30.6 Stereochemistry of Cycloadditions
3 min read•may 7, 2024
Cycloadditions are fascinating reactions where two π systems combine to form new σ bonds. The stereochemistry of these reactions is governed by orbital interactions, determining whether bonds form on the same or opposite faces of the reactants.
Understanding stereochemistry is crucial for predicting and controlling product formation. Factors like vs geometry, thermal vs photochemical conditions, and all play key roles in determining reaction outcomes and product structures.
Stereochemistry of Cycloadditions
Suprafacial vs antarafacial geometries
Top images from around the web for Suprafacial vs antarafacial geometries
Solvent Effects on the Mechanistic of Ketene and Halogenated Ketene Cycloadditions with ... View original
Is this image relevant?
4.5. Stereochemistry of reactions | Organic Chemistry 1: An open textbook View original
Is this image relevant?
Flow synthesis of cyclobutanones via [2 + 2] cycloaddition of keteneiminium salts and ethylene ... View original
Is this image relevant?
Solvent Effects on the Mechanistic of Ketene and Halogenated Ketene Cycloadditions with ... View original
Is this image relevant?
4.5. Stereochemistry of reactions | Organic Chemistry 1: An open textbook View original
Is this image relevant?
1 of 3
Top images from around the web for Suprafacial vs antarafacial geometries
Solvent Effects on the Mechanistic of Ketene and Halogenated Ketene Cycloadditions with ... View original
Is this image relevant?
4.5. Stereochemistry of reactions | Organic Chemistry 1: An open textbook View original
Is this image relevant?
Flow synthesis of cyclobutanones via [2 + 2] cycloaddition of keteneiminium salts and ethylene ... View original
Is this image relevant?
Solvent Effects on the Mechanistic of Ketene and Halogenated Ketene Cycloadditions with ... View original
Is this image relevant?
4.5. Stereochemistry of reactions | Organic Chemistry 1: An open textbook View original
Is this image relevant?
1 of 3
- Suprafacial geometry
- New bonds form on the same face of the π system maintains stereochemistry (cis-butadiene forms cis-cyclobutane)
- Favored in most cycloaddition reactions due to better orbital overlap and lower activation energy
- Antarafacial geometry
- New bonds form on opposite faces of the π system inverts stereochemistry (trans-butadiene forms cis-cyclobutane)
- Less common due to geometric constraints requires a large distance between the termini of the π system (trans-cyclooctene)
Frontier orbital theory in cycloadditions
- Frontier Molecular Orbital (FMO) theory
- Reactivity and stereochemistry determined by the interaction of the highest occupied molecular orbital () and the ###Lowest_unoccupied_molecular_orbital_()_0### explains and
- Orbital symmetry considerations play a crucial role in determining allowed and forbidden reactions
- Thermal cycloadditions
- Electron flow from the HOMO of the electron-rich component () to the LUMO of the electron-poor component ()
- Favors suprafacial geometry due to better orbital overlap maximizes bonding interactions
- predict allowed reactions have a total of electrons in the participating π system ( for Diels-Alder)
- Photochemical cycloadditions
- One component is excited by light, promoting an electron from the HOMO to the LUMO changes frontier orbital interactions
- Electron flow from the LUMO of the excited component to the LUMO of the ground-state component enables new reaction pathways
- Allows for antarafacial geometry due to the involvement of antibonding orbitals reduces steric hindrance
- Woodward-Hoffmann rules predict allowed reactions have a total of electrons in the participating π system ( for )
Stereochemistry of cycloaddition reactions
- [4+2] cycloadditions (Diels-Alder reactions)
- Thermally allowed, photochemically forbidden with a cyclic transition state
- Suprafacial geometry with respect to both the diene and the dienophile addition across both components
- rule: favors the transition state with maximum secondary orbital overlap (endo product over )
- Stereochemistry of the diene is retained in the product ( required) enables stereospecific synthesis
- Can create new in the product, potentially leading to the formation of
- [2+2] cycloadditions
- Thermally forbidden, photochemically allowed proceeds via a stepwise radical mechanism
- Suprafacial geometry with respect to both components in photochemical reactions leads to syn addition
- Antarafacial geometry possible in thermal reactions with highly constrained systems (trans-cyclooctene)
- Stereochemistry of the components is retained in the product (head-to-head and tail-to-tail arrangement) allows stereocontrol
Pericyclic reactions and cycloadditions
- Cycloadditions are a subset of , which involve a concerted rearrangement of electrons through a cyclic transition state
- Pericyclic reactions are governed by orbital symmetry considerations, which determine their stereochemical outcomes
- Other examples of pericyclic reactions include electrocyclic reactions and sigmatropic rearrangements
Key Terms to Review (29)
[2+2] Cycloaddition: [2+2] cycloaddition is a type of pericyclic reaction where two pi bonds (typically from alkenes or alkynes) combine to form a cyclobutane or cyclobutene ring. This reaction is a key concept in understanding the stereochemistry and reactivity of various organic transformations.
