Synthetic Reagents: Wilkinson catalyst and Witting reagent MCQs With Answer

Introduction

This quiz-focused blog examines two essential synthetic reagents frequently encountered in advanced organic chemistry and medicinal chemistry synthesis: Wilkinson catalyst and Wittig reagent. Aimed at M.Pharm students, the content combines mechanistic insight, practical aspects, and selectivity considerations relevant to drug molecule construction. You will review electronic structure, catalytic cycles, ligand effects, substrate scope, preparation methods, and stereochemical outcomes. Questions test understanding of oxidative addition, migratory insertion, ylide generation, oxaphosphetane intermediates, and how reaction conditions influence E/Z alkene formation. This concise set of MCQs is ideal for exam revision, classroom discussion, or self-assessment when mastering reagent behavior in complex synthetic routes.

Q1. Which description best represents the electronic and coordination state of Wilkinson’s catalyst RhCl(PPh3)3 in its stable isolated form?

• Rhodium(III), octahedral, 18-electron complex
• Rhodium(II), square planar, 16-electron complex
• Rhodium(I), square planar, 16-electron complex
• Rhodium(0), tetrahedral, 14-electron complex

Correct Answer: Rhodium(I), square planar, 16-electron complex

Q2. What is the initial and essential step in the catalytic hydrogenation cycle promoted by Wilkinson’s catalyst?

• Oxidative addition of alkene to Rh(I)
• Ligand dissociation (loss of a PPh3) to generate a vacant site
• Reductive elimination to release the hydrogenated product
• Transmetalation with boron reagents

Correct Answer: Ligand dissociation (loss of a PPh3) to generate a vacant site

Q3. During alkene hydrogenation with Wilkinson’s catalyst, molecular hydrogen is activated by which mechanistic step?

• σ-Bond metathesis between H–H and Rh–Cl
• Oxidative addition of H2 to Rh(I) to form a dihydride Rh(III) species
• Nucleophilic attack of hydride on coordinated alkene
• Radical hydrogen abstraction from H2

Correct Answer: Oxidative addition of H2 to Rh(I) to form a dihydride Rh(III) species

Q4. Wilkinson’s catalyst is known to give which stereochemical outcome when hydrogenating a simple alkene?

• Anti addition giving trans-alkane stereochemistry
• Syn addition leading to both hydrogens delivered from the same face
• Radical-mediated mixture of stereoisomers
• No stereochemical control; racemic mixture of enantiomers

Correct Answer: Syn addition leading to both hydrogens delivered from the same face

Q5. Which substrate is most likely to poison Wilkinson’s catalyst and decrease its hydrogenation activity?

• Tertiary alkene without heteroatoms
• Alkene bearing a thiol or sulfide functional group
• Saturated hydrocarbon chain
• Simple terminal alkene with no coordinating groups

Correct Answer: Alkene bearing a thiol or sulfide functional group

Q6. Which modification of Wilkinson-type catalysts is commonly used to increase reactivity toward internal and hindered alkenes?

• Replacing PPh3 with more donating or bulky phosphines to tune dissociation
• Adding stronger coordinating halides to block sites
• Converting Rh(I) to Rh(IV) salts
• Introducing perfluorinated alkyl ligands to decrease electron density

Correct Answer: Replacing PPh3 with more donating or bulky phosphines to tune dissociation

Q7. Which statement about the role of PPh3 ligands in Wilkinson’s catalyst is correct?

• PPh3 ligands are irreversibly bound and never dissociate in catalysis
• PPh3 must dissociate to provide an open coordination site for substrate binding
• PPh3 acts solely as a hydrogen carrier in the mechanism
• PPh3 is oxidized to triphenylphosphine oxide during hydrogenation

Correct Answer: PPh3 must dissociate to provide an open coordination site for substrate binding

Q8. Which experimental condition typically slows down hydrogenation using Wilkinson’s catalyst?

• Increasing H2 pressure
• Using coordinating solvents like pyridine
• Raising temperature moderately
• Using non-coordinating solvents like hexane

Correct Answer: Using coordinating solvents like pyridine

Q9. In the context of catalytic hydrogenation with Wilkinson’s catalyst, what is the primary reason trisubstituted alkenes are hydrogenated more slowly than monosubstituted alkenes?

• Higher electron deficiency of trisubstituted alkenes
• Steric hindrance limits coordination to the Rh center and slows insertion
• Trisubstituted alkenes form strong covalent bonds with Rh that stop catalysis
• They preferentially undergo polymerization rather than hydrogenation

Correct Answer: Steric hindrance limits coordination to the Rh center and slows insertion

Q10. Which mechanistic step in Wilkinson-catalyzed hydrogenation is responsible for formation of the C–H bonds in the product?

