Dependence of Enantioselectivity on the Ligand/Metal Ratio in the Asymmetric Michael Addition of Indole to Benzylidene Malonates: Electronic Influence of Substrates

Abstract

Simple bis(oxazoline) ligands, especially azabis(oxazolines), can promote the copper(II)-catalyzed Michael addition of indoles to benzylidene malonates with up to >99 % ee (ee=enantiomeric excess), provided that the ligand/metal ratio is tuned meticulously with particular regard to the electronic properties of the substrate. Despite a common paradigm followed in many asymmetric catalyses, an excess of chiral ligand is not always beneficial. In fact any excess of ligand has to be avoided to reach excellent enantioselectivities when electron-rich benzylidene malonates are used. On the contrary, malonates carrying an electron-withdrawing group require an excess of ligand for an optimum ee value. A correlation of optical yields versus the sigma(I) values of several para substituents shows a sigmoid trajectory. In the presence of an additive, such as triflate, the significance of the ligand/metal ratio vanishes and very good enantioselectivities are achieved at any rate--no matter whether electron-donating or withdrawing substituents are present.

A New CopperII/Isopropylidene‐2,2‐bis(oxazoline) Catalyst and Its Stable Reactive Complex with Acryloyloxazolidinone in Enantioselective Reactions

“…Some intriguing results have been reported, in which lithium triflate seems to stabilize a pentacoordinated Cu II complex involved in the enantioselective asymmetric Michael addition of indole to benzylidene malonates 19. Therefore, both DA and 1,3‐DC have been tested under the above catalytic conditions, with the addition of 1 or 5 equivalents of LiOTf.…”

Synthesis of novel thiophene‐based chiral ligands and their application in asymmetric Henry reaction

“…Schätz et al . reported that ligand/metal ratio influences enantioselectivity, and the effect of the ligand/metal ratio was tested at room temperature (Table ).…”

“Catalysis in a Tea Bag”: Synthesis, Catalytic Performance and Recycling of Dendrimer‐Immobilised Bis‐ and Trisoxazoline Copper Catalysts

“…[26] We note though that Reiser et al have found that in some cases pentacoordinate Cu II species may be effective as catalysts, [27] but apparently not with strong donors such as the third oxazoline moiety present in the trisox ligands employed in this study.…”