Organocatalytic enantioselective synthesis of β-nitrophosphonates, 2-amino-4H-chromenes and oxindole derivatives
Performing asymmetric transformations is one of the most challenging areas of organic chemistry. Most importantly, within a chiral surrounding, two enantiomeric biologically active agents often behave differently. Therefore, to develop an enantioselective synthesis of the desired enantiomer in an asymmetric transformation is highly desirable in medicinal chemistry as well as in the pharmaceutical industry. Over the last ten years the field of organocatalysis has grown from a small collection of unique or unusual chemical reactions to a thriving area of research with a very broad scope of reactions, and atypical reactivities and selectivities. It has now become a well-established approach for asymmetric organic synthesis. This dissertation describes the highly enantioselective synthesis of β-nitrophosphonates, 2-amino-4 H -chromenes, and oxindole derivatives using organocatalytic approaches. These derivatives have been identified as versatile synthetic intermediates in the synthesis of a multitude of important chiral compounds. The organocatalysts used in this study are bifunctional and are capable of activating both the electrophile and the nucleophile simultaneously and frequently demonstrate superior reactivity and stereoselectivity. This dissertation work demonstrates that cinchona alkaloid- derived thioureas are superior organocatalysts for the synthesis of enantiomerically enriched biologically active molecules, such as?-nitrophosphonates, 2-amino-4 H -chromenes, and oxindole derivatives. The formation of non-covalent adducts between the catalyst and substrate(s) through hydrogen bonding and/or ionic interactions within the catalytic cycle are the key to the high stereoselectivities achieved in these reactions.