Pericyclic Reactions Part 3: Sigmatropic Shifts (Cope Rearrangement, Claisen Rearrangement)
TLDRThis tutorial delves into sigmatropic shifts, a subclass of pericyclic reactions distinct from cycloadditions. It explains how sigma bonds break and reform, following the 4n + 2 rule for allowed reactions. Examples include the [3,3] shift in 1,5-hexadiene and the Cope rearrangement, which can be driven by ring strain or stabilizing the product. The Oxy-Cope and anionic Oxy-Cope rearrangements, along with the Claisen rearrangement, are highlighted for their synthetic utility in forming carbonyl compounds and expanding rings, with a focus on the impact of bond enthalpies and aromaticity.
Takeaways
- 🔍 Sigmatropic shifts are a subclass of pericyclic reactions, differing from cycloadditions by involving the breaking and reforming of a sigma bond at a different location.
- 🌡️ These reactions typically require elevated temperatures and are governed by the 4n + 2 rule, which is also applicable to cycloadditions.
- 🔢 The [3,3] shift is a specific type of sigmatropic rearrangement where the sigma bond breaks between two carbons three atoms apart in each of two fragments and reforms between carbons three atoms apart.
- 🔄 The transition state of a [3,3] shift is considered aromatic in character, which contributes to its stabilization and allows the reaction to proceed.
- ❌ A [1,3] shift is not favorable due to the anti-aromatic nature of the transition state, making such rearrangements rare.
- 💡 Sigmatropic shifts can be illustrated using 1,5-hexadiene, which undergoes cyclization to shuffle the connectivity of atoms without changing the compound.
- 📉 The equilibrium of sigmatropic shifts can be influenced by the presence of substituents, leading to a preference for one structural form over another.
- 🔑 The synthetic utility of sigmatropic shifts can be enhanced by destabilizing the reactant or stabilizing the product, as seen in the Oxy-Cope rearrangement.
- 🔄 The Claisen rearrangement is a variation of the sigmatropic shift where an oxygen atom replaces a carbon atom, resulting in the formation of a carbonyl group and favoring the product side of the equilibrium.
- 🧪 The Claisen rearrangement can be driven by the formation of a stable enol which tautomerizes to a carbonyl compound, even at the cost of momentarily breaking aromaticity.
- 📚 Other types of sigmatropic shifts, such as the [1,5] hydride shift, exist but are less synthetically useful, though they still result in stable conjugated systems.
Q & A
What are cycloaddition reactions and how do they differ from sigmatropic shifts?
-Cycloaddition reactions, such as the Diels-Alder reaction, involve the formation of six-membered or five-membered rings through a single concerted step, forming two new sigma bonds at the expense of pi bonds. Sigmatropic shifts, on the other hand, involve the breaking and reforming of a sigma bond at a different location, and these reactions are subject to the 4n + 2 rule.
What is the significance of the 4n + 2 rule in pericyclic reactions?
-The 4n + 2 rule dictates which pericyclic reactions, including cycloadditions and sigmatropic shifts, are allowed. It states that reactions involving 4n + 2 pi electrons are allowed to proceed, leading to stable transition states.
Can you explain the concept of a [3,3] sigmatropic shift using the example of 1,5-hexadiene?
-A [3,3] sigmatropic shift is a reaction where a sigma bond between two carbons moves to a new position three carbons away in each of the two fragments involved. In the case of 1,5-hexadiene, heating the compound leads to cyclization and a shift in the sigma bond, resulting in a change in the connectivity of the atoms without altering the overall compound.
Why is a [1,3] shift not favorable according to the script?
-A [1,3] shift is not favorable because it would involve four pi and two sigma electrons, which totals to six, an anti-aromatic number. This makes the process energetically unfavorable and rarely observed.
What is a degenerate system in the context of sigmatropic shifts?
-A degenerate system in sigmatropic shifts refers to a scenario where the product of the reaction is the same as the starting material. This can only be differentiated by isotopic labeling or other means, and results in a one-to-one mixture with chair-like transition states.
How can the synthetic utility of sigmatropic shifts be enhanced?
-The synthetic utility of sigmatropic shifts can be enhanced by destabilizing the reactant or stabilizing the product. For example, incorporating ring strain or forming a more stable product through bond enthalpies can drive the reaction in a unidirectional manner.
What is the Cope rearrangement and under what conditions does it usually occur?
-The Cope rearrangement is a type of sigmatropic shift that involves the rearrangement of a 1,5-diene. It usually requires high temperatures, around 200 degrees Celsius, to proceed and can lead to an equilibrium that favors one form over the other.
How does the Oxy-Cope rearrangement differ from the Cope rearrangement?
-The Oxy-Cope rearrangement is a variation of the Cope rearrangement where a hydroxyl group is involved, leading to the formation of an enol which tautomerizes to a carbonyl compound. This modification stabilizes the product and can make the reaction favorable even at room temperature.
What is the Claisen rearrangement and how is it used in synthesis?
-The Claisen rearrangement is a type of sigmatropic shift where an oxygen atom replaces one of the carbon atoms in the original molecule, leading to the formation of an aldehyde. It is used to synthesize gamma-delta unsaturated carbonyl compounds and is driven by the stability of the carbonyl group.
How do substituents affect the Claisen rearrangement and the configuration of the resulting olefin?
