Organic Chemistry
Table of Contents
Olefin metathesis is a game-changing reaction in organic chemistry. It lets us make rings and rearrange carbon-carbon double bonds in ways that were once super tricky. This opens up new paths for making complex molecules and materials.
The star players here are ruthenium catalysts. They're like Swiss Army knives - versatile, tough, and able to work with all sorts of chemical groups. This flexibility makes olefin metathesis a go-to tool for chemists tackling tough synthesis challenges.
Intramolecular Olefin Metathesis
Ring-closing metathesis in organic synthesis
- Ring-closing metathesis (RCM) is a powerful tool in organic synthesis for creating cyclic compounds from acyclic dienes (olefins)
- Enables the formation of medium to large-sized rings (cyclopentanes, cyclohexanes, cycloheptanes) that are otherwise difficult to synthesize
- Driven by the release of volatile olefins (ethylene, propylene) as byproducts, shifting the equilibrium towards the cyclic product
- The release of ring strain can provide an additional driving force for the reaction
- Mechanism of RCM proceeds via a metal-alkylidene catalyst (Grubbs, Hoveyda-Grubbs) that undergoes a series of [2+2] cycloaddition and retro-cycloaddition steps
- Initial [2+2] cycloaddition between the metal-alkylidene and one of the substrate olefins forms a metallacyclobutane intermediate
- Retro-[2+2] cycloaddition of the metallacyclobutane releases ethylene and generates a new metal-alkylidene species
- The new metal-alkylidene reacts with the second olefin, forming another metallacyclobutane intermediate
- A final retro-[2+2] cycloaddition releases the cyclic product and regenerates the original metal-alkylidene catalyst
- Applications of RCM span a wide range of synthetic targets
- Construction of macrocyclic compounds (musks, pheromones) and complex natural products (epothilones, ansa-bridged peptides)
- Synthesis of unsaturated heterocycles (dihydrofurans, dihydropyrroles, dihydrothiophenes) and fused ring systems (decalins, indanes)
- Preparation of cyclic peptides and peptidomimetics with enhanced stability and bioavailability
Ru(II) complexes as metathesis catalysts
- Ruthenium(II) complexes have emerged as the most versatile and widely used catalysts for olefin metathesis reactions
- Exhibit high catalytic activity, selectivity, and tolerance towards various functional groups (alcohols, amides, esters)
- Examples include Grubbs catalysts (1st, 2nd, and 3rd generation) and Hoveyda-Grubbs catalysts with N-heterocyclic carbene (NHC) ligands
- Ru(II) metathesis catalysts feature a well-defined structure with a central Ru(II) atom coordinated to neutral (phosphines, NHCs) and anionic ligands (halides, pseudohalides)
- The Ru-alkylidene moiety acts as the active site for olefin metathesis, initiating the catalytic cycle
- Steric and electronic properties of the ligands can be tuned to optimize catalytic performance and stability
- Mechanism of Ru(II)-catalyzed RCM involves the dissociation of a neutral ligand to generate a 14-electron active species
- The active species undergoes [2+2] cycloaddition with the substrate olefin, forming a metallacyclobutane intermediate
- Retro-[2+2] cycloaddition of the metallacyclobutane releases the cyclic product and regenerates the active Ru(II) species
- Advantages of Ru(II) catalysts over other transition metal complexes (Mo, W) include
- Higher functional group tolerance and compatibility with protic solvents (methanol, water) and mild reaction conditions (room temperature, low catalyst loadings)
- Improved stability and lower sensitivity to air and moisture, enabling easier handling and storage
Intramolecular vs intermolecular olefin metathesis
- Intramolecular olefin metathesis involves the formation of cyclic structures within a single molecule
- Ring-closing metathesis (RCM) is a prime example, leading to the synthesis of cyclic compounds (cycloalkenes, heterocycles) from acyclic dienes
- Intramolecular metathesis can also be used to incorporate cyclic units into linear polymers, modifying their properties (glass transition temperature, crystallinity)
- Intermolecular olefin metathesis involves the formation of new C-C bonds between different molecules
- Acyclic diene metathesis (ADMET) polymerization is a step-growth process that converts $\alpha,\omega$-dienes into unsaturated polymers with well-defined structures
- Produces polymers with narrow molecular weight distributions ($M_w/M_n < 2$) and controllable molecular weights ($10^3 - 10^5$ g/mol)
- Allows for the incorporation of functional groups (esters, ethers, amides) into the polymer backbone
- Ring-opening metathesis polymerization (ROMP) is a chain-growth process that converts strained cyclic olefins (norbornene, cyclopentene) into high-molecular-weight polymers
- Produces polymers with low polydispersity indices ($M_w/M_n < 1.1$) and controllable architectures (linear, branched, cross-linked)
- Enables the synthesis of functional polymers (polyelectrolytes, biomaterials) by using substituted cyclic olefin monomers
