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Migratory insertion

Migratory insertion is a fundamental in wherein a cis-positioned anionic , such as an alkyl or group (denoted as X), migrates to an adjacent neutral unsaturated (Y, such as or an ), resulting in the formation of a new X–Y σ bond and a new metal–Y bond while generating a vacant coordination site at the metal center. This process, which maintains the metal's formal but reduces its electron count by two (typically from 18 to 16 electrons), is stereospecific, proceeding with retention of configuration at the migrating group and syn addition geometry. The mechanism of migratory insertion requires the migrating X ligand and the unsaturated Y ligand to occupy adjacent (cis) positions in the coordination sphere, enabling the X group to transfer directly onto Y without dissociation. Early mechanistic studies, such as those by Calderazzo in the , demonstrated this through the reaction of methylmanganese pentacarbonyl with additional , where the migrates to form an acyl complex, confirming that the alkyl rather than the CO ligand is the migrating species. Reactivity is influenced by factors including metal identity (faster for early metals and first-row elements), electronic effects (electron-deficient metals promote insertion), steric hindrance at the metal, and external acids that coordinate to Y and facilitate migration. The reverse process, β-elimination, can undo the insertion, making these steps reversible under certain conditions. CO insertion represents the archetypal and most studied form of migratory insertion, classified as a 1,1-insertion due to the linear geometry of CO, and it plays a central role in catalytic cycles like (oxo process) and reactions. In contrast, 1,2-insertions involve π-bound ligands like s or s, where the X group adds across the multiple bond in a syn manner, establishing up to two new stereocenters with high diastereoselectivity. Notable examples include insertions in for and alkyne , as well as polyene insertions leading to η³-allyl complexes. These transformations are pivotal in synthetic applications, enabling the construction of carbon–carbon and carbon–heteroatom bonds in , cross-coupling, and C–H activation processes across late transition metals like Rh, Pd, and Pt.

Fundamentals

Definition and Scope

Migratory insertion is a fundamental in wherein a bound to a center, typically an anionic group such as an alkyl, aryl, or , migrates to an adjacent coordinated unsaturated , such as (CO) or an , resulting in the formation of a new metal- bond and cleavage of the original metal- bond to the unsaturated . This process effectively combines the two ligands into a single unit while generating a coordination vacancy at the metal, often facilitating subsequent reactivity in catalytic cycles. Migratory insertion is commonly observed in complexes of late transition metals, particularly d⁸ metals in groups 8–10 (such as iron, , , , , , and ), though it also occurs in early transition metals with potentially faster rates. It is distinguished from related processes like , which involves the coupling of two ligands to form a neutral that departs from the metal, thereby reducing the coordination sphere without forming an inserted ligand, and from sigma-bond metathesis, which typically occurs in early transition metal systems and involves concerted bond breaking and forming without a clear migratory component. Unlike these, migratory insertion preserves the overall of the metal while altering the ligand framework. The concept was first proposed by Richard F. Heck and David S. Breslow in 1961, who described the mechanism involving CO insertion into a metal-alkyl bond during studies of olefin reactions with hydrotetracarbonyl, laying the groundwork for understanding its role in catalytic processes like . Migratory insertion presupposes familiarity with basic coordination chemistry principles, including the , which often governs the stability of organometallic complexes involved; the reaction typically requires the migrating and the unsaturated ligand to be in a arrangement to enable the concerted migration. This geometric prerequisite ensures efficient overlap of orbitals during the insertion step.

