Asymmetric synthesis – partial MCQs With Answer

Asymmetric synthesis – partial MCQs With Answer

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Asymmetric synthesis is a cornerstone of modern pharmaceutical chemistry, focusing on stereoselective methods to produce one enantiomer over another. This topic covers chiral catalysts, auxiliaries, organocatalysis, asymmetric hydrogenation, epoxidation and addition reactions, plus analytical techniques like chiral HPLC and optical rotation to determine enantiomeric excess. For B. Pharm students, understanding enantioselectivity, stereochemical models (Felkin–Anh, chelation control), resolution techniques and regulatory relevance is essential for drug design and safety. Mastery of mechanisms and catalyst selection improves synthesis efficiency and reduces toxic enantiomer formation. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary goal of asymmetric synthesis in pharmaceutical chemistry?

  • To produce racemic mixtures for screening
  • To selectively prepare one enantiomer over the other
  • To increase reaction temperature to speed up syntheses
  • To avoid using chiral reagents

Correct Answer: To selectively prepare one enantiomer over the other

Q2. Which term describes the excess of one enantiomer over the other in a mixture?

  • Optical purity
  • Enantiomeric excess
  • Racemic ratio
  • Conversion rate

Correct Answer: Enantiomeric excess

Q3. Which analytical technique is commonly used to separate and quantify enantiomers?

  • Gas chromatography with non-chiral column
  • Chiral high-performance liquid chromatography (chiral HPLC)
  • Infrared spectroscopy
  • Ultraviolet-visible spectroscopy

Correct Answer: Chiral high-performance liquid chromatography (chiral HPLC)

Q4. The Felkin–Anh model is used to predict stereochemical outcome for nucleophilic addition to which functional group?

  • Amide nitrogen
  • Aldehydes and ketones (carbonyls)
  • Carboxylic acids
  • Alkenes

Correct Answer: Aldehydes and ketones (carbonyls)

Q5. Which reagent/catalyst is associated with asymmetric epoxidation of allylic alcohols (Sharpless epoxidation)?

  • Ti(OiPr)4 with diethyl tartrate (DET)
  • Pd/C and H2
  • mCPBA alone
  • Grignard reagent

Correct Answer: Ti(OiPr)4 with diethyl tartrate (DET)

Q6. What does the term “enantioselectivity” formally describe?

  • The rate of reaction
  • The preference for forming one enantiomer over another
  • Total yield of a synthesis
  • The molecular weight distribution

Correct Answer: The preference for forming one enantiomer over another

Q7. Which chiral ligand is commonly used in asymmetric hydrogenation catalysts (e.g., Noyori–Ikariya, Rh–BINAP)?

  • Pyridine
  • BINAP
  • DMF
  • Boric acid

Correct Answer: BINAP

Q8. What is kinetic resolution in the context of chiral compounds?

  • Converting a racemate into a single enantiomer by completely removing one enantiomer
  • Separating enantiomers by crystallization without reactivity differences
  • Using different reaction rates for two enantiomers to preferentially modify or consume one
  • Racemizing one enantiomer to achieve equilibrium

Correct Answer: Using different reaction rates for two enantiomers to preferentially modify or consume one

Q9. Which organocatalyst is famous for catalyzing asymmetric aldol reactions via enamine activation?

  • Lithium aluminum hydride
  • L-proline
  • Sodium hydroxide
  • Tetrabutylammonium bromide

Correct Answer: L-proline

Q10. Which concept describes a center that can become stereogenic after a chemical transformation (i.e., attack on a planar prochiral center)?

  • Pseudoasymmetry
  • Prochiral center
  • Mesomerism
  • Atropisomerism

Correct Answer: Prochiral center

Q11. In asymmetric hydrogenation, which metal is commonly used with chiral ligands for reduction of C=C bonds in pharmaceuticals?

  • Iron without ligands
  • Rhodium with chiral phosphine ligands
  • Sodium metal
  • Mercury

Correct Answer: Rhodium with chiral phosphine ligands

Q12. Which of the following describes a chiral auxiliary?

  • An achiral catalyst that speeds a reaction
  • A removable chiral group used to induce stereochemistry during a reaction
  • A solvent that improves selectivity
  • A permanently attached functional group that doesn’t influence stereochemistry

Correct Answer: A removable chiral group used to induce stereochemistry during a reaction

Q13. What is dynamic kinetic resolution (DKR)?

