Named Reactions: Sharpless asymmetric epoxidation MCQs With Answer

Introduction: Sharpless asymmetric epoxidation is a cornerstone named reaction in asymmetric synthesis, widely used for preparing enantioenriched epoxides from allylic alcohols. This blog presents 20 focused MCQs with answers tailored for M.Pharm students studying MPC 102T Advanced Organic Chemistry I. Questions cover reagents, mechanism, stereochemical models, reaction conditions, substrate scope, limitations, and pharmaceutical applications, plus practical tips for experimental setups and exam preparation. Each question emphasizes conceptual understanding and problem-solving relevant to drug synthesis and chiral building blocks. Use these MCQs to test knowledge, reinforce key principles, and prepare for viva and written exams while deepening insight into asymmetric oxidations in medicinal chemistry.

Q1. Which set of reagents is the classical combination used in Sharpless asymmetric epoxidation?

• Ti(OiPr)4, diethyl tartrate (DET), tert-butyl hydroperoxide (TBHP)
• MCPBA and DMAP
• KMnO4 in acetone
• Mn(salen) catalyst and NaOCl

Correct Answer: Ti(OiPr)4, diethyl tartrate (DET), tert-butyl hydroperoxide (TBHP)

Q2. What is the primary role of the allylic alcohol group in substrates undergoing Sharpless asymmetric epoxidation?

• To coordinate to titanium and direct the oxygen transfer for high enantioselectivity
• To act as the stoichiometric oxidant
• To be displaced by tert-butyl hydroperoxide
• To act as a leaving group during epoxide formation

Correct Answer: To coordinate to titanium and direct the oxygen transfer for high enantioselectivity

Q3. How does the choice of (+)-DET versus (−)-DET influence the Sharpless epoxidation?

• They produce opposite enantiomers of the epoxide when all other conditions are constant
• They change only the reaction rate, not the stereochemistry
• They convert the reaction from catalytic to stoichiometric
• They determine whether TBHP or H2O2 is the oxidant

Correct Answer: They produce opposite enantiomers of the epoxide when all other conditions are constant

Q4. What are the typical temperature conditions for achieving high enantioselectivity in Sharpless asymmetric epoxidation?

• Low temperatures such as −20 °C to −78 °C
• Refluxing in ethanol
• Room temperature with strong base
• High temperatures above 100 °C

Correct Answer: Low temperatures such as −20 °C to −78 °C

Q5. Which intermediate is central to the accepted mechanism of Sharpless asymmetric epoxidation?

• A titanium–peroxo (Ti–OO–) chiral complex that transfers oxygen to the coordinated alkene
• A free radical generated from TBHP that attacks the alkene
• An iron-oxo species similar to cytochrome P450
• A concerted peracid epoxidation intermediate identical to m-CPBA

Correct Answer: A titanium–peroxo (Ti–OO–) chiral complex that transfers oxygen to the coordinated alkene

Q6. Why are molecular sieves or dry solvents often used in Sharpless epoxidation protocols?

• To remove water and prevent hydrolysis of the titanium complex, maintaining catalyst activity and selectivity
• To act as a co-catalyst that increases reaction rate
• To stabilize TBHP by forming adducts
• To catalyze isomerization of the alkene prior to epoxidation

Correct Answer: To remove water and prevent hydrolysis of the titanium complex, maintaining catalyst activity and selectivity

Q7. Which class of alkenes gives the highest enantioselectivity under Sharpless epoxidation?

• Allylic alcohols (substrates with a free allylic hydroxyl group)
• Unfunctionalized terminal alkenes without directing groups
• Internal trisubstituted alkenes lacking proximal functionalities
• Conjugated enones

Correct Answer: Allylic alcohols (substrates with a free allylic hydroxyl group)

Q8. Is the Sharpless asymmetric epoxidation catalytic in titanium and the chiral tartrate ligand?

• Yes; catalytic amounts of titanium and tartrate ligand are commonly used with stoichiometric oxidant
• No; titanium and tartrate must be used in large stoichiometric excess
• No; the reaction proceeds only with organometallic catalysts such as Pd
• Yes; but the oxidant is catalytic and the ligand is stoichiometric

Correct Answer: Yes; catalytic amounts of titanium and tartrate ligand are commonly used with stoichiometric oxidant

Q9. Which oxidant is conventionally used in Sharpless asymmetric epoxidation?

