Sigmatropic rearrangements are a crucial class of pericyclic reactions in organic chemistry. These reactions involve the migration of a σ bond across a π system, resulting in the reorganization of bonding electrons. Understanding different types of sigmatropic rearrangements helps predict reaction outcomes and design synthetic strategies.
The mechanism of sigmatropic rearrangements follows a concerted process, governed by orbital symmetry principles described by the . These reactions involve simultaneous bond breaking and formation, leading to high and predictable product stereochemistry. The concept of suprafacial vs antarafacial shifts is essential in understanding the relative orientation of orbitals during rearrangements.
Types of sigmatropic rearrangements
Sigmatropic rearrangements constitute a crucial class of pericyclic reactions in organic chemistry
These reactions involve the migration of a σ bond across a π system, resulting in the reorganization of bonding electrons
Understanding different types of sigmatropic rearrangements aids in predicting reaction outcomes and designing synthetic strategies
[1,3] Sigmatropic rearrangements
Involve the migration of a σ bond over a 3-atom system
Generally thermodynamically unfavorable for carbon systems due to high activation energy
Commonly observed in hydrogen migrations (hydrogen shifts)
Can occur in heteroatom systems (oxygen, nitrogen)
Applications include tautomerization reactions and certain natural product syntheses
[1,5] Sigmatropic rearrangements
Entail the migration of a σ bond over a 5-atom system
Thermodynamically favorable and widely observed in organic synthesis
Proceed through a 6-membered , lowering the activation energy
Common examples include hydrogen shifts in cyclopentadiene systems
Play crucial roles in the biosynthesis of terpenes and steroids
[1,7] Sigmatropic rearrangements
Involve the migration of a σ bond over a 7-atom system
Less common than [1,5] shifts but still synthetically useful
Observed in extended π systems (heptatriene derivatives)
Can be utilized in the synthesis of complex natural products
Often compete with electrocyclic reactions in certain systems
[3,3] Sigmatropic rearrangements
Encompass a group of important reactions including Cope and Claisen rearrangements
Involve the simultaneous breaking and forming of two σ bonds
Proceed through a 6-membered cyclic transition state
Highly stereospecific, preserving stereochemical information
Widely used in organic synthesis for carbon-carbon bond formation
Mechanism of sigmatropic rearrangements
Sigmatropic rearrangements follow a concerted mechanism, meaning bond breaking and formation occur simultaneously
These reactions are governed by orbital symmetry principles, as described by the Woodward-Hoffmann rules
Understanding the mechanism aids in predicting reaction outcomes and designing synthetic strategies
Concerted electron movement
Involves simultaneous breaking and forming of bonds without intermediates
Electrons flow in a cyclic manner, maintaining a closed shell configuration
Results in lower activation energies compared to stepwise processes
Leads to high stereoselectivity and predictable product stereochemistry
Can be visualized using curved arrow notation to show electron movement
Suprafacial vs antarafacial shifts
Describes the relative orientation of orbitals during the rearrangement
Suprafacial shifts occur on the same face of the π system
More common due to better orbital overlap
Observed in [1,5] and [3,3] sigmatropic rearrangements
Antarafacial shifts involve opposite faces of the π system
Less common due to poor orbital overlap
Sometimes observed in [1,3] and [1,7] rearrangements
Determination of facial selectivity depends on orbital symmetry considerations
Orbital symmetry considerations
Based on the during the reaction
Involves analysis of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)
Determines whether a reaction is thermally or photochemically allowed
Helps predict the stereochemical outcome of the rearrangement
Utilizes correlation diagrams to visualize orbital interactions
Woodward-Hoffmann rules
Fundamental principles governing pericyclic reactions, including sigmatropic rearrangements
Developed by Robert Burns Woodward and Roald Hoffmann in the 1960s
Provide a theoretical framework for predicting the feasibility and stereochemistry of pericyclic reactions
Thermal reactions
Occur in the ground state electronic configuration
Follow the rule of (4n+2) electrons for allowed reactions
[1,5] sigmatropic shifts are thermally allowed (6 electrons involved)
[1,3] sigmatropic shifts are thermally forbidden (4 electrons involved)
Thermal reactions often proceed suprafacially due to better orbital overlap
Photochemical reactions
Involve excited state electronic configurations
Follow the rule of 4n electrons for allowed reactions
[1,3] sigmatropic shifts become allowed under photochemical conditions
[1,5] sigmatropic shifts are photochemically forbidden
Can sometimes proceed through antarafacial pathways due to altered orbital symmetry
Correlation diagrams
Graphical representations of orbital energy changes during a reaction
Help visualize the conservation of orbital symmetry
