Migratory Insertion

Introduction

Many organometallic reactions involve the insertion of an unsaturated ligand (Y) into an adjacent metal-ligand bond (M–X). This process is typically accompanied by the coordination of another ligand (L) to fill the vacant site created by the insertion, as illustrated in Figure 1. The incoming ligand (L) can be any Lewis base, including the solvent. Such intramolecular transformations are known as migratory insertion reactions.

Figure 1: An unsaturated ligand (Y) inserts into the M–X bond, while an incoming ligand (L) coordinates to the vacant site.

Migratory insertion reactions in organometallic chemistry follow several key principles:

1. Oxidation State Conservation

   • The metal’s formal oxidation state remains unchanged unless the inserting ligand (Y) is an alkylidene (R₂C=) or alkylidyne (RC≡) ligand.

2. Cis Requirement for Reactivity

   • The migrating ligand (X) and inserting ligand (Y) must be adjacent (cis) in the metal’s coordination sphere.

   • If cis sites are blocked (e.g., by a tetradentate macrocyclic ligand), both forward and reverse migratory insertions are inhibited.

3. Role of Vacant Coordination Sites

   • The forward reaction creates a vacant site, which is required for the reverse reaction (e.g., β-hydride elimination).

   • Coordinatively saturated (18-electron) metal alkyls cannot undergo β-hydride elimination unless a ligand dissociates first.

4. Stereochemistry at Chiral Centers

   • If X is a chiral carbon center, insertion typically proceeds with retention of configuration at that carbon.

5. Migration Pathways

   • Two possible mechanisms exist:
     (i) X migrates onto Y, with the new ligand occupying Y’s original site.
     (ii) Y inserts into M–X, with the new ligand occupying X’s original site.

6. Thermodynamic Control

   • The equilibrium position depends on the relative strengths of the M–X, M–Y, and M–(YX) bonds.

7. Acceleration by Oxidation or Lewis Acids

   • One-electron oxidation of X–M–Y often accelerates insertion.

   • Lewis acids can also facilitate migratory insertions.

Classification of Migratory Insertions

Migratory insertions fall into two broad categories:

1. Single-Atom-Bound Ligands (e.g., CO, isocyanides).

2. Two-Atom-Bound Ligands (e.g., olefins, dienes).

 

Insertions of Carbon Monoxide

A fundamental reaction in organometallic chemistry is the migratory insertion of carbon monoxide, where a metal alkyl carbonyl complex transforms into an acyl complex while incorporating an additional ligand (L) (Figure 2). This classic transformation occurs across diverse metal centers, including transition metals, as well as d⁰ and d¹⁰ systems. The process involves migration of an alkyl group to a neighboring CO ligand, forming a new metal-acyl bond (R-C=O-M) and generating a coordination vacancy that is subsequently filled by an incoming ligand. The reaction is often reversible, with the equilibrium position influenced by factors such as metal electron count, ligand environment, and reaction conditions. This insertion process plays a critical role in numerous catalytic cycles, including industrial processes like hydroformylation, demonstrating both its fundamental importance and practical applications in synthetic chemistry.

Figure 2

 

a. Kinetics of Insertion Reactions

• Two Step Mechanism

1. Dissociation Step:

 

 

 

 

• • • Strong nucleophiles (e.g., PMe₃) accelerate this step.

• • • Rate depends on solvent polarity and metal-ligand bond strength.

  • The intermediate M(COR) is a 16-electron species.

     

    2. Ligand Capture Step:

    • Strong nucleophiles (e.g., PMe₃) accelerate this step.

    

• Observed Rate Laws

  • First-order: If $k^2[\text{L}]\gg k^{-1}$ (ligand capture is fast).

  • Second-order: If $k^{-1}\gg k^2[\text{L}]$ (reversion to alkyl dominates).

  • Mixed-order: At intermediate conditions (e.g., RMn(CO)₅ + CO at low pressures).

• Competing One-Step Mechanism

  • Some systems (e.g., CpMo(CO)₃Me + PMePh₂) react via direct attack:

    $$\text{Rate}=k^3[\text{M(CO)R}][\text{L}]$$

  • This path is less solvent-sensitive, possibly involving ring-slippage.

