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,