The design, synthesis, and utility of sulfinyl imine-based ligands for asymmetric catalysis

The preparation of molecules in enantiomerically pure form is of great importance due to the inherent chirality of biological systems. The properties and activities of many natural products and medicinal chemistry targets of interest to the organic chemist are linked to their unique stereochemical arrangement. Many methods are available for the preparation of enantiomerically pure compounds, including the separation of diastereomers, enzymatic resolution, chemical kinetic resolution, and asymmetric synthesis. Perhaps the most powerful method is the catalytic preparation of enantiomerically pure compounds from achiral starting materials. This was most recently highlighted by the presentation of the Nobel Prize in Chemistry to K. Barry Sharpless, Ryoji Noyori, and William S. Knowles for their contributions to the development of asymmetric catalysis.; Described herein is the application of N-tert-butanesulfinyl imine derivatives to the asymmetric synthesis of small molecules. The ability of sulfinyl imines to serve as chiral dienophiles in the hetero