Entwicklung katalytischer Kreuzkupplungs- und Hydroaminierungsreaktionen

Abstract

In recent years great efforts have been taken for the development of highly active catalysts in the field of hydroamination- and cross-coupling-reactions. However, there is still a lack of generally applicable and user-friendly methodologies. In the present work, a sequential protocol for the synthesis of 2-aryl/alkenyl substituted indoles using low priced 2-chloro anilines and alkynes was developed. A Broensted-acid catalyzed intramolecular hydroamination of non-activated alkenes disclosed an atom-economical approach to functionalized pyrrolidine derivatives. Air-stable heteroatom substituted secondary phosphine oxide (HASPO) TADDOLP(O)H-ligand allowed for the use of aryl chlorides in palladium-catalyzed Kumada-Corriu couplings. Easily accessible air-stable HASPO-ligand PinP(O)H enabled palladium-catalyzed Kumada-Corriu cross-couplings of not only electron-rich and electron-poor tosylates but also heterocyclic tosylates. The use of a diaminophosphine chloride as preligand in palladium-catalyzed Suzuki-Miyaura couplings allowed the application of various functionalized chlorides under mild reaction conditions. Direct arylation reactions represent economical and ecological attractive alternatives compared to traditional cross-coupling reactions. A novel regioselective palladium-catalyzed domino synthesis of N-substituted as well N-H-free annulated heterocycles using cheap ortho-dihalides was developed without the need for protecting-group transformations. Further, the first use of functionalized tosylates for palladium-catalyzed direct arylation of various heterocyclic compounds was demonstrated. Additionally, a direct arylation methodology with aryl bromides catalyzed by an inexpensive ruthenium-catalyst, which do not require the use of additional phosphorous-based (pre)ligands has been presented. It was found that catalytic amounts of mesityl carboxylic acid enabled ruthenium-catalyzed directed direct arylations with diverse directing groups using bromides, chlorides and tosylates as electrophiles in apolar toluene as solvent.