Organic Chemistry: Concepts and Applications - Headley Allan D. 2020

Addition Reactions Involving Carbonyls and Nitriles
9.7 Addition of Enolates to Carbonyl Compounds

As we have seen in Chapter 7 on acids and bases, enolates are created by the abstraction of an alpha-proton of carbonyl compounds to give a resonance-stabilized enolate conjugate base as shown in Reaction (9-49).

(9-49)

Enolates are nucleophiles and they react with carbonyl compounds in a similar manner as any of the nucleophiles mentioned earlier in this chapter. Shown in Reaction (9-50) is the addition of the enolate of ethanal to another molecule of ethanal.

(9-50)

Reactions of this type in which an enolate of a carbonyl compound reacts with another mole of the carbonyl compound in the presence of a base are known as aldol condensation reactions and they are very useful reactions for the synthesis of new carbon—carbon bonds to make larger molecules as shown in Reaction (9-51).

(9-51)

For such aldol adducts, the elimination of water is possible to give a very stable unsaturated α,β-unsaturated compound as shown in Reaction (9-52).

(9-52)

For carbonyl compounds that have only one type of α-hydrogen(s), it is possible for its enolate to react with another carbonyl compound that does not have α-hydrogen(s) as shown in the Reaction (9-53).

(9-53)

Such aldol condensation reactions are known as crossed-aldol condensation reactions.

It is possible to have an intramolecular aldol condensation as shown in Reaction (9-54).

(9-54)

As demonstrated above, it is possible to have loss of water to give the α,β-unsaturated carbonyl compound as shown in Reaction (9-55).

(9-55)

The addition of an enolate to an α,β-unsaturated carbonyl takes place in a 1,4 manner, instead of a 1,2 addition as discussed thus far. This type of addition is also known as a Michael addition as shown in Reaction (9-56).

(9-56)βα

The final step involves a keto-enol tautomerization, which favors the formation of the keto form as shown in Reaction (9-56).

The combination of the Michael addition with the aldol reaction to form a cyclic system is known as the Robinson annulation, which also means ring-formation reaction. The first step of a Robinson annulation, which is a Michael addition reaction, is shown in Reaction (9-57).

(9-57)

In the next step of the reaction, an enolate is formed from the ketone in the presence of a base as shown in Reaction (9-58).

(9-58)

Note that there are other possible ring formations, but the six-member ring is the most stable. In the final step of the reaction, loss of water occurs to form the α,β-unsaturated compound as shown in Reaction (9-59).

(9-59)

Another example of the Robinson annulation reaction is shown in Reaction (9-60).

(9-60)