3.4 Synthesis and Reactions of Organometallic Compounds

Organometallic compounds are key players in inorganic chemistry, featuring bonds between metals and carbon atoms. They come in various forms, from ionic to covalent, and their structure depends on the metal's coordination geometry and ligand properties.

Making organometallics involves methods like transmetallation, oxidative addition, and direct metallation. These compounds are super useful in organic synthesis, enabling new bond formation and serving as versatile intermediates in multi-step reactions.

Synthesis of organometallic compounds

Bonding and structure of organometallic compounds

• Organometallic compounds contain at least one bond between a metal atom and a carbon atom of an organic molecule
  • The metal-carbon bond can be ionic or covalent in character, depending on the electronegativity difference between the metal and carbon
  • Ionic organometallic compounds (organolithium, Grignard reagents) feature a highly polarized metal-carbon bond, with a partially negative charge on the carbon atom
  • Covalent organometallic compounds (ferrocene, Zeise's salt) have a more balanced electron distribution between the metal and carbon atoms
• The structure of organometallic compounds is influenced by the coordination geometry of the metal center and the steric and electronic properties of the ligands
  • Common coordination geometries include linear, trigonal planar, tetrahedral, square planar, and octahedral
  • The hapticity of a ligand (denoted as η) indicates the number of contiguous atoms in the ligand that are bonded to the metal center (η1, η2, η3, etc.)

Synthetic methods for preparing organometallic compounds

• Transmetallation is a reaction where an organometallic compound exchanges its organic group with another organometallic compound or a metal salt
  • This method is used to prepare organometallic compounds with specific desired organic groups
  • Example: the reaction of a Grignard reagent (RMgX) with a transition metal halide (MXn) to form a transition metal organometallic compound (RnM)
• Oxidative addition is a reaction where a metal inserts into a covalent bond of a substrate, increasing the oxidation state of the metal by two units
  • This method can be used to prepare organometallic compounds from alkyl halides or hydrogen gas
  • Example: the reaction of a low-valent metal complex (Mn) with an alkyl halide (R-X) to form an oxidative addition product (Mn+2(R)(X))
• Direct metallation involves the reaction of a metal with an organic compound, typically involving C-H bond activation
  • This method is used to prepare organometallic compounds directly from hydrocarbons
  • Example: the reaction of a transition metal complex (MLn) with a hydrocarbon (R-H) to form a metal-alkyl complex (MLn-1(R))
• Reductive elimination is the reverse of oxidative addition, where a high-valent organometallic compound eliminates two ligands to form a new covalent bond, reducing the oxidation state of the metal by two units
  • This method can be used to prepare organometallic compounds with specific desired ligands
  • Example: the elimination of an alkyl group and a halide from a high-valent metal complex (Mn+2(R)(X)) to form a metal complex (Mn) and an organic product (R-X)
• Ligand exchange reactions involve the substitution of one ligand for another on an organometallic compound
  • This method is used to fine-tune the reactivity and selectivity of organometallic reagents
  • Example: the replacement of a carbonyl ligand (CO) with a phosphine ligand (PR3) in a metal carbonyl complex (M(CO)n) to form a metal phosphine complex (M(CO)n-1(PR3))

Key reactions in organometallic chemistry

Ligand substitution reactions

• Ligand substitution reactions involve the exchange of one ligand for another on an organometallic compound
  • The incoming ligand displaces the leaving ligand, typically following a dissociative or associative mechanism
  • Dissociative substitution occurs when the leaving ligand departs first, forming an intermediate with a reduced coordination number, followed by the attachment of the incoming ligand
  • Associative substitution occurs when the incoming ligand attaches first, forming an intermediate with an increased coordination number, followed by the departure of the leaving ligand
• The rate and mechanism of ligand substitution reactions depend on the metal center, its oxidation state, and the nature of the ligands
  • First-order kinetics are observed for dissociative substitution, while second-order kinetics are observed for associative substitution
  • Steric and electronic factors influence the relative rates of dissociative and associative substitution
  • Example: the substitution of a carbonyl ligand (CO) with a phosphine ligand (PR3) in a metal carbonyl complex (M(CO)n) can proceed via a dissociative or associative mechanism, depending on the metal and the ligands

Oxidative addition and reductive elimination reactions

• Oxidative addition is a key reaction where a metal center inserts into a covalent bond of a substrate, increasing the oxidation state and coordination number of the metal
  • This reaction is favored by low-valent, electron-rich metal centers and substrates with relatively weak covalent bonds
  • Concerted oxidative addition occurs when the metal center simultaneously breaks the covalent bond of the substrate and forms two new metal-ligand bonds in a single step
  • SN2-type oxidative addition occurs when the metal center attacks the substrate in an SN2-like manner, breaking the covalent bond and forming a new metal-ligand bond in a single step
  • Example: the oxidative addition of an alkyl halide (R-X) to a low-valent metal complex (Mn) to form an oxidative addition product (Mn+2(R)(X))
• Reductive elimination is the reverse of oxidative addition, where a high-valent organometallic compound eliminates two ligands to form a new covalent bond, reducing the oxidation state and coordination number of the metal
  • This reaction is favored by high-valent, electron-poor metal centers and ligands that can form stable covalent bonds
  • Example: the reductive elimination of an alkyl group and a halide from a high-valent metal complex (Mn+2(R)(X)) to form a metal complex (Mn) and an organic product (R-X)
• Migratory insertion reactions involve the insertion of an unsaturated ligand (e.g., CO, alkene, alkyne) into a metal-ligand bond
  • This reaction increases the oxidation state of the metal and forms a new metal-carbon bond
  • Example: the insertion of carbon monoxide (CO) into a metal-alkyl bond (M-R) to form an acyl complex (M-C(O)R)

