Pyridyl thioesters lactones

Carboxylic esters, especially lactones, are conveniently obtained via the pyridyl thioesters (18). Some examples are given in Scheme 1. The 2-pyridyl thiol ester method can be further improved if silver ions (AgC104) are used as activators. Corey and Brunelle have also introduced other heterocyclic disulfides, and (19) was found to be superior to other reagents tested for the formation of lactones from w-hydroxyalkanoic acids. 

One example of lactonization promoted by Ag was reported. Addition of 1 eq. of silver perchlorate to the 2-pyridyl thioester of 15-hydroxypentadecanoic acid in benzene gave a mixture of the monomeric, dimeric, and trimeric lactones in 44% yield within 30 min. at 20°. 

Alternatives to the established double activation method for the lactonization of >-hydroxy-acids via 2-pyridyl thioesters are use of the more reactive 4-(2-amino-6-methyl)pyrimidyl analogues " or mixtures of 2-chloro-6-methyl-l,3-diphenylpyridinium tetrafluoroborate, 2,6-dimethylpyridine, and benzyl-triethylammonium chloride in refluxing 1,2-dichloroethane. ... 

The 2-pyridyl and related 2-imidazolyl disulfides have found special use in the closure of large lactone rings.118 This type of structure is encountered in a number of antibiotics which, because of the presence of numerous other sensitive functional groups, require mild conditions for cyclization. It has been suggested that the pyridyl and imidazoyl thioesters function by a mechanism in which the heterocyclic nitrogen acts as... 

Corey and Nicolaou used the S-pyridyl ester [19], which was generated by Mukaiyama thioester formation using 2,2 -dipyridyl disulfide and PPhj [20], as an activated precursor for lactonization. In 1976, they first accomphshed the total synthesis of some macrolide molecules including recifeioUde (15), as shown in Scheme 5.1 [21]. 

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