Organometallic Reactions I: Reactions That Occur at the Metal
Ligand Substitution Oxidative Addition Reductive Elimination Actors and spectators
Actor ligands are those that dissociate or undergo a chemical transformation (where the chemistry takes place!)
Spectator ligands remain unchanged during chemical transformations They provide solubility, stability, electronic and steric influence (where ligand design is !) Ligand Substitution Ligand substitution reactions: overview
Studied systematically for the reactions of phosphines with metal carbonyls (Basolo) Classification D Dissociative (comparable to the SN1 limiting case) A Associative (comparable to the SN2 limiting case) I Interchange / Intermediate • Ia (comparable to typical SN2 reactions) • Id (comparable to typical SN1 reactions) Notes: "Labile" and "Inert" are kinetic terms "Stable" and "Unstable" are thermodynamic terms Ligand Substitution Reactions
Substitution reactions can be:
Associative (SN2)
Dissociative (SN1)
They can involve - 2e ligands: CO, PR3 C2H4, … one electron ligands. Ligand Substitution Reactions The following trends have been observed
1. M-L bonds from two-electron donors such as CO are at most half as strong as the familiar C-H and C-C bonds in organic chemistry, thus dissociative mechanisms are possible. 2. Polyhapto ligands such as η6- cyclopentadienyl and η6-arene have much stronger M-L bonds than CO and will not undergo dissociative substitution Ligand Substitution Reactions
3. M-L bond strengths in general increases down a triad as third row> second row > first row. Note that there are many exceptions.
4. The general order of bond strengths has been established: Cp > MexC6H6-x > C6H6 > CO ~ PMe3 ~ Olefin > PPh3 >Py > CH3CN >THF , acetone, ethanol Dissociative Mechanism
Only bond breaking is involved in the formation of an intermediate of decreased coordination number. Typical of 18e- complexes Dissociative displacements
Observed for 18e carbonyls 8 10 6 Rates: d > Td d > Oh d Y-intermediate is favored by L being a good π-donor; T- intermediate is favored by a high trans-effect L. Rates for TM: 3rd row < 2nd row > 1st row Dissociation is accelerated for bulky ligands. Weakly bound solvent molecules are often useful ligands synthetically. Associative substitutions
Often adopted by 16e complexes:
Found for 18e complexes that have a ligand which can rearrange (slip): Associative Mechanism Bond making is involved in the formation of an intermediate or transition state of increased coordination number. Associative Mechanism Bond making is involved in the formation of an intermediate or transition state of increased coordination number.
Fast
Associative mechanisms are typical of 16e- complexes. Associative Mechanism Associative substitution reactions involving coordinatively unsaturated 16- electron systems are relatively fast (rates ~ 104 sec). Rearrangements of coordinatively unsaturated species
When a ligand dissociates, one of the remaining ligands rearranges to fill the vacant site created: the reverse of the slippage process. Analogous to neighboring group participation in organic chemistry Synthesis: nucleophilic attack on the metal
Very useful and rather general method
Common reagents are RLi, RMgX (or R2Mg), ZnR2, AlR3, BR3, and PbR . 4 15 Ligand Substitution Reactivity of Coordinated Ligands Why care about substitution ?
Basic premise about metal-catalyzed reactions: Reactions happen in the coordination sphere of the metal Reactants (substrates) come in, react, and leave again Binding or dissociation of a ligand is often the slow, rate- determining step
This premise is not always correct, but it applies in the vast majority of cases. Notable exceptions: Electron-transfer reactions Activation of a single substrate for external attack peroxy-acids for olefin epoxidation CO and olefins for nucleophilic attack Dissociative ligand substitution
Example:
Factors influencing ease of dissociation: 1st row < 2nd row > 3rd row 8 10 6 d -ML5 > d -ML4 > d -ML6 stable ligands (CO, olefins, Cl-) dissociate
easily (as opposed to e.g. CH3, Cp). Dissociative substitution in ML6
16-e ML5 complexes are usually fluxional; the reaction proceeds with partial inversion, partial retention of stereochemistry.
The 5-coordinate intermediates are normally too reactive to be observed unless one uses matrix isolation techniques. Associative ligand substitution
Example:
Sometimes the solvent is involved. Reactivity of cis-platin: Ligand Rearrangement
Several ligands can switch between n-e and (n-2)-e situations, thus enabling associative reactions of an apparently saturated complex: Redox-induced ligand substitution
Unlike 18-e complexes, 17-e and 19-e complexes are labile. Oxidation and reduction can induce rapid ligand substitution.
