Asymmetric Pd-NHC*-catalyzed coupling reactions 


University of Geneva, Department of Organic Chemistry, 30 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland


Very high asymmetric inductions result in the palladium catalyzed intramolecular arylation of amides to give 3,3-disubstituted oxindoles and 3-spiro-oxindoles when new in-situ generated chiral non-racemic N-heterocyclic carbenes are employed. Structural studies show that conformational locking to avoid allylic strain is the key for understanding the role of the different elements in these ligands. In another application of in situ-generated Pd-NHC* catalysts, asymmetric coupling reactions involving C(sp3)-H bonds are studied. Highly enantioenriched indolines are accessible via this route. Remarkably, although this homogeneously catalyzed reaction requires high temperature (140-160°C) excellent asymmetric recognition of an enantiotopic C-H bond in an unactivated methylene unit has been realized. Most recent discoveries are regiodivergent reactions with cases where a racemic mixture is transformed into two equal parts of two structurally different indoline products of very high enantiomeric purity. Finally, promising results of enantioselective Suzuki-Miyaura aryl-aryl coupling reactions were obtained using chiral PEPPSI catalysts incorporating the NHC* ligands.


Chiral transition metal catalysts (ML*) target the efficient preparation of single enantiomers of chiral building blocks for the construction of bioactive products and chiral materials. Single enantiomers are required since interactions of one or the other mirror image of the same compound with organisms can have drastically different consequences.
Chiral ligands (L*) impart electronic tuning to the metal catalyst and provide a steric environment that, when chosen judiciously, leads to the formation of highly enantiomerically enriched products. Bidentate phosphorous ligands have a long and outstanding record of achievement in asymmetric catalysis (1). The bidentate ligands ensure stability and the chiral backbone controls the stereodirecting elements in the reaction zone. Looking for new possibilities in catalysis, our laboratory has focused on catalysts with monodentate chiral non-racemic N-heterocyclic carbene (NHC*) ligands. NHC-ligands form very strong and robust complexes but, lacking a chiral backbone, steric control of reactions with an M-NHC* unit is difficult to achieve (2). The solution ...