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Subject Chemistry
Paper No and Title 9; Organic Chemistry-III Module No and Title 32 : Sigmatropic rearrangements
Module Tag CHE_P9_M32
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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TABLE OF CONTENTS
1. Learning Outcomes 2. Introduction 3. Nomenclature and stereochemistry of sigmatropic rearrangements 4. Reactions involving sigmatropic rearrangements 4.1 [1, 2] shifts 4.2 [1, 3] shifts 4.3 [1, 5] shifts 4.4 [1, 7] shifts 4.5 [3, 3] shifts 4.6 [5, 5] shifts 5. Summary
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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1. Learning Outcomes
After studying this module, you shall be able to
• Know what are sigmatropic rearrangements • Learn nomenclature of sigmatropic rearrangements • Identify rules governing feasibility and stereochemistry of sigmatropic rearrangements • Evaluate various order sigmatropic shifts • Analyze synthetic utility of sigmatropic rearrangements
2. Introduction
Sigmatropic rearrangements (sigma designation from single carbon-carbon bonds and tropos (Greek) meaning turn) are a class of unimolecular pericyclic reactions. This class of reactions are characterized by the migration of a σ bond adjacent to one or more π systems, to a new position in a molecule, 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. Following is an example of [3, 3] sigmatropic shift.
2 2 3 R 1 3 R 1 3, 3 shift
1 3 1 3 R R 2 2
3. Nomenclature and stereochemistry of sigmatropic reactions
Sigmatropic rearrangements are classified based on an order which is expressed by a set of two digits in brackets: [i, j], these numbers are determined by counting the atoms over which each end of the σ bond has moved. Each of the original termini is given the number 1. For a sigmatropic shift if the sum of i and j is an even number, it indicates the involvement of a neutral, all C atom chain. If on the other hand, the sum is odd it indicates involvement of a charged C atom or a heteroatom lone pair replacing the carbon to carbon double bond.
When determining the order of a sigmatropic shift involving a hydrogen atom migration, it is important to count across all atoms of the chain involved in the reaction rather than only across the closest atoms. Following are the examples of some of the sigmatropic shift reactions.
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. For these reactions the feasibility of reactions due
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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to stereochemical constrains is governed by the total number of π electrons present in the substrate. 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.
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
Antarafacial and suprafacial are terms that are described in Woodward-Hoffmann rules, to describe relative orientations of molecular orbitals for bond formation. Woodward-Hoffmann rules are based on conservation of orbital symmetry. In a sigmatropic shift, if the hydrogen atom or migrating group 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 atom or migrating group leaves one surface and arrives on the opposite surface, it is called antarafacial reaction. The [1, 5] hydrogen shift involves a suprafacial reaction, where the hydrogen leaves the upper surface at C-1 and arrives at the upper surface at C-5 as shown below.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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This involves a 6 member cyclic transition state. In the transition state the hydrogen atom is in contact with both ends of the chain at the same time. This calls for the molecule to adopt the cisoid conformation as a must requirement.
For the [1, 7] shift with 8 electrons, antarafacial pathway is taken up, in which the hydrogen atom leaves the upper surface of C-1 and arrives on the lower surface at C-7.
To understand the stereochemistry of products formed as a result of sigmatropic rearrangements, Woodward-Hoffmann rules can be applied to various substrates under thermal or photochemical reaction conditions. In the following diagram some possible theoretical combinations are shown. Here “a” stands for antarafacial, “s” for suprafacial, “r” for retention and “i” for inversion.
C Heat hν Heat hν Heat hν C C
ar sr sr ar ar sr si ai ai si si ai
[1, 3] [1, 5] [1, 7]
C C C sr ar ar sr sr ar ai si si ai ai si
[1, 2] [1, 4] [1, 6]
C C C ar sr sr ar ar sr si ai ai si si ai
[1, 2] [1, 4] [1, 6]
In practice, these rules can be summed up as;
• For supra/supra or antara/antara [i, j]-sigmatropic shifts, if i + j = (4n + 2), they are thermally allowed and if i + j = 4n, they are photochemically allowed.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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• For supra/antara [i, j]-sigmatropic shifts, if i + j = 4n, they are thermally allowed, and if i + j = (4n + 2) they are photochemically allowed.
4. Reactions involving sigmatropic shifts
4.1 [1, 2] shift
Let us consider [1, 2] shifts involving ionic conjugated systems. A number of name reactions follow such migrations. For example, in the reaction, if the migration terminus, migration origin and migrating groups all are the carbon atoms then the reaction is known as Wagner-Meerwein rearrangement. If the migration terminus is a nitrogen atom it may be a Curtius, Beckmann or Losson rearrangement.
When the migration terminus is oxygen atom, it is characteristic Baeyer-Villiger reaction. All these reactions are known to take place with retention of configuration in the migrating group. In contrast [1, 2] shifts in anions are rare as they are symmetry forbidden.