Reduction promotes dissociative substitution. Oxidation promotes associative substitution. In favourable cases, the product oxidizes/reduces the starting material ⇒ redox catalysis. Redox-induced ligand substitution
Initiation by added reductant.
Sometimes, radical abstraction produces a 17-e species Photochemical ligand substitution
Visible light can excite an electron from an M-L bonding orbital to an M-L antibonding orbital (Ligand Field transition, LF). This often results in fast ligand dissociation.
Requirement: the complex must absorb, so it must have a color! or use UV if the complex absorbs there Photochemical ligand substitution
Some ligands have a low-lying π* orbital and undergo Metal-to- Ligand Charge Transfer (MLCT) excitation. This leads to easy associative substitution. The excited state is formally (n-1)-e ! Similar to oxidation-induced substitution
HOMO LUMO
M-M bonds dissociate easily (homolysis) on irradiation ⇒ (n-1)-e associative substitution Electrophilic and nucleophilic attack on activated ligands
Electron-rich metal fragment: ligands activated for electrophilic attack.
H2O is acidic enough to protonate this coordinated ethene. Without the metal, protonating ethene requires H2SO4 or similar. Electrophilic and nucleophilic attack on activated ligands
Electron-poor metal fragment: ligands activated for nucleophilic attack.
BuLi does not add to free benzene, it would at best metallate it (and even that is hard to do). Electrophilic attack on ligand
Hapticity may increase or decrease. Formal oxidation state of metal may increase. Electrophilic Addition
Is formally oxidation of Fe(0) to FeII (the ligand becomes anionic). Ligand hapticity increases to compensate for loss of electron. Electrophilic abstraction
Electrophilic abstraction + + also by Ph3C , H
Alkyl exchange also starts with electrophilic attack: Electrophilic attack at the metal
If the metal has lone pairs, it may compete with the ligand for electrophilic attack Transfer of the electrophile to the ligand may then still occur in a separate subsequent step Electrophilic attack at the metal
Can be the start of oxidative addition
(although this could also happen via concerted addition)
Key reaction in the Monsanto acetic acid process: One reaction, multiple mechanisms
Concerted addition, mostly with non-polar X-Y bonds
H2, silanes, alkanes, O2, ... Arene C-H bonds more reactive than alkane C-H bonds (!)
Intermediate A is a σ-complex. Reaction may stop here if metal-centered lone pairs are not readily available. Final product expected to have cis X,Y groups. One reaction, many applications
Oxidative addition is a key step in many transition-metal catalyzed reactions Main exception: olefin polymerization The easy of addition (or elimination) can be tuned by the electronic and steric properties of the ancillary ligands The most common applications involve:
a) Late transition metals (platinum metals) b) C-X, H-H or Si-H bonds
Many are not too sensitive to O2 and H2O and are now routinely used in organic synthesis.
Oxdative addition, reductive elimination The Heck reaction
Pd often added in the form of Pd2(dba)3. dba, not quite an innocent ligand
Usually with phosphine ligands. Typical catalyst loading: 1-5%. But there are examples with turnovers of 106 or more Heterogenous Pd precursors can also be used, but the reaction itself happens in solution The Heck reaction
For most systems, we don't know the coordination environment of Pd during catalysis.
At best, we can detect one or more resting states.
The dramatic effects of ligand variation show that at least one ligand is bound to Pd for at least part of the cycle. The Heck reaction
Works well with aryl iodides, bromides Slow with chlorides Hardly any activity with acetates etc. Challenges for "green chemistry"
Pt is ineffective Probably gets "stuck" somewhere in the cycle Suzuki and Stille coupling
Glorified Wurtz coupling
Many variations, mainly in the choice of electrophile
Instead of B(OH)2 or SnMe3, also MgCl, ZnBr, etc
The Suzuki and Stille variations use convenient, air-stable starting materials Suzuki and Stille coupling
The oxidative addition and reductive elimination steps have been studied extensively.
