Enediynes macrocycle synthesis

Several examples of the application of Pd/Cu-catalyzed cross-coupling for synthesis of alkynyl ketones, terminal acetylenes, enediyne macrocycles, and enediyne polymers are given. 

Another important application of this protocol for the synthesis of enediynes is its use in the synthesis of natural products containing enediyne macrocycles, such as esperam-icin/calicheamicinf " and dynemicin as discussed in Sect. III.2.18. Some applications to the synthesis of unnatural macrocycles have also been reported (Scheme... 

In the total synthesis of the strained cyclic enediynes 145, the highly substituted macrocyclic enediyne was constructed by intermolecular two-fold Pd-catalzed coupling of the a,ftj-di(iodoalkyne) moietes in 144 with cw-l,2-bis(trimethylstannyl)ethene in 80% yield [Eq. (49)] [70]. 

Despite some uncertainty in the expected olefin geometry, the utility of the RBR is anply demonstrated by its application to the synthesis of many diverse targets. These include dendrimers, cyclophanes, modified carbohydrates such as C-glycosides and exoglycals, alkaloids, terpene derivatives, enediynes, amino acids, stilbenes, and macrocycles.The remainder of this chapter presents examples of the RBR that are pertinent to the strategic considerations oudined previously and illustrate its scope as a versatile and powerful synthetic method. 

Scheme 3.115 Structure and synthesis of 19-membered macrocyclic enediynes 3.865 and 3.866. r.t., room temperature.

Scheme 3.116 Structure and synthesis of 14-membered macrocyclic enediynes 3.867, 3.868, and 3.869.

Konig, B., Fricke, T., Dix, I. and Jones, P.G. (1997) Synthesis and structure of macrocyclic diaza-bis-enediynes. Journal of Chemical Research, Synopses, (2), 68-69. 

Wardel, H. and Wiest, O., Enediynes in 11-membered rights. Synthesis and structure of highly strained but unusually stable macrocycles, /. Org. Chem., 67, 388, 2002. 

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