Formal total synthesis of the PKC inhibitor, balanol: preparation of the fully protected benzophenone fragment

Application of an intramolecular Heck reaction for the construction of the balanol aryl core structure

A new synthetic route to unsymmetrically substituted benzophenones, relying upon iron-mediated reactions in all of the key steps, is described. The key buiding block, η6-2-chloro-carbomethoxybenzene-η5-cyclopentadienyl iron hexafluorophosphate (4), is reacted with a variety of substituted phenols, providing diaryl ether complexes (6). After hydrolysis of the ester functionalities, these complexes are subjected to Friedel−Crafts conditions. The efficiency of this intramolecular acylation reaction is very much dependent upon the substituents on the phenols. If these are appropriately chosen, xanthone complexes are isolated in fair to good yields. Regioselective ring-opening, using oxygen-nucleophiles, delivers substituted benzophenone complexes. After regioselective nucleophilic addition of cyanide ion, performed in the presence of DDQ, highly substituted benzophenones are isolated. To demonstrate the applicability of the new route, a formal synthesis of the benzophenone moiety of the protein kinase C inhib...

J.Peter Nilsson

Papers

A divergent route to substituted benzophenones based on cationic η6-(Arene)iron intermediates.