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Subject Chemistry
Paper No and Title 9; Organic Chemistry-III
Module No and Title 27; Classification of Pericyclic Reactions
Module Tag CHE_P9_M27
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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TABLE OF CONTENTS
1. Learning Outcomes 2. Introduction 3. Classification of pericyclic reactions 3.1 Electrocyclic reaction 3.2 Cycloaddition reactions 3.3 Sigmatropic rearrangements 3.4 Group transfer reactions 4. Woodward-Hoffmann rules and pericyclic reactions 5. Summary
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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1. Learning Outcomes
After studying this module, you shall be able to
• Know what are pericyclic reactions • Learn about classification of pericyclic reactions • Identify electrocyclic reaction, cycloaddition and sigmatropic shifts • Evaluate application of Woodward-Hoffmann rules to pericyclic reactions • Analyze which type of pericyclic mechanism is operative in a reaction
2. Introduction
Based on mechanism, chemical reactions are broadly classified as ionic, free radical and pericyclic reactions. Pericyclic reactions are a unique set of reactions that takes place through a cyclic transition state in a concerted fashion and exhibit high levels of stereospecificity. Additionally, for pericyclic reactions no intermediates have been isolated and the reactions are free from changes in solvent polarity, free radical generators and even catalysts (although lately Lewis acid catalysis has been reported for some reactions). All these reactions are potentially reversible in nature.
Unlike ionic reactions, for pericyclic reactions there is no definite sense of direction to the movement of electrons as the electrons move in a cyclic manner. There is also a difference between a synchronous reaction and a multi-stage concerted process as in synchronous reaction all bond-making and bond-breaking events take place simultaneously, but in a multi-stage concerted process some events precede others without producing an intermediate state. Most of the pericyclic reactions are concerted and may or may not be synchronous.
Though some of the pericyclic reactions occur spontaneously, but in major of them introduction of energy either in the form of heat or light is required. Moreover product depends on the source of energy used.
3. Classification of pericyclic reactions
All pericyclic reactions share common features discussed above. They are classified into following four categories
3.1 Electrocyclic reactions 3.2 Cycloaddition 3.3 Sigmatropic rearrangements 3.4 Group transfer reactions
Let us understand each type of these reactions in detail CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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3.1 Electrocyclic reactions
Electrocyclic reactions are characterized by the creation of a ring from an open chain conjugated system, with a σ bond forming across the ends of the conjugated system or opening of a cyclic system under ring strain to give rise to a diene. Electrocyclic reactions are unimolecular in nature.
Most of the electrocyclic reactions are ring closing and a few are ring opening in conformationally strained systems such as cyclobutene. Electrocyclic ring closing reactions have been observed for cationic and anionic polyene species such as allyl cations as well.
If we look at the stereochemistry of electrocyclic reactions, in the following reaction one stereoisomer gave rise to one specific product only.
H
CH3 CH3
CH3 CH3 H trans, cis, trans triene cis
H
CH3 CH3
CH3
H
CH3 trans, cis, cis triene trans
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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The stereospecificity of electrocyclic reaction can be explained based on Frontier molecular orbital (FMO) theory, especially considering the HOMO of the triene, the mode of bond rotation decides stereochemistry of product formed.
There are two known modes of bond rotation namely conrotation and disrotation as shown below.
If we consider termini of the HOMO of the triene system, it can be seen that the end groups must rotate in a disrotatory manner (twist in opposite directions, when observed front-on) to form the bond. On the other hand, when photoactivated, an electron moves from the HOMO of triene to the next orbital, the LUMO (now this orbital contains an electron and it is no longer unoccupied). In this photo excited system ring will close in the opposite direction as compared to the thermal system and moreover the groups will conrotate i.e., they will twist in the same way to form the sigma bond.
As electrocyclic reactions are reversible, whether ring opening/closing will take place is determined by thermodynamics. However, the stereochemistry of product formed is not influenced by the thermodynamic stability rules.
In another example, thermal ring opening reaction of 3,4-dimethylcyclobutene (which may exist as cis and trans isomers) gives hexadiene (which may be cis, cis/ cis, trans/ trans, trans isomers). In the reaction, cis 3,4-dimethylcyclobutene on ring opening gave only cis, trans product, while trans 3,4-dimethylcyclobutene isomer, leads to formation of trans-trans diene.