Reactivity of organometallic compounds

Factors influencing reactivity

• The reactivity of organometallic compounds depends on the metal center, its oxidation state, and the nature of the ligands
  • Electron-rich, low-valent metal centers are typically more reactive than electron-poor, high-valent metal centers
  • The d-electron count of the metal center influences its reactivity and stability (e.g., 16-electron complexes are more reactive than 18-electron complexes)
• The steric and electronic properties of ligands can significantly influence the reactivity of organometallic compounds
  • Bulky ligands can hinder certain reactions due to steric crowding, while electron-donating or electron-withdrawing ligands can modulate the electron density at the metal center
  • The Tolman cone angle is a measure of the steric bulk of a ligand, which can be used to predict the likelihood of ligand dissociation and the stability of different coordination geometries
  • Example: the use of bulky, electron-rich phosphine ligands (PR3) can stabilize low-valent metal centers and promote oxidative addition reactions

Predictive tools for organometallic reactivity

• The 18-electron rule can be used to predict the stability and reactivity of organometallic compounds
  • Compounds with 18 valence electrons are generally stable and less reactive, while compounds with fewer than 18 valence electrons are more reactive and prone to oxidative addition or ligand coordination
  • Example: a 16-electron square planar complex (ML4) is more likely to undergo oxidative addition than an 18-electron octahedral complex (ML6)
• The Caulton-Eisenstein rules can be used to predict the preferred geometry of four-coordinate, d8 metal complexes based on the relative π-acceptor strengths of the ligands
  • Strong π-acceptor ligands favor a square planar geometry, while weak π-acceptor ligands favor a tetrahedral geometry
  • Example: a d8 metal complex with two strong π-acceptor ligands (e.g., CO) and two weak π-acceptor ligands (e.g., Cl) is likely to adopt a square planar geometry
• Organometallic reactions often follow a characteristic sequence of elementary steps, such as oxidative addition, migratory insertion, and reductive elimination
  • By identifying the likely elementary steps, the overall reaction outcome can be predicted
  • Example: a catalytic cycle for a cross-coupling reaction might involve oxidative addition of an aryl halide (Ar-X) to a low-valent metal complex (Mn), transmetallation with an organometallic reagent (R-M'), migratory insertion to form a new C-C bond, and reductive elimination to release the coupled product (Ar-R) and regenerate the active catalyst (Mn)

Multi-step syntheses with organometallics

Organometallic compounds as versatile intermediates

• Organometallic compounds are versatile intermediates in organic synthesis, enabling the formation of new carbon-carbon and carbon-heteroatom bonds under mild conditions with high selectivity
  • The reactivity of organometallic intermediates can be tuned by the choice of metal, ligands, and reaction conditions
  • Organometallic intermediates can be used in a wide range of synthetic transformations, including nucleophilic addition, nucleophilic substitution, and cross-coupling reactions
• Retrosynthetic analysis can be used to plan multi-step syntheses involving organometallic intermediates
  • The target molecule is disconnected into simpler precursors, and organometallic reagents are chosen based on their reactivity and selectivity
  • Example: the synthesis of a complex natural product might involve the disconnection of key C-C bonds, which can be formed using organometallic intermediates such as Grignard reagents or organolithium compounds

Examples of organometallic reagents in organic synthesis

• Transition metal-catalyzed cross-coupling reactions, such as the Suzuki, Negishi, and Heck reactions, are powerful methods for forming new carbon-carbon bonds using organometallic intermediates
  • These reactions typically involve a catalytic cycle of oxidative addition, transmetallation, and reductive elimination steps
  • Example: the Suzuki coupling of an aryl halide (Ar-X) with an arylboronic acid (Ar-B(OH)2) using a palladium catalyst to form a biaryl product (Ar-Ar)
• Grignard reagents (organomagnesium compounds) are widely used in organic synthesis for the formation of new carbon-carbon bonds and the introduction of functional groups
  • Grignard reagents can be used in nucleophilic addition reactions with carbonyl compounds, followed by hydrolysis to form alcohols
  • Example: the reaction of a Grignard reagent (RMgX) with a ketone (R'C(O)R'') to form a tertiary alcohol (R'R''C(OH)R) after hydrolysis
• Organolithium reagents are highly reactive organometallic compounds that can be used in nucleophilic addition reactions, nucleophilic substitution reactions, and metal-halogen exchange reactions
  • The high reactivity of organolithium reagents often requires low temperatures and strict moisture and air exclusion
  • Example: the reaction of an organolithium compound (RLi) with a ketone (R'C(O)R'') to form a tertiary alcohol (R'R''C(OH)R) after hydrolysis
• Gilman reagents (organocuprates) are less reactive than organolithium reagents but offer greater selectivity in organic synthesis
  • Gilman reagents can be used in conjugate addition reactions, nucleophilic substitution reactions, and cross-coupling reactions
  • Example: the conjugate addition of a Gilman reagent (R2CuLi) to an α,β-unsaturated ketone (R'C(O)CH=CHR'') to form a 1,4-addition product (R'C(O)CH(R)CH2R'')
• Transition metal hydrides, such as borohydrides and aluminum hydrides, are valuable reducing agents in organic synthesis
  • These organometallic reagents can selectively reduce functional groups, such as carbonyl compounds, esters, and nitriles, under mild conditions
  • Example: the reduction of an ester (RC(O)OR') with lithium aluminum hydride (LiAlH4) to form a primary alcohol (RCH2OH)