Unit 1 Flashcards
What is the structure of Wilkinson’s catalyst and what reaction does it catalyse?
[Rh(PPh3)3(Cl)]
It catalyses the hydrogenation of alkenes to the alkane
Calculate the NVE, oxidation state and dn configuration for Wilkinsons catalyst
16 e, Rh(I) and d8
What are the steps in the catalytic cycle for the hydrogenation of an alkene using Wilkinson’s catalyst?
- OA of H2
- Alkene coord
- MI (RDS) of an H onto the alkene
- RE → alkane product
What is the turn-over limiting step for the hydrogenation of an alkene using Wilkinson’s catalyst?
Migratory insertion
What factors effect the selectivity of Wilkinsons catalyst?
Unconjugated alkenes + alkynes hydrogenated
* Donor solvents (e.g. ethanol) speed up rxn since e density is increased → helps MI step (RDS)
* Less substituted alkenes preferred as highly substituted alkenes bind more weakly to M → MI has a higher activation barrier → decreases the rate
* Kinetic control: preference for the reduction of less substituted double bond
* high level of functional group tolerance → doesn’t reduce nitro groups
What is the productivity of a catalyst?
Mass of product per moles of catalyst per unit time, g/mmol.h or g/mol.h
What is a catalysts turnover number (TON) and formula?
How many times a catalyst completes a complete cycle of the reaction in a given time before becoming deactivated
TON = moles of product / moles of catalyst
What is the turnover frequency TOF of a catalyst?
Number of moles of product per moles of catalyst per unit time
TOF = TON / time (s⁻¹, h⁻¹, min⁻¹)
What is methanol carbonylation?
Conversion of methanol to acetic acid by the addition of CO
What are the two processes used for methanol carbonylation
- Monsanto process
- BP’s Cativa process
What is the catalyst for the Monsanto process of methanol carbonylation, its VE count, electronic configuration and geometry?
[Rh(CO)₂I₂]- , 16e, d8 and SP
Draw the mechanism for the Monsanto Process of methanol carbonylation
- Organometallic cycle:
* OA of methyl iodide (RDS)
* Migratory insertion of CO → intermediate 18 e- acyl complex
* Reductive elimination → acetic acid + regeneration of catalyst - Organic cycle:
* methanol reacts rapidly w/ HI - CH3I + H2O
* Acyl iodide reacts w/ H2O (hydrolysed) → acetic acid that we want as a product which regenerates HI
Why won’t methanol oxidatively add to Rh?
The hydroxyl group (-OH) is a weak leaving so it’s not good at OA which is an SN2 like reaction, need good LG + OH is not a good LG whereas I- = good LG
Explain the OA step in the Monsanto process?
SN2-like
* [Rh(CO)2I2]– is highly nucleophilic (-ve charge)
* Neutral analogues of [Rh(CO)2I2]– e.g. [Rh(AsPh3)2(CO)I] = 105 times less reactive
* Can be accelerated by electron donor ligands (e.g. PEt3) but these are unstable in real reactor conditions: PEt3 + HI -> [HPEt3]I after ligand dissociation
What are the main issues with the Monsanto process?
*↑ [HI] and [H₂O] is needed to stabilise the catalyst to prevent formation of insoluble Rh(III) salts
*↑ [H₂O] → CO loss via WGS rxn:
H₂O + CO → CO₂ + H₂ → ∼ 30% of CO to be lost, + H2 → product purity issues
*HI is v corrosive + requires expensive reactor metallurgy
What is the catalyst for BP’s Cativa process for methanol carbonylation?
[Ir(CO)₂I₂]-
Why is the OA of iodide methane in BP’s Cativa process is much faster than the Monsanto Process?
Ir has a higher e- density than Rh ∴ has greater nucleophilicity
OA is accelerated by stronger Ir-Me and Ir-I bond
Why is the migratory insertion of CO in BP’s Cativa process slower than the Monsanto Process?
Ir has a higher e- density than Rh ∴ has greater nucleophilicity
Migratory insertion is slowed by stronger Ir-Me bond
How is the migratory insertion step sped up in BP’s Cativa process?
Rate = k[Ir][CO]/[Iodide] ∴ removing iodide ligand from will speed up reaction
Promoter = group 3 halide, e.g. InCl3 or Ru-CO complexes
Acts as iodide ‘shuttle’→ forms neutral [Ir(CH3)(CO)3I2] complex
- Replace I w/ CO ∴ catalyst = neutral [Ir(CH3)(CO)3I2]
- Migratory insertion is fast since CO = good π acceptor ligand (removes e- density from M → makes Ir-Me bond weaker → faster rxn
- Add iodide back in + loose CO
Draw the mechanism for BP’s Cativa Process?