These reactions take place via conrotatory motion about the C3-C4 bond in a four-member cyclic transition state. CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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3.2 Cycloaddition reaction
Cycloaddition reactions involve concerted combination of two π-electron systems to form a ring system. Cycloaddition reactions are described as [i+j] additions, when a system of “i” conjugated atoms combines with a structure consisting of “j” conjugated atoms. In cycloaddition reactions carbon–carbon bond formation takes place without any use of a nucleophile or electrophile. Among the pericyclic reactions, cycloadditions are most abundant and useful set of reactions. [4+2] cyclization is most common type of cycloaddition reaction .Diels-Alder reaction falls in this category of cycloaddtion reactions. The utility of this reaction lies in two simultaneous C-C bond formations, which, with suitable substrates may lead to creation of four new stereogenic centers in the product. In Diels-Alder terminology the two reactants are referred to as the diene and the dienophile. OAc OAc
H3COOC COOCH3
[4+2] + Benzene, 80 °C
COOCH3 COOCH3
OAc OAc Diene Dienophile Adduct Cycloaddition reactions involve bond formation at the ends of both the reacting molecules. This requires proper orientation of orbitals so that effective overlap may give rise to product formation. Reactions where the new bonds being formed are on the same surface are called suprafacial on that component. For the [4+2] cycloaddition reaction, since the new bonds are being formed at the same surface so the reaction is suprafacial on both the diene and dienophile as well. Following are various arrangements of orbitals in [4+2] π system that may give rise to suprafacial and antarafacial orbital overlap to give rise to bond formation.
2 1 2 1 1' 1' 3 3 Suprafacial components 4 2' 2' 4
2 1 2 1 1' 1' 3 3 Antarafacial components 4 2' 4 2'
Orbital orientation for [4+2] cycloaddition
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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On the other hand, antarafacial reaction requires bond formation between orbitals at two different surfaces. Almost all pericyclic cycloaddition reactions go by suprafacial mode on both the components as antarafacial overlap would require a most unusually long and flexible conjugated system. This suprafacial approach therefore makes stereochemistry of products predictable. That is, if the diene with substituents at each end forms new bonds to one surface, the product will have a preserved stereochemistry.
1,3 dipolar cycloaddition are another important class of cycloaddition reactions. In this reaction, molecules with 1,3 dipoles (azides, ozone, nitro compounds) react with alkenes or alkynes or their hetero atom substituted analogues in a [3+2] cycloaddition fashion, giving rise to a cyclic products. As an example of [3+2] cycloaddition, substituted ethyne undergoes 1,3-dipolar addition with azides to give triazoles. .
N N N N 0 °C, 12-16h 98 % COOMe
COOMe
For photochemical cycloaddition if the total number of electrons is 4n then the cycloaddition is feasible. As a result, alkenes give four member ring in photo cycloaddition reactions by self coupling or by cross coupling.
Chelotropic reactions are a special group of cycloaddition in which the two bonds are made or broken to the same atom. Thus sulfur dioxide adds to butadiene to give an adduct, for which the sulfur has provided a lone pair to one of the σ bonds and has received electrons in the formation of the other.
+ :SO2 SO2
It is an oxidative addition to the sulfur dioxide, changing oxidation state of sulfur from +4 to +6.
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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3.3 Sigmatropic shift
Sigmatropic rearrangements are a class of pericyclic reactions defined by the migration of a σ bond adjacent to one or more π systems, with the π systems becoming reorganized in the process. In the reaction the total number of σ or π-bonds does not change as the reactant and the product have the same number of bonds. The σ bond that migrates may be in the middle of the system or at the end of the system. These reactions are intra-molecular in nature and generally do not require a catalyst for their completion. These type of rearrangement reactions are labelled by using two numbers which are set in brackets [i, j], these numbers refer to the relative distance (in atoms) at each end of the σ-bond which has moved. Sigmatropic rearrangements [1, n] are common for hydrogen atom shift with known examples of n = 2, 3, 4, 5, 6, 7 and even for longer chains.
2 3 R R 1 [1, 3]
H H 3 R 4 R 2 [1, 5] 5 1 H H 4 5 R 3 R 6 [1, 7] 2 7
H H 1
If the hydrogen leaves one surface of the conjugated system, and arrives at the other end of the same surface, the reaction is said to be suprafacial. On the other hand, if the hydrogen leaves one surface and arrives on the opposite surface, it is called antarafacial reaction.
For these reactions the feasibility of reactions due to stereo chemical constrains is governed by the total number of π electrons present in the substrate and mode of reaction. If the total number of π electrons is (4n+2) than suprafacial pathway is allowed and if the total number of π electrons is 4n, than antarafacial pathway is allowed.
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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The [3,3] sigmatropic rearrangement of 1,5-dienes or allyl vinyl ethers, known respectively as the Cope and Claisen rearrangements, are among the most common and important sigmatropic reactions.
