Pyrrolophenanthridinium alkaloid

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. 

Stark, L. M., Lin, X.-F., Flippin, L. A. Total Synthesis of Amaryllidaceae Pyrrolophenanthridinium Alkaloids via the Ziegler-Ullmann Reaction Tortuosine, Criasbetaine, and Ungeremine. J. Org. Chem. 2000, 65, 3227-3230. 

C-Aromatic lycorine-type alkaloids have been discovered in the plants of the Amaryllidaceae family. Two new 2-oxo-pyrrolophenanthridinium alkaloids, zefbetaine (59) and zeflabetaine (60), together with several known Amaryllidaceae alkaloids, have been isolated from fresh mature seeds of Zephranthes flava by gradient solvent extraction, chromatography, and deri-vatization (108). Their structures were characterized by comprehensive spectroscopic methods, chemical transformations, and synthesis. They are listed in Fig. 9. 

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