Question

Draw ‘generic’ retrons for the following transforms and then provide a molecule that contains these retrons.

•Aldol Reaction

•Mannich Reaction

•Aldol Condensation

•Diels-Alder Cycloadditon

•Michael Addition

•Claisen Condensation

•Claisen Rearrangement

•α-alkylation of enolates

Answer 1

Aldol Reaction

Aldol' is an abbreviation of aldehyde and alcohol. When the enolate of an aldehyde or a ketone reacts at the α-carbon with the carbonyl of another molecule under basic or acidic conditions to obtain β-hydroxy aldehyde or ketone, this reaction is called Aldol Reaction.

Mannich Reaction

This multi-component condensation of a nonenolizable aldehyde, a primary or secondary amine and an enolizable carbonyl compound affords aminomethylated products. The iminium derivative of the aldehyde is the acceptor in the reaction.

Aldol Condensation

In some cases, the adducts obtained from the Aldol Addition can easily be converted (in situ) to α,β-unsaturated carbonyl compounds, either thermally or under acidic or basic catalysis. The formation of the conjugated system is the driving force for this spontaneous dehydration. Under a variety of protocols, the condensation product can be obtained directly without isolation of the aldol.

Diels-Alder Cycloadditon

The [4+2]-cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an electrocyclic reaction that involves the 4 π-electrons of the diene and 2 π-electrons of the dienophile. The driving force of the reaction is the formation of new σ-bonds, which are energetically more stable than the π-bonds.

Michael Addition

he 1,4-addition (or conjugate addition) of resonance-stabilized carbanions. The Michael Addition is thermodynamically controlled; the reaction donors are active methylenes such as malonates and nitroalkanes, and the acceptors are activated olefins such as α,β-unsaturated carbonyl compounds.

Examples for donor

Examples for acceptor

Claisen Condensation

The Claisen Condensation between esters containing α-hydrogens, promoted by a base such as sodium ethoxide, affords β-ketoesters. The driving force is the formation of the stabilized anion of the β-keto ester. If two different esters are used, an essentially statistical mixture of all four products is generally obtained, and the preparation does not have high synthetic utility.

However, if one of the ester partners has enolizable α-hydrogens and the other does not (e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be synthetically useful. If ketones or nitriles are used as the donor in this condensation reaction, a β-diketone or a β-ketonitrile is obtained, respectively.

The use of stronger bases, e.g. sodium amide or sodium hydride instead of sodium ethoxide, often increases the yield.

Claisen Rearrangement

The aliphatic Claisen Rearrangement is a [3,3]-sigmatropic rearrangement in which an allyl vinyl ether is converted thermally to an unsaturated carbonyl compound.

The aromatic Claisen Rearrangement is accompanied by a rearomatization:

Aliphatic system

aromatic system

α-alkylation of enolates

• Enolates are good nucleophiles and reaction with alkyl halides via S_N2 type reactions.
• This allows alkyl groups to be introduced in the a-positions.
• Since the reaction is an S_N2 reaction, methyl and primary halides are most suitable for alkylation reactions.
• There can be problems due to competing condensation reactions.

Enolate formation

SN2 attack