General Mechanism

Migratory insertion is a fundamental organometallic reaction involving the insertion of an unsaturated , such as or an , into a metal-ligand σ-bond, typically an M–R or M–H bond. The process proceeds in a stepwise manner: first, the unsaturated ligand (denoted as X) coordinates to the metal center in a MLn(R)(X), where M is the metal, L represents supporting ligands, R is the migrating group (e.g., alkyl or ), and n is the . This coordination positions X cis to R, enabling the subsequent cis-migration of R to one of the atoms of X. The migration forms a new σ-bond between R and X, yielding an acyl or alkyl derivative, MLn-1(RX), and generating a vacant coordination site at the metal. This overall transformation can be represented as: \text{ML}_n(\text{R})(\text{X}) \rightarrow \text{ML}_{n-1}(\text{RX}) The reaction is concerted and intramolecular, preserving the electron count by reducing it from 18 to 16 electrons at the metal, often necessitating the entry of an external to restore coordinative saturation. Kinetically, migratory insertion is typically first-order with respect to the concentration of the organometallic complex, indicating a unimolecular rate-determining step dominated by the itself rather than ligand coordination or . The activation barrier for this step arises from the partial breaking of the M–R bond and formation of the R–X bond, with rates influenced by the nature of the metal and but generally exhibiting pseudo-first-order dependence under saturating conditions of the unsaturated . For instance, studies on methylmanganese pentacarbonyl demonstrate this unimolecular pathway, with the step exhibiting an of approximately 20 kcal/mol. In terms of , the migration occurs with complete retention of configuration at the migrating carbon center, consistent with a concerted lacking discrete intermediates that could invert stereochemistry. The process requires the migrating group and the unsaturated to be cis and coplanar, leading to syn addition across the ligand; this stereoelectronic constraint can result in anti-Markovnikov in insertions involving unsymmetrical alkenes and hydrides. The resembles a three-center interaction, where the metal, migrating group, and ligand atom form a bridged structure. Theoretically, the migratory insertion is driven by favorable orbital interactions between a filled metal d-orbital and the empty π* orbital of the unsaturated , facilitating back-donation that weakens the M–R and promotes . Computational analyses, such as extended Hückel calculations on model systems like CH3(CO)5, reveal a with significant mixing of the M–R σ orbital into ligand-based orbitals, forming a partial three-center that stabilizes the pathway. This orbital overlap underscores the reaction's preference for cis geometry and its role in catalytic cycles.

Migratory Aptitude and Factors

Order of Migration

In migratory insertion reactions, the relative tendency of different σ-bound groups to migrate, known as , generally follows the series H > aryl > alkyl (with primary > secondary > tertiary), followed by lower aptitudes for groups such as alkoxides (OR) and amides (NR₂). This order arises from a combination of factors, such as the ability to donate during migration, and , where bulkier groups face higher barriers. For instance, within alkyl groups, primary substituents like methyl exhibit higher aptitude than tertiary ones due to reduced steric hindrance in the four-center . Exceptions occur with sterically demanding aryl or tertiary alkyl groups, which can invert the expected order relative to less hindered analogs by increasing the . Experimental evidence for this hierarchy comes from competition experiments in rhodium and palladium complexes. In rhodium-based catalysts, such as Cp*Rh(P(OMe)₃)(C₂H₄)R⁺ (R = H or CH₂CH₃), the migrates preferentially over the during insertion, with a rate ratio k_H/k_Et of approximately 10⁴ at , reflecting a barrier difference of about 5 kcal/mol. Similar preferences are observed in palladium systems, where aryl groups outcompete primary alkyls in insertion steps, as demonstrated by kinetic studies on mixed Ph/Me-Pd complexes. These competitions highlight the dominance of hydrides and aryls, with alkyl migration becoming competitive only under conditions favoring the product stability. Computational studies provide further insights into these aptitudes through analysis of barriers and bond dissociation energies. calculations on complexes reveal that migration to alkenes has a ΔG‡ 6–10 kcal/ lower than alkyl migration, attributed to superior σ-donation and orbital overlap in the M–H–C , as well as lower M–H bond dissociation energies (typically 50–60 kcal/) compared to M–alkyl bonds (55–70 kcal/). For aryl versus alkyl, the phenyl group's π-system facilitates better stabilization of the partial positive charge in the , lowering the barrier by 2–4 kcal/ relative to methyl. In cases involving OR or NR₂, higher barriers (ΔG‡ > 20 kcal/) stem from poorer donor ability and increased in the M–X bond, making these groups less competitive.

