Enantioselective synthesis of cyclic beta-amino alcohols via tandem hydroalumination-cyclization-reduction of ethoxycarbonyl vinyl sulfoximines and application to the synthesis of potential aggrecanase inhibitors

摘要

The beta-amino alcohol moiety is a common structural component in a wide variety of natural occurring compounds, synthetic pharmacologically important molecules, ligands and chiral auxiliaries for asymmetric synthesis. Due to the fact that the stereochemistry of the beta-amino alcohol moiety is important for biological activity and for chirality transfer, asymmetric synthesis of compounds containing beta-amino alcohol functionality has drawn considerable attention. This thesis describes enantioselective synthesis of cyclic beta-amino alcohols starting from ethoxycarbonyl vinyl sulfoximines, which are prepared from cyclic bis(allylsulfoximine)titanium complexes and N-tert-butylsulfonyl alpha-imino ester. The application of sulfoximine substituted bicyclic 1,2-amino alcohol in the synthesis of potential aggrecanase inhibitor is described.