Advances in the Synthesis of Fluorinated Scaffolds by Transition Metal-Catalyzed C-H Bond Activation.

Thanks to the unique features of the fluorine atom and the fluorinated groups, fluorine-containing molecules are essential. Therefore, the search for new fluorinated groups as well as straightforward and original methodologies for their installation is of prime importance. Especially, the combination of organofluorine chemistry with transition metal-catalyzed C-H bond functionalization reactions offered straightforward tools to access original fluorinated scaffolds. In this context, over the last years, our group focused on the development of original methodologies to synthesize fluorine-containing molecules with a special attention to emergent fluorinated groups. The present account highlights our recent contributions to the synthesis of highly value-added fluorine-containing compounds by transition metal-catalyzed C-H bond activation.

Late-stage C-H amination of abietane diterpenoids.

This study aims at highlighting the synthetic versatility of the rhodium-catalyzed C-H amination reactions using iodine(iii) oxidants for the late-stage functionalization of natural products. Inter- and intramolecular nitrene insertions have been performed from various abietane diterpenoids, leading to the amination of the C-3, C-6, C-7, C-11 and C-15 positions. Ca. 20 aminated compounds have been isolated with yields of up to 86% and high levels of regio-, chemo- and stereoselectivities.

Synthesis and cytotoxic activity evaluation of dihydrocucurbitacin B and cucurbitacin B derivatives.

Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.