Influencing Factors

Several factors influence the rate and selectivity of migratory insertion reactions in organometallic complexes, including steric and properties of , as well as external conditions such as and . These variables modulate the energy and the polarization of the metal-ligand bonds involved in the migration process. play a significant role, where bulky s, such as phosphines with large Tolman cone angles, generally accelerate the migratory insertion due to steric relief in the product, where the acyl or inserted occupies less space than the separate σ- and unsaturated s. For instance, phosphines with larger cone angles (e.g., P(t-Bu)₃, cone angle ~182°) often facilitate faster insertion rates compared to smaller analogs like PMe₃ (cone angle ~118°), as the increased bulk promotes the reaction by reducing congestion in the product. In contrast, certain bidentate phosphines with wider bite angles (e.g., , bite angle >99°) can accelerate insertion by stabilizing the through enhanced . Electronic effects are equally critical, with electron-withdrawing substituents on the metal or ligands promoting faster migration by increasing the electrophilicity of the metal center and polarizing the M-R bond toward heterolysis in the transition state. For example, in rhodium complexes, ligands bearing electron-poor groups like p-CF₃-substituted phosphines enhance insertion rates (e.g., 5.6 × 10⁻⁴ s⁻¹) relative to electron-donating p-OMe variants (2.8 × 10⁻⁴ s⁻¹), as they reduce back-donation to the inserting ligand and facilitate bond breaking. Additionally, in catalytic cycles, prior oxidative addition to a low-valent metal (e.g., Pd(0) to Pd(II)) heightens migratory aptitude by rendering the metal more electron-deficient, thereby lowering the activation barrier for subsequent insertion./14%3A_Organometallic_Reactions_and_Catalysis/14.02%3A_Reactions_Invloving_Modification_of_Unsaturated_Ligands/14.2.03%3A_Migratory_Insertion-12-Insertions) Ligand multiplicity and geometry further dictate reactivity, as migratory insertion requires cis coordination of the migrating group and the inserting ; trans influences from strongly donating or π-acceptor ligands in the opposite position can reduce rates by stabilizing the pre-insertion complex. Bidentate ligands enforcing geometry often outperform monodentate ones by preorganizing the reactive site, though excessive rigidity may impose steric penalties. Solvent and temperature also modulate outcomes: polar solvents stabilize polar transition states, slightly accelerating rates (e.g., faster than THF by ~20% in systems), while higher temperatures (e.g., 70°C vs. ) increase rates exponentially via Arrhenius behavior, often promoting reversible insertions in endothermic processes.

Carbonyl Insertions

CO Insertion into M-C Bonds

The insertion of carbon monoxide (CO) into metal-carbon σ-bonds is a fundamental migratory insertion process in organometallic chemistry, wherein an alkyl or aryl group migrates from the metal center to the carbon atom of a coordinated CO ligand, forming an η¹-acyl complex. This reaction, represented by the equation M–CR + CO → M–C(O)R (where R is an alkyl or aryl substituent), proceeds through a cis migration, requiring the M–C and M–CO units to be adjacent in the coordination sphere. The mechanism involves the alkyl group acting as a nucleophile toward the electrophilic carbon of the CO ligand, facilitated by back-donation from the metal that polarizes the CO bond. Kinetically, the process typically follows a rate law of rate = k[M–R][CO], indicating a bimolecular where coordination precedes migration, though in some systems, the rate-determining step is the migration itself. The reaction rate is accelerated by electron-deficient metals, such as Pd(II) compared to Pd(0), due to increased electrophilicity of the carbon upon coordination to a positively charged or oxidized metal center, which enhances the susceptibility to nucleophilic attack by the migrating group. This electronic effect underscores the preference for higher oxidation states in carbonylation catalysis. A notable application is the acetic acid process, developed in the 1970s, where rhodium-catalyzed of proceeds via CO insertion into a Rh–CH₃ bond to form an acetyl intermediate, ultimately yielding acetic acid. In this system, the cis arrangement of the methyl and CO ligands is enforced by the octahedral geometry and iodide ligands, promoting efficient insertion. While generally irreversible under ambient conditions due to the stability of the acyl-metal bond, reversibility (decarbonylation) can occur at elevated temperatures or with electron-rich metals, though it is rare in typical catalytic cycles. Regarding , the retains at the carbon of the migrating group. Chelating ligands often enforce the required orientation, enhancing selectivity in asymmetric variants.

