A palladium-catalyzed cross-coupling reaction between the arylstannane 5c and the bicyclic vinyl bromide 3, which was obtained by a Diels—Alder reaction, provided the substituted bicyclo[2.2.2]octa-2,5-diene 6. A subsequent ozonolysis of the less substituted double bond of 6 followed by reduction of the intermediate with sodium borohydride provided the highly functionalized cyclohexene 8. This compound can be viewed as a substructure of the antitumor antibiotic dynemicin A.

Dynemicin A is a member of the family of enediyne natural products. It is unique in that it combines a ten-membered enediyne with an anthraquinone substructure. These features stimulated the development of synthetic approaches to the natural product itself and of analogs thereof. This review summarizes the total syntheses of dynemicin A. In addition, an overview of the known analogs is presented. The analogs can be classified according to the designed trigger mechanism. Most of the analogs contain a removable carbamate on the nitrogen atom. Others are quite similar to the natural lead in that they contain a quinone substructure, which upon reduction causes opening of the oxirane ring. In addition, there are analogs that contain an aromatic sector, the enediyne, and the oxirane ring but lack the nitrogen heterocycle. In these compounds the aryl ring assumes a different conformation from that in dynemicin A. Many of the simplified analogs proved to be quite active in vitro as well in vivo against murine tumor models. A highlight is compound 30 which is much more active than dynemicin A itself. However, looking at all analogs there is no clear-cut correlation between the DNA-cleaving ability at neutral pH and the in vitro results. From this one might conclude that there are possibly two mechanisms for antitumor activity. One involves diradical formation whereas the other might be due to a ligand-receptor interaction.

Utilizing a cross-coupling reaction between the arylstannane 5 and the iodoenone 7, the arylcyclohexenone 8 was prepared. This compound was then transformed into the enediyne aldehydes 16a,b. Treatment of 16a with cat. amounts of TBAF gave rise to the macrocyclic dynemicin analog 17a. This was converted to the phenolic enediyne 18.

Electron-rich arylstannanes were found to couple with α-iodoenones in the presence of Pd2(dba)3·CHCl3, a weak-coordinating ligand [AsPh3 or Pd(o-tol)3] and CuI (0.75-1.0 equiv) to give sterically hindered α-arylcyclohexenones 15–20. In addition, compounds 19, 22 and 23 were prepared by Suzuki coupling reactions of the cyclohexyl derivatives 7c,f and 11, respectively, with the arylboronic acid 21.