 

b. Stereochemistry at Carbon

• Retention of Configuration: Most CO insertions proceed with retention at chiral carbons (e.g., three-alkyl → three-acyl in Equation 6.6).

• Racemization: Rare, occurs only in radical pathways.

• Inversion: Never observed in CO insertion (but seen in decarbonylation, e.g., photolysis of iron complexes) as shown in Figure 3.

Figure 3: CO insertion into alkenyl-metal bonds proceeds stereospecifically with complete retention of configuration, as demonstrated by both cis- and trans-CH=CHPh groups maintaining their geometry during migration. The reverse decarbonylation reaction similarly preserves stereochemistry, exemplified by RhCl(PPh₃)₃-catalyzed decarbonylation of E-PhCH=C(Et)CHO retaining the E-alkene configuration. These observations confirm both processes occur through concerted intramolecular pathways without disrupting the original alkene stereochemistry.

 

c. Stereochemistry at Metal

• Variable Outcomes: Depends on metal geometry and ligands.

  • Fe, Ru, Rh, Ir complexes: May show retention or inversion at the metal.

• Calderazzo's Study on CO insertion in MeMN(CO)₅ investigated the carbonylation of MeMn(CO)₅ using ¹³CO labeling and IR spectroscopy to track stereochemical outcomes.
  

  • Retention of Configuration: Methyl migration (not CO insertion) was confirmed by ¹³C NMR, showing the methyl group moves to an adjacent CO while the incoming ligand (L) occupies the vacated site (Figure 4)

  • Product Ratios Support Methyl Migration:

    • Expected ratio: a:b:d = 1:2:1 (if methyl migrates).

    • If CO inserted instead, no product "d" would form.

    • Experimental results (with L = CO in acetone/THF or L = P(OCH₂)₃CCH₃ in THF/HMPA) matched the 1:2:1 ratio, confirming methyl migration.

  • Decarbonylation (Reverse Reaction): Also studied, showing the same stereochemical integrity.

  • Intermediate Structure: A rigid square-pyramidal intermediate explains the observed kinetics and product distribution.

Figure4: Stereochemical outcome of MeMn(CO)₅ carbonylation: Methyl migration to adjacent CO (retention) gives products a, b, d in a 1:2:1 ratio, excluding formal CO insertion pathways

• • Pseudotetrahedral complexes (e.g., 5): Free from trans effects but can invert under high [L].

• Trans Effects & Rearrangements: Complicate mechanistic interpretations.

 

d. The Unsaturated Intermediate (M(COR))

• 16-Electron Intermediate: Often undetectable but critical.

• Possible Structures:

  • η¹-Acyl: Linear M–C=O. Coordinately unsatured η¹-Acyls of rhodium (Figure 5), iridium, and platinum are known.

Figure 5: The isolable rhodium acyl complex undergoes decarbonylation, with preliminary X-ray structures revealing both square pyramidal and trigonal bipyramidal (axial phosphines) geometries; labile halide ligands prevent stereochemical determination of the decarbonylation mechanism.

• • η²-Acyl: Bent M–(C=O) (e.g., complexes in Figure 6). The η²-binding mode (acyl oxygen → metal) enhances configurational stability in 16-electron intermediates, preventing rearrangement and preserving stereochemistry during migratory insertion

Figure 6: In most carbonylation reactions, the 16-electron intermediate cannot be directly observed, leading to ongoing debate about its exact structure. However, its stability may be explained by the acyl oxygen occupying the vacant coordination site, forming an η²-acyl complex.

• Solvation Effects: Polar solvents stabilize intermediates (e.g., THF vs. DMSO).

 

e. Solvent Effects

• Rate Acceleration by Polar Solvents

  • DMF vs. Mesitylene: 10⁴× faster in DMF for RMn(CO)₅ + CyNH₂.

  • THF Derivatives:

    • 21 (THF) ≈ 22 (3-Me-THF) > 23 (2-Me-THF) > 24 (2,5-Me₂-THF).

    • Methyl substitution reduces nucleophilicity, slowing $k^1$.]

