New Methods of Imidazole Functionalization - From Imidazole to Marine Alkaloids

The pyrrole-imidazole family of marine alkaloids, the so-called oroidin natural products, exhibits an impressive diversity of structural motifs. The majority of these natural products contain one or more imidazole moieties intricately embedded within a polycyclic framework and thus present significant challenges to extant synthetic methods. Our approach to this problem has centered on the development of methods for the elaboration of simple imidazoles. This Account describes the results of these efforts leading to the development of a variety of methods, including cycloadditions, oxidative and transition-metal-catalyzed reactions. 1 Diels-Alder Chemistry of Vinylimidazoles 1.1 Substitution of 4(5)-Iodoimidazole 1.2 Selective Deiodination of 4,5-Diiodoimidazoles 1.3 Isomerization of 4/5-Iodoimidazoles 2 Substituent Effects 2.1 Vinyl Substituents 2.2 Substituents at the 2-Position 3 Intramolecular Variants 4 Fused to Spiro Systems 4.1 Regiochemistry and Mechanism 5 Ring-Closing Metathesis 6 Pd-(pi)-Allyl Chemistry of Imidazole Derivatives 7 Summary