Highly Enantioselective Michael Additions of Indole to Benzylidene Malonate Using Simple Bis(oxazoline) Ligands: Importance of Metal/Ligand Ratio

Simple bis(oxazoline) ligands, especially azabis(oxazolines), can catalyze the copper-catalyzed addition of indoles to benzylidene malonates in up to >99% ee, provided that excess of chiral ligand is avoided. The paradigm followed in many asymmetric catalyses that an excess of chiral ligand with respect to the metal should improve enantioselectivity because a background reaction by free metal is suppressed, is not applicable here, which might call for revisiting some of the many copper(II)−bis(oxazoline)-catalyzed processes known.