Asymmetric Synthesis Methods: chiral pool, auxiliaries, catalytic asymmetric routes MCQs With Answer

Asymmetric Synthesis Methods: chiral pool, auxiliaries, catalytic asymmetric routes MCQs With Answer

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Introduction: Asymmetric synthesis is central to modern pharmaceutical chemistry because the biological activity of drugs often depends on molecular chirality. This blog focuses on three practical approaches: the chiral pool (using naturally available enantiopure building blocks), chiral auxiliaries (temporary stereodirecting groups that enforce diastereoselectivity), and catalytic asymmetric routes (metal-/organocatalysis, enzymatic methods). The MCQs that follow are designed for M.Pharm students preparing for MPC 202T Advanced Organic Chemistry II, emphasizing mechanistic reasoning, choice of reagents, stereochemical models and pharmaceutical applications. These questions strengthen conceptual understanding and exam readiness while reflecting real synthetic decision-making in drug development.

Q1. Which of the following best describes the “chiral pool” approach in asymmetric synthesis?

  • Using racemic mixtures followed by chromatographic separation
  • Employing naturally abundant enantiomerically pure compounds as starting materials
  • Generating chirality exclusively by asymmetric catalysis from achiral substrates
  • Using chiral auxiliaries to induce stereochemistry during a single step

Correct Answer: Employing naturally abundant enantiomerically pure compounds as starting materials

Q2. Which is a primary advantage of using a chiral pool starting material in pharmaceutical synthesis?

  • It eliminates the need to monitor enantiomeric excess during reactions
  • It guarantees 100% yield for all subsequent steps
  • It provides inherent stereochemical information often with high enantiopurity and cost-effectiveness
  • It avoids the need for purification of intermediates

Correct Answer: It provides inherent stereochemical information often with high enantiopurity and cost-effectiveness

Q3. Which property is essential for an effective chiral auxiliary?

  • It must permanently alter the molecular framework and remain in the final drug
  • It must be costly and difficult to prepare to ensure uniqueness
  • It must induce high diastereoselectivity and be easily installed and removed under mild conditions
  • It must racemize under the reaction conditions to average stereochemistry

Correct Answer: It must induce high diastereoselectivity and be easily installed and removed under mild conditions

Q4. The Evans oxazolidinone auxiliary is most commonly used to control stereochemistry in which type of transformation?

  • Radical halogenation of alkanes
  • Enolate alkylation and acylation reactions
  • Electrophilic aromatic substitution
  • Asymmetric hydrogenation of alkenes

Correct Answer: Enolate alkylation and acylation reactions

Q5. Which statement correctly explains why Evans auxiliaries give high stereocontrol in enolate reactions?

  • They act as strong Lewis acids to activate the electrophile
  • They rigidly bias the enolate geometry and shield one face, directing nucleophile approach
  • They are chiral catalysts that turnover during the reaction
  • They racemize the substrate to produce a single enantiomer thermodynamically

Correct Answer: They rigidly bias the enolate geometry and shield one face, directing nucleophile approach

Q6. Oppolzer’s sultam is valued as a chiral auxiliary because it:

  • Cannot be recovered after use and therefore drives reactions irreversibly
  • Provides efficient diastereoselection and can be removed reductively to reveal the target functionality
  • Is achiral but forms chiral complexes with metals
  • Is only useful for radical-based transformations

Correct Answer: Provides efficient diastereoselection and can be removed reductively to reveal the target functionality

Q7. The Corey–Bakshi–Shibata (CBS) catalyst is an oxazaborolidine used mainly for:

  • Asymmetric epoxidation of alkenes
  • Asymmetric reduction of ketones via enantioselective hydride delivery from borane
  • Asymmetric hydrogenation of activated alkenes with H2 gas
  • Enantioselective cycloaddition reactions

Correct Answer: Asymmetric reduction of ketones via enantioselective hydride delivery from borane

Q8. Which metal–ligand system is classically associated with high enantioselectivity in hydrogenation of prochiral olefins in industry?

  • Pd/C without chiral ligand
  • Ru-BINAP and related Ru-diamine or Rh-BINAP catalyst systems
  • FeCl3 with racemic phosphines
  • CuI with tertiary amines

Correct Answer: Ru-BINAP and related Ru-diamine or Rh-BINAP catalyst systems

Q9. Sharpless asymmetric epoxidation requires which functional group on the substrate to achieve high enantioselectivity?