CO Insertion into M-H Bonds

The insertion of (CO) into metal- (M-H) bonds proceeds through a migratory insertion , wherein the ligand migrates to the carbon atom of a coordinated CO ligand, forming a metal formyl of the general form M-C(O)H. This process can be represented by the equation: \text{M-H} + \text{CO} \rightarrow \text{M-C(O)H} The reaction is typically reversible under mild conditions, driven by the thermodynamic instability of the resulting formyl ligand, which often decomposes back to the original M-H species and free CO. Unlike alkyl migrations, hydride insertions are less favored due to the lower migratory aptitude of H relative to carbon-based groups, limiting their prevalence in organometallic systems. Metal formyl complexes were first isolated and characterized in 1979 with the species [(η⁵-C₅H₅)Re(NO)(PPh₃)(CHO)], synthesized via hydride delivery to a carbonyl precursor, marking a in understanding CO reduction pathways. Such complexes are particularly observed in early metals, where high metal basicity facilitates the insertion; for instance, treatment of the [Zr(NHSiᵗBu₃)₃H] with yields a transient η²-C,O-formyl that further evolves into oxymethylene or ethenediolate species. These examples highlight the role of sterically demanding ligands in stabilizing otherwise elusive formyls. In catalytic contexts, M-H/CO insertions are implicated as key steps in reductive processes, notably serving as intermediates in homogeneous models of the water-gas shift reaction (WGSR), where formyl formation precedes C-H bond cleavage to generate H₂ and ₂. Spectroscopic characterization provides definitive evidence for these species: the formyl C-O stretch appears in the IR spectrum at 1530–1630 cm⁻¹, significantly red-shifted from the 2143 cm⁻¹ of free due to partial double-bond character and metal back-donation, while the characteristic C-H stretch occurs at 2546–2635 cm⁻¹. This lower C-O frequency underscores the weakened bond in formyls compared to terminal carbonyls (typically 1900–2000 cm⁻¹).

Unsaturated Hydrocarbon Insertions

Alkene Insertion into M-C Bonds

The insertion of s into metal-carbon bonds is a key elementary step in , wherein an alkyl or migrates from the metal center to a coordinated , resulting in the formation of a new, longer-chain metal-alkyl complex. This process, often termed 1,2-migratory insertion, proceeds via a concerted without the formation of discrete intermediates, where the migrating group attaches to the more substituted (internal) carbon of the , yielding a β-alkyl species. The general reaction can be depicted as: \text{M--R} + \ce{CH2=CHR'} \rightarrow \text{M--CH2CH(R')R} This transformation requires a vacant coordination site cis to the alkyl group for alkene binding and is facilitated by electron-deficient metal centers, which enhance the electrophilicity of the coordinated alkene. Regioselectivity in these insertions is governed by steric and electronic factors, with the 2,1-insertion mode—wherein the metal binds to the more substituted alkene carbon, akin to Markovnikov orientation—predominating in late transition metal systems such as palladium or nickel complexes. This preference arises from the stabilization of the transition state by electron-withdrawing substituents on the alkene or ligands that modulate metal electron density, while alkene substitution patterns (e.g., terminal vs. internal) further influence the outcome by altering steric congestion at the insertion site. In early transition metal contexts, 1,2-insertion is more common, aligning the growing chain linearly. A pivotal application of this insertion lies in Ziegler-Natta polymerization, discovered in the 1950s, where successive alkene insertions into a metal-alkyl bond at the enable controlled chain growth to form polyolefins like and . The Cossee-Arlman mechanism describes this propagation step, emphasizing the role of octahedral coordination at centers with a single alkyl chain and a vacant site for monomer binding. Kinetically, insertions into M-C bonds are typically reversible under mild conditions, with the microscopic reverse—β-hydride elimination from the β-alkyl product—competing effectively to regenerate the starting olefin complex and limit chain propagation or induce . This is particularly pronounced in systems lacking steric bulk to suppress elimination pathways. The migratory aptitude of the carbon-based group follows established trends (e.g., aryl > alkyl), influencing competition with other ligands if present.

