Retrosynthesis: Functional Group Interconversion (FGI) and addition strategies MCQs With Answer

Retrosynthesis: Functional Group Interconversion (FGI) and addition strategies MCQs With Answer

This quiz collection is designed for M.Pharm students studying MPC 102T Advanced Organic Chemistry I, focusing on retrosynthetic planning using functional group interconversion (FGI) and addition strategies. The questions probe practical decision-making: choosing appropriate FGIs to enable disconnections, selecting reagents for chemoselective transformations, and applying addition reactions to build skeletons with defined regiochemistry and stereochemistry. Emphasis is on mechanistic rationale (umpolung, homologation, conjugate addition, epoxide openings, and protection/deprotection strategies) so you can integrate FGI choices into robust synthetic routes. Answers are provided to reinforce learning and aid exam preparation.

Q1. Which statement best defines Functional Group Interconversion (FGI) in retrosynthetic analysis?

• Transforming one functional group into another to enable a strategic disconnection
• Adding atoms to increase molecular complexity without changing functional groups
• Using protecting groups to temporarily mask a functional group
• Cleaving carbon–carbon bonds to break a molecule into fragments

Correct Answer: Transforming one functional group into another to enable a strategic disconnection

Q2. Which reagent is most commonly used for the mild oxidation of a primary alcohol to an aldehyde without overoxidation to carboxylic acid?

• Jones reagent (CrO3/H2SO4)
• PCC (pyridinium chlorochromate) in dichloromethane
• KMnO4, basic aqueous
• H2/Pd (catalytic hydrogenation)

Correct Answer: PCC (pyridinium chlorochromate) in dichloromethane

Q3. Which reagent is the standard choice to reduce a carboxylic acid to the corresponding primary alcohol?

• NaBH4 in ethanol
• LiAlH4 in dry ether
• H2, Pd/C
• BF3·OEt2

Correct Answer: LiAlH4 in dry ether

Q4. To convert an alkene into the corresponding alkyl bromide with anti-Markovnikov regiochemistry, which condition is appropriate?

• HBr in the presence of peroxides (radical addition)
• HBr with ROH and strong acid
• Br2 in CCl4 (bromination)
• Hydroboration-oxidation followed by bromination

Correct Answer: HBr in the presence of peroxides (radical addition)

Q5. Which reagent pair is characteristic for converting a carbonyl compound into an alkene via the Wittig reaction?

• Ph3P=CHR (phosphonium ylide) with aldehyde/ketone
• LiAlH4 followed by PCC
• OsO4, NMO
• HIO4 cleavage

Correct Answer: Ph3P=CHR (phosphonium ylide) with aldehyde/ketone

Q6. Which homologation method is classically used to increase the carbon chain of a carboxylic acid by one carbon atom (–CH2– insertion)?

• Arndt–Eistert homologation via acid chloride → diazoketone → Wolff rearrangement
• Wittig methylenation of the acid
• Pinnick oxidation of aldehyde
• Bouveault–Blanc reduction

Correct Answer: Arndt–Eistert homologation via acid chloride → diazoketone → Wolff rearrangement

Q7. Which strategy is commonly used to achieve “umpolung” (reversal of polarity) of a carbonyl carbon for C–C bond formation?

• Use of 1,3-dithiane (Corey–Seebach) followed by deprotonation and alkylation
• Direct nucleophilic addition of Grignard reagent to aldehyde
• Hydrogenation over Pd/C
• Epoxidation then ring opening under acidic conditions

Correct Answer: Use of 1,3-dithiane (Corey–Seebach) followed by deprotonation and alkylation

Q8. Which addition strategy is most appropriate to form a carbon–carbon bond at the β-position of an α,β-unsaturated carbonyl compound?

• Michael (conjugate) addition of a stabilized enolate or nucleophile
• Direct 1,2-addition of a hard nucleophile such as RMgX
• Electrophilic aromatic substitution
• Wolff–Kishner reduction

Correct Answer: Michael (conjugate) addition of a stabilized enolate or nucleophile

Q9. Hydroboration–oxidation of a terminal alkene gives which regiochemical and stereochemical outcome?

• Markovnikov addition and anti stereochemistry
• Anti-Markovnikov regiochemistry with syn stereochemical addition
• Markovnikov regiochemistry with syn addition
• Anti-Markovnikov with anti stereochemistry

Correct Answer: Anti-Markovnikov regiochemistry with syn stereochemical addition

Q10. Regarding regioselectivity in epoxide ring opening, which statement is correct comparing acidic and basic conditions?

