Corey-Nicolaou method

Lactone ring expansion. The lithio derivative from this sulfoxide (LDA) reacts with lactones to form adducts which on further treatment with KH and then r-BuLi are transformed into ketenes. Acidification regenerates lactones of one size larger. This reaction sequence works well for expansion of 5- and 6-membered lactones. For the synthesis of macrolides, it is necessary to quench the ketene with pyridine-2-thiol and use the Corey-Nicolaou method to effect reclosure of the lactone ring. 

In 1980, Venkataraman and Wagle [43] reported cyanuric chloride (Scheme 6.2) in the synthesis of macrolactones from the corresponding seco-acids, whose mechanism is closely related to the Corey-Nicolaou method. 

Macrolactonization of CD-hydroxyl-acid using 2,2 -dipyridyl disulfide. Also known as Corey-Nicolaou double activation method. 

Due to the prevalence of many macrolide natural products, Yamaguchi s esterification has been used extensively in the total syntheses of such compounds. Increasingly, Yamaguchi s method has succeeded where other notable esterification conditions have failed. A recent example involves the coupling of two monomers to form the clavosolide A dimer.17 The Corey-Nicolaou protocol mentioned previously gave only a 30% conversion whereas the Yamaguchi esterification resulted in a clean reaction with a 66% yield. 

Phthalic anhydride and 2.1 eqs. DBU added to a soln. of racemic 3-chloromethyl-2-hydroxymethyl-1-methyl-2,5-dihydropyrrolium chloride in DMF under argon, and stirred at room temp, for 24 h - phthaloylsynthanecine A. Y 86%. The method affords higher yields than the Corey-Nicolaou lactonisation. F.e. inch 11-membered dilactones s. R.H. Barbour, D.J. Robins, J. Chem. Soc. Perkin Trans. I 1988, 1169-72 from diols with Bu2SnOcf. H. Niwa et al.. Bull. Chem. Soc. Japan 61, 3017-9 (1988). 

Corey-Nicolaou (pyridine-thiol ester) method to form th e final 371... 

Extension of the traditional Yamaguchi/Corey-Nicolaou/Keck macrolactonization protocols (see Scheme 2.1) [5] to catalytic variants can address some of the drawbacks of classical methods. Mixed anhydrides can undergo cyclization with Lewis adds such as Sc,1i, Zr, and Hf [125,126].Trostetol. reported the use of ethoxyacetylene as a stoichiometric activating agent, installed via Ru catalysis [127], later applied to the synthesis of apicularen A (Scheme 2.67) [128]. 

Corey-Nicolaou S-Pyridyl Ester Lactonization Method... 

Table 5. Yields of the lactones 56 and of the dilides 57 according to the cesium method [51] and according to the method of Corey and Nicolaou [2]...

Corey EJ, Nicolaou KC (1974) An Efficient and Mild Lactonization Method for the Synthesis of Macrolides. J Am Chem Soc 96 5614... 

Macrolactonization. When a carboxylic acid is treated with 2,2 -dipyridyl disulfide in the presence of Triphenylphosphine, the corresponding 2-pyridinethiol ester is formed. Corey and Nicolaou have developed an efficient method for the synthesis of macrocyclic lactones based on these 2-pyridinethiol esters. When an m-hydroxy thiolester is heated in refluxing xylene under high dilution conditions (10 M, typically accomplished with syringe pump techniques), macrolactonization occurs, liberating triphenylphosphine oxide and pyridinethione. The reaction is quite general and is believed to proceed by a double activation mechanism in which the basic 2-pyridinethiol ester simultaneously activates both the hydroxy and the carboxylic acid moieties with a single proton transfer. It has been shown that the cyclization rate is not affected by the presence of acids, bases, or any of the possible reaction contaminants. ... 

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