- OA of MeI (fast)
- Rather than slow MI
- Replace I w/ CO ∴ catalyst = neutral [Ir(CH3)(CO)3I2]
* via a promoter (lewis acid I= v big,soft anion ∴ needs fairly soft lewis acid or TM Ru-CO complexes
rather than slow MI
loss of Iodide via promoter
addition of CO - Fast CO MI
* Additon of iodide via promoter → back into main cycle
* Forms acetyl complex - Reductive elimination to regenerate catalyst
What are the advantages of of BP’s Cativa Process?
Catalyst = more stable at ↓ [H2O] – WGSR not a problem
IR = cheaper than Rh
Product is purer – fewer distillation columns required
What is hydroformylation?
Conversion of an alkene to a linear (desired) and branched aldehyde
Alkene + CO + H₂ → RCOH
What is the catalyst used in hydroformylation?
Pre-catalys = [Co(CO)₄(H)], Co (1), SP, d8
Active catalyst = [Co(CO)₃(H)]
Or Rh carbonyl complex
Draw the mechanism for the unmodified Cobalt catalyst used in hydroformylation
- Alkene coordination
Binds to M centre → TBP compound - 1,2 migratory insertion
* Co-H in cis orientation to Co-alkene
* Hydride undergoes MI w/ alkene → alkyl
* Side rxn: 2,1 migratory insertion of alkene → i-alkene (iso/ branched) - CO coordination
* 5 coordinate species - Migratory insertion
* Alkyl in cis orientation to carbonyl
* Alkyl undergoes MI w/ carbonyl → acyl
* Forms metallic ketone - OA of H2
* Concerted OA:
* H2 = non-polar
* Co (1) = low OS + 4 coordinate species - Reductive elimination
* Organic group in cis orientation to hydride
* Forms n-aldehyde product (linear)
What is the RDS of unmodified cobalt hydroformylation?
OA of H2
What is the rate equation of unmodified cobalt hydroformylation?
Rate = k [Co][alkene][H2][CO]-1
Why is the unmodified cobalt hydroformylation reaction run at high CO pressure and temperature despite the inverse [CO] order?
Inverse order in CO due to need for CO dissociation from pre-catalyst to form 16e active species
Implies rxn should run under ↓ [CO] → faster catalyst decomp + ↓ l:b selectivity (bc of competitive Co-catalysed alkene isomerisation)
Rxn = run at high CO P + ↑ T to ↑ productivity
What are the issues with the HCo(CO)4 catalysed used in hydroformylation ?
V high P (200+ bar)
Poor catalyst stability
High catalyst volatility
2 isomeric aldehydes in linear : branched ratios of 3 : 1.
How could you improve the HCo(CO)₄ catalyst used for hydroformylation?
Employ a modified phosphine ligand:
Lower CO pressure
Linear : branched ratio improved
Or use a Rhodium modified catalyst:
* Good l:b regioselectivity, stability + cat activity (> Co by 1000x)
How does the addition of phosphine ligands affect the catalyst stability and activity in hydroformylation reaction?
- Electronic effect
* Phosphine ligand stabilises Co-CO bond via sigma donation to Co centre + back bonding to CO ligands
*Makes Co-CO bond stronger against decomposition
* ↓ CO P is required, 80 bar (stronger Co-CO bonds) - Steric effect:
* Linear selectivity is enhanced (l:b ratio ↑ 8 : 1)
* bulkier system promotes linear product in 1,2 insertion step
Give 2 examples of phosphine ligands used in phosphine modified catalyst?
PR3 = P (n-Bu)3, or phobane
Draw the mechanism of the Phosphine modified Co catalyst?
- Pre-cat = CoH(PR3)(CO)3]
- Loss of CO → vacant site on active cat
- Active cat: [CoH(PR3)(CO)2], 16e, SP
- Alkene coordination
* Side rxns: hydrogenation of aldehyde → alcohols - Migratory insertion
- CO coordination
- Migratory insertion
- OA of H2
- Reductive elimination
What two hydrogenation reactions occur due to addition of phosphine ligands in Co hydroformylation reaction?
- Hydrogenation of aldehydes → Alcohols
- Hydrogenation of alkenes → alkanes - waste side product ~15 %
Draw the mechanism for the hydrogenation of aldehydes to alcohols side reaction that occurs in the phosphine modified cobalt catalyst in hydroformylation
- Coordination of aldehyde formed from hydroformylation rxn
- Migratory insertion of aldehyde
* Forms metal alkoxide species - OA of H2
- Reductive elimination
* Generates alcohol
What is the rate in the Rhodium modified catalyst in hydroformylation reaction?
