Palladiumkatalysierte C(sp2)-H-Funktionalisierung : neue Strategien zur selektiven Synthese disubstituierter planar chiraler [2.2]Paracyclophane

Abstract

Substituted [2.2]paracyclophanes are used as ligands, auxiliaries and catalysts in asymmetric synthesis due to their planar chirality. Herein, disubstituted [2.2]paracyclophanes have shown very high activity and selectivity compared to monosubstituted [2.2]paracyclophanes. However, their synthesis is still quite challenging and a regioselective functionalization of monosubstituted [2.2]paracyclophanes is restricted to a few special examples. Therefore, new strategies for the regioselective synthesis of disubstituted [2.2]paracyclophanes were investigated within this thesis. The first part describes a palladium-mediated synthesis of planar chiral carbazoles bearing a [2.2]paracyclophane backbone. These carbazoles were obtained by a palladium-catalyzed Buchwald-Hartwig amination of 4-bromo[2.2]paracyclophane and aniline or aniline derivatives followed by an intramolecular palladium-mediated cyclization under oxidative conditions. The corresponding carbazoles were formed in moderate to good yields by an ortho-selective, double C–H-functionalization of N-phenyl[2.2]paracyclophanylamines as the key step. Afterwards, the palladium-catalyzed intermolecular C–H-functionalization of various donor-substituted [2.2]paracyclophanes was investigated. A broad range of amido-, imino/oximo- and heterocyclic-substituted [2.2]paracyclophanes was prepared and their directing properties were tested in a palladium-catalyzed direct acetoxylation. Among the donor-substituted [2.2]paracyclophanes tested, both planar chiral oximethers and -acetate as well as pyridinyl- and pyrazolylsubstituted [2.2]paracyclophanes were used successfully. Ortho-acetoxylated [2.2]paracyclophanes were formed in good yields up to 87% in the presence of 1-5 mol% palladium acetate. Further functionalization of the ortho-acetoxylated [2.2]paracyclophanes yielded in promising N,O- or O,O-chelators/-ligands. In addition to the investigation of the palladium-catalyzed direct ortho-acetoxylation a mild method for the para-selective functionalization of N-acetyl-4-amino[2.2]paracyclophane was developed. The para-position was activated selectively in the presence of a hypervalent iodine(III)reagent under metal-free conditions. Using this strategy planar chiral Paracetamol derivatives were obtained in moderate to good yields