[4+2] Cycloaddition: The [4+2] cycloaddition, also known as the Diels-Alder reaction, is a fundamental organic chemistry transformation where a conjugated diene (4 π electrons) and a dienophile (2 π electrons) combine to form a cyclohexene ring system. This pericyclic reaction is a powerful tool for the synthesis of complex cyclic compounds.
Antarafacial: Antarafacial is a term used to describe the stereochemical relationship between the new bonds formed in a pericyclic reaction. It refers to the orientation of the newly formed bonds relative to the existing bonds in the reactant molecule, specifically when they are on opposite faces of the cyclic transition state.
Anti: The term 'anti' in the context of stereochemistry refers to the spatial orientation of substituents or groups in a chemical structure. It describes a configuration where two groups or atoms are positioned on opposite sides of a reference plane or axis.
Chiral Centers: Chiral centers are atoms within a molecule that have four different substituents attached, resulting in a non-superimposable mirror image. This asymmetry gives rise to the concept of chirality, which is essential in understanding optical activity, meso compounds, and the stereochemistry of various organic reactions and biomolecules.
Concerted Mechanism: A concerted mechanism refers to a reaction that occurs in a single, continuous step without the formation of any discrete intermediates. In a concerted mechanism, the bonds that are being formed and broken happen simultaneously, leading to the product in a single, coordinated process.
Cycloaddition: Cycloaddition is a fundamental organic chemistry reaction in which two or more unsaturated molecules, or parts of the same molecule, combine to form a cyclic adduct. This process is a powerful tool for the synthesis of a wide range of carbocyclic and heterocyclic compounds, and it is particularly important in the context of alkene oxidation, carbene addition, the Diels-Alder reaction, and various thermal electrocyclic and cycloaddition reactions.
Diels-Alder Reaction: The Diels-Alder reaction is a type of cycloaddition reaction in organic chemistry where a conjugated diene reacts with a dienophile to form a cyclic product. It is a powerful tool for the synthesis of complex cyclic compounds and is widely used in organic synthesis.
Diels–Alder cycloaddition reaction: The Diels–Alder cycloaddition reaction is a chemical process in organic chemistry where a conjugated diene reacts with a substituted alkene (dienophile) to form a six-membered ring. This reaction occurs through a single, concerted step without the formation of intermediates.
Diene: A diene is a hydrocarbon compound that contains two carbon-carbon double bonds. Dienes are important in the context of various organic chemistry topics, including electrophilic additions to conjugated dienes, the Diels-Alder reaction, cycloaddition reactions, and pericyclic reactions.
Dienophile: A dienophile is a chemical species that is capable of undergoing a Diels-Alder cycloaddition reaction. It is an electrophilic component that reacts with a diene, the nucleophilic component, to form a cyclic product.
Endo: In the context of cycloadditions, the term 'endo' refers to a specific stereochemical orientation of the reactants in a cycloaddition reaction. It describes the spatial arrangement of the substituents on the reacting molecules, which can have a significant impact on the outcome and selectivity of the reaction.
Exo: Exo refers to the stereochemistry of cycloaddition reactions, where the new bonds formed are on the same side of the reactants. This term is crucial in understanding the stereochemical outcomes of these important organic transformations.
Frontier Molecular Orbital Theory: Frontier Molecular Orbital Theory is a model that describes the reactivity of organic molecules based on the behavior of their highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). It provides a framework for understanding and predicting the outcomes of pericyclic reactions, such as the Diels-Alder cycloaddition reaction.
