Site-selective Ru-catalyzed C-H bond alkenylation with biologically relevant isoindolinones: a case of catalyst performance controlled by subtle stereo-electronic effects of the weak directing group

Yu-Chao Yuan (1) , Christian Bruneau (1) , Thierry Roisnel (1) , Rafael Gramage-Doria (1)

1 ISCR - Institut des Sciences Chimiques de Rennes

The first use of biologically relevant isoindolinones as weak directing groups in transition metal-catalyzed carbon-carbon bond formation via C-H bond functionalization is presented. Notably, besides the presence of two aromatic C-H sites available for functionalization, selective mono-alkenylation in the ortho-position with respect to the nitrogen atom were achieved with a readily available ruthenium catalyst. The scalability, versatility and high functional group tolerance of the catalysis enabled the late-stage functionalization of biologically relevant indoprofen and further derivatizations. Preliminary mechanistic studies indicate (1) the ease of the C-H bond activation step, (2) the key role of the carbonyl group as a weak directing group throughout the catalytic cycle and (3) the unexpected subtle differences associated between cyclic amides and imides as weak directing groups in ruthenium-catalyzed C-H bond alkenylation reactions. The isolation and role of an unprecedented off-cycle ruthenium complex is discussed as well.

Domaines: Chimie

Yu-Chao Yuan, Christian Bruneau, Thierry Roisnel, Rafael Gramage-Doria. Site-selective Ru-catalyzed C-H bond alkenylation with biologically relevant isoindolinones: a case of catalyst performance controlled by subtle stereo-electronic effects of the weak directing group. Catalysis Science & Technology, 2019, 9 (17), pp.4711-4717. ⟨10.1039/c9cy01231a⟩. ⟨hal-02303389⟩