Development of New Chiral Bicyclic Ligands : Applications in Catalytic Asymmetric Transfer Hydrogenation, Epoxidations, and Epoxide Rearrangements

Abstract: This thesis describes the synthesis and application of new chiral bicyclic ligands and their application in asymmetric catalysis. The studies involved: [i] The development of novel chiral bicyclic amino sulfur ligands and their use in transfer hydrogenation. [ii] The development of the kinetic resolution of racemic epoxide through the use of chiral lithium amides. [iii] The synthesis and application of chiral bicyclic amine in the organocatalysed epoxidation of alkenes. [iv] Development and application of new chiral diamine ligands in the rearrangement of epoxides into allylic alcohols.[i] The preparation of two-series of amino thiol ligands based on the structure of camphor is described, together with their application in the iridium-catalysed asymmetric transfer hydrogenation of acetophenone using isopropanol as the hydrogen source. Excellent activity and good enantioselectivity have been achieved using 2 mol% of chiral ligand in combination with [IrCl(COD)]2.[ii] The chiral diamines (1S,3R,4R)-3-(pyrrolidine-1-ylmethyl)-2-aza-bicyclo[2.2.1]heptane and its (2R,5R)-dimethylpyrrolidine derivative were applied to the kinetic resolution of a variety of racemic 5-7 membered cycloalkene oxides with lithium diisopropylamide (LDA) as the bulk base. Using 5 mol% of the chiral diamines, both unreacted epoxides and allylic alcohols could be produced in enantiomeric excess up to 99%.[iii] The synthesis of chiral bicyclic amines and their use in the organocatalysed epoxidation of alkene has been described. Using a substoichiometric amount of the chiral amines and aldehydes as ligands precursors, with Oxone® as oxidant, a good activity but moderate enantioselectivity was observed for the epoxidation of trans-stilbene. [iv] The preparation of 6-substituted-7-bromo-aza-bicyclo[2.2.1]heptanes via nucleophilic addition of organocopper reagents to 3-bromo-1-azoniatricyclo[2.2.1.0]heptyle bromide has been described. These compounds have been utilised as chiral building blocks in the preparation of novel chiral diamine ligands, which have been successfully applied to the catalysed asymmetric rearrangement of epoxide into the corresponding allylic alcohol.