  • Sequential crystallization steps to enrich one enantiomer
  • Combining racemization of the substrate with enantioselective conversion to give high yield of single enantiomer
  • Using only one enantiomer as starting material
  • Heating to equilibrium to get racemate

Correct Answer: Combining racemization of the substrate with enantioselective conversion to give high yield of single enantiomer

Q14. Which measurement directly provides the sign and magnitude of optical rotation of a chiral sample?

  • NMR spectroscopy
  • Polarimetry
  • Mass spectrometry
  • IR spectroscopy

Correct Answer: Polarimetry

Q15. The Jacobsen epoxidation uses which type of catalyst for asymmetric epoxidation of unfunctionalized alkenes?

  • Manganese salen (Mn-salen) complexes
  • Platinum oxide
  • Aluminum isopropoxide
  • Rhodium carbenes

Correct Answer: Manganese salen (Mn-salen) complexes

Q16. Which model predicts stereochemical outcome influenced by chelation between metal and substrate during nucleophilic addition?

  • Walden inversion
  • Chelation control model
  • Markovnikov rule
  • Hückel rule

Correct Answer: Chelation control model

Q17. Enantiomeric excess (ee) can be calculated from enantiomer percentages. If a sample contains 80% R and 20% S, what is the ee?

  • 20%
  • 60%
  • 80%
  • 100%

Correct Answer: 60%

Q18. Which technique gives stereochemical configuration and relative stereochemistry through through-space coupling and NOE effects?

  • IR spectroscopy
  • 1D proton NMR only
  • Nuclear Overhauser Effect (NOE) NMR experiments
  • Mass spectrometry

Correct Answer: Nuclear Overhauser Effect (NOE) NMR experiments

Q19. What is the role of a chiral phase-transfer catalyst in asymmetric synthesis?

  • To transfer chiral ligands into the gas phase
  • To facilitate enantioselective reactions between phase-separated reagents by shuttling ionic species
  • To act as a reducing agent
  • To remove solvents selectively

Correct Answer: To facilitate enantioselective reactions between phase-separated reagents by shuttling ionic species

Q20. Which of the following is an example of a chiral pool approach?

  • Using benzene as starting material
  • Using naturally occurring chiral building blocks like L-serine to synthesize complex molecules
  • Racemization to obtain both enantiomers
  • Random screening of chiral catalysts

Correct Answer: Using naturally occurring chiral building blocks like L-serine to synthesize complex molecules

Q21. Which term refers to diastereomers formed in unequal amounts during a stereoselective reaction?

  • Racemate
  • Diastereomeric excess (de)
  • Enantiomeric purity
  • Optical inversion

Correct Answer: Diastereomeric excess (de)

Q22. Oppolzer’s sultam is commonly used as which of the following?

  • An achiral solvent
  • A chiral auxiliary for asymmetric synthesis
  • A racemic catalyst
  • An oxidizing agent

Correct Answer: A chiral auxiliary for asymmetric synthesis

Q23. In asymmetric reactions, what does “matched” and “mismatched” pair refer to?

  • Matching two achiral reagents
  • Compatibility or opposition between chiral substrate stereochemistry and chiral reagent/catalyst leading to enhanced or reduced selectivity
  • Matching solvent polarity
  • Whether reagents are enantiomers

Correct Answer: Compatibility or opposition between chiral substrate stereochemistry and chiral reagent/catalyst leading to enhanced or reduced selectivity

Q24. Which synthetic method converts an achiral substrate into a chiral product by controlled formation of a stereocenter at the transition state level?

  • Asymmetric induction using chiral catalysts
  • Simple heating without catalysts
  • Stoichiometric racemization
  • Photolysis only

Correct Answer: Asymmetric induction using chiral catalysts

Q25. Which of the following describes atropisomerism relevant to drug molecules?

  • Stereochemistry due to restricted rotation around a single bond producing stable conformational enantiomers
  • Stereochemistry arising from sp3 centers only
  • A type of nuclear spin isomerism
  • Optical activity due to metal complexes

Correct Answer: Stereochemistry due to restricted rotation around a single bond producing stable conformational enantiomers

Q26. Which mechanism explains inversion of configuration at a stereocenter during nucleophilic substitution?

  • SNi mechanism
  • SN2 mechanism
  • Radical chain mechanism
  • Electrophilic aromatic substitution

Correct Answer: SN2 mechanism

Q27. Which of the following asymmetric reactions is typically catalyzed by proline derivatives or other small organocatalysts?