• Rate Inhibition by Coordinating Solvents

  • DMSO: Binds tightly to intermediates (e.g., 20 in Equation 6.12), slowing final ligand substitution.

  • Ion-Pairing Effects: Tight ion pairs (e.g., Z⁺ = Li⁺) accelerate reactions.

• Catalysis by Additives

  • Ph₃P=O: Accelerates RMn(CO)₅ → RC(O)Mn(CO)₄ (Equation 6.13).

  • SnCl₂: Promotes Pt(II) carbonylations via labile SnCl₃⁻ ligands.

 

f. The Incoming Ligand (L)

• Types of L: CO, PR₃, amines, halides, metal anions.

• Nucleophilicity Matters:

  • Me₃P > PhMe₂P > Ph₂MeP > CO (Equation 6.4).

  • Strong donors increase rate and selectivity.

• CO vs. Other Ligands:

  • Inserted CO does not come from free CO (unless exchange occurs).

 

g. Thermodynamics of M–R Bond Cleavage

• Bond Strength Trends
  

• Ligand (L)	D(Mn–L) (kcal/mol)	L	Reactivity
  PhCH₂–	29	I-	Low insertion
  CH₃–	44	Br-	High insertion
  CF₃–	49	Cl-	No insertion

  • Benzyl (PhCH₂–): Weak but less reactive than Me–.

  • CF₃–: Does not insert (thermodynamically uphill).

• Decarbonylation of Rhenium Acyls

  • Phenyl (33) > Methyl (34) in stability ($K^{eq}=50$).

  • Methyl migrates 30× faster than phenyl.

h. Electronic Effects of R Groups

• Electron-donating R: Accelerate insertion (e.g., alkyl > benzyl).

• Electron-withdrawing R: Inhibit insertion (e.g., CF₃–, acyl).

• Steric Effects: Bulky R groups (e.g., (Me₃Si)₂CH–) can dominate.

 

i. Redox-Promoted Insertions

• • Oxidation Catalysis (Figure 7)

  • Fe(II) → Fe(III): Increases $K^{eq}$ by 10¹¹.

  • Ag⁺, Cp₂Fe⁺: Catalyze CO insertion.

Figure 7: Oxidative catalysis dramatically accelerates CO insertion: Fe(II)→Fe(III) oxidation increases equilibrium constant (Keq) by 10¹¹, while Ag⁺ and Cp₂Fe⁺ serve as efficient redox catalysts by promoting electron transfer in the reaction pathway.

• Reduction Catalysis

• • Electrocatalysis: Anionic acyl reduces neutral alkyl, propagating the reaction.

 

j. The Requirement for a Cis Coordination Site

• Macrocyclic Complexes:

  • Tetradentate ligands block adjacent sites, preventing insertion.

  • No CO/R proximity → No reaction (kinetic inhibition).

• Acetonitrile Complexes: Weakly bound but non-adjacent vacancies don’t help.

 

Insertions of Other Ligands Bound Through a Single Atom

a. Thiocarbonyl Insertion

• Few migratory insertions involving the CS ligand have been studied, but those that have exhibit striking differences compared to analogous carbonyl insertions. For example, when osmium(II) aryl thiocarbonyl complexes were heated, the aryl group preferentially and irreversibly formed η²-thioacyl complexes (Figure 8). One such η²-thioacyl complex was structurally characterized, revealing considerable Os–C double bond and C–S single bond character within the η²-thioacyl ligand. Although these experiments did not elucidate the stereochemical nature of the intramolecular CS migratory insertion, some interesting conclusions can be drawn: CS insertion is preferred over CO and CNR insertions.

  The most remarkable insertion reaction of the thiocarbonyl group is Roper and Collins’s discovery that hydride migratory insertion affords a stable blue thioformyl complex. This contrasts sharply with ordinary formyl ligand formation via hydride carbonyl insertion, which is typically endothermic.

  

Figure 8: Oxidative catalysis dramatically accelerates CO insertion: Fe(II)→Fe(III) oxidation increases equilibrium constant (Keq) by 10¹¹, while Ag⁺ and Cp₂Fe⁺ serve as efficient redox catalysts by promoting electron transfer in the reaction pathway.

b. Isonitriles

• The isonitrile ligand (RNC) is electronically and structurally similar to carbon monoxide (CO), but it undergoes migratory insertions much more readily. A key factor contributing to this difference is the greater tendency of iminoacyl complexes (formed after insertion) to adopt an η²-bonding mode, which enhances their reactivity.

