Corey–Nicolaou macrolactonization

E466669

Corey–Nicolaou macrolactonization is a widely used organic synthesis reaction that forms large-ring lactones from hydroxy acids via an activated ester intermediate.

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Statements (43)

Predicate Object
instanceOf macrolactonization reaction
named reaction
organic reaction
advantage applicable to sensitive functional groups
high chemoselectivity for intramolecular lactonization
useful for large-ring formation
bondsFormed ester bond
lactone C–O bond
category Corey reactions NERFINISHED
lactonization reactions
developedBy Elias James Corey NERFINISHED
K. C. Nicolaou NERFINISHED
field natural product synthesis
organic synthesis
formsProduct large-ring lactone
macrolactone
limitation can compete with intermolecular esterification at high concentration
requires preorganization of hydroxy acid chain
mechanisticFeature activated ester intermediate
intramolecular esterification
namedAfter Elias James Corey NERFINISHED
K. C. Nicolaou NERFINISHED
reactionClass esterification
ring-closing reaction
reactionOutcome ring-closure with loss of small molecule byproduct
reactionType lactonization
macrocyclization
relatedTo Mitsunobu macrolactonization NERFINISHED
Yamaguchi macrolactonization NERFINISHED
ringSize macrocyclic ring
selectivity favors intramolecular over intermolecular ester formation
startingMaterial hydroxy acid
ω-hydroxy carboxylic acid
substrateScope primary alcohol-containing hydroxy acids
secondary alcohol-containing hydroxy acids
transformation converts hydroxy acid to macrocyclic ester
typicalCondition dehydrative cyclization
high-dilution conditions
typicalRingSize 12- to 30-membered ring
usedFor formation of macrocyclic lactones under mild conditions
synthesis of macrocyclic natural products
usedIn total synthesis of macrocyclic polyketides
total synthesis of macrolide antibiotics

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E. J. Corey developedMethod Corey–Nicolaou macrolactonization