-In the Claisen rearrangement, substituents prefer to occupy pseudo-equatorial positions in the chair-like transition state, which influences the configuration of the resulting olefin. This typically results in the formation of E-configured olefins rather than Z-configured ones.
Can you provide an example of how aromaticity can be temporarily destroyed in a Claisen rearrangement?
-Yes, the script mentions a case where a phenyl ether undergoes a [3,3] Claisen rearrangement despite the need to momentarily break the aromaticity of the benzene ring. The driving force for this is the subsequent tautomerization that restores aromaticity.
What is the significance of bond enthalpies in the Oxy-Cope rearrangement?
-Bond enthalpies play a crucial role in stabilizing the product of the Oxy-Cope rearrangement. The strong carbon-oxygen double bond in the resulting aldehyde contributes to the overall stability and drives the reaction towards product formation.
How do anionic Oxy-Cope rearrangements differ from the standard Oxy-Cope rearrangement?
-Anionic Oxy-Cope rearrangements involve an oxyanion instead of a hydroxyl group. The anion is initially localized on the oxygen, making the starting material unstable. After the shift, the anion becomes resonance stabilized, which is prevalent in synthesis and can occur even at room temperature.
Outlines
🔍 Sigmatropic Shifts and Cycloaddition Reactions
This paragraph introduces sigmatropic shifts as a subclass of pericyclic reactions, contrasting them with cycloadditions such as the Diels-Alder reaction. Sigmatropic shifts involve the migration of a sigma bond to a new position, often occurring at elevated temperatures and following the 4n + 2 rule. The paragraph uses 1,5-hexadiene as an example to illustrate a [3,3] shift, explaining the numbering system and the aromatic transition state that stabilizes the reaction. It also discusses the unfavorability of a [1,3] shift due to its anti-aromatic nature. The concept of degenerate systems is introduced, where the product and starting material are the same, and the impact of substituents on shifting the equilibrium towards one structure is explained. The paragraph concludes with an introduction to the Cope rearrangement, which requires high temperatures and the synthetic utility of the technique, including strategies to enhance its effectiveness through ring strain and product stabilization.
🌡️ Synthetic Applications of Sigmatropic Shifts
The second paragraph delves into the synthetic applications of sigmatropic shifts, focusing on the Oxy-Cope rearrangement and its variations. It describes how the presence of a hydroxyl group can lead to the formation of an enol and subsequently an aldehyde, highlighting the role of bond enthalpies in stabilizing the product. The paragraph also discusses the anionic Oxy-Cope rearrangement, where an oxyanion is involved, and how this can occur at room temperature due to the resonance stabilization of the anion. An example of ring expansion through the Oxy-Cope rearrangement is provided, involving a substituted cyclobutanone and a vinyl Grignard reagent. The Claisen rearrangement is introduced as a method for synthesizing gamma-delta unsaturated carbonyl compounds, with a focus on the impact of substituent positions and olefin configurations. The paragraph concludes with a discussion on the [1,5] hydride shift and its synthetic utility, emphasizing the driving force of conjugation and the potential for aromaticity restoration in certain cases.
Mindmap
Keywords
💡Cycloaddition reactions
💡Pericyclic reactions
💡Sigmatropic shifts
💡[3,3] shift
💡4n + 2 rule
💡Cope rearrangement
💡Oxy-Cope rearrangement
💡Claisen rearrangement
💡Aromaticity
💡E and Z configuration
Highlights
Cycloaddition reactions, such as Diels-Alder, involve the formation of six-membered or five-membered rings in a single concerted step.
Sigmatropic shifts are a subclass of pericyclic reactions where a sigma bond is broken and reformed at a distance.
Sigmatropic shifts occur at elevated temperatures and follow the 4n + 2 rule for allowed reactions.
1,5-hexadiene undergoes cyclization upon heating, demonstrating a sigma bond shift with connectivity changes.
The [3,3] shift in 1,5-hexadiene is an example of a sigmatropic rearrangement.
Sigma bond shifts can be tracked by numbering the carbons involved, as seen in the [3,3] shift.
The [3,3] shift is allowed as it involves six electrons, with a transition state that can be aromatic.
A [1,3] shift is not favorable due to its anti-aromatic nature and is rarely observed.
Degenerate systems in sigmatropic shifts result in a 1:1 mixture of starting material and product.
Substituents can affect the equilibrium of sigmatropic shifts, favoring one structure over another.
The Cope rearrangement is a type of sigmatropic shift that requires high temperatures for reaction.
Organic chemists have developed methods to enhance the synthetic utility of sigmatropic shifts.
Incorporating ring strain or stabilizing the product can make sigmatropic shifts more favorable.
The Oxy-Cope rearrangement involves the formation of an enol that tautomerizes to a carbonyl group.
Anionic Oxy-Cope rearrangement allows sigmatropic shifts to occur at room temperature.
The Claisen rearrangement is a variation that synthesizes gamma-delta unsaturated carbonyl compounds.
Substituents in Claisen rearrangements prefer pseudo-equatorial positions for stability.
The driving force of carbonyl formation can overcome the loss of aromaticity in certain rearrangements.
Phenyl and vinyl ethers are suitable substrates for Claisen rearrangement due to aromaticity restoration.
Other sigmatropic shifts, like the [1,5] hydride shift, involve the migration of a hydride group.
Transcripts
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