Question

Question: What reaction conditions—base, solvent, and temperature—are needed to convert ketone A to either B or C by an intramolecular alkylation reaction?

Short answer

Answer

conversion of A into B

conversion of A into C

Step-by-step solution

Kinetic and thermodynamic enolates.

Kinetic enolates are less substituted enolates, favored by a strong base, polar aprotic solvent, and low temperatures e.g., LDA.

Thermodynamic enolates are more substituted enolates, favored by a strong base, protic solvent, and higher or room temperature e.g.,NaOCH₂CH₃ .

Condition and mechanism for conversion of A

Condition for conversion of A into B

LDA is a strong non-nucleophilic base and it abstracts a proton from the position of the less hindered side of the carbonyl carbon and forms kinetic enolate in a polar aprotic solvent (THF) at low temperature (-78 degree) and undergoes intramolecular nucleophilic substitution to give the desired cyclic product - B.

Condition for conversion of A into C

NaOCH₂CH₃ in CH₃CH₂OH (a protic solvent) is a strong base and favors the removal of a proton from the more substituted carbon at room temperature, to form the thermodynamic enolate and undergo intramolecular nucleophilic substitution to give the desired cyclic product C.

Conversion of A into C