involving 3-methyl-1,5-hexadiene.

(18-28)σ

Note that for these reactions, the π electrons are not conjugated, but since a sigma bond is involved in the rearrangement and since a cyclic transition state is formed as shown in Reaction (18-28), these reactions are classified as pericyclic reactions. The type of reaction given in Reaction (18-28) is described as a [3,3] sigmatropic rearrangement and is also known as the Cope rearrangement. The number three indicates the three atoms that are separated from the sigma bonds to be formed and broken, as illustrated below. A look at the transition state clearly shows the three atoms that are involved in the bond-making and bond-breaking process.

Another example of the nomenclature of a cope rearrangement is shown in Reaction (18-29).

(18-29)

Note that for this sigmatropic reaction, there is one atom (the hydrogen) on one side of the sigma bond to be formed and broken and five atoms on the other side, hence the name [1,5] sigmatropic reaction. If the reactants, and hence products, contain an oxygen atom as part of the cyclic rearrangement framework, this type of reaction is known as a Claisen rearrangement, as shown in Reaction (18-30).

(18-30)

Problem 18.5

Give the product for the following Claisen rearrangements.