Aldol

Reaction
Base-catalyzed aldol
reaction:

• As the enolate is consumed, more of the starting aldehyde transforms into

the enolate so the aldol reaction continues.

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Aldol reaction with
ketones:

• It favours starting materials due to steric hindrance.

• The reverse reaction is known as a retro-aldol
reaction.

2
 Acid-catalyzed aldol
reaction:

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 Crossed aldol
reaction
• an aldol reaction with two different
aldehydes.

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 e.g. Claisen–Schmidt reaction
• Aldol reaction between a ketone and a non-
enolizable
aldehyde

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 • The selectivity is controlled because the
aldehyde used has no acidic proton (no α-proton).
• Only one product is formed.

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 g. Crossed aldols using strong bases

Another way to drive the formation of a single product:

• Use of a strong base to control the formation of an
enolate.
• Once enolate formed, aldehyde is added.

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 Aldol condensation:
Elimination
• Elimination reaction with a Loss of water after
aldol
reaction so after formation of enols or enones.
• Elimination is driven by heating the reaction.

Base-catalyzed aldol condensation:

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 This Elimination is an E1cb reaction:
• a unimolecular elimination reaction in which an acidic proton
is removed to make the conjugate base before the leaving
group leaves
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 Acid-catalyzed aldol
condensation:
• Under acidic conditions, the aldols are prone to -
eliminations because good leaving groups are generated.

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 In the presence of a strong
base:
• When strong bases are used in aldol reactions, -eliminations
usually do not occur.
• The strong bases require aprotic solvents, so the aldol products do
not have good-enough leaving for elimination.

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Intramolecular aldol
reactions
• If a molecule has two carbonyl functions where at least one
can form an enolate, an aldol reaction and condensation can
occur intramolecularly.
• If two or more products are possible, the reaction will favour
the ring with the least strain.
• In general, small rings have the following relative stabilities: S3<
S4<< S5< S6

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Limited
Mechanism
: O O

NaOH 5 or 6
EtOH, membered
O
heat
chaleu rings
r

O O O

H NaOH EtOH

EtOH O
O O

O O E1bc! O
H NaOH –OH–

ou
OH (or EtONa) OH

Carbonyls- 13
II
 Reactions with 1,3-Dicarbonyl compounds (Ketone or
aldehyde)
 Selective alkylations: 1,3-Dicarbonyl enolates act as nucleophiles in
SN2 reactions.

• Alkylation smaller
group
of first to reduce
steric hindrance upon
the second addition.

 Selective aldol reaction and condensation with 1,3-dicarbonyl

compounds

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 Summary of enolates reacting with a variety of
electrophiles:

15
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 Summary of aldol
reactions

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Summary of aldol β- to α,β
condensation: unsaturated elimination form -
carbonyl.

Retrosynthetic analysis of aldol-related

reactions

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Limited
Retrosynthetic analysis using dicarbonyl
compounds

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Limited