Rate = k [Rh][alkene][H2]0[CO]-1[PPh3]-1
- Pre-cat = Rh (I), 18E, TBP, loss of PPh3 → active cat
- Active cat = Rh (1), 16 VE, SP
- Alkene coordination RDS
- MI
- CO coordination
- 1,1 MI
- OA
- RE
How does using Rhodium increase the stability of the catalyst in hydroformylation
Rh is a 2nd row TM ∴ has a stronger M-L bond whilst Co is 1st row TM
What is a disadvantage of Rh modified catalyst used in hydroformylation?
Rh is more expensive
Name 2 processes that use Rh phosphine modified catalysts
- Ruhrchemie/Rhone–Poulenc process
- Eastman kodak process
Draw structure of bisbi ligand used in Eastman Kodak process and comment on structure, activity
- 9 membered chelates
- V flexible w/ a large + variable bite angle (spans both 90-120 degrees in TBP complexes)
- Catalyst activity 10x > phosphine mod cats
- High l:b ratio 25:1
- Dissociation of 1 P-donor does not (necessarily) -> ligand loss (chelate effect)
- Despite being a 9 membered chelate, the unsaturated bonds lead to fewer degrees of rotational freedom than sat analogues -> higher chelate effect
chelating diphosphine ligand with diaryl structure - when it coords to Rh makes 9 membered ring
Draw structure of TPPTs ligand used in Ruhrchemie/Rhone–Poulenc process
- V water soluble catalyst due to suffocated groups
- Biphasic catalysis w/ reagents in organic phase
- Rxn occurs at interface
- Allows facile product separation + catalyst recycling
Which alkenes use the Ruhrchemie/Rhone–Poulenc process
Propene + butene
What is a phosphite
Instead of alkyl or arly have alkoxide group instead
How effect do phosphite modified Rh based catalysts have on hydroformylation?
200x activity of PPh3 analogue
Easier CO dissociation (phosphite more pi acidic than phosphine)
BUT dissociated phosphite readily undergoes hydrolysis → cat deactivation
Name a process that utilises phosphite modified Rh catalyst
Union carbide process
Draw structure of phosphite ligand used Union carbide process
Rh cat = 50x more active than PPh3 analogue
Ring provides kinetic stability against hydrolysis
tBu group makes ligand environment more hydrophobic
Reduces hydrolysis
Increases steric bulk → maximising l:b ratio (=80)
What is cross coupling?
Coupling of a boronic ester / acid with an aryl halide / vinyl halide
Draw the mechanism for the Suzuki cross coupling
Loss of 2 PPh3 ligands to form active e- rich catalyst w/ vacant bonding sites
- OA of aryl halide (Pd inserts between halide and C) Pd = oxidised + carbon is reduced
- Transmetallation (RDS)
* base reacts w/ boronic acid –
* exchange R group on B for X group on Pd (2 metals exchange R groups)
NaOH → R-B(OH)₃⁻ → X-B(OH)₃⁻ → NaX + B(OH)₃ - Ligand swap with the metal
- Trans-cis-isomerization
* now have 2 alkyl or aryl group on cis orientation - Reductive elimination –
* Concerted step
* Doesn’t occur if the 2 regions are trans to each other
- 2 organic regions form single bond + give Pd 2 e-‘s back → pd reduced to Pd 0
- generates product + addition of phosphine regenerates catalyst
Why would the rate of a Pd(PR₃)₄ catalysed Suzuki reaction increase when R follows:
CMe₃ > CHMe₂ > (CH₂)Me > Me
Oxidative addition favoured with bulky phosphine ligands since the Pd will more readily lose one of the bulky phosphines during OA in order to remove steric strain
Why is a strong base such as NaOH used in the Suzuki reaction?
Anionic, 4 CN boron compounds are significantly more amenable to transmetallation.
This can be achieved by adding a hard base, such as hydroxide. Therefore R-B(OH)₂ doesn’t work but R-⁻B(OH)₃ does
Why can’t you use sp3 carbon centres in the Suzuki reaction?
β-hydride elimination can occur which will just reduce the alkyl chain to an alkene and release HX as a byproduct
Why does the OA rate of Suzuki cross-coupling increase with more bulky sterically hindered ligands?
Usually steric crowding ≠ fast addn
However, Low CN = important
↑ steric crowding by PPh3 LGs facilitates LG de-coordination + enables rxn to proceed faster
Why are aryl-bromides in the Suzuki cross coupling?