Plot molecular orbitals of reactants and products on the same energy scale
Allowed reactions show smooth connections between reactant and product orbitals
Forbidden reactions display orbital crossings, indicating high activation energy
Cope rearrangement
A of 1,5-dienes
Discovered by Arthur C. Cope in 1940
Reversible reaction that often reaches an equilibrium
Widely used in organic synthesis for carbon-carbon bond formation
Serves as a model system for studying pericyclic reactions
Mechanism and stereochemistry
Proceeds through a chair-like transition state
Concerted process with simultaneous breaking and forming of bonds
Stereospecific reaction preserving the relative stereochemistry of substituents
Follows suprafacial shift mechanism on both components
Rate of reaction influenced by substituents and ring strain
Synthetic applications
Used to create new carbon-carbon bonds and rearrange carbon skeletons
Employed in the synthesis of complex natural products (terpenes, steroids)
Allows for the introduction of unsaturation at specific positions
Can be used to generate cyclohexene rings from acyclic precursors
Valuable tool for creating quaternary carbon centers
Oxy-Cope rearrangement
Variant of the involving an alcohol substituent
Proceeds through an enolate intermediate after rearrangement
Irreversible due to the formation of a stable carbonyl compound
Often performed under anionic conditions to enhance reactivity
Used in the synthesis of medium-sized rings and complex natural products
Claisen rearrangement
A [3,3] sigmatropic rearrangement of allyl vinyl ethers
Discovered by Ludwig Claisen in 1912
Versatile reaction for forming carbon-carbon bonds
Produces γ,δ-unsaturated carbonyl compounds
Widely used in natural product synthesis and pharmaceutical chemistry
Aliphatic Claisen rearrangement
Involves rearrangement of allyl vinyl ethers
Proceeds through a chair-like transition state
Typically requires high temperatures (150-200°C)
Stereospecific reaction with predictable stereochemistry
Used to create quaternary carbon centers and introduce unsaturation
Aromatic Claisen rearrangement
Rearrangement of allyl phenyl ethers
Results in the formation of o-allylphenols
Often followed by a second [3,3] shift (para-)
Used in the synthesis of natural products (eugenol, chavicol)
Can be catalyzed by Lewis acids to lower reaction temperature
Ireland-Claisen rearrangement
Variant of the Claisen rearrangement involving silyl ketene acetals
Proceeds under milder conditions compared to the classical Claisen rearrangement
Allows for greater control over stereochemistry through enolate geometry
Widely used in the synthesis of α,β-unsaturated carboxylic acids
Can be performed asymmetrically using chiral auxiliaries or catalysts
Other important rearrangements
Sigmatropic rearrangements encompass a diverse set of reactions beyond Cope and Claisen
These reactions often involve heteroatoms or aromatic systems
Understanding these rearrangements expands the synthetic toolkit for organic chemists
Benzidine rearrangement
[5,5] sigmatropic rearrangement of N,N'-diaryhydrazines
Competes with the Stevens rearrangement under certain conditions
Useful for introducing substituents ortho to benzylic amines
Mechanism involves ylide formation followed by sigmatropic shift
Wittig rearrangement
[2,3] sigmatropic rearrangement of ethers to alcohols
Initiated by treatment with strong bases (organolithium reagents)
Proceeds through a betaine intermediate
Useful for converting benzyl ethers to ortho-substituted phenols
Can be used in conjunction with other reactions for complex transformations
Stereochemistry in sigmatropic reactions
Sigmatropic rearrangements often display high levels of stereoselectivity
Understanding stereochemical outcomes aids in predicting reaction products
Stereochemistry can be controlled through substrate design and reaction conditions
Retention vs inversion
Refers to the stereochemical fate of migrating groups
Retention maintains the original stereochemistry of the migrating group
Inversion results in opposite stereochemistry of the migrating group
Outcome depends on the type of sigmatropic shift and orbital symmetry considerations
[3,3] rearrangements typically proceed with retention of configuration
Chirality transfer
Process of transferring chiral information from reactants to products
Observed in many sigmatropic rearrangements due to their concerted nature
Allows for the creation of new stereogenic centers with predictable stereochemistry
Useful in asymmetric synthesis and natural product
Can be enhanced through the use of chiral auxiliaries or catalysts
Stereospecificity
Refers to the formation of a single stereoisomer from a single stereoisomeric starting material
Characteristic of many sigmatropic rearrangements due to their concerted mechanism
Allows for precise control over product stereochemistry
Important in the synthesis of complex natural products with multiple stereocenters
Can be used to determine the absolute configuration of unknown compounds
Synthetic applications
Sigmatropic rearrangements serve as powerful tools in organic synthesis
These reactions enable the construction of complex molecular architectures
Understanding their applications aids in designing efficient synthetic routes
