Pericyclic Reactions Part 4: Electrocyclizations (Conrotatory/Disrotatory and Nazarov Cyclizations)

Professor Dave Explains

30 Apr 202107:27

EducationalLearning

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TLDRThis tutorial explores pericyclic reactions, focusing on electrocyclizations, which involve the formation or opening of rings through the rearrangement of pi and sigma bonds. It discusses the reversible nature of these reactions, their stereochemistry governed by frontier orbital theory, and the specific rules for 6-electron and 4-electron cyclizations. The script also highlights a synthetic technique involving a double electrocyclization/Diels-Alder cascade, demonstrating the power and stereoselectivity of these reactions in constructing complex molecular structures, including the Nazarov cyclization as an example of creating five-membered rings.

Takeaways

🔬 The script discusses pericyclic reactions, starting with [4 + 2] cycloadditions like the Diels-Alder reaction, where two molecules form a cyclic compound with two new sigma bonds.
🔄 It then moves on to [3,3] sigmatropic shifts, where a sigma bond is broken and reformed in a new location through a pi cloud.
💫 The concept of 6-electron electrocyclization is introduced, where a new ring forms intramolecularly with the creation of one sigma bond and the loss of one pi bond, exemplified by 1,3,5-hexatriene.
↔️ Electrocyclizations are reversible, allowing for both ring formation and ring opening, with equilibrium typically favoring ring formation due to the stronger sigma bond.
🧬 Stereochemistry plays a crucial role in pericyclic reactions, and the script explains how the stereochemistry of electrocyclizations can be understood using frontier orbital theory.
🔍 For 6-electron cyclizations, a disrotatory motion of the triene termini is necessary for sigma bond formation, resulting in cis substituents in the product.
🚫 If the central double bond is E in an E, Z, Z triene, cyclization cannot occur, highlighting the importance of substrate geometry in these reactions.
🔬 4-electron cyclizations are less common due to anti-aromatic transition states and ring strain but are possible, as demonstrated with an E,E-diene undergoing conrotatory motion.
🔄 The equilibrium in 4-electron cyclizations leans more towards the reactant than the product, which can be exploited for further chemical reactions.
🌀 The script describes a double electrocyclization/Diels-Alder cascade, showcasing how multiple reactions can occur sequentially to yield complex products with high stereoselectivity.
📚 The Nazarov cyclization is highlighted as an important example of forming five-membered rings, involving protonation of carbonyls and conrotatory cyclization.
🛠️ Electrocyclizations are presented as a powerful synthetic tool in the laboratory, enabling the production of rings of various sizes with strong stereoselectivity.

Q & A

What is a [4 + 2] cycloaddition reaction?
-A [4 + 2] cycloaddition reaction, such as the Diels-Alder reaction, involves the combination of two separate molecules to form a cyclic compound with the generation of two new sigma bonds.
What is the significance of [3,3] sigmatropic shifts in pericyclic reactions?
-[3,3] Sigmatropic shifts are pericyclic reactions where a single sigma bond is broken and reformed in a new location via a pi cloud, leading to a change in the molecule's structure without altering the overall molecular formula.
What is a 6-electron electrocyclization reaction?
-A 6-electron electrocyclization is a pericyclic reaction where a new ring forms intramolecularly by the production of one sigma bond and the loss of one pi bond, as exemplified by the reaction involving 1,3,5-hexatriene.
Why is the equilibrium in electrocyclization reactions typically in favor of ring formation?
-The equilibrium in electrocyclization reactions usually lies towards ring formation because the process involves the replacement of a weaker pi bond with a stronger sigma bond.
What is the role of stereochemistry in electrocyclization reactions?
-Stereochemistry plays a crucial role in electrocyclization reactions as it dictates the spatial arrangement of atoms in the product. It is governed by specific rules and can be explained using frontier orbital theory.
What is the disrotatory fashion in the context of 6-electron cyclizations?
-In 6-electron cyclizations, the disrotatory fashion refers to the rotation of the termini of the triene in opposite directions to generate in-phase direct overlap for the formation of a new sigma bond, resulting in cis substituents in the product.
Why are 4-electron cyclizations less common compared to other electrocyclizations?
-4-electron cyclizations are less common due to the anti-aromatic character of the transition state and the ring strain associated with the formation of four-membered rings.
What is the conrotatory fashion in the context of 4-electron cyclizations?
-In 4-electron cyclizations, the conrotatory fashion refers to the rotation of the termini of the diene in the same direction to achieve in-phase direct overlap for the formation of a new sigma bond, resulting in a trans cyclobutene.
How can the equilibrium of electrocyclization reactions be utilized in synthetic chemistry?
-The direction of the equilibrium in electrocyclization reactions can be exploited to perform interesting chemistry, such as the conversion of cyclobutene to a diene, which can then participate in Diels-Alder reactions with other molecules like maleic anhydride.
What is the significance of the double electrocyclization/Diels-Alder cascade reaction?
-The double electrocyclization/Diels-Alder cascade reaction is significant because it allows for the rapid succession of three reactions to yield a complex polycyclic product with high stereoselectivity, determined by the rules of the reactions involved.
What is the Nazarov cyclization and how does it differ from other electrocyclizations?
-The Nazarov cyclization is a specific type of electrocyclization that involves a strong acid and results in the formation of a cyclopentenone ring. It differs from other electrocyclizations by involving protonation of a carbonyl group and proceeding through a conrotatory cyclization followed by elimination and tautomerization steps.
How do electrocyclizations contribute to the synthesis of different ring sizes?
-Electrocyclizations contribute to the synthesis of different ring sizes by allowing the formation of rings through various substrates and charge configurations, often with strong stereoselectivity, which is invaluable for creating complex molecular structures in the laboratory.