- Aryl iodides = easily cross-coupled, while aryl chlorides = v slow + aryl fluorides dont undergo cross-coupling.
- C-X bond strength affects OA Ea
- aryl-iodides → side rxns so aryl-bromide used
What is the role of coordination in Suzuki cross-coupling reactions?
Initial coordination between TM + halide (X) brings the boronic acid or Grignard reagent closer to M center.
Stronger coordination is observed for the Grignard reagent compared to the boronic acid.
The presence of a base enhances the reactivity of the boronic acid and aids in the initial coordination between the substrate and the transition metal catalyst.
Replacing the halide (X) with OH- creates a stronger interaction, promoting efficient transmetallation.
What is the heck reaction?
Coupling of alkene with a aryl halide / vinyl halide
What is one key difference between the Suzuki reaction and Heck and Buchwald-Hartwig amination
Heck reaction and Buchwald-Hartwig amination have no transmetallation
Draw the mechanism for the Heck reaction
Low CN Pd species
Ligands: 2 bulky phosphine ligands
- OA of Aryl halide
- Ligand substitution
* Alkene comes in + displaces 1 of the remaining L ligands in a L subs rxn - Migratory insertion (2,1-insertion = mimics sterics)
* alkene in cis orientation to Pd Aryl e.g. Pd sigma cabron bond - B-hydride elimination
* Have beta hydrogens and low CN Pd species - Ligand substitution
- Reductive elimination -> trans isomer
What is Buchwald-Hartwig amination?
Coupling of an aryl halide with an amine.
Ar-X + NHR₂ → Ar-NR₂
Why is a strong base e.g. (NaOt-Bu) needed for Buchwald-Hartwig amination?
- Forms new C-N bond Ar-Nr2 = aryl amine
- Deprotonation of NH occurs after coord to Pd (↑ acidity at this stage)
- Wide range of N nucleophiles tolerated
Draw the Buchwald-Hartwig amination mechanism?
Low CN Pd (0)
1. OA of aryl halide
2. Nucleophilic substitution type rxn:
* Instead of transmetallation
* Amine acts as a nucleophile → nu sub rxn happens on Pd
* by coordinating amine to metal increases acidity of proton compared to free amine - sufficiently acidic - strong base come in deprotonates it -lose base salt make key intermediate
3. Reductive elimination
Intramolecular amination
Aryl halide + amine in same molecule
Xantpos - chelating phosphine LG
Intermolecular amination
Using trifalates → acts v similarly to aryl bromide
BINAP ligand (more complex phosphine ligand)
What are the two cycles involved in alkene hydrogenation?
The neutral cycle using Wilkinson’s catalyst and the cationic cycle with Rh(I) catalyst
In the neutral cycle of alkene hydrogenation, what is the order of steps?
- OA 1st
- Alkene coord 2nd
- Solvent used is neutral 2e- donor
What are the key components of the cationic cycle in alkene hydrogenation?
- Rh (I)
- Alkene coord 1st
- OA 2nd
- Chelating phosphine
- Weakly coordinating anion e.g. BF4 → don’t act as LG bc -ve charge more diffuse
How can chiral diphosphine ligands contribute to stereoselective catalytic hydrogenation?
By coordinating with prochiral alkenes. The attack of the metal on different faces of the prochiral alkene leads to two diastereomers:
1. Sterically favoured - less steric bulk
2. Sterically unfavoured – steric clash between 2 bulky R groups
Examples:
A + B = different (P-chiral) e.g. DIPAMP LG
A + B = same but chiral backbone sets conformation of chelate ring
What is a key complication in achieving stereoselectivity in alkene hydrogenation?
The most stable diastereomer does not necessarily lead to the major product. Stereoselectivity is influenced by the specific reaction pathways and energy barriers (Ea) for each diastereomer
Provide a real example of stereoselective hydrogenation?
L-DOPA, used in the treatment of Parkinson’s disease, undergoes asymmetric hydrogenation. The rate of OA for the minor diastereomer is significantly faster: 600x > major diastereomer
* Steps after OA (MI, etc) = fast + irreversible
* Faster OA of minor diasteromer ‘locks in’ that stereochemical outcome
Draw the mechanism for the stereoselective alkene hydrogenation of L-DOPA formation?
- pre catalyst + substrate in centre
- 2 possible routes:
1.Coordination to form intermediate I = favoured - OA
- MI
- RE → product or can go to intermediate I’ = least favoured
2. Coordination to form intermediate I’ = disfavoured