  • An internal alkyne
  • An allylic alcohol
  • A benzylic chloride
  • A terminal alkane

Correct Answer: An allylic alcohol

Q10. Jacobsen (Mn–salen) and Katsuki Mn catalysts are primarily used for:

  • Asymmetric dihydroxylation of allylic alcohols
  • Asymmetric epoxidation of unfunctionalized alkenes
  • Asymmetric hydrogenation of imines
  • Enzyme-catalyzed ester hydrolysis

Correct Answer: Asymmetric epoxidation of unfunctionalized alkenes

Q11. In asymmetric phase-transfer catalysis (PTC), which class of catalysts is commonly used to induce chirality?

  • Cinchona alkaloid-derived quaternary ammonium salts
  • Achiral crown ethers
  • Simple tertiary amines like triethylamine
  • Aromatic sulfonic acids

Correct Answer: Cinchona alkaloid-derived quaternary ammonium salts

Q12. What is the maximum theoretical yield of a single enantiomer product from a classical kinetic resolution of a racemate without in‑situ racemization?

  • 100% because one enantiomer is exclusively converted
  • 75% since one enantiomer reacts faster
  • 50% because only one enantiomer is selectively transformed
  • 0% because racemates cannot be resolved kinetically

Correct Answer: 50% because only one enantiomer is selectively transformed

Q13. Dynamic kinetic resolution (DKR) can surpass the 50% yield limit of classical kinetic resolution because it involves:

  • Simultaneous racemization of the substrate and selective transformation of one enantiomer
  • Use of stoichiometric chiral auxiliaries without turnover
  • Complete suppression of any racemization during the process
  • Physical separation of enantiomers by chromatography only

Correct Answer: Simultaneous racemization of the substrate and selective transformation of one enantiomer

Q14. In asymmetric dihydroxylation (Sharpless AD), the chiral ligand that directs facial selectivity is typically derived from:

  • Cinchona alkaloids for primary alcohols
  • Diethyl tartrate used with OsO4 in AD-mix α or β
  • Triphenylphosphine for radical dihydroxylation
  • Chiral carbenes coordinated to rhodium

Correct Answer: Diethyl tartrate used with OsO4 in AD-mix α or β

Q15. In the context of stereochemical models, which model is most often invoked to predict the major product in nucleophilic addition to a carbonyl adjacent to a stereogenic center?

  • Markovnikov’s rule
  • Felkin–Anh model
  • Hückel aromaticity rule
  • Woodward–Hoffmann conservation of orbital symmetry

Correct Answer: Felkin–Anh model

Q16. The term “matched/mismatched pair” refers to which situation in asymmetric synthesis?

  • When two achiral reagents form a chiral product
  • When the stereochemistry of a chiral reagent and a chiral catalyst/auxiliary either reinforce (matched) or oppose (mismatched) stereochemical induction
  • When enantiomers form diastereomers upon reaction
  • When racemic mixtures are separated by distillation

Correct Answer: When the stereochemistry of a chiral reagent and a chiral catalyst/auxiliary either reinforce (matched) or oppose (mismatched) stereochemical induction

Q17. Which technique is most appropriate for quantitative measurement of enantiomeric excess (ee) of a chiral drug intermediate?

  • Thin-layer chromatography (TLC) without chiral stationary phase
  • Polarimetry without concentration and pathlength standardization
  • Chiral HPLC or GC with a chiral stationary phase
  • Infrared spectroscopy (IR) of the racemate

Correct Answer: Chiral HPLC or GC with a chiral stationary phase

Q18. Which catalytic method is commonly used for enantioselective allylic substitution (Tsuji–Trost-type) reactions?

  • Pd-catalyzed allylic substitution with chiral phosphine or PHOX ligands
  • Radical halogenation using NBS
  • Base-catalyzed aldol condensation without chiral induction
  • Acid-catalyzed dehydration of alcohols

Correct Answer: Pd-catalyzed allylic substitution with chiral phosphine or PHOX ligands

Q19. Which of the following is an example of organocatalysis used in asymmetric synthesis?

  • Ruthenium–BINAP catalyzed hydrogenation
  • Lipase-catalyzed ester hydrolysis
  • Cinchona-derived quinuclidine catalyzing asymmetric Michael addition
  • OsO4-mediated dihydroxylation with diethyl tartrate

Correct Answer: Cinchona-derived quinuclidine catalyzing asymmetric Michael addition

Q20. Lipase-catalyzed kinetic resolution of secondary alcohols in organic synthesis is widely used because:

  • Lipases require high temperatures incompatible with most substrates
  • They provide high enantioselectivity under mild, often solvent-tolerant conditions and can employ simple acyl donors
  • They racemize the substrate to give racemic products analytically
  • They are only effective on primary amines and not alcohols

Correct Answer: They provide high enantioselectivity under mild, often solvent-tolerant conditions and can employ simple acyl donors

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