C-H activation Flashcards
E-factor
Mass of waste / mass of products
General C-H activation partial catalytic cycle using a directing group
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Benefits of C-H activation catalysis
Atom efficient
Easier to purify the products (fewer by-products)
Problems with C-H activation catalysis
Need efficient catalysts
Need to understand stoichiometric reactions in order to develop catalysis
Why is activation of C-H bonds attractive?
Many hydrocarbons e.g. methane, benzene are cheap and abundant so could be valuable feedstocks
In an ideal world, we would be able to use C-H activation to selectively functionalise these unfunctionalised alkanes without the need for directing groups
Two methods for activating a C-H bond
- Sigma-bond metathesis
2. Oxidative addition
An overall C-H activation equation (OA)
LnM + R-H —> LnM-H(-R)
Thermodynamic problems for C-H activation
DeltaS = C-H activation is disfavoured entropically (2 molecules --> 1 molecule) DeltaH = reaction must be sufficiently exothermic to overcome the loss of entropy
Why is C-H activation harder than H-H activation?
Energy required to break H-H = 436 kJ mol-1
Energy release on forming M-H = 311 kJ mol-1
Energy required to break H3C-H = 436 kJ mol-1
Energy released on forming M-CH3 = 235 kJ mol-1
i.e. H-H and H3C-H bonds have similar strengths
Less energy is released on forming a metal-carbon than metal-hydrogen bond, so H3C-H activation is less favoured
Bond enthalpies for Ph-H activation
Energy required to break Ph-H bond = 460 kJ mol-1 (more energy required than for general C-H due to breaking aromaticity)
Energy released on formation of Ph-M = 344 kJ mol-1 (more energy released because there are opportunities for donating electron density onto the metal (ring acting as ‘electron pump’) and backbonding from the metal onto the ring (ring acting as ‘electron sink’))
Why does spontaneous complex decomposition occur with M-alkyl complexes?
Because M-C bond is so weak
(and C-H bond is strong)
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Kinetic problems for C-H activation
Issues generally related to sterics
Difficult for metal to approach sp3 C-H bond without encountering severe steric hindrance (draw)
Therefore sp3 C-H bond activation often has a very high activation energy
Stability of product from C-H activation
M-C complexes can undergo beta/gamma-hydride elimination
Intramolecular C-H activation
Easier than intermolecular!
Thermodynamics: entropically neutral (just 1 molecule reacting with itself) and chelate formed (chelate effect = driving force)
Kinetics: complex is pre-disposed to C-H activation because the C-H is already in close proximity to the metal centre
Agostic interactions
If the C-H bond is weakened through interaction with the metal centre but not completely broken
Occurs when the C-H bond of a substituent on a ligand interacts with an unsaturated metal centre (requires an empty orbital on the metal to accept the electron density)
Can get alpha- and beta-agostic interactions (draw)
Electronics of agostic interactions
Similar to the bonding in B2H6
2 electrons are donated from the C-H bond to the metal centre – 3 centre-2 electron bonding
(i.e. contributes 2 electrons to valence electron count)
The metal contributes an empty orbital to the 3c-2e bond
Agostic interactions with non-d0 metals
Metal can backdonate electron density into sigma* C-H (strengthens interaction)
But if the backbonding is too strong, the C-H bond is fully cleaved (‘activated’) and the metal alkyl-hydride complex is formed
If sigma-donation is too weak, the agostic interaction is unlikely to occur
Analytical techniques to detect/determine the presence of agostic interactions
Increase in C-H bond length can be detected by neutron diffraction
Normal C-H = 110 pm, agostic C-H = 113-119 pm
Short M—H contacts
1.8-2.3 A (but this is longer than a normal M-H bond which is 1.5-165 A)
Narrow M-H-C bond angles
90-140 degrees
Reduced coupling constants in 1H NMR due to Karplus relationship
Normal C-H = 120-130 Hz, agostic C-H = 75-100 Hz
Upfield shift in 1H NMR
-5 to -15 ppm (due to hydridic character)
IR stretching frequency lower - consistent with a longer, weaker C-H bond
Normal C-H = 3000-2800 cm-1, agostic C-H = 2700-2300 cm-1
Anagostic interactions
Any M-H-C interactions that do not involve 3c-2e bonds
i.e. not quite an agostic interaction, very limited exchange of electron density between M and H
What are anagostic interactions characterised by?