- Acyclic diene metathesis (ADMET) polymerization is a step-growth process that converts $\alpha,\omega$-dienes into unsaturated polymers with well-defined structures
- Key differences between intramolecular and intermolecular olefin metathesis in polymer synthesis
- Intramolecular metathesis modifies existing polymers by introducing cyclic structures, while intermolecular metathesis creates new polymer chains or cross-links
- Intramolecular metathesis is used to fine-tune polymer properties, while intermolecular metathesis is used to synthesize polymers with desired structures and functionalities
Transition metal catalysis in olefin metathesis
- Olefin metathesis reactions are catalyzed by transition metal complexes, which facilitate the rearrangement of carbon-carbon double bonds
- The catalytic cycle involves the formation of a metal-carbene complex, which acts as the active species in the metathesis reaction
- Transition metal catalysts enable the metathesis reaction to proceed under mild conditions and with high selectivity
- The choice of transition metal and ligands can significantly influence the reactivity, selectivity, and functional group tolerance of the metathesis reaction
Key Terms to Review (32)
Ring-opening metathesis polymerization (ROMP): Ring-opening metathesis polymerization (ROMP) is a type of polymerization process that involves the opening of cyclic olefins (ring molecules) and their transformation into linear polymers through the use of specific catalysts. This method allows for the creation of polymers with tailored properties by controlling the structure of the starting material.
Acyclic diene metathesis (ADMET): Acyclic Diene Metathesis (ADMET) is a polymerization technique in organic chemistry that involves the reaction of acyclic diene precursors to form polymers through a metathesis mechanism. This process enables the construction of long polymer chains by sequentially adding double bonds between carbon atoms.
Ring Strain: Ring strain refers to the inherent instability and high-energy state of cyclic organic compounds, particularly those with small ring sizes, due to the distortion of bond angles and bond lengths from their ideal values. This concept is central to understanding the properties and reactivity of cycloalkanes and other cyclic structures.
Cyclopentene: Cyclopentene is a cyclic alkene with the molecular formula C₅H₈. It is a key structural component in organic chemistry, with important applications in the context of calculating the degree of unsaturation, olefin metathesis polymerization, and intramolecular olefin metathesis.
Retro-cycloaddition: Retro-cycloaddition is a reverse pericyclic reaction in which a cyclic compound undergoes cleavage to form two or more acyclic products. This process is the reverse of a cycloaddition reaction, where smaller molecules combine to form a cyclic product.
Norbornene: Norbornene, also known as bicyclo[2.2.1]hept-2-ene, is a cyclic alkene compound that is commonly used in organic chemistry, particularly in the context of the Diels-Alder reaction and olefin metathesis polymerization. It is a strained, bicyclic hydrocarbon with a rigid structure that exhibits unique reactivity and applications.
Cyclohexanes: Cyclohexanes are a class of saturated, alicyclic hydrocarbons with a six-membered carbon ring. They are closely related to the reduction of aromatic compounds and the intramolecular olefin metathesis reaction, two important topics in organic chemistry.
[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.
ROMP: ROMP, or Ring-Opening Metathesis Polymerization, is a type of olefin metathesis reaction used to create polymeric materials. It involves the opening of cyclic olefins to form linear polymers through the rearrangement of carbon-carbon double bonds.
Cyclopentanes: Cyclopentanes are a class of cyclic alkanes with a five-membered carbon ring structure. They are an important structural motif in organic chemistry, particularly in the context of intramolecular olefin metathesis reactions.
Grubbs Catalyst: The Grubbs catalyst is a type of organometallic compound used as a catalyst in olefin metathesis reactions. It is named after its inventor, American chemist Robert H. Grubbs, who was awarded the Nobel Prize in Chemistry for his work on this catalyst.
Metal-Alkylidene: A metal-alkylidene is a reactive species in organic chemistry where a metal atom is bonded to a carbon atom that is also double-bonded to another carbon atom. These species are key intermediates in various metal-catalyzed transformations, including olefin metathesis reactions.
Epothilones: Epothilones are a class of natural products that exhibit potent anti-cancer activity by stabilizing microtubules, similar to the mechanism of action of taxanes. They are of great interest in the field of organic chemistry and medicinal chemistry due to their potential as chemotherapeutic agents.
Metallacyclobutane: A metallacyclobutane is a cyclic organic compound containing a metal atom as part of the ring structure. It is a key intermediate in olefin metathesis reactions, which are important for the synthesis of new carbon-carbon bonds and the formation of polymers.