Alkene Insertion into M-H Bonds

Alkene insertion into metal- bonds, a process known as hydrometalation, involves the migration of the to the coordinated , forming a metal-alkyl . This reaction is central to several catalytic transformations, particularly the reduction of unsaturated hydrocarbons. The general proceeds via coordination of the to the metal center, followed by migration of the across the C=C . The transformation is regioselective, adhering to anti-Markovnikov orientation, as depicted in the following equation: \ce{M-H + CH2=CHR -> M-CH2CH2R} This regiochemistry arises because the hydride, acting as a nucleophile, adds to the less substituted carbon of the alkene, while the metal binds to the more substituted carbon, stabilizing the resulting alkyl species. The stereochemistry of the insertion is strictly syn, with both the hydride and the metal adding to the same face of the alkene double bond, preserving the geometry and leading to cis-alkyl products in asymmetric variants. In rhodium-catalyzed systems, such as Wilkinson's catalyst [\ce{RhCl(PPh3)3}], this step favors the formation of linear alkyl complexes for terminal alkenes. The preference for linear products stems from steric factors: branched isomers are prone to rapid β-hydride elimination, reverting to alkene and regenerating the hydride, whereas linear alkyls proceed to reductive elimination. This insertion is a pivotal step in the hydrogenation cycle, where the dihydride precursor undergoes oxidative addition of H₂, followed by alkene coordination and hydride migration./04:Fundamentals_of_Organometallic_Chemistry/4.05:Migratory_Insertion-_12-Insertions) In certain catalytic systems, particularly those involving early or mid-s, the hydrometalation pathway may compete with alternative routes involving direct of molecular hydrogen to the metal-alkene , potentially bypassing the discrete migration step. However, in late like those of and , the migratory insertion dominates due to favorable energetics and effects that lower the barrier for transfer.

Alkyne Insertions

Alkyne migratory insertions involve the addition of a coordinated ligand to a metal-carbon (M–C) or metal-hydride (M–H) bond, typically proceeding with stereochemistry to yield vinyl metal complexes. In the case of insertion into an M–C bond, a complex such as [M–R] reacts with an alkyne RC≡CR' to form [M–C(R)=CR'R], where the R group from the metal migrates to one carbon of the alkyne, preserving the double bond in the product. Similarly, insertion into an M–H bond generates [M–C(R)=CHR'], a process observed in various systems including , , and complexes. These reactions are fundamental steps in forming C–C bonds while maintaining unsaturation, distinguishing them from insertions that produce saturated alkyl species. The mechanism of alkyne insertion closely resembles that of alkenes, involving coordination of the followed by of the M–C or M–H group to the alkyne's π-system, but the product retains a C=C bond rather than becoming fully saturated. is primarily governed by factors, with the migrating group typically adding to the carbon that best stabilizes the developing partial positive charge; for example, in terminal alkynes, electron-withdrawing substituents on the alkyne favor insertion where the metal binds to the terminal carbon, while electron-rich alkynes promote the opposite . also play a role, particularly with bulky substituents, influencing the approach of the alkyne to the metal center. This control is evident in nickel-catalyzed systems, where substituent effects on the alkyne dictate the product's regiochemistry during insertion. Alkyne insertions are pivotal in catalytic processes such as alkyne polymerization and hydroalkylation, exemplified by Reppe's pioneering nickel-catalyzed cyclotrimerization of in the 1950s, which relies on successive migratory insertions to assemble derivatives from three alkyne units. In modern catalysis, sequential alkyne insertions into Pd–C bonds enable the formation of complex metallacycles, as demonstrated in the synthesis of eight-membered rings from ortho-metalated amines and alkynes. These examples highlight the versatility of Ni and Pd catalysts in promoting controlled . However, a key challenge lies in managing multiple insertions, which can lead to uncontrolled oligomer formation and reduced selectivity, necessitating design to limit chain growth. The parallels to alkene insertions are evident in the shared migratory pathway, but alkyne processes uniquely enable conjugated products absent in saturated cases.