Natural product synthesis
Sigmatropic rearrangements used to construct complex carbon skeletons
Employed in the synthesis of terpenes, alkaloids, and other bioactive molecules
Allow for the introduction of specific stereochemistry and functionality
Often used in key steps to rapidly increase molecular complexity
Examples include the synthesis of prostaglandins, vitamin D, and taxol
Pharmaceutical applications
Sigmatropic rearrangements utilized in the synthesis of drug molecules
Enable the creation of specific structural motifs found in pharmaceuticals
Used to introduce chirality and control stereochemistry in drug synthesis
Employed in both discovery chemistry and process development
Applications include the synthesis of anti-inflammatory and anti-cancer drugs
Materials science
Sigmatropic rearrangements applied in the synthesis of functional materials
Used to create polymers with specific properties (conductivity, flexibility)
Employed in the synthesis of liquid crystals and photochromic compounds
Enable the construction of complex molecular machines and switches
Applications in the development of organic electronics and smart materials
Computational studies
Computational methods provide valuable insights into sigmatropic rearrangements
These studies aid in understanding reaction mechanisms and predicting outcomes
Computational approaches complement experimental investigations in organic chemistry
Transition state modeling
Involves calculating the geometry and energy of reaction transition states
Utilizes quantum mechanical methods (DFT, ab initio calculations)
Helps elucidate the detailed mechanism of sigmatropic rearrangements
Provides insights into stereochemical outcomes and regioselectivity
Aids in designing new reactions and optimizing existing processes
Energy profile analysis
Involves mapping the potential energy surface of a reaction
Calculates activation energies and reaction thermodynamics
Helps predict the feasibility and reversibility of sigmatropic rearrangements
Allows comparison of competing reaction pathways
Useful for understanding the effects of substituents and reaction conditions
Reaction rate predictions
Utilizes transition state theory to estimate reaction rates
Considers factors such as temperature, solvent effects, and catalysts
Helps in optimizing reaction conditions for synthetic applications
Allows for the prediction of kinetic vs thermodynamic product ratios
Aids in understanding the competition between different reaction pathways
Key Terms to Review (18)
[1,3] sigmatropic rearrangement: A [1,3] sigmatropic rearrangement is a type of molecular rearrangement in which a sigma bond and a pi bond are involved in a migration process, leading to the reorganization of atoms or groups in a molecule. This rearrangement specifically involves the shifting of a substituent from one atom to another that is separated by one single bond, effectively transforming the molecular structure. The concept is essential in understanding how certain reactions can occur through concerted mechanisms and plays a significant role in various synthetic pathways.
[3,3] sigmatropic rearrangement: [3,3] sigmatropic rearrangement is a type of pericyclic reaction where a sigma bond and a π bond rearrange their connectivity through a concerted process, involving a migration of a substituent across a six-membered cyclic transition state. This rearrangement typically involves the movement of two pairs of electrons, allowing for the conversion of starting materials into new products, showcasing the fascinating interplay between molecular orbitals and bonding interactions.
1,5 Sigmatropic Rearrangement: A 1,5 sigmatropic rearrangement is a specific type of molecular rearrangement where a sigma bond is broken and reformed between atoms separated by four other atoms in the same molecule. This process involves the migration of a substituent or atom from one position to another within the molecule, allowing for structural changes that can significantly affect the properties and reactivity of the compound. It is a key concept in understanding how certain organic reactions occur and how molecular rearrangements can lead to different products.
1,7 sigmatropic rearrangement: A 1,7 sigmatropic rearrangement is a type of pericyclic reaction where a sigma bond moves between two atoms while a π bond is formed or broken, specifically involving the migration of a substituent from the first to the seventh position on a carbon chain. This rearrangement typically occurs in the presence of heat or light and can be facilitated by specific catalysts. Understanding this reaction is crucial for grasping the broader concepts of molecular rearrangements and reactivity patterns in organic chemistry.
Carbocation: A carbocation is a positively charged carbon species that has only six valence electrons instead of the usual eight, making it highly reactive and often a key intermediate in many organic reactions. These unstable ions are critical in mechanisms such as sigmatropic rearrangements, where their formation and stability influence the direction and outcome of the reaction. Their reactivity is largely determined by factors like the nature of substituents and sterics around the carbocation.
