Macrolactonization Keck method

The 15-hydroxy acids 10a and 10b (Scheme 2) were cyclized with the reliable Yamaguchi (2,4,6-trichlorobenzoylchloride, TEA, DMAP, toluene) [10, 11, 13, 16] and Keck methods (DCC, DMAP, DMAPxHCl, CHCI3) [23, 28]. Both delivered the macrolactones in good to excellent yields, the first (90 % 9b and 78 % 9c) being superior to the latter. 

Boden, E. P., Keck, G. E. Proton-transfer steps in Steglich esterification a very practical new method for macrolactonization. J. Org. Chem. 1985, 50, 2394-2395. 

Boden and Keck [53] developed a practical method for macrolactonization by treatment with DCC and DMAP in the presence of DMAP-HCl the original esterification procedures using DCC and DMAP or 4-pyrrolidinopyridine were reported by Neises and Steglich [54] and Hassner and Alexanian [55] independently. This method worked very efficiently for the macrolactonization (92% yield) in the total synthesis of cytovaricin (196) (see Scheme 29 later in this chapter). 

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]. 

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