Corey–Nicolaou macrolactonization is a named reaction of organic chemistry, for the synthesis of lactones from hydroxy acids, found in 1974. The reaction should take place in a polar aprotic solvent with mild conditions, with the use of 2,2'-Dipyridyldisulfide and triphenylphosphine.
Mechanism:
Example:
To hydroxy acid (50 mg, 0.157 mmol) was added 2,2′-dipyridyl disulfide (Aldrithol-2, 47 mg, 0.213 mmol) and Ph3P (58 mg, 0.221 mmol). The mixture was dissolved in 10 mL of degassed benzene. The solution was stirred at rt for 3 h. At the end of time, the mixture was added to refluxing benzene (105 mL) containing AgClO4 (0.168 g, 0.81 mmol) over 12 h via a syringe pump. After the first addition was complete, the residual was washed with another 8 mL of benzene that was then added to the refluxing reaction mixture over 4 h. The solution was refluxed for an additional 2 h after the second addition was completed. This mixture was cooled to room temperature and filtered through Celite. The solvent was concentrated, and the mixture was purified by flash column chromatography (hex/ EtOAc ) 10/1, 230-400 mesh silica gel) to afford an inseparable mixture of conformational isomers with ca. 7.25:5:1 ratio (15.4 mg, 33%) as a pale yellow semi-oil.
Andrus, M. B.; Shih, T.-L. J. Org. Chem. 1996, 61, 8780–8785.