In Stevens rearrangement a [1, 2] shift reaction occurs in an anionic substrate.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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4.2 [1, 3] shift
Thermally the antarafacial shift of carbon is symmetrically allowed with double bond acting as the antarafacial component but this does not happen because of difficulties of achieving effective orbital overlap. In practice, suprafacial shift of carbon occurs with inversion of configuration, where σ bond takes up the role of antarafacial component. This was not possible for hydrogen
atom as it has only s orbital and lacks p-orbital. If we look at the orbital picture it becomes clear that the newly formed bond is a little longer and thus should not be very plausible.
Symmetry allowed but barely Takes place with silyl group reasonable migration
Nevertheless, the reaction has been shown to take place for suprafacial shift of silyl groups at 500 °C with long Si-C bonds making it feasible.
Photochemically, a suprafacial shift with retention of configuration in the migrating group is allowed and a number of such examples are known. A reversible [1, 3] shift in verbenone (a plant derived terpene) to give chrysanthenone is such an example of photochemical alkyl shift.
Another example of photochemically allowed [1, 3] sigmatropic shift in steroids is shown below.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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4.3 [1, 5] shift
As compared to [1, 3] shifts, in the case of [1, 5] shift the suprafacial thermal rearrangements are quite common, while photochemical rearrangements are rarely observed. Following reaction gives an example of [1, 5] shift.
Antarafacial [1, 5] hydride shifts are possible although less commonly observed under photochemical irradiation.
[1, 5] migration of functional groups such as methyl and phenyl are thermally allowed.
Walk rearrangements: In a bicyclic molecule, the migration of a divalent group, such as O, S, N R or CR2, which is part of a three-member ring, is commonly referred to as a walk rearrangement. This is a [1, n] sigmatropic shift. An example of such a rearrangement is shown below.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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The [1, 5] shift, in the walk rearrangement of norcaradienes is expected to proceed suprafacially with a retention of stereochemistry.
4.4 [1, 7] shift
Photochemical [1, 7] - shifts are suprafacial and there are many examples of such reactions.
4.5 [3, 3] shift
These are synthetically useful and there are several name reactions that fall under [3, 3] sigmatropic shift category. The popularity of [3, 3]-sigmatropic rearrangements in organic synthesis is due to the ability of such reactions to generate stereogenic centers from the sp2- hybridized carbons. Claisen and Cope rearrangements are important name reactions of this class; however, they will be discussed in the next module. Following are a few examples of other most common [3, 3] sigmatropic rearrangement reactions.
Fisher Indole synthesis: It is a chemical reaction that involves synthesis of the aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone. This reaction takes place under acidic conditions.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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Carroll rearrangement: Is a reaction that involves transformation of a β-keto allyl ester into a α- allyl-β-ketocarboxylic acid. This substrate undergoes decarboxylation giving γ,δ-allylketone as the final product.
Ireland-Claisen rearrangement: This is an organic reaction of great utility as it creates two stereogenic centers with high levels of specificity arises as the transition state involves a chair like structure
Mislow-Evans rearrangement: It is a [2, 3] type of sigmatropic rearrangement reaction that results in the formation of allylic alcohols from allylic sulfoxides. The reaction is useful for creating particular stereoisomers of the alcohol as it is highly diastereoselective and the chirality at the sulfur atom can be transmitted to the carbon next to the oxygen in the product through a sulfenate intermediate which involves suprafacial shift of functionality.
4.6 [5, 5] shift
Now let us consider the 10 electron systems that include [5, 5] sigmatropic shifts.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements
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4 2 3 5 1 [5, 5]
5 3 1 4 2
The [5, 5] sigmatropic rearrangement of 2, 4-pentadienylphenyl ethers can be considered a homologous to Claisen rearrangement.
1 OH 1 O O 2
2 3 4 3 [5, 5]
4 5
5 H
5. Summary
Ø One of the important class of pericyclic reactions is sigmatropic reactions. Ø Sigmatropic rearrangements involve migration of a σ bond adjacent to a π bond(s) system leading to reorganization of the π bond system. Ø In the reaction the total number of σ or π-bonds does not change. Ø Sigmatropic rearrangements are classified based on an order which is expressed by a set of two digits in brackets [i, j]. Ø The shifts can be suprafacial or antarafacial depending upon the number of electrons and reaction conditions. Ø The products’s stereochemistry in case of sigmatropic reactions is anticipated using Woodward-Hoffmann rules. Ø For supra/supra or antara/antara [i, j]-sigmatropic shifts, if i+j = (4n + 2), they are thermally allowed and if i + j = 4n, they are photochemically allowed. Ø For supra/antara [i, j]-sigmatropic shifts, if i + j = 4n, they are thermally allowed, and if i+j = (4n + 2) they are photochemically allowed. Ø Some sigmatropic rearrangements involve polar components in the substrate. Ø [3, 3] sigmatropic shifts are involved in a number of name reactions such as Claisen rearrangement, Fisher Indole synthesis, and Carroll rearrangement.
CHEMISTRY PAPER No.9 : Organic Chemistry-III MODULE No. 32 : Sigmatropic rearrangements