Long M—H interactions 2.3-2.9 A
Large M-H-C interactions 110-170 degrees
Downfield shift in 1H NMR (i.e. a non-hydridic, H-bonding-type interaction)
Examples of intermolecular C-H activation reactions with isolated products
See flashcards
Common features of intermolecular C-H activation reactions with isolated sp3 products
Low coordination number
Sigma-donor ligands on metal centre e.g. PR3 (R=alkyl)
No net change in oxidation state (complex first undergoes reductive elimination to form really low coordinate, highly reactive species that then undergoes oxidative addition)
Mechanistic studies on Bergman C-H activation reaction
Two possibilities for reaction mechanism
- Reductive elimination/oxidative addition
- Radical process
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Whitesides investigation into his C-H activation reaction
Whitesides knew that the first step involved reductive elimination of neopentane
Wanted to investigate whether this was facilitated by a Cy group in the phosphine ligand undergoing its own C-H activation to form a chelate and stabilise the low-coordinate Pt centre
Found that this didn’t happen - the bidentate phosphine ligand is ‘tied back’ so the Cy can’t swing round to be in close enough proximity for C-H activation
Steric clash between the neopentane ligand and the Cy groups leads to instability, which facilitates neopentane loss
The unstable, low-coordinate Pt complex formed then reacts with the cyclopropane in solution to form a strong Pt-C bond
This product also has less steric repulsion than the neopentane
Probing reactivity of intermolecular C-H activation reactions
Mainly using deuterium labelling studies
Draw out cycle
Rearrangement mechanism in H/D exchange studies for intermolecular C-H activation
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Eta2 H-D complex formation and rotation is most likely because it can interact with the d0 Nb centre
Cp is a strong field ligand (electron withdrawing, good pi-acceptor) and the high oxidation state (electron poor) Nb is poor at pi-back-bonding to H-D, therefore H-D can rotate freely
How to probe/prove the rearrangement mechanism experimentally
Variable temperatures?
Lower temps = less rotation
NMR studies of this?
Electron-rich metal centre MO interactions for C-H activation
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Metal is likely to be in a low oxidation state e.g. late TMs Ir(I), Pd(II), with d electrons available to donate electron density (strong pi-back-donation) Almost nucleophilic in character - metal centre can 'attack' C-H bond Key interaction = back-donation from filled metal d orbital into sigma* C-H Metal orbitals (HOMO/LUMO) are high energy Therefore likely to cleave C-H bond (i.e. C-H activation) via oxidative addition
Electron-poor metal centre MO interactions for C-H activation
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Metal is likely to be in a high oxidation state e.g. Pd(IV) or early TMs that are d0 (therefore want to accept electron density)
Minimal pi-back-donation
Metal orbitals (HOMO/LUMO) are lower energy
Key interaction = donation of electron density from sigma C-H into sigma orbital (LUMO) on metal
Therefore deprotonation is likely (H is acidified, metal centre effectively acting as a base)
Main message from MO diagrams of C-H activation for electron rich/poor metals
Need to tune the metal system appropriately in order to obtain desired reactivity (i.e. to get oxidative addition/deprotonation)
Easier method for probing a reaction using deuterium labelling
Use a deutero solvent rather than a deuterated complex (synthetically challenging to make)
Probing reaction mechanism in tungsten-mediated C-H activation
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Properties of metal complex needed for catalytic C-H activation
Low oxidation state metal i.e. late TMs e.g. Rh(I), Ir(I), Pd(0), Pd(II)
Low coordinate metal centre so there are 2 vacant coordination sites at which oxidative addition can take place
Catalytic cycle for C-H activation using low-coordinate Rh complex to functionalise a completely inactivated alkane
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Sigma-bond metathesis
Need a metal sigma bond e.g. M-CR3, M-NR2 etc
Complex to be C-H activated also needs a sigma bond (i.e. the C-H bond)
Concerted process that occurs via a 4-membered sigma-complex
Product is often volatile, which provides a driving force for the reaction
Types of metals required for sigma-bond metathesis
Occurs with d0 metals
(Oxidative addition with d0 metals is forbidden because they have no electrons to lose!)
Generally occurs with the early TMs i.e. groups 3/4/5 in +3/+4/+5 oxidation states - oxidative addition is only possible with mid- and late-TMs
Also occurs with some mid TMs e.g. Fe2+ (iron doesn’t really carry out 2 electron chemistry so would rather do sigma-bond metathesis than OA)
How can you prove the intermediacy/formation of the 4-membered sigma complex?
Using vibrational spectroscopy
(Draw)
Slight increase in CO stretching frequency suggests a slightly shorter CO bond due to less back-donation from the Rh centre - likely because the Rh is now also interacting with C-H as part of the sigma complex so has less electron density to donate back
Final comparison of OA/SBM
OA = electron-rich metal centres, oxidation state capable of undergoing 2e oxidation, low coordinate metal centre
SBM = electron-poor metal (d0), need a metal with a metal-sigma bond in the starting material
Examples of sigma-bond metathesis reactions
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