Outlines

00:00

🔬 Pericyclic Reactions and Electrocyclizations

This paragraph delves into pericyclic reactions, focusing on electrocyclizations. It begins with an overview of [4+2] cycloadditions like the Diels-Alder reaction, which involves the formation of a cyclic compound through the creation of two sigma bonds. The discussion then shifts to [3,3] sigmatropic shifts and introduces the concept of 6-electron electrocyclizations, exemplified by the transformation of 1,3,5-hexatriene into a six-membered ring. The paragraph highlights the reversibility of these reactions and the preference for ring formation due to the substitution of a weaker pi bond with a stronger sigma bond. Stereochemistry is addressed through frontier orbital theory, with specific rules for [4+2] and 6-electron cyclizations, including the disrotatory and conrotatory fashions of bond formation. The paragraph concludes with an exploration of 4-electron cyclizations, their challenges due to anti-aromatic character and ring strain, and a creative application involving the reaction of cyclobutene with maleic anhydride, leading to a complex polycyclic structure through a series of electrocyclizations and Diels-Alder reactions.

05:04

🌀 Double Electrocyclization/Diels-Alder Cascade and Nazarov Cyclization

The second paragraph discusses a sophisticated sequence of reactions known as a double electrocyclization/Diels-Alder cascade, which results in a product with eight determined chiral centers, showcasing the high stereoselectivity of these reactions. It also touches on the possibility of forming five-membered rings through the Nazarov cyclization, a process that involves protonation of carbonyls by strong acids, followed by cyclization and tautomerization to yield cyclopentenone. The paragraph emphasizes the synthetic utility of electrocyclizations, which allows for the creation of rings of various sizes with strong stereoselectivity, a valuable asset in laboratory chemistry. The summary concludes the survey of pericyclic reactions, highlighting their power and versatility in organic synthesis.

Mindmap

Keywords

💡Pericyclic reactions

Pericyclic reactions are a class of organic reactions that involve the concerted rearrangement of π and σ bonds. They are central to the script's theme as they encompass a variety of reactions, including electrocyclizations and cycloadditions. The video discusses different types of pericyclic reactions, such as the Diels-Alder reaction and sigmatropic shifts, highlighting their significance in organic synthesis.

💡Diels-Alder reaction

The Diels-Alder reaction is a [4+2] cycloaddition, a specific type of pericyclic reaction where a diene reacts with a dienophile to form a six-membered ring. It is a key concept in the script, illustrating the formation of cyclic compounds through the creation of two new sigma bonds, exemplifying the power of pericyclic reactions in constructing complex molecular structures.

💡[3,3] sigmatropic shifts

[3,3] Sigmatropic shifts are pericyclic reactions where a σ bond moves from one position to another within a molecule, facilitated by a π system. The script mentions this to demonstrate how a single bond's repositioning can lead to significant changes in molecular structure, showcasing the versatility of pericyclic reactions.

💡6-electron electrocyclization

6-electron electrocyclization is a pericyclic reaction where a new ring is formed intramolecularly by the creation of one sigma bond and the loss of one pi bond. The script uses 1,3,5-hexatriene as an example to explain this process, which is crucial for understanding the formation of cyclic structures and the concept of bond reorganization in pericyclic reactions.

💡Stereochemistry

Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules. In the context of the script, it is important for understanding how the spatial orientation of molecules affects pericyclic reactions, such as electrocyclizations, and how these reactions can be controlled to yield specific stereoisomers.