  • Diels–Alder reaction with metal catalysts only
  • Aldol reaction via enamine activation
  • Free radical polymerization
  • Nucleophilic aromatic substitution

Correct Answer: Aldol reaction via enamine activation

Q28. When designing an asymmetric synthesis for a pharmaceutical candidate, which factor is most critical to avoid adverse effects?

  • Minimizing cost only
  • Controlling stereochemical purity to avoid biologically active undesired enantiomers
  • Using the heaviest catalysts available
  • Maximizing reaction temperature

Correct Answer: Controlling stereochemical purity to avoid biologically active undesired enantiomers

Q29. What is the relationship between optical purity and enantiomeric excess?

  • They are unrelated concepts
  • Optical purity is an older term often equivalent to enantiomeric excess when specific rotations are identical
  • Optical purity is always twice the ee
  • ee is always zero if optical purity is nonzero

Correct Answer: Optical purity is an older term often equivalent to enantiomeric excess when specific rotations are identical

Q30. Which reaction is an example of asymmetric addition to carbonyl compounds using chiral boron reagents?

  • Cornforth reduction
  • Brown asymmetric allylation (using chiral allylboranes)
  • Wurtz coupling
  • Friedel–Crafts acylation

Correct Answer: Brown asymmetric allylation (using chiral allylboranes)

Q31. In the context of asymmetric catalysis, what does turnover frequency (TOF) describe?

  • Number of catalytic cycles per unit time per catalyst active site
  • The maximum temperature achievable
  • The amount of solvent used
  • The molecular weight of product

Correct Answer: Number of catalytic cycles per unit time per catalyst active site

Q32. Which method can be used to resolve enantiomers by forming diastereomeric salts with chiral acids or bases?

  • Enzymatic resolution only
  • Classical resolution by crystallization of diastereomeric salts
  • Flash chromatography on achiral silica
  • Direct sublimation

Correct Answer: Classical resolution by crystallization of diastereomeric salts

Q33. A reaction gives product with 92% ee. What fraction of the major enantiomer is present (as a percentage)?

  • 96%
  • 46%
  • 96% and 4% minor enantiomer, so 96% major
  • 92% major and 8% minor

Correct Answer: 96% and 4% minor enantiomer, so 96% major

Q34. Which chiral ligand pair is often used in asymmetric dihydroxylation (Sharpless AD) reactions?

  • DIPAMP
  • AD-mix-α or AD-mix-β containing chiral cinchona alkaloid-derived ligands
  • PPh3 only
  • EDTA

Correct Answer: AD-mix-α or AD-mix-β containing chiral cinchona alkaloid-derived ligands

Q35. Which stereochemical outcome would you expect if a nucleophile attacks a carbonyl under chelation control with a Lewis acidic metal coordinating both carbonyl oxygen and an adjacent heteroatom?

  • Random attack from both faces equally
  • Attack from the face dictated by chelation geometry, often opposite to Felkin prediction
  • Always inversion at adjacent stereocenter
  • No reaction occurs

Correct Answer: Attack from the face dictated by chelation geometry, often opposite to Felkin prediction

Q36. Which enzyme-catalyzed process is widely used for enantioselective hydrolysis or esterification in pharmaceutical synthesis?

  • Cytochrome P450 oxidation only
  • Lipase-catalyzed kinetic resolution
  • Diels–Alderase solely
  • Dehydration by acid catalysts

Correct Answer: Lipase-catalyzed kinetic resolution

Q37. Which is the best description of “chiral recognition” in chromatographic separation of enantiomers?

  • Both enantiomers have identical retention times
  • Differential interactions between enantiomers and a chiral stationary phase leading to separation
  • Separation achieved by boiling point differences
  • Use of UV detection only

Correct Answer: Differential interactions between enantiomers and a chiral stationary phase leading to separation

Q38. In asymmetric synthesis, why are chiral ligands often preferred over stoichiometric chiral auxiliaries?

  • They are used in catalytic amounts and can provide high atom economy and reduced waste
  • They are always cheaper to synthesize
  • Auxiliaries never control stereochemistry
  • Chiral ligands are always achiral

Correct Answer: They are used in catalytic amounts and can provide high atom economy and reduced waste

Q39. Which is a common method to determine absolute configuration of a single enantiomeric compound?