Other Ligand Insertions

CO2 and Heteroatom Insertions

Migratory insertion of (CO₂) into metal-carbon (M–C) bonds represents a key step in the activation and utilization of this for reactions. The process typically involves the nucleophilic attack by the alkyl or on the electrophilic CO₂, leading to the formation of a metal species, as depicted in the equation: \text{M–R} + \text{CO}_2 \rightarrow \text{M–OC(O)R} This insertion is more challenging than analogous reactions with CO or alkenes due to CO₂'s poor π-acidity and high activation barriers, often exceeding 20 kcal/mol for late transition metals, which limits its migratory aptitude. In early transition metal systems, such as zirconium alkyl complexes, CO₂ insertion proceeds efficiently under mild conditions, forming stable carboxylates that serve as intermediates in polymerization or coupling catalysis. For instance, the reaction of (Cp*)₂Zr(CH₂Ph) with CO₂ yields the corresponding benzoate complex, highlighting the role of d⁰ metals in stabilizing the product through oxophilicity. Research since the early 2000s has focused on late transition metals like nickel and palladium, where pincer ligands enhance reactivity for CO₂ valorization. In pincer-supported Pd(II) methyl complexes, such as (ᵗBuPBP)Pd(CH₃), insertion occurs at room temperature via an Sᴱ₂ (outer-sphere) mechanism, with experimental activation enthalpies as low as 10.9 kcal/mol in coordinating solvents like pyridine, which stabilize the transition state. Comparative studies reveal that primary alkyl groups insert faster than secondary or benzyl ones due to steric effects, while aryl substituents exhibit barriers around 34 kcal/mol, precluding insertion under ambient conditions. These systems are pivotal in catalytic carboxylation of C–H or C–X bonds, enabling sustainable C–C bond formation from CO₂. Lewis acids or hemilabile ligands can further lower barriers by polarizing CO₂ or facilitating substrate approach. Heteroatom-containing molecules like sulfur dioxide (SO₂) undergo analogous migratory insertions into M–C bonds, though these are less common and typically require specific conditions. SO₂ insertion into –alkyl bonds produces metal sulfonates or sulfinates, as seen in the reaction of [(dppp)Pd(Me)(OEt₂)]⁺ with SO₂ to form a dimeric sulfinate complex [(dppp)Pd(OS(O)Me)]₂²⁺, confirmed by . This process is rare outside group 10 metals and often proceeds via initial SO₂ coordination as an η¹-S or η²-(S,O) , followed by migration, with applications in . In platinum systems, SO₂ inserts into Pt–C σ-bonds at elevated temperatures (~50°C), yielding sulfinate derivatives that underscore the ligand's versatility in both monodentate and bridging modes. Overall, these insertions highlight SO₂'s unique ability to form both C–S and M–O bonds, contrasting with CO₂'s products, but face similar energetic hurdles without supportive ligands.

Nitrogen- and Oxygen-Containing Insertions

Migratory insertion reactions involving nitrogen- and oxygen-containing unsaturated ligands represent specialized transformations in , where ligands such as isocyanides and epoxides participate in bond-forming steps analogous to those with but influenced by distinct electronic properties. These processes typically proceed via a 1,1-migratory insertion , in which a cis-disposed group migrates from the metal center to the coordinated , forming new metal-ligand bonds. For nitrogen-containing ligands like isocyanides (R'NC), the insertion into a metal-carbon bond (M-R) yields an imidoyl complex (M-N=CR'R'), with the atom binding to the metal and the migrating group attaching to the carbon. This step mirrors CO insertion in its concertedly nature but incorporates , enabling the synthesis of nitrogen-rich heterocycles. Palladium-catalyzed isocyanide insertions, developed since the 1990s, have become prominent for constructing complex nitrogen-containing frameworks, particularly in pharmaceutical synthesis. For instance, the oxidative imidoylative cross-coupling of aryl halides with s and nucleophiles, such as boronic acids in a modified Suzuki-Miyaura reaction, produces biaryl ketones or amides via selective insertion into the Pd-C bond followed by . These reactions exhibit high , driven by the nucleophilicity of the migrating group; electron-rich alkyl or aryl migrants favor rapid insertion over competing pathways like β-hydride elimination. Representative applications include the synthesis of 4-aminoquinolines and oxadiazoles, key motifs in drugs like angiotensin II receptor antagonists and EGFR inhibitors, highlighting the method's utility in production. In contrast, insertions of oxygen-containing unsaturated ligands, such as , are rarer due to competing over-reduction pathways that lead to aldehydes or further hydrogenolysis products. In ruthenium-catalyzed hydrogenolysis of , the process involves coordination of the epoxide followed by nucleophilic attack or concerted transfer of a from the metal center (Ru-H) onto the less substituted carbon, opening the ring to form a metal-alkoxide intermediate that protonates to yield secondary alcohols. This regioselective Markovnikov addition, achieving >99% branched selectivity for aliphatic , provides an efficient route to alcohols but is prone to side reactions from excessive reduction, limiting its prevalence compared to nitrogen analogs.

