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Dependence of Enantioselectivity on the Ligand/Metal Ratio in the Asymmetric Michael Addition of Indole to Benzylidene Malonates: Electronic Influence of Substrates
Author(s) -
Schätz Alexander,
Rasappan Ramesh,
Hager Markus,
Gissibl Anja,
Reiser Oliver
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800508
Subject(s) - ligand (biochemistry) , chemistry , substrate (aquarium) , polar effect , metal , oxazoline , enantiomeric excess , enantiomer , trifluoromethanesulfonate , medicinal chemistry , indole test , stereochemistry , enantioselective synthesis , organic chemistry , catalysis , receptor , biochemistry , oceanography , geology
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 σ 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.