Synthesis of Novel Chiral Bicyclic Ligands and their Application in Iridium-Catalyzed Reactions

• Main Author: Trifonova, Anna
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Avdelningen för organisk kemi 2005
• Subjects: Organic chemistry; asymmetric catalysis; Diels-Alder reaction; transfer hydrogenation; hydrogenation; amino-oxazoline; phosphine-oxazoline; imine; olefin; Organisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5783; http://nbn-resolving.de/urn:isbn:91-554-6243-X

The synthesis of 2-aza-norborane derivatives is presented. The use of these compounds in preparation of Ir catalysts for asymmetric hydrogenations is described. The evaluation and optimization of the catalysts as well as the mechanistic aspects of the catalytic process are discussed. The use of non-activated iminodieniphiles in stereoselective aza-Diels-Alder reaction has expanded the scope of the reaction and provided a convenient root for preparation of 2-aza-norboranes, analogues of which were developed into novel bicyclic 2-aza-norbornyl-oxazoline ligands for Ir-catalyzed asymmetric transfer hydrogenations. Using ths Ir complexes acetophenone was hydrogenated in 79% ee. 2-Aza-norbornyl-oxazolines were also developed into novel N,P-ligands. Resulting phosphine-oxazolines were evaluated in Ir-catalyzed asymmetric hydrogenation of structurally diverse imines and olefins. Optimization of ligands was performed through: 1) Alteration of the stereoconfiguration at the 5’-position as well as variation of the size and geometry of the substituents at this position; 2) Screening through various phosphine substituents of the ligand. Both directions of optimization reflect on the influence of the ligands’ sterik bulk on stereoselectivity of catalytic process. High performance catalysts were developed for both transformations allowing asymmetric hydrogenation of imines with 92% ee and asymmetric hydrogenation of olefins with 99% ee. Possible mechanisms for these transformations were suggested based on computational studies. Selectivity model for rationalization of results of Ir-catalyzed olefin hydrogenation also was designed.