An Investigation of a Palladium Catalysed Biaryl Synthesis of Pyrrolophenanthridine Derivatives. Extension of the Heck Reaction

The pyrrolo[3,2,1-de]phenanthridine skeleton has been found in a large number of natural products from the plants of almost all of the genera of the family Amaryllidaceae. Examples of these compounds include assoanine1 (1), oxoassoanine2 (2), hippadine3 (3) and ungeremine4 (4) amongst others5. These compounds (Figure 1) are of interest as synthetic targets not only for the development of synthetic methodology but also for their biological activities6. An important feature of the pyrrolo[3,2,1-de]phenanthridine skeleton is the biaryl linkage and this has often been a central subject of the synthetic methodology employed for the construction of these, and a diverse range of phenanthridine or benzophenanthridine derivatives7. The Heck reaction8 is a versatile methodology for the formation of new C-C bonds, particularly for the coupling of an aromatic halide with an olefin9. The corresponding biaryl synthesis where hydrogen halide is eliminated from the two aromatic components is a recent extension of the Heck reaction10, whereas the corresponding biaryl synthesis using an oxidative addition reaction with stoichiometric quantities of palladium salts has been more extensively studied11.