Synthesis of amino- and hydroxyl-substituted bridged bicyclic compounds and their application in asymmetric catalysis

Abstract: In this work, hydroxyl- and amino-substituted bridged bicyclic compounds based on bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane and bicyclo[3.3.1]nonane were synthesized and investigated for use in asymmetric catalysis. An improved process for the preparation of an optically active key intermediate for the synthesis of bicyclo[2.2.2]octane-derivatives, using genetically engineered yeast, was developed. Optically active key intermediates for the synthesis of bicyclo[2.2.1]heptane-derivatives were achieved by enzymatic resolution using Novozym 435. The possibility to use genetically engineered yeast strains for kinetic resolution of a bicyclic epoxyketone was also investigated. The structurally rigid aminoalcohols and diols based on bicyclo[2.2.1]heptane and bicyclo[2.2.2]octane were tested as catalysts in the diethylzinc addition to benzaldehyde. Chiral cleft-shaped molecules based on dibenzobicyclo[3.3.1]nonane were synthesized and applied as hydrogen-bonding organocatalysts in an asymmetric hetero-Diels-Alder reaction.