HOMO: HOMO, or Highest Occupied Molecular Orbital, is a fundamental concept in molecular orbital theory that describes the highest energy level occupied by electrons in a molecule. This term is crucial in understanding the stability, reactivity, and spectroscopic properties of organic compounds, particularly in the context of conjugated systems, pericyclic reactions, and the chemistry of vision.
Homotopic: In the context of 1H NMR spectroscopy and proton equivalence, homotopic protons are those that can be interchanged by a symmetry operation without changing the molecule's overall spatial arrangement. These protons have identical chemical environments and therefore exhibit identical chemical shifts in NMR spectroscopy.
Lowest unoccupied molecular orbital (LUMO): The LUMO is the lowest energy molecular orbital that does not contain electrons but can accept them during chemical reactions or excitations. It plays a crucial role in determining the reactivity and properties of molecules, especially in conjugated systems analyzed by ultraviolet spectroscopy.
LUMO: LUMO, or Lowest Unoccupied Molecular Orbital, is a fundamental concept in molecular orbital theory that describes the energy level of the highest-energy orbital that is not occupied by electrons in the ground state of a molecule. The LUMO is crucial in understanding the stability and reactivity of conjugated systems, as well as the behavior of molecules in various photochemical and pericyclic reactions.
Orbital Symmetry: Orbital symmetry is a fundamental concept in organic chemistry that describes the spatial arrangement and interaction of molecular orbitals involved in pericyclic reactions, such as electrocyclic reactions, cycloadditions, and sigmatropic rearrangements. It helps predict the stereochemical outcomes and feasibility of these concerted reactions.
Pericyclic Reactions: Pericyclic reactions are a class of organic reactions that involve the concerted rearrangement of pi-electrons within a cyclic transition state. These reactions are characterized by their unique mechanism, which allows for the formation or cleavage of cyclic structures through the simultaneous breaking and forming of chemical bonds.
Regioselectivity: Regioselectivity refers to the preference of a chemical reaction to occur at a specific site or region of a molecule, leading to the formation of one regioisomeric product over another. This concept is particularly important in the context of electrophilic addition reactions of alkenes, electrophilic aromatic substitution, and other organic transformations.
S-Cis conformation: In organic chemistry, the s-cis conformation describes the arrangement of atoms in a conjugated diene system where the diene is in a planar, extended conformation, allowing for optimal orbital overlap. This arrangement is crucial for the Diels–Alder reaction to occur as it facilitates the interaction between the diene and the dienophile.
S-cis Conformation: The s-cis conformation refers to the spatial arrangement of atoms in a molecule where two substituents are positioned on the same side of a carbon-carbon double bond. This structural feature is particularly relevant in the context of the Diels-Alder cycloaddition reaction and the stereochemistry of cycloadditions.
Stepwise Mechanism: A stepwise mechanism is a reaction pathway that proceeds through a series of discrete, sequential steps rather than a single, concerted transformation. In this type of mechanism, the reaction occurs in a step-by-step fashion, with the formation of intermediate species that are then further converted to the final products.
Stereoisomers: Stereoisomers are molecules that have the same molecular formula and connectivity, but differ in the three-dimensional arrangement of their atoms in space. This spatial arrangement of atoms leads to different physical and chemical properties, even though the atoms are connected in the same way.
Stereoselectivity: Stereoselectivity refers to the preference of a chemical reaction to form one stereoisomeric product over another. It is a crucial concept in organic chemistry that describes the ability of a reaction to control the spatial arrangement of atoms in the final product.
Suprafacial: Suprafacial refers to a specific type of stereochemical orientation in pericyclic reactions, where the new bonds are formed on the same side of the reacting species. This term is particularly relevant in the context of understanding the stereochemistry of cycloadditions and the rules governing pericyclic reactions.
Syn: In the context of stereochemistry of cycloadditions, the term 'syn' refers to the spatial arrangement of substituents or atoms on a molecule relative to one another. Specifically, it describes a configuration where two groups or atoms are positioned on the same side of a particular bond or plane.
Woodward-Hoffmann Rules: The Woodward-Hoffmann rules are a set of principles that describe the stereochemical outcomes of pericyclic reactions, such as electrocyclic reactions, cycloadditions, and sigmatropic rearrangements. These rules provide a framework for predicting the feasibility and stereochemistry of these types of organic reactions based on the topology of the molecular orbitals involved.