💡Frontier orbital theory

Frontier orbital theory is a concept used to predict the stereochemistry of pericyclic reactions. The script briefly mentions this theory as a tool for understanding the orientation of p orbitals during bond formation in electrocyclizations, providing guidelines for predicting the stereochemical outcomes of these reactions.

💡Disrotatory and conrotatory

Disrotatory and conrotatory refer to the rotational movements of p orbitals during electrocyclization. The script explains that disrotatory motion leads to the formation of a new sigma bond with substituents in a cis configuration, while conrotatory motion results in a trans configuration. These terms are essential for understanding the stereochemical control in pericyclic reactions.

💡4-electron cyclizations

4-electron cyclizations are less common pericyclic reactions that involve the formation of a four-membered ring. The script points out that these reactions are less favored due to the anti-aromatic character of the transition state and ring strain, but they can still be utilized in synthetic chemistry, as demonstrated with the example of E,E-diene.

💡Cyclobutene

Cyclobutene is a specific type of cycloalkene with a four-membered ring. The script uses cyclobutene to illustrate 4-electron cyclizations and to demonstrate how the equilibrium of such reactions can be exploited in synthetic chemistry, such as in the reaction with maleic anhydride to form a diene for a subsequent Diels-Alder reaction.

💡Double electrocyclization/Diels-Alder cascade

A double electrocyclization/Diels-Alder cascade refers to a sequence of reactions involving two electrocyclizations followed by a Diels-Alder reaction. The script describes this process using a tetraene and maleic anhydride to form a complex polycyclic structure, highlighting the synthetic utility and stereoselectivity of pericyclic reactions in creating intricate molecular architectures.

💡Nazarov cyclization

Nazarov cyclization is a specific type of pericyclic reaction that involves the formation of a five-membered ring through the action of a strong acid. The script explains the mechanism of this reaction, which involves protonation, cyclization, and tautomerization steps, resulting in a cyclopentenone product. This reaction exemplifies the diversity of ring sizes that can be synthesized using pericyclic reactions.

Highlights

Introduction to pericyclic reactions, including [4+2] cycloadditions like the Diels-Alder reaction.

Exploration of [3,3] sigmatropic shifts involving the movement of a single sigma bond via a pi cloud.

Discussion of 6-electron electrocyclization, a process forming a new ring through the creation of a sigma bond and loss of a pi bond.

Illustration of 1,3,5-hexatriene's role in forming a six-membered ring through pi bond shuffling.

Reversibility of electrocyclizations and the possibility of electrocyclic ring opening.

Equilibrium preference for ring formation due to pi bond replacement with a stronger sigma bond.

Introduction to stereochemistry in pericyclic reactions and its explanation through frontier orbital theory.

Explanation of disrotatory and conrotatory movements in the context of [4+2] and [4+4] electrocyclizations.

Impact of substituent positions on the stereochemistry of the product in 6-electron cyclizations.

Challenges and possibilities of 4-electron cyclizations due to anti-aromatic transition states and ring strain.

Use of equilibrium direction in electrocyclizations for synthetic chemistry applications.

Demonstration of a double electrocyclization/Diels-Alder cascade for complex polycyclic structure synthesis.

Stereoselectivity in electrocyclizations and its significance in determining chiral centers.

Capability of generating five-membered rings through Nazarov cyclization with strong acid.

Mechanism of Nazarov cyclization involving protonation of carbonyls and cyclization steps.

The power of electrocyclizations as a synthetic tool for producing rings of different sizes with strong stereoselectivity.

Conclusion summarizing the importance of pericyclic reactions in synthetic chemistry and their practical applications.

Transcripts

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Takeaways

Q & A

What is a [4 + 2] cycloaddition reaction?

What is the significance of [3,3] sigmatropic shifts in pericyclic reactions?

What is a 6-electron electrocyclization reaction?

Why is the equilibrium in electrocyclization reactions typically in favor of ring formation?

What is the role of stereochemistry in electrocyclization reactions?

What is the disrotatory fashion in the context of 6-electron cyclizations?

Why are 4-electron cyclizations less common compared to other electrocyclizations?

What is the conrotatory fashion in the context of 4-electron cyclizations?

How can the equilibrium of electrocyclization reactions be utilized in synthetic chemistry?

What is the significance of the double electrocyclization/Diels-Alder cascade reaction?

What is the Nazarov cyclization and how does it differ from other electrocyclizations?

How do electrocyclizations contribute to the synthesis of different ring sizes?