O O OH
250 °C [3, 3] shift
H C H C 3 3 H3C
CH CH 3 3 CH3
Claisen rearrangement
H
CH3 120 °C CH O 3 [3, 3] shift O
O CH3 Cope rearrangement
3.4 Group transfer reactions
Unlike all the pericyclic reactions that we have discussed so far, group transfer reactions involves a pericyclic process where one or more atoms/group of atoms gets transferred from a molecule to another. Therefore, group transfer reactions do not have a specific conversion of π bonds into σ bonds or vice versa. Group transfer reactions are less common than other types of pericyclic reactions. Like all other pericyclic reactions, they too are concerted and follow the Woodward- Hoffmann rules. Ene reaction is among the most studied example of group transfer reactions.
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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The reaction between an alkene which has an allylic hydrogen which is known as the ene and a compound containing a multiple bond i.e the enophile is known as ene reaction which is also termed as Alder-ene Reaction. They resemble [1, 5] sigmatropic rearrangement since a σ bond moves, and they also resemble cycloadditions like Diels-Alder reaction, with one of the π bond of the diene being replaced by a σ bond. Nevertheless, since the reaction is bimolecular and no ring is formed, they are neither sigmatropic shifts nor cycloaddition reactions. Following are examples of ene reactions.
R H COOMe R COOMe R
230 °C, 50h +
COOMe AlCl3 O H COOMe + 25°C, 48h OMe
CH2
Electron withdrawing groups on the enophile and electron donating groups on the ene favor the reaction. Lewis acid catalyst such as AlCl3 also lead to rate enhancement for ene reactions.
4. Woodward Hoffmann rules and Pericyclic reactions
Out of the four types of pericyclic reactions, three types of reactions can be distinguished by the number of σ bonds made or broken. The following diagram gives a summary of number of bonds formed or broken.
Another unifying theme for pericyclic reaction is the Woodward-Hoffmann rules that govern feasibility and stereospecificity of pericyclic reactions. According to the Woodward-Hoffmann rules, the reactions in which symmetry of molecular orbital (MO) is conserved involve a relatively low energy transition state and thus are symmetry allowed. In contrast, in the reactions where symmetry of orbitals is destroyed by bringing one or more orbitals out of phase, the energy CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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of transition state becomes too high because of antibonding interaction & therefore reaction becomes symmetry forbidden.
Another important rule is the fact that thermally allowed reactions are forbidden photochemically and vice versa. Also the products formed as a result of thermal tractions have opposite stereochemistry than products of a photochemical reaction.
Table 1: Woodward-Hoffmann selection rules applied to various pericyclic reactions
Thermal Light Electrocyclic reaction 4n Con Dis 4n+2 Dis Con Cycloaddition reaction [p+q] 4n ps+qa or pa+qs ps+qs or pa+qa 4n+2 ps+qs or pa+qa ps+qa or pa+qs Sigmatropic shift [i, j] 4n is+ja or ia+js is+js or ia+ja 4n+2 is+js or ia+ja is+ja or ia+js
Here a; antarafacial, s; suprafacial
It is important to note that symmetry forbidden reaction might as well proceed if sufficient energy is provided to the reaction.
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions
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5. Summary
Ø Pericyclic reactions are a group of reactions that takes place via a cyclic transition state in a concerted fashion. Ø Pericyclic reactions are induced either thermally or photochemically. Ø Pericyclic reactions are highly stereospecific. Ø Pericyclic reactions are classified into four different classes namely; electrocyclic reactions, cycloaddition reactions, sigmatropic rearrangements and group transfer reactions. Ø Electrocyclic reactions are characterized by creation of rings from open chain conjugated systems or opening of cyclic molecules under ring strain. Ø The stereochemistry of electrocyclic reactions is decided by conrotatory or disrotatory motion of orbitals for effective overlap. Ø Cycloaddition reaction involves concerted combination of two π electron system to form a cyclic product. Ø Stereospecificity in cycloaddition reactions is maintained by suprafacial or antarafacial interactions of orbital overlap. Ø Sigmatropic reactions are defined by movement of a σ bond adjacent to one or more π systems with reorganization of π system in the process. Ø Group transfer reactions involve transfer of one or more groups or atoms from one molecule to another in a pericyclic reaction fashion. Ø Woodward-Hoffmann rules governs all the pericyclic reactions. Ø A reaction forbidden by Woodward-Hoffmann rule may still take place with input of large amount of energy.
CHEMISTRY PAPER No. 9; Organic Chemistry-III MODULE No. 27; Classification of pericyclic reactions