Corey–Nicolaou macrolactonization explained

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]

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]}

See also

• Shiina macrolactonization
• Ružička reaction

Notes and References

1. Corey. Elias James. Elias James Corey. Nicolaou. Kyriacos Costa. K. C. Nicolaou. Efficient and mild lactonization method for the synthesis of macrolides. . Journal of the American Chemical Society. 1974-08-01. 96. 17. 5614–5616. 10.1021/ja00824a073.
2. Corey . Elias James . Nicolaou . Kyriacos Costa . Melvin . Lawrence S. Jr. . Elias James Corey . K. C. Nicolaou . Synthesis of novel macrocyclic lactones in the prostaglandin and polyether antibiotic series . . 1975 . 97 . 3 . 653–654 . 10.1021/ja00836a036. 1133366 .
3. Meng. Qingchang. Hesse. Manfred. Ring-closure methods in the synthesis of macrocyclic natural products. Topics in Current Chemistry. 1992. 161. 107–176. 10.1007/3-540-54348-1_9. 978-3-540-54348-0.
4. Corey . Elias James . Brunelle . Daniel J. . Stork . Philip J. . Elias James Corey . Mechanistic studies on the double activation method for the synthesis of macrocyclic lactones . . 1976 . 17 . 38 . 3405–3408 . 10.1016/S0040-4039(00)93056-9.
5. Behinpour . Kevian . Hopkins . Andrew . Williiams . Andrew . Macrolide ring closuke: "Double activation" mechanism . . 1981 . 22 . 4 . 275–278 . 10.1016/0040-4039(81)80074-3.