• Under acidic conditions nucleophiles attack the less substituted carbon; under basic they attack the more substituted carbon
• Under acidic conditions nucleophiles attack the more substituted carbon; under basic they attack the less substituted carbon
• Both acidic and basic conditions give exclusive attack at the more substituted carbon
• Both acidic and basic conditions give exclusive attack at the less substituted carbon

Correct Answer: Under acidic conditions nucleophiles attack the more substituted carbon; under basic they attack the less substituted carbon

Q11. What oxidizing reagent is typically used for the oxidative cleavage of a vicinal diol to two carbonyl fragments under mild conditions?

• Periodic acid (HIO4) or sodium periodate (NaIO4)
• LiAlH4
• H2, Pd/C
• PCC in CH2Cl2

Correct Answer: Periodic acid (HIO4) or sodium periodate (NaIO4)

Q12. Which reagent efficiently reduces a nitrile (–C≡N) to the corresponding primary amine under non-hydrogenative conditions?

• NaBH4 in methanol
• LiAlH4 followed by aqueous workup
• KMnO4 oxidative conditions
• PCC

Correct Answer: LiAlH4 followed by aqueous workup

Q13. For complete removal of a carbonyl group (conversion of R–C(=O)–R’ to R–CH2–R’), which named reduction is performed under strongly basic high-temperature conditions?

• Clemmensen reduction (Zn(Hg), HCl)
• Wolff–Kishner reduction (hydrazine, strong base, heat)
• Bouveault–Blanc reduction
• Meerwein–Ponndorf–Verley reduction

Correct Answer: Wolff–Kishner reduction (hydrazine, strong base, heat)

Q14. Which functional group interconversion is commonly used to convert a poor leaving hydroxyl into a good leaving group for subsequent SN2 substitution?

• Convert alcohol to tosylate using p-toluenesulfonyl chloride (TsCl) and pyridine
• Oxidize alcohol to ketone using PCC
• Reduce alcohol to alkane using LiAlH4
• Convert alcohol to ether using Williamson ether synthesis

Correct Answer: Convert alcohol to tosylate using p-toluenesulfonyl chloride (TsCl) and pyridine

Q15. Which approach provides an acyl anion equivalent in retrosynthesis for building ketones by C–C bond formation at the carbonyl carbon?

• Use of Grignard reagents directly on esters
• Corey–Seebach 1,3-dithiane methodology to generate a nucleophilic carbon adjacent to sulfur
• Direct Friedel–Crafts acylation of benzene
• Radical halogenation followed by substitution

Correct Answer: Corey–Seebach 1,3-dithiane methodology to generate a nucleophilic carbon adjacent to sulfur

Q16. Which reagent combination gives syn-dihydroxylation of an alkene to form a vicinal diol with retention of stereochemistry?

• KMnO4, hot basic conditions
• OsO4 with N-methylmorpholine N-oxide (NMO) or t-BuOOH
• O3 followed by reductive workup
• Br2 in H2O (bromohydrin formation)

Correct Answer: OsO4 with N-methylmorpholine N-oxide (NMO) or t-BuOOH

Q17. Which reagent will reduce an ester directly to its corresponding primary alcohol?

• NaBH4 at 0 °C
• LiAlH4 in dry ether followed by aqueous workup
• PCC in CH2Cl2
• HIO4

Correct Answer: LiAlH4 in dry ether followed by aqueous workup

Q18. When opening an epoxide with a Grignard reagent (RMgX), which carbon of the epoxide is attacked and why?

• The more substituted carbon, because the reaction proceeds via a carbocation intermediate
• The less substituted carbon, because organometallics behave as strong nucleophiles in SN2-like attack
• The oxygen atom is replaced directly without ring opening
• Attack occurs exclusively at the carbon bearing the electron-withdrawing group

Correct Answer: The less substituted carbon, because organometallics behave as strong nucleophiles in SN2-like attack

Q19. Which reagent is used in a one-step FGI to convert a primary alkyl halide into a nitrile, thereby effectively extending the carbon framework by one carbon?

• NaCN in polar aprotic solvent (e.g., DMSO, DMF)
• H2, Pd/C and NH3
• LiAlH4
• KMnO4 oxidative substitution

Correct Answer: NaCN in polar aprotic solvent (e.g., DMSO, DMF)

Q20. Which hydrogenation condition selectively converts an alkyne to the cis (Z) alkene without over-reducing to the alkane?

• H2 with Lindlar’s catalyst (Pd/CaCO3 poisoned with lead or quinoline)
• H2 with Pd/C (unpoisoned)
• Na/NH3 (Birch conditions)
• KMnO4, neutral water

Correct Answer: H2 with Lindlar’s catalyst (Pd/CaCO3 poisoned with lead or quinoline)

Download