Chiral N-heterocyclic carbene ligands for asymmetric catalytic oxindole synthesis

摘要

The Pd-catalysed asymmetric intramolecular α-arylation of amide enolates containing heteroatom substituents gives chiral 3-alkoxy or 3-aminooxindoles in high yield and with enantio-selectivities up to 97% ee when a new chiral N-heterocyclic carbene ligand is used.rnOxindoles containing a quaternary benzylic center constitute a common structural motif in many natural products and biologically active compounds. Among them, oxindoles with heteroatoms at the stereogenic center are a useful class of compounds in the field of medicinal chemistry, including the potent growth hormone secretagogue SM-130686 (A), the clinical candidate AG-041R (B) as gastrin/CCK-B receptor antagonist and SSR-149415 (C), a drug now in clinical trials for treatment of anxiety and depression. Owing to the significance of this structural motif, the development of a catalytic asymmetric synthetic method for these compounds is highly valuable.