Applications in Catalysis

Carbonylation Reactions

Carbonylation reactions represent a cornerstone of industrial where migratory insertion of (CO) into metal-carbon or metal-hydride bonds enables the synthesis of carboxylic acids and derivatives. These processes, pivotal in producing , leverage the reversible nature of CO insertion to form acyl intermediates under controlled conditions of high CO , which suppresses the backward and drives forward reactivity. The Monsanto process, commercialized in the 1970s by Monsanto Company, utilizes a rhodium-iodide catalyst system for the carbonylation of methanol to acetic acid. In this cycle, methyl iodide (CH₃I) undergoes oxidative addition to a rhodium(I) species, such as [Rh(CO)₂I₂]⁻, forming a methyl-rhodium intermediate, followed by CO migratory insertion to generate the acetyl-rhodium complex, CH₃C(O)-Rh. The oxidative addition step is rate-determining in the rhodium system, but the subsequent acyl formation via insertion is integral to the catalytic turnover, with the overall reaction proceeding at 150–200°C and 30–40 atm CO pressure. An advancement, the Cativa process introduced by BP Chemicals in 1996, employs an iridium-iodide catalyst promoted by or other metal iodides to enhance activity and stability. Here, the migratory insertion of into the iridium-methyl bond constitutes the rate-determining step for acyl formation, accelerated by promoters that facilitate iodide abstraction and coordination; the cycle integrates similarly with CH₃I preceding insertion to yield CH₃C(O)-Ir. Operating at milder conditions (180°C, 30 atm), this process offers higher productivity and reduced usage compared to . Global production of acetic acid via these carbonylation routes is approximately 19.6 million metric tons annually as of 2025, underscoring their economic scale and reliance on migratory insertion efficiency. High pressure in both processes mitigates the reversibility of insertion, favoring irreversible of the acyl-iodide product. Variations of carbonylation extend to , such as the production of through carbonylation reactions, where CO insertion into metal- bonds forms N-acyl intermediates that hydrolyze to the target . This approach, detailed in patented methods, highlights the versatility of migratory insertion in manufacturing.