  • Measuring boiling point only
  • X-ray crystallography with anomalous dispersion
  • Thin-layer chromatography
  • Mass spectrometry fragmentation pattern

Correct Answer: X-ray crystallography with anomalous dispersion

Q40. Which catalytic asymmetric reaction is commonly used to form C–C bonds with high enantioselectivity and often uses chiral Lewis acids?

  • Hydrogenolysis
  • Diels–Alder cycloaddition under chiral Lewis acid catalysis
  • Free radical polymerization
  • Halogenation with chlorine gas

Correct Answer: Diels–Alder cycloaddition under chiral Lewis acid catalysis

Q41. What is the primary pharmacological concern when administering racemic drugs?

  • Racemic mixtures are always more potent
  • One enantiomer may be inactive or harmful while the other is therapeutic, affecting safety and efficacy
  • Racemates have better taste
  • No regulatory concerns exist

Correct Answer: One enantiomer may be inactive or harmful while the other is therapeutic, affecting safety and efficacy

Q42. Which of the following is a stereochemical descriptor system used to assign absolute configuration at stereocenters?

  • cis/trans only
  • Cahn–Ingold–Prelog (R/S) priority rules
  • H and L notation
  • Alpha and beta exclusively

Correct Answer: Cahn–Ingold–Prelog (R/S) priority rules

Q43. In an asymmetric Michael addition catalyzed by a chiral secondary amine, what intermediate typically forms to activate the nucleophile?

  • Imine or enamine intermediate
  • A radical cation
  • A carbocation stabilized by solvent
  • A phosphoryl intermediate

Correct Answer: Imine or enamine intermediate

Q44. Which synthetic route is favored when a drug candidate requires a single enantiomer and large-scale production is needed with minimal waste?

  • Stoichiometric resolution with high waste
  • Asymmetric catalysis (enantioselective catalysis) for scalable high ee and low waste
  • Random racemization
  • Nonselective thermal methods

Correct Answer: Asymmetric catalysis (enantioselective catalysis) for scalable high ee and low waste

Q45. Which chiral reagent is key in the Corey–Bakshi–Shibata (CBS) reduction to obtain enantioenriched secondary alcohols?

  • Chiral oxazaborolidine catalyst
  • Hydrogen peroxide
  • Sodium borohydride alone
  • Grignard reagent

Correct Answer: Chiral oxazaborolidine catalyst

Q46. What is racemization and why is it important to control during asymmetric synthesis?

  • Conversion of a racemate into a single enantiomer; it increases purity
  • Interconversion of enantiomers leading to loss of enantiomeric excess; it undermines stereochemical control and drug efficacy
  • Formation of diastereomers only
  • Change in melting point without stereochemical impact

Correct Answer: Interconversion of enantiomers leading to loss of enantiomeric excess; it undermines stereochemical control and drug efficacy

Q47. Which pair best exemplifies reagent control versus substrate control in asymmetric synthesis?

  • Using a chiral catalyst to dictate stereochemistry vs. using an existing stereocenter in substrate to direct new stereocenter formation
  • Heating vs cooling
  • Solvent polarity vs temperature
  • Using a racemate vs achiral solvent

Correct Answer: Using a chiral catalyst to dictate stereochemistry vs. using an existing stereocenter in substrate to direct new stereocenter formation

Q48. Which approach can increase enantioselectivity by converting a single stereocenter into multiple stereocenters with high control?

  • Random functional group interconversion
  • Asymmetric cascade (tandem) reactions that build complexity in one sequence
  • Prolonged reflux without catalyst
  • Simple dilution of reactants

Correct Answer: Asymmetric cascade (tandem) reactions that build complexity in one sequence

Q49. When reporting ee for pharmaceutical regulatory submissions, which practice is expected?

  • Provide approximate ee without analytical details
  • Provide validated analytical method details and accurate ee or enantiomeric ratio measurements
  • Report only optical rotation sign without magnitude
  • Omit stereochemical data completely

Correct Answer: Provide validated analytical method details and accurate ee or enantiomeric ratio measurements

Q50. Which strategy is most effective to access both enantiomers of a chiral drug candidate for biological testing?

  • Only synthesize racemic mixture and hope for both activities
  • Develop enantioselective routes to each enantiomer (using opposite enantiomer of catalyst or chiral auxiliary) or separate by chiral chromatography
  • Ignore stereochemistry and test achiral impurities
  • Rely exclusively on computational models

Correct Answer: Develop enantioselective routes to each enantiomer (using opposite enantiomer of catalyst or chiral auxiliary) or separate by chiral chromatography

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