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JEE Advanced 2023 Paper 1 · Chemistry · General Organic Chemistry and Isomerism · hard

2-Methylcyclohexanone is converted into P by LDA in THF at -78^circC followed by CH3I, and into Q by NaOEt in EtOH at room temperature followed by…

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2-Methylcyclohexanone is converted into P\mathbf{P} by LDA in THF at −78∘C-78^\circ\mathrm{C} followed by CH3I\mathrm{CH_3I}, and into Q\mathbf{Q} by NaOEt\mathrm{NaOEt} in EtOH\mathrm{EtOH} at room temperature followed by CH3I\mathrm{CH_3I} (major products in each case). The ketone P\mathbf{P} (all of its stereoisomers together) is reduced by NaBH4\mathrm{NaBH_4} to give a mixture of alcohols R\mathbf{R}. Identify P\mathbf{P}, Q\mathbf{Q} and the total number of stereoisomers (enantiomers counted separately) of the alcohol R\mathbf{R} that are possible.
  1. A. P\mathbf{P} = 2,2-dimethylcyclohexanone; Q\mathbf{Q} = 2,6-dimethylcyclohexanone; R\mathbf{R} has 44 stereoisomers
  2. B. P\mathbf{P} = 2,6-dimethylcyclohexanone; Q\mathbf{Q} = 2,2-dimethylcyclohexanone; R\mathbf{R} has 33 stereoisomers
  3. C. P\mathbf{P} = 2,6-dimethylcyclohexanone; Q\mathbf{Q} = 2,2-dimethylcyclohexanone; R\mathbf{R} has 44 stereoisomers
  4. D. P\mathbf{P} = 2,6-dimethylcyclohexanone; Q\mathbf{Q} = 2,2-dimethylcyclohexanone; R\mathbf{R} has 88 stereoisomers
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Answer: (C) P\mathbf{P} = 2,6-dimethylcyclohexanone; Q\mathbf{Q} = 2,2-dimethylcyclohexanone; R\mathbf{R} has 44 stereoisomers

LDA is bulky and strong and, at −78∘C-78^\circ\mathrm{C}, removes the more accessible proton of the less substituted α\alpha-carbon (kinetic enolate); methylation therefore gives P\mathbf{P} = 2,6-dimethylcyclohexanone. NaOEt\mathrm{NaOEt}/EtOH\mathrm{EtOH} is reversible and gives the more substituted, more stable (thermodynamic) enolate, so methylation at that carbon gives Q\mathbf{Q} = 2,2-dimethylcyclohexanone. R\mathbf{R} is 2,6-dimethylcyclohexan-1-ol, which has three stereocentres (C1\mathrm{C1}, C2\mathrm{C2}, C6\mathrm{C6}) in a ring with a symmetric substitution pattern. For cis-2,6-dimethyl the OH\mathrm{OH} may be cis or trans to both methyls: 2 meso compounds. For trans-2,6-dimethyl (chiral) the OH\mathrm{OH} is necessarily cis to one methyl and trans to the other, and the two choices are the same by the C2C_2 relation, giving one enantiomeric pair: 2 isomers. Total =2+2=4=2+2=4. Answer: (C).
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