  While double migratory insertions are rare for CO, isonitriles exhibit a strong propensity to undergo multiple sequential insertions, making them more versatile in organometallic reactions.

c. Nitrosyls

• The isonitrile ligand (RNC) is structurally and electronically similar to carbon monoxide (CO), yet it undergoes migratory insertion reactions far more readily. One contributing factor is the greater tendency of iminoacyl complexes (formed after insertion) to adopt an η²-bonding mode, which enhances reactivity.

  Unlike CO, for which double migratory insertions are rare, isonitriles frequently undergo multiple sequential insertions, demonstrating their higher reactivity.

  Nitrosyl (NO) Migratory Insertion Reactions

  Although nitrosyl complexes are formally isoelectronic with carbonyl complexes, their migratory insertion reactions have been studied less extensively. While such insertions do occur, the resulting products are often unstable and undergo further reactions.

  When triphenylphosphine (PPh₃) is the entering ligand, the rate of nitroalkane formation is independent of phosphine concentration. This suggests that an unsaturated intermediate is rap

  idly trapped by the phosphine. The mechanism appears analogous to that of carbonyl insertion, except that:

  1. The rate-determining step (k₁) involves NO migration.

  2. Phosphine coordination (k₂[L]) is fast (where k₂[L] >> k₁).

  The first detailed study of NO migratory insertion (see Figure 9)

Figure 9: In the presence of phosphine ligands (L), the reaction proceeds to form stable nitroalkane complexes. Isotopic labeling experiments confirmed an intramolecular insertion mechanism, as no crossover products were detected.

d. Carbene Insertion

• • Hydride elimination from a tungsten complex yields an ethylene complex (Figure 10).

  • Abstraction of a hydrogen atom from a cationic tungsten complex is thought to generate an intermediate cationic carbene, but only the benzyl derivative was isolated (β-hydride elimination was not possible in this case).

  • Reaction with a powerful alkylating agent could produce a cationic iridium alkyl carbene complex, but only the ethyl complex was observed.

  • The rates of both types of reactions are increased by a positive charge on the carbene complex. The migration of X to the carbene carbon is reversible if X = H, Cl, or OR; even alkyl carbene insertions can be reversible, particularly when the carbene ligands are stabilized by heteroatoms or are electrophilic. However, multistep carbene insertion can occur. For example, unsaturated transition metal alkyls promote the polymerization of diazomethane to form polymethylene complexes.

  • Several examples of apparent alkyl carbene insertions are shown in Figure 10. In each case, a presumed alkyl carbene complex was generated in situ, but only the resulting insertion product (or a derivative) was detected. For instance figure 10 illustrates examples of apparent alkyl carbene insertions, where only the final insertion products were detected.

 

Figure 10: Observed products from presumed alkyl carbene intermediates, where only insertion or derived species were isolated.

 

e. Hydride - Carbene Insertion

• This class of reactions is typically discussed in the context of their reverse process: α-hydride elimination, where alkyl complexes convert into alkylidene hydride complexes. This transformation was first demonstrated by Cooper and Green using a tungsten methyl complex and later elucidated in detail by Schrock with tantalum derivatives.

 

• Key Features of α-Hydride Elimination

  • Less common than β-hydride elimination, but the two processes can sometimes compete.

  • Favored for alkyl groups without β-hydrogens (e.g., methyl, benzyl, neopentyl, trimethylsilylmethyl).

  • Typically observed in early transition metal complexes (e.g., d⁰ Group IV and V metals).

  • Steric crowding promotes α-hydride elimination, as the M–C–C angle widens upon conversion from an alkyl to an alkylidene.

• Fate of the Hydride-Carbene Tautomer
• The hydride-carbene intermediate is often unstable and rarely observed, as reductive elimination (forming an alkane) frequently occurs instead. Some stable examples, however, have been isolated.
• Mechanistic Pathways
  • Two possible mechanisms are proposed:

1. 1. 1. Classical α-Hydride Elimination – Involves direct hydride migration to the metal.