Claisen rearrangement: The Claisen rearrangement is a type of sigmatropic rearrangement where an allylic ester transforms into a γ,δ-unsaturated carbonyl compound through the migration of the acyl group. This process involves the breaking and forming of bonds in a concerted manner, making it an essential reaction in organic synthesis for creating complex molecules from simpler ones.
Conservation of orbital symmetry: Conservation of orbital symmetry is a principle that states during a chemical reaction, the symmetry of molecular orbitals must be conserved in order for the reaction to occur. This principle is crucial in determining the feasibility and outcome of pericyclic reactions, where the electronic structure plays a significant role in the transition state formation.
Cope Rearrangement: The Cope rearrangement is a [3,3]-sigmatropic rearrangement that involves the migration of a substituent group from one part of a diene to another, resulting in an isomeric product. This reaction is particularly significant because it exemplifies how molecular structure can be altered through the concerted movement of bonds and atoms without intermediates, highlighting the principles of pericyclic reactions and thermal rearrangements.
Electron-withdrawing groups: Electron-withdrawing groups (EWGs) are substituents that pull electron density away from a molecule, typically through resonance or inductive effects. These groups can significantly influence the reactivity and stability of various organic compounds, particularly those containing benzene rings, during reactions like sigmatropic rearrangements or when assessing the basicity of amines.
Frontier Molecular Orbitals: Frontier molecular orbitals refer to the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) in a molecule. These orbitals play a crucial role in determining the reactivity and properties of molecules, particularly during reactions such as sigmatropic rearrangements, where electrons are rearranged, leading to structural changes in the molecule.
Nucleophiles: Nucleophiles are species that donate an electron pair to form a chemical bond in a reaction. They are often characterized by their negative charge or lone pairs of electrons, which enable them to attack positively charged or electron-deficient centers, making them crucial in many chemical reactions. Their role is particularly significant in rearrangements and synthetic strategies, where they can facilitate the transformation of molecular structures.
Overlap Criteria: Overlap criteria refer to the specific conditions that must be satisfied for a sigmatropic rearrangement to occur, involving the proper alignment and interaction of orbitals during the transition state. This concept ensures that the necessary molecular orbitals can overlap effectively, allowing for the reorganization of bonds while maintaining the overall connectivity of atoms. Understanding these criteria is crucial for predicting reaction outcomes and mechanisms in sigmatropic rearrangements.
Regioselectivity: Regioselectivity refers to the preference of a chemical reaction to occur at one location over others in a molecule, leading to the formation of a specific structural isomer. This concept is critical in understanding how different reactions can yield varying products based on the reactive sites available in the starting materials, affecting synthesis and reactivity in organic chemistry.
Stereoselectivity: Stereoselectivity is the preference of a chemical reaction to produce one stereoisomer over another when multiple stereoisomers are possible. This property is crucial in organic chemistry as it directly influences the biological activity and properties of the compounds formed, making it vital for the development of pharmaceuticals and other chemical products.
Target-oriented synthesis: Target-oriented synthesis is a strategic approach in organic chemistry that focuses on designing synthetic pathways to produce specific target molecules efficiently. This method emphasizes the planning of reactions and intermediates to optimize yield and selectivity, ensuring that the desired compound is synthesized in a systematic manner. By prioritizing the end product, chemists can streamline their processes and minimize by-products.
Total Synthesis: Total synthesis refers to the complete chemical process of constructing complex organic molecules from simpler starting materials, often aiming to replicate natural products. This method allows chemists to understand the intricacies of molecular structures and their reactivity, thus contributing to fields such as pharmaceuticals and materials science.
Transition State: The transition state is a high-energy, unstable configuration of atoms that occurs during a chemical reaction, representing the point at which reactants are transformed into products. This state is critical because it marks the highest energy point along the reaction pathway, and its structure can provide insights into the mechanisms and kinetics of reactions. Understanding transition states helps in predicting reaction outcomes and designing synthetic strategies effectively.
Woodward-Hoffmann rules: Woodward-Hoffmann rules are a set of principles that predict the outcomes of pericyclic reactions based on the conservation of orbital symmetry. They help determine whether certain reactions, such as electrocyclic reactions, sigmatropic rearrangements, and cycloadditions, will occur under thermal or photochemical conditions, guiding chemists in understanding how molecular orbitals behave during these processes.