Cycloheptanes: Cycloheptanes are cyclic alkanes with a seven-membered ring structure. They are an important class of organic compounds that are studied in the context of intramolecular olefin metathesis reactions.
Hoveyda-Grubbs Catalyst: The Hoveyda-Grubbs catalyst is a type of ruthenium-based olefin metathesis catalyst that is widely used in organic synthesis. It is a modified version of the Grubbs catalyst, featuring a chelating benzylidene ligand that provides enhanced stability and selectivity in various metathesis reactions.
RCM: RCM, or Ring-Closing Metathesis, is a powerful organic chemistry reaction that allows for the formation of cyclic alkenes from acyclic dienes. It is a type of olefin metathesis reaction that is widely used in the synthesis of complex organic molecules.
ADMET: ADMET is a set of pharmacokinetic properties that describe the absorption, distribution, metabolism, and excretion of a drug molecule in the body. It is a crucial consideration in the development and evaluation of new drug candidates.
Dihydrothiophenes: Dihydrothiophenes are cyclic organic compounds containing a five-membered ring with two carbon atoms and one sulfur atom. They are closely related to the intramolecular olefin metathesis reactions, which are important in organic synthesis.
Dihydrofurans: Dihydrofurans are cyclic organic compounds containing a five-membered ring with two carbon atoms and one oxygen atom. They are closely related to the furan class of heterocyclic compounds and play an important role in the context of intramolecular olefin metathesis reactions.
Metathesis: Metathesis is a type of organic reaction where two molecules exchange parts, typically involving the rearrangement of chemical bonds. It is a powerful tool in organic synthesis, particularly in the context of olefin metathesis reactions.
Macrocyclic Compounds: Macrocyclic compounds are cyclic organic molecules that contain a large number of atoms, typically 12 or more, in the ring structure. These compounds exhibit unique chemical and physical properties that arise from their distinctive molecular architecture.
Dihydropyrroles: Dihydropyrroles are a class of heterocyclic organic compounds containing a five-membered ring with two carbon atoms and one nitrogen atom, where two of the carbon atoms are saturated. These compounds are important intermediates in the synthesis of various biologically active molecules and natural products.
Ring-Closing Metathesis: Ring-Closing Metathesis (RCM) is a type of olefin metathesis reaction in organic chemistry where a cyclic alkene is formed from an acyclic diene precursor. It is a powerful tool for the synthesis of various cyclic compounds, including natural products and pharmaceuticals.
Ansa-Bridged Peptides: Ansa-bridged peptides are a class of cyclic peptides characterized by the presence of a covalent bridge, or 'ansa', that connects two non-adjacent positions within the peptide backbone. This structural feature confers rigidity and unique conformational properties to the peptide, which can influence its biological activity and interactions.
Ru(II) Complexes: Ru(II) complexes are a class of organometallic compounds featuring a central ruthenium(II) atom coordinated to various ligands. These complexes have found widespread applications in areas such as catalysis, photochemistry, and molecular electronics due to their unique electronic and structural properties.
NHC ligands: NHC ligands, or N-heterocyclic carbene ligands, are a class of neutral, two-electron donor ligands that have become increasingly important in organometallic chemistry and catalysis. These ligands coordinate to metal centers through the carbene carbon atom, forming stable metal-carbene complexes.
Transition Metal Catalysis: Transition metal catalysis is the use of transition metal complexes to facilitate and accelerate chemical reactions. These metals, with their partially filled d-orbitals, can participate in various bonding interactions and redox processes that enable them to act as catalysts, lowering the activation energy and increasing the rate of reactions.
Ru-alkylidene: A Ru-alkylidene is a type of metal-carbene complex, specifically involving a ruthenium (Ru) atom bonded to a carbon atom in a double bond configuration. These complexes are crucial intermediates in olefin metathesis reactions, a powerful tool for the formation of carbon-carbon double bonds.
Carbene Complex: A carbene complex is a type of organometallic compound where a carbene, a neutral divalent carbon species, is bound to a metal center. These complexes play a crucial role in various organic reactions, particularly in the context of intramolecular olefin metathesis.
N-heterocyclic carbene: N-heterocyclic carbenes (NHCs) are a class of stable, neutral, and highly nucleophilic carbenes that contain at least one nitrogen atom in the heterocyclic ring. These reactive species have found widespread applications in organic synthesis, particularly in the field of intramolecular olefin metathesis reactions.
Olefin: An olefin, also known as an alkene, is a type of organic compound that contains a carbon-carbon double bond. Olefins are characterized by their high reactivity and play a crucial role in the context of intramolecular olefin metathesis, a powerful organic reaction.