      2. Four-Center Pathway (α-H Abstraction) – A hydride-metal bond does not form.

• • Distinguishing between these mechanisms in multistep reactions can be challenging, as both may operate under different conditions.

 

Insertions of Alkenes and Alkynes

a. Hydride Migrations to Olefins

• The intramolecular hydride insertion into a coordinated olefin is a key step in reactions like hydrogenation and hydroformylation, proceeding via a cis, four-centered transition state where the hydride, metal, and olefin are coplanar.
• This stereochemical requirement ensures that olefin hydrogenation (Figure 11) is typically cis-selective, with "agostic" alkyl intermediates resembling the transition state.

Figure 11: Mechanism of hydride-olefin insertion (β-hydride elimination), showing the coplanar transition state and slipped olefin alignment.

b. Decomposition of Metal Allkyls by β-Hydride Elimiantion

• Whitesides studied the thermal decomposition of cis-PtR₂(PPh₃)₂ and related metallacyclic complexes (e.g., cis-Pt(CH₂)₄(PPh₃)₂). Key observations (see Figure 12):

  • Acyclic dialkyls (e.g., 11a, figure 12) decompose via first-order kinetics, inhibited by added PPh₃, indicating phosphine dissociation precedes β-hydride elimination. The reaction concludes with reductive elimination of hydride and alkyl, yielding n-butane and sometimes trapping Pt(0) species (11b).

  • Metallacyclic complexes (e.g., 11c, figure 12) are ~10⁴ times more thermally stable than acyclic analogs. Their decomposition occurs via non-β-elimination pathways, attributed to an unfavorable M–C–C–H dihedral angle that prevents the planar transition state required for β-hydride elimination.

  • Electronic and Structural Influences:

    • Some alkyls (e.g., β-hydroxyethyl groups) rapidly decompose via β-hydride migration (e.g., Wacker oxidation, where an α-hydroxyethyl-Pd intermediate forms acetaldehyde).

    • Reactivity is governed by steric constraints (e.g., ring strain in metallacycles) and electronic destabilization of the metal-alkyl bond.

Figure 12: Thermal decomposition pathways of acyclic and metallacyclic Pt(II) alkyls, illustrating β-hydride elimination and alternative decomposition mechanisms.

 

c. Apparent Hydride-Olefin Insertions and β-Hydride Eliminations

• Hydride-Olefin Insertion
  • Involves the addition of a metal hydride (M–H) to a coordinated olefin, forming an alkyl complex.
  • Proceeds via a cis, four-centered transition state, requiring coplanar alignment of M–H and the olefin.
  • Critical in catalytic cycles like hydrogenation and hydroformylation (J. Am. Chem. Soc., 1998, *120*, 7143).
• β-Hydride Elimination
  • The reverse of insertion, converting metal alkyls into olefin and M–H.
  • Favored for alkyls with β-hydrogens and metals with vacant coordination sites.
  • Steric/electronic factors control competition with alternative pathways (e.g., α-elimination).

• Both processes are reversible and pivotal in C–H activation and olefin functionalization. Their interplay dictates selectivity in catalysis (e.g., polymerization, Wacker oxidation).

d. Migratory Insertions Involving Carbon sigma Bonded Groups

• Migratory Insertion in Catalysis
  • Many transition metal-catalyzed reactions (e.g., Ziegler-Natta polymerization, olefin dimerization) involve alkyl-olefin migratory insertion to form C–C bonds.
  • Prior to Watson’s 1982 work, direct observation of this step was rare, though it was central to proposed mechanisms (J. Am. Chem. Soc., 1982, *104*, 337).
  • Thermodynamically, alkyl-olefin insertion is more favorable than hydride-olefin insertion, but the latter has a lower kinetic barrier.

• Stability and Reactivity Contrasts
  • Hydride-olefin complexes (e.g., 13a) are rare and reactive, often undergoing rapid insertion (e.g., catalytic olefin isomerization).
  • Alkyl-olefin complexes (e.g., 13b) are typically stable; the methyl analog shows no insertion tendency.
  • Steric/electronic factors dictate stability: Hydrides favor insertion, while alkyls resist it unless activated.

