Chapter 10, Problem 10.10P

Interpretation Introduction

(a)

Interpretation:

The major product for the given reaction is to be predicted, and complete detailed mechanism is to be drawn.

Concept introduction:

LDA and alkoxide are the bases that can be used to alkylate the alpha carbon atoms in ketones. The regioselectivity can be controlled by the choice of base and reaction conditions.

An excess of lithium diisopropylamide (LDA) at low temperature causes alkylation to occur at the less substituted $\text{α}$ carbon of a ketone. The alkylation of the alpha carbon in ketones via the base LDA takes place under the kinetic control as the reaction is irreversible.

Alkoxide bases ${\text{(RO}}^{\text{-}}\text{)}$ cause alkylation to occur at the more highly substituted $\text{α}$ carbon of a ketone. The alkylation of the alpha carbon in ketones via the base alkoxide takes place under the thermodynamic control as the reaction is reversible. Enolate ion is the intermediate formed in the mechanism of these reactions. The alkylation of alpha carbon atom in ketones by a base follows ${\text{S}}_{\text{N}}\text{2}$ mechanism pathway.

Interpretation Introduction

(b)

Interpretation:

The complete mechanism for the given reaction in which ${\text{KOC(CH}}_{\text{3}}{\text{)}}_{\text{3}}$ is used as the base instead of LDA is to be shown, and the major product is to be predicted.

Concept introduction:

When ${\text{KOC(CH}}_{\text{3}}{\text{)}}_{\text{3}}$ or ${\text{NaOC(CH}}_{\text{3}}{\text{)}}_{\text{3}}$ are used as base, then ${\text{K}}_{\text{eq}}$ for the proton transfer step is slightly less than one and makes $\Delta {\text{G}}_{\text{rxn}}^{\text{o}}$ slightly positive. If two distinct enolate anions can be produced, then the more stable of the two is called the thermodynamic enolate anion, which has greater abundance prior to the ${\text{S}}_{\text{N}}\text{2}$ step.