Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium-catalyzed intramolecular C-H functionalization.
BACKGROUND
Small polyfunctionalized heterocyclic compounds play important roles in the drug discovery process and in the isolation and structural identification of biological macromolecules. It is expected that ready access to diverse sets of heterocycles can not only help improving the known biological and pharmacokinetic properties of drugs, but also assist the discovery of molecules that exhibit biological effects beyond those associated with previously known macromolecules. By virtue of their inherent convergence, high productivity, their exploratory and complexity-generating power, multicomponent reactions (MCRs) are undoubtedly well suited for creating molecular diversity. The combination of MCRs with an efficient post-functionalization reaction has proven to be an efficient strategy to increase the skeleton diversity.


RESULTS
The Ugi reaction of an o-iodobenzaldehyde (2), an aniline (3), an isocyanide (4), and a carboxylic acid (5) afforded alpha-acetamido-alpha-phenylacetamide (6) in good to excellent yields. The palladium-catalyzed intramolecular C-H functionalization of these adducts under ligandless conditions provided the functionalized dihydrophenanthridines (1).


CONCLUSIONS
Highly functionalized dihydrophenanthridines are synthesized in only two steps from readily accessible starting materials in good to excellent overall yields.
Bonnaterre
Florence
F
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France. florence.bonnaterre@syngenta.com
Bois-Choussy
Michèle
M
Zhu
Jieping
J