• Tert-butyl hydroperoxide (TBHP)
• Hydrogen peroxide (H2O2) only
• Meta-chloroperbenzoic acid (m-CPBA)
• Potassium permanganate (KMnO4)

Correct Answer: Tert-butyl hydroperoxide (TBHP)

Q10. The Sharpless stereochemical model explains enantioselection based on:

• Coordination of the allylic alcohol to a chiral Ti–tartrate–peroxo complex leading to a preferred oxygen approach geometry
• A free radical abstraction followed by chiral recombination
• Non-selective external delivery of oxygen by TBHP
• Hydrogen-bonding of TBHP to the substrate without metal coordination

Correct Answer: Coordination of the allylic alcohol to a chiral Ti–tartrate–peroxo complex leading to a preferred oxygen approach geometry

Q11. Which useful transformation related to Sharpless epoxidation is frequently employed in asymmetric synthesis?

• Kinetic resolution of racemic allylic alcohols via enantioselective epoxidation
• Radical polymerization of allylic alcohols
• Direct oxidation of alcohols to ketones
• Hydroboration–oxidation of alkenes

Correct Answer: Kinetic resolution of racemic allylic alcohols via enantioselective epoxidation

Q12. Which limitation is commonly associated with Sharpless asymmetric epoxidation?

• It gives poor enantioselectivity for non-allylic or highly substituted alkenes lacking coordinating OH groups
• It cannot be performed below 0 °C
• It is ineffective for allylic alcohols and prefers ethers
• It always requires stoichiometric amounts of chiral tartrate

Correct Answer: It gives poor enantioselectivity for non-allylic or highly substituted alkenes lacking coordinating OH groups

Q13. For a given allylic alcohol substrate, using (+)-diethyl tartrate instead of (−)-diethyl tartrate will generally:

• Give the opposite absolute configuration of the resulting epoxide
• Double the reaction rate without changing configuration
• Have no effect on stereochemistry but reduce yield
• Cause the substrate to decompose

Correct Answer: Give the opposite absolute configuration of the resulting epoxide

Q14. Which epoxidation method is generally more suitable than Sharpless for unfunctionalized alkenes (no allylic OH)?

• Jacobsen–Katsuki (Mn–salen) epoxidation
• Sharpless asymmetric epoxidation (no change)
• Swern oxidation
• Oxymercuration–demercuration

Correct Answer: Jacobsen–Katsuki (Mn–salen) epoxidation

Q15. Which solvent is commonly used in Sharpless asymmetric epoxidation protocols to achieve good selectivity?

• Dichloromethane (CH2Cl2)
• Water
• Absolute methanol
• Dimethyl sulfoxide (DMSO)

Correct Answer: Dichloromethane (CH2Cl2)

Q16. How does the geometry (E or Z) of a substituted double bond in an allylic alcohol influence the Sharpless epoxidation?

• The E/Z geometry affects the facial selectivity and therefore the absolute configuration obtained
• Geometry has no influence; only the tartrate enantiomer matters
• Z alkenes cannot be epoxidized by this method
• The reaction converts E to Z before epoxidation, so original geometry is irrelevant

Correct Answer: The E/Z geometry affects the facial selectivity and therefore the absolute configuration obtained

Q17. What is the main role of diethyl tartrate (DET) in the Sharpless epoxidation?

• To act as a chiral ligand that complexes with titanium creating the chiral oxidizing species
• To function as the primary oxidant
• To act as a base to deprotonate the allylic alcohol
• To bind and deactivate TBHP

Correct Answer: To act as a chiral ligand that complexes with titanium creating the chiral oxidizing species

Q18. For well-behaved allylic alcohol substrates, what range of enantiomeric excess (ee) is typically expected with optimized Sharpless epoxidation?

• Greater than 90% ee
• 20–40% ee
• Approximately racemic (0–5% ee)
• 40–60% ee

Correct Answer: Greater than 90% ee

Q19. Why is the Sharpless asymmetric epoxidation important in pharmaceutical synthesis?

• It provides access to enantiopure epoxides that serve as versatile chiral intermediates for drug molecules
• It is primarily used for large-scale polymer production only
• It selectively oxidizes aromatic rings to phenols
• It eliminates the need for any protecting groups in all syntheses

Correct Answer: It provides access to enantiopure epoxides that serve as versatile chiral intermediates for drug molecules

Q20. Which Nobel Prize fact is correctly associated with the developer of the Sharpless asymmetric epoxidation?

• K. Barry Sharpless was awarded the Nobel Prize in Chemistry in 2001 for his work on chirally catalyzed oxidation reactions
• K. Barry Sharpless received the Nobel Prize in 1995 for polymer chemistry
• The Sharpless epoxidation was developed after Sharpless received his Nobel Prize in 2010
• Sharpless won the Nobel Prize for discovery of fullerenes

Correct Answer: K. Barry Sharpless was awarded the Nobel Prize in Chemistry in 2001 for his work on chirally catalyzed oxidation reactions

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