Chiral Primary Amine-catalyzed Double Michael Addition Reactions

The Michael addition reaction represents one of the most powerful synthetic tools for the formation of carbon-carbon bonds in organic synthesis. The development of asymmetric organocatalysis grown at such an extraordinary pace that significant progress has been made during the past years in asymmetric Michael reactions.Asymmetric aminocatalysis has been become a powerful and well-established synthetic tool for the chemo-and enantioselective functionalization of carbonyl compounds. In the past decade, this field has grown at such an extraordinary pace that it is now recognized as an independent research area of synthetic chemistry, where the target is the preparation of any chiral molecule in an efficient, rapid, and stereoselective manner.Primary amines derived from natural cinchona alkaloids are demonstrated to be excellent catalysts for a number of asymmetric reactions of carbonyl compounds. In this thesis, asymmetric Michael addition reactions of isatylidene malononitriles to a, β-unsaturated ketones catalyzed by9-amino-9-deoxyepiquinidine.The combination of a cinchona-based chiral primary amine and a (R)-BINOL-phosphoric acid has been demonstrated as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with a,β-unsaturated ketones, to provide the novel chiral spiro [cyclohexane-1,3’-indoline]-2’,3-diones in high yields (88-99%) with excellent diastereo-and enantioselectivities (94:6->99:1dr’s,95->99%ee"s).