• Coordination of alkene to Rh center
• Migratory insertion of alkene into an Rh–H bond followed by reductive elimination
• Oxidative addition of the alkene to give a di-alkyl Rh complex
• Ligand exchange between PPh3 and substrate

Correct Answer: Migratory insertion of alkene into an Rh–H bond followed by reductive elimination

Q11. Wittig reagents (phosphonium ylides) are typically prepared by which sequence?

• Deprotonation of a phosphine oxide followed by alkylation
• Alkylation of triphenylphosphine to give a phosphonium salt, then deprotonation to form the ylide
• Oxidative addition of alkyl halide to elemental phosphorus
• Direct condensation of aldehydes with phosphines to form ylide

Correct Answer: Alkylation of triphenylphosphine to give a phosphonium salt, then deprotonation to form the ylide

Q12. Which base is most commonly used to generate a non-stabilized Wittig ylide from a phosphonium salt in laboratory practice?

• Potassium carbonate (K2CO3)
• Sodium borohydride (NaBH4)
• n-Butyllithium (n-BuLi)
• Acetic acid

Correct Answer: n-Butyllithium (n-BuLi)

Q13. Which factor primarily determines whether a Wittig reaction gives Z (cis) or E (trans) alkene products?

• The solvent polarity only
• Whether the ylide is stabilized (electron-withdrawing groups) or non-stabilized
• The presence of catalytic hydrogenation conditions
• The concentration of triphenylphosphine oxide formed

Correct Answer: Whether the ylide is stabilized (electron-withdrawing groups) or non-stabilized

Q14. Which statement correctly describes stereochemical outcome trends for Wittig reactions?

• Non-stabilized ylides generally give predominantly Z-alkenes; stabilized ylides favor E-alkenes
• All ylides give exclusively E-alkenes regardless of substitution
• All ylides give exclusively Z-alkenes regardless of substitution
• Stereochemistry cannot be predicted and is always a 50:50 mixture

Correct Answer: Non-stabilized ylides generally give predominantly Z-alkenes; stabilized ylides favor E-alkenes

Q15. What is the key four-membered intermediate invoked in the Wittig reaction mechanism that collapses to give alkene and triphenylphosphine oxide?

• Oxetane
• Oxaphosphetane
• Benzyl carbocation
• Phosphorane radical

Correct Answer: Oxaphosphetane

Q16. Which limitation is commonly associated with the Wittig reaction when applied to complex molecules in medicinal chemistry?

• It cannot form carbon–carbon double bonds
• Triphenylphosphine oxide by-product is often difficult to remove from polar products
• It selectively reacts with carboxylic acids but not aldehydes
• It invariably racemizes adjacent stereocenters

Correct Answer: Triphenylphosphine oxide by-product is often difficult to remove from polar products

Q17. What is a common synthetic strategy to obtain E-alkenes from aldehydes/ketones when Wittig provides Z-rich mixtures?

• Use stabilized ylides or Horner–Wadsworth–Emmons reagents for better E-selectivity
• Increase the amount of triphenylphosphine salt formed
• Carry out the reaction under high vacuum to favor E-products
• Replace aldehyde with an alcohol and run the Wittig

Correct Answer: Use stabilized ylides or Horner–Wadsworth–Emmons reagents for better E-selectivity

Q18. Which statement about the reactivity of stabilized versus non-stabilized phosphonium ylides is correct?

• Stabilized ylides are more nucleophilic and more reactive toward ketones than non-stabilized ylides
• Non-stabilized ylides are more reactive (nucleophilic) and often give faster reactions with aldehydes
• Both types have identical reactivity and selectivity patterns
• Stabilized ylides decompose immediately and are not used synthetically

Correct Answer: Non-stabilized ylides are more reactive (nucleophilic) and often give faster reactions with aldehydes

Q19. Which of the following transformations is NOT typically achieved directly by a Wittig reaction?

• Conversion of an aldehyde to a terminal alkene
• Conversion of a ketone to a trisubstituted alkene
• Direct conversion of an ester to an alkene (without prior modification)
• Synthesis of conjugated dienes using appropriate ylides

Correct Answer: Direct conversion of an ester to an alkene (without prior modification)

Q20. In synthesis planning for drug-like molecules, when would you prefer using Wilkinson’s catalyst versus a heterogeneous hydrogenation catalyst (e.g., Pd/C)?

• When a highly heterogeneous, unselective hydrogenation is required
• When homogeneous, chemoselective hydrogenation of alkenes in presence of reducible heteroatoms or sensitive functional groups is needed
• When large-scale filtration is impossible and catalyst recovery is undesired
• When the substrate contains sulfur functionality that must be retained

Correct Answer: When homogeneous, chemoselective hydrogenation of alkenes in presence of reducible heteroatoms or sensitive functional groups is needed

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