Chapter 21, Problem 59DSP

The Enolate Chemistry of Dianionss

The synthetic applications of carbanions as reagents for carbon $\text{–}$ carbon bond formation have beenhighlighted numerous times throughout this text. All of the reagents covered so far have a net charge of $\text{–1}$; that is, they aremonoanions. Are there others with a $\text{–2}$ charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis?

Consider acetic acid:

The pKa of acetic acid is $\text{4}\text{.7}$, which corresponds to ionization of the $\text{O-H}$ group. The pKa

for ionization of a $\text{C-H}$ bond of acetate ion is $\text{33}$. None of the negative charge of the monoanion

is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a

nucleophile in carbon $\text{–}$ carbon bond-forming reactions.

Diisopropylamine has a pKa of $\text{36}$, which makes lithium diisopropylamide (LDA) a strong

enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give

dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis.

Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step $\text{1}$) before treating with LDA (step $\text{2}$). Because the dianion is a strong base, the alkyl halide used in step $\text{3}$ must be methyl or primary. A pH adjustment (step $\text{4}$) converts the resulting carboxylate salt to the desired carboxylic acid.

The dianions of α-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones.

Dianions have been prepared from $\text{β-keto esters}$ by double deprotonation using a number of strong bases including LDA.

Protons on the $\text{α}$ carbon of $\text{β-keto esters}$ are flanked by two carbonyl groups and are far more acidic than those on the $\text{γ}$ carbon. In the dianion, therefore, the $\text{γ}$ carbon is more basic and more nucleophilic. Alkylation of the monoanion of $\text{β-keto acids}$ occurs at the $\text{α}$ carbon. Alkylation of the dianion occurs at the $\text{γ}$ carbon.

$\text{β-Diketones}$ behave similarly to $\text{β-keto esters}$. Sodium or potassium amide in liquid ammonia is a suitable $\text{base/solvent}$ system in this case.

What is the product of the reaction of the dianion in Problem $\text{21}\text{.58}$ with cyclohexanone?

Predict the major organic product(s) of the following reaction