Bicyclic Ligands and Catalysts in Asymmetric Synthesis

Abstract: Synthesis of compounds based on the structurally rigid bicyclo[2.2.2]octane and the dibenzobicyclo[3.3.1]nonane frameworks and also their application as ligands and catalysts in asymmetric synthesis are described. For the synthesis of 1,3-diols based on the bicyclo[2.2.2]octane framework, an improved synthesis of the starting material bicyclo[2.2.2]octan-2,6-dione was developed and performed at 0.5 kg scale, as well as an effective synthetic route to the target diols. A genetically engineered Saccharomyces cerevisiae strain was used for the preparation of key intermediates for the synthesis of 1,4-diols based on the bicyclo[2.2.2]octane framework. The 1,3- and 1,4-diols, together with Ti(OiPr)4, were tested as catalysts in the asymmetric reduction of acetophenone with catecholborane and in the asymmetric addition of dimethylphosphite to aldehydes. Several chiral cleft molecules (diols, amino alcohols and diamines) based on the dibenzobicyclo[3.3.1]nonane framework were synthesized and applied as organocatalysts in an asymmetric hetero-Diels-Alder reaction. A primary diamine based on the dibenzobicyclo[3.3.1]nonane framework was used as the rigid central part for the synthesis of two chiral selectors with different length of their achiral spacers. These selectors were used for the preparation of two new chiral stationary phases, which were evaluated by chromatography (HPLC).