Polymerization and Oligomerization

Migratory insertion plays a central role in the of s using Ziegler-Natta catalysts, as described by the Cossee-Arlman mechanism. In this model, the on the center, typically generated from TiCl₄ reduced by an alkylaluminum cocatalyst such as AlEt₃ or methylaluminoxane (MAO), features a vacant coordination site adjacent to a metal-alkyl . The coordinates to the metal, followed by migratory insertion of the growing into the metal- , propagating the . This stepwise insertion of s like or into the Ti-alkyl enables the formation of high-molecular-weight polyolefins, with the heterogeneous nature of traditional Ziegler-Natta systems (e.g., TiCl₃ supported on MgCl₂) contributing to broad molecular weight distributions due to multiple types. The advent of single-site metallocene catalysts in the and revolutionized stereocontrol in polymerization through precise migratory insertion mechanisms. Chiral zirconocene complexes, such as [Me₂Si(η⁵-C₅H₄Ind)₂]ZrCl₂ activated by MAO, facilitate highly regioselective and stereospecific 1,2-insertion of into the Zr-alkyl bond, yielding isotactic with narrow polydispersity and tunable . The reaction proceeds via coordination of the to the cationic metal center, followed by of the alkyl chain to form a new Zr-C bond, as exemplified by: \text{M-Me} + n \ \ce{CH2=CHMe} \rightarrow \text{M-(CH2CHMe)_n-Me} This approach allows for the production of isotactic polypropylene with high melting points and mechanical strength, enabling advanced polymer architectures not achievable with traditional catalysts. In oligomerization processes, migratory insertion similarly drives the controlled assembly of short-chain alkenes. The Shell Higher Olefin Process (SHOP), operational since 1977, employs a homogeneous nickel-phosphine catalyst to oligomerize ethylene into linear α-olefins like 1-hexene via successive insertions of ethylene into a Ni-H bond, followed by β-H elimination to release the product and regenerate the active species. This nickel-mediated cycle produces a Poisson distribution of oligomers (primarily C₄–C₂₀), with subsequent isomerization and metathesis steps optimizing selectivity for valuable products like 1-hexene used in linear low-density polyethylene production. The balance between rapid migratory insertion and competing chain-transfer pathways ensures low molecular weights typical of oligomers. The molecular weight of polymers and oligomers in these systems is governed by the competition between migratory insertion and β-hydride elimination. In metallocene and Ziegler-Natta catalysis, frequent β-elimination from the growing chain terminus generates a metal-hydride species, leading to chain termination and lower molecular weights, while suppressed β-elimination (e.g., via sterically hindered ligands) favors prolonged insertion sequences and higher degrees of . This kinetic interplay allows catalyst design to tailor product properties, such as achieving ultrahigh molecular weight when insertion rates exceed elimination by orders of magnitude.

Hydroformylation and Related Processes

, also known as the oxo process, is a catalytic reaction that converts alkenes, hydrogen, and into aldehydes, with the overall transformation represented as RCH=CH₂ + H₂ + CO → RCH₂CH₂CHO (linear) or RCH₂CH(CHO)CH₃ (branched). This process was discovered in 1938 by Otto Roelen at during investigations related to the Fischer-Tropsch synthesis, initially using catalysts. Industrially, it employs either - or -based catalysts, with rhodium systems offering higher activity and selectivity under milder conditions (80–120°C, 15–25 bar) compared to cobalt (120–170°C, 200–300 bar). The catalytic cycle hinges on migratory insertion steps, typically beginning with coordination of the alkene to a hydrido-metal species such as HCo(CO)₄ or HRh(CO)(PPh₃)₃, followed by 1,2-insertion of the metal-hydride bond across the alkene to yield an alkyl-metal intermediate (linear or branched depending on orientation). Subsequent insertion of CO into the M–alkyl bond produces an acyl-metal complex, followed by oxidative addition of H₂ and reductive elimination of the aldehyde, regenerating the catalyst. These insertions are pivotal, as the hydride migration establishes the C–H bond while CO insertion forms the formyl group, enabling the atom-economical addition across the alkene. On an industrial scale, produces approximately 14 million metric tons of annually as of 2025, primarily from propene to yield butanal, which is further converted to for use in plasticizers such as di(2-ethylhexyl) phthalate (DEHP) in PVC manufacturing. The , expressed as the linear-to-branched (l/b) aldehyde ratio, is critically controlled by ligands; for instance, (PPh₃) in catalysts promotes high linear selectivity (l/b ≈ 8–15:1) by stabilizing the for anti-Markovnikov insertion, whereas bulkier or bidentate phosphines further enhance this preference. Related processes, such as hydrosilylation, analogously involve migratory insertion of alkenes into metal–silicon or metal–hydride bonds to add silanes (R₃Si–H) across unsaturated substrates, yielding organosilicon compounds used in polymers and adhesives. In these reactions, typically catalyzed by or complexes, the insertion step mirrors by forming a σ-alkyl intermediate that undergoes with the silyl group.