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
editThe 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
editOther heterocyclic disulfides have been used in place of 2,2'-dipyridyldisulfide.[6][7][8][9]
See also
editReferences
edit- ^ Corey, Elias James; Nicolaou, Kyriacos Costa (1974-08-01). "Efficient and mild lactonization method for the synthesis of macrolides". Journal of the American Chemical Society. 96 (17): 5614–5616. doi:10.1021/ja00824a073.
- ^ Corey, Elias James; Nicolaou, Kyriacos Costa; Melvin, Lawrence S. Jr. (1975). "Synthesis of novel macrocyclic lactones in the prostaglandin and polyether antibiotic series". Journal of the American Chemical Society. 97 (3): 653–654. doi:10.1021/ja00836a036. PMID 1133366.
- ^ Meng, Qingchang; Hesse, Manfred (1992). "Ring-closure methods in the synthesis of macrocyclic natural products". Topics in Current Chemistry. 161: 107–176. doi:10.1007/3-540-54348-1_9. ISBN 978-3-540-54348-0.
- ^ Corey, Elias James; Brunelle, Daniel J.; Stork, Philip J. (1976). "Mechanistic studies on the double activation method for the synthesis of macrocyclic lactones". Tetrahedron Letters. 17 (38): 3405–3408. doi:10.1016/S0040-4039(00)93056-9.
- ^ Behinpour, Kevian; Hopkins, Andrew; Williiams, Andrew (1981). "Macrolide ring closuke: "Double activation" mechanism". Tetrahedron Letters. 22 (4): 275–278. doi:10.1016/0040-4039(81)80074-3.
- ^ Corey, Elias James; Clark, David A. (1979). "A new method for the synthesis of 2-pyridinethiol carboxylic esters". Tetrahedron Letters. 20 (31): 2875–2878. doi:10.1016/S0040-4039(01)86439-X.
- ^ Corey, Elias James; Brunelle, Daniel J. (1976). "New reagents for the conversion of hydroxy acids to macrolactones by the double activation method". Tetrahedron Letters. 17 (38): 3409–3412. doi:10.1016/S0040-4039(00)93057-0.
- ^ Schmidt, Ulrich; Heermann, Dieter (1979). "Ester and Lactone Formation with the Reagent 1,2-Dihydro-4,6-dimethyl-2-thioxo-3-pyridinecarbonitrile". Angewandte Chemie International Edition. 18 (4): 308–309. doi:10.1002/anie.197903082.
- ^ Nimitz, Jonathan S.; Wollenberg, Robert H. (1978). "Macrolide ring closure. Silver ion promoted lactonization of ω-hydroxy thiolesters of 2-amino-4-mercapto-6-methylpyrimidine". Tetrahedron Letters. 19 (38): 3523–3526. doi:10.1016/S0040-4039(01)94982-2.