Much less is known about the mechanism of the substitution step. The literature mentions "open" (3-center) and "closed" (4-center) mechanisms
This may well be different for different electrophiles. Association-Dissociation of Lewis acids
Lewis acids are electron acceptors, e.g. BF3, AlX3, ZnX2
H H
W: + BF3 W BF3 H H
This shows that a metal complex may act as a Lewis base
The resulting bonds are weak and these complexes are called adducts Association-Dissociation of Lewis bases
A Lewis base is a neutral, 2e ligand “L” (CO, PR3, H2O, NH3, C2H4,…) in this case the metal is the Lewis acid
HCo(CO)4 HCo(CO)3 + CO
For 18-e complexes, dissociative mechanisms only For <18-e complexes dissociative and associative mechanisms are possible Nucleophilic displacement (SN2)
Methyl, allyl, acyl, and benzyl halides
The ligands have a strong effect on the nucleophilicity of the metal center.
Reactivity of R-X: • X: I > Br > Cl • R: Me > Et > iPr > tBu
If chiral RX are used then inversion of configuration is observed: Sigma-bond metathesis
It avoids the TD barriers of the C-H activation / substitution step. It is found for early TM with d0 configuration. Why position β cannot be C
The reaction is best described as a nucleophilic substitution of H at either C or Si in the coordination sphere of Ln. The transition state is a pentacoordinated - - anionic CH5 or SiH5 which is energetically highly unfavorable for C and much more favorable for Si.
The energy barrier for C at the β position is lowered with electronegative substituents (F), known to stabilize a hypervalent species, but not vinyl or phenyl. Electrophilic activation Pd2+, Pt2+ and/or Pt4+, Hg2+, Tl3+.
Shilov, 1972
Alkane activation step σ bond metathesis with high-valent, late TMs Midterm 2005: Recently, Hartwig et al. (J. Am. Chem. Soc. 2005, 127, 14263-14278) published mechanistic studies on the functionalization of arenes by diboron reagents catalyzed by iridium complexes:
For each step shown in the catalytic cycle indicate the mechanism (type of reaction). Where you can envision more than one possibility, write down all of them (at least two) discussing arguments that support your proposal or that are against it (at least one of each). If you consider that some intermediates are not shown, draw those intermediates. Indicate formal oxidation state and electron count for each iridium complex. Endo methyl migration: aromatic stablization energy
Jim D. Atwood, Michael J. Wovkulich and David C. Sonnenberger, Acc. Chem. Res. 1983, 16, 350-355 Role of Ligand Substitution in Ferrocytochrome c Folding Jason R. Telford, F. Akif Tezcan, Harry B. Gray, and Jay R. Winkler Biochemistry, 1999, 38, 1944-1949
Factors Influencing the Reactivity of Transition-Metal Complexes
Effective Atomic Number (EAN)
① Diamagnetic organometallic complexes of transition metals may exist in significant concentration at moderate temperature only if the metal valence shell contains 16 or 18 electrons.
② Organometallic reactions, including catalytic ones, proceed by elementary steps involving only species with 16 or 18 electrons. Coordination Number and Geometry
A simple d orbital only σ bonding angular overlap analysis of structural preference energies for ML6, ML5, and ML4 geometries shows that for 6 a d atom, the ML6 geometry is strongly favored relative to either ML5 8 or ML4. For a d atom, the ML5 trigonal bipyramid is favored relative to
ML6 or tetrahedral ML4, but a square-planar geometry is equally preferred (hence the large number of 16-electron square-planar d8 complexes). For a d10 atom, there is no distinction in angular overlap terms between square-planar and tetrahedral ML4 geometries although the latter will be preferred in terms of minimization of ligand-ligand repulsions.
James A. S. Howell & Philip M. Burkinshaw, Chem. Rev. 1983, 83, 557-599 Volume changes accompanying ligand substitution reactions assuming a negligible change in volume of the first coordination sphere of the complex trans directing effect rationalized within the general accepted associative process on square-planar complexes Cl- promoted inversion of square-pyramidal [FeCl(porphyrin)] complexes
David T. Richens, Chem. Rev. 2005, 105, 1961-2002
Shunsuke Sato, Yuji Ohashi, Osamu Ishitani, Ana Maria Blanco- Rodrıguez, Antonın Vlcek, Jr., Taiju Unno, and Kazuhide Koike, Inorg. Chem. 2007, 46, 3531-3540 “Inverse-Electron-Demand” Ligand Substitution in Palladium(0)-Olefin Complexes Shannon S. Stahl, Joseph L. Thorman, Namal de Silva, Ilia A. Guzei, and Robert W. Clark, J. AM. CHEM. SOC. 2003, 125, 12-13
J. Phys. Chem. 1996, 100, 18363-18370
Organometallics, 1986, 5, 1703-1706