Ziegler-modified Ullmann

The Ziegler-modified Ullmann reaction was used for the total synthesis of pyrrolophenanthridinium alkaloid tortuosine by L.A. Flippin and co-workers. First, A/-Boc-5-methoxyindoline was lithiated at C7 with s-BuLi in the presence of TMEDA, and then it was transmetallated to the corresponding organocopper species that smoothly underwent the Ullmann reaction with a 3-iodoaryl imine. The resulting biaryl product was treated with anhydrous HCI in chloroform, which promoted the cyclization followed by dehydration to give the natural product. 

The short synthesis of the pyrrolophenanthridone alkaloid hippadine was accomplished by D.C. Harrowven and co-workers. " The key step of the synthetic sequence was the Ziegler modified intramolecular Ullmann biaryl coupling between two aryl bromides. One of the aryl halides was 7-bromoindole which was prepared using the Bartoli indole synthesis. The second aryl bromide was connected to 7-bromoindole via a simple A/-alkylation. 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclobexylbnine of two identical aromatic aldehydes were coupled by an Ullmann coupling reaction modified by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THE, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared to protect the aldehyde during ring metalation with. -BuLi. ... 

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