Figure 13: Cobalt hydride (13a) and methyl (13b) complexes demonstrating contrasting reactivity in migratory insertion. Hydride-olefin insertion is rapid, while alkyl-olefin systems remain stable.

• Stereochemistry and Regiochemistry
  • Alkyl migration occurs with retention of configuration at carbon, and addition to the olefin is syn-selective.
  • Regiochemistry can follow Markovnikov (Path A) or anti-Markovnikov (Path B) pathways (see Figure 14).
  • Control factors are complex: Steric bulk (e.g., ligand crowding) and metal electronics (e.g., d-electron count) play key roles.

Figure 14: Regiochemical outcomes of alkyl-olefin insertion: Markovnikov (Path A) vs. anti-Markovnikov (Path B) addition, influenced by steric and electronic effects.

e. Acyl-Olefin Insertions

• Enhanced Reactivity of Acyl-Metal Bonds

• • Coordinated olefins insert more readily into acyl-metal bonds than into alkyl-metal bonds, enabling unique catalytic transformations.
  • This reactivity is exploited in copolymerizations of ethylene and CO, yielding polyketones and polyketoesters.
  • Palladium(II) and Rhodium(I) complexes catalyze these reactions efficiently in the presence of alcohol cosolvents (J. Organomet. Chem., 1995, *504*, 1-2).

• Mechanistic Pathway for Copolymerization

  • Kinetic studies support a stepwise chain-growth mechanism involving two key intermediates.

  • A metal-alkyl species (formed via olefin insertion).

  • A metal-acyl species (formed via CO insertion).

  • Initiation occurs via a metal hydride, likely generated from the water-gas shift reaction (CO + H₂O → CO₂ + H₂).

    Chain termination is triggered by alcohol attack, releasing the polymer product.

• Applications and Selectivity
• • The process produces alternating copolymers (e.g., polyketones) with high regioselectivity.
  • Alcohol choice (e.g., methanol vs. ethanol) influences the ratio of polyketones to polyketoesters.
  • Industrial applications include high-performance thermoplastics with tunable properties (Chem. Rev., 1996, *96*, 663-682).

 

f. Acetylene Insertions

• Many reactions are believed to involve acetylene insertions. Examples include catalytic trimerization [111] and, in certain cases, carboalkoxylation of acetylenes. A well-studied case is the migratory insertion of acetylene, as illustrated in Figure 14.

  Norton’s kinetic analysis of this and related reactions supports the proposed mechanism. The reaction’s kinetic behavior—both in the absence and presence of varying amounts of added phosphine—indicates a rapid pre-equilibrium prior to the rate-determining insertion step (k₂). When no phosphine ligand (L) is added, a substantial equilibrium concentration of the acetylene complex is present at the start of the reaction.

  The mechanism suggests that adding a phosphine (such as tritolylphosphine) substitutes into the complex via this equilibrium step, as shown in Figure 14. These reactions are concluded to proceed through a four-coordinate intermediate, with a four-center orientation involving the metal, the acyl carbon, and the two acetylenic carbons. This mechanism aligns with the theoretical predictions of Thorn and Hoffmann.

  As with analogous olefin insertions, the stereochemistry of the addition is cis.

  

Figure 14. Proposed mechanism for acetylene migratory insertion, involving a four-coordinate intermediate with cis-addition stereochemistry, supported by kinetic studies and theoretical analysis.

g. Alkyl Insertions into Polyenes and Related Systems

• Migratory Insertion in Extended π-Systems – Conjugated dienes and other extended olefinic systems commonly undergo migratory insertion into metal-alkyl bonds, as seen in diene polymerization and related catalytic transformations.

• Stereospecific Intramolecular Insertion – An example is the intramolecular insertion of a diene complex, which proceeds with syn stereochemistry to form an anti η³-allyl complex, serving as a key stereochemical probe for the mechanism.

• General Applicability – This stereochemical test for intramolecular migratory insertions can be extended to other π-complexes, helping elucidate reaction pathways in metal-catalyzed polyfunctionalizations.

 

Conclusion