Corey–Nicolaou macrolactonization

Corey–Nicolaou macrolactonization is a named reaction of organic chemistry, for the synthesis of lactones from hydroxy acids, found in 1974.^[1][2] The reaction uses 2,2'-dipyridyldisulfide and triphenylphosphine as reagents and runs in polar aprotic solvent under mild conditions.^[3]

Corey–Nicolaou macrolactonization
Named after	Elias James Corey K. C. Nicolaou
Reaction type	Name reaction

Mechanism

The hydroxy acid first reacts with the 2,2'-Dipyridyldisulfide to form the corresponding 2-pyridinethiol ester, and after a proton transfer, the alkoxide attacks the carbonyl carbon, forming a tetrahedral transition state, before resolving back to the desired lactone and 2-pyridinethione.^[4][5]

Variants

Other heterocyclic disulfides have been used in place of 2,2'-dipyridyldisulfide.^[6][7][8][9]

See also

• Shiina macrolactonization
• Ružička reaction