Résumé
New binepine ligands have been synthesized, and characterized and have been shown to induce high diastereo- and enantioselectivity in the intramolecular arylation of primary and secondary C(sp3)–H bonds, giving rise to fused cyclopentanes. The ligands were obtained as bench-stable phosphonium tetrafluoroborate salts that can be directly employed in catalysis. It was shown that a ferrocenyl P-substituent on the ligand allows achievement of high stereoselectivities in combination with potassium carbonate for the arylation of primary C–H bonds under unprecedentedly low temperature (90 °C) and catalyst loading (1–2 mol % Pd/2–3 mol % ligand). Using a base-free precatalyst, carbonate was shown to be the active base and to provide higher stereoselectivities than acetate and pivalate. The more difficult arylation of secondary C–H bonds could also be achieved and required fine-tuning of the ligand structure and the carbonate countercation. This method allowed generation of fused tricyclic products containing three adjacent stereocenters as single diastereoisomers and with moderate to high enantioselectivity. Experimental data indicated that the enantiodetermining C–H activation step involves a monoligated species. DFT (PBE0-D3) calculations were performed with a prototypical binepine ligand to understand the origin of the enantioselectivity. The preference for the major enantiomer was traced to the establishment of a more efficient network of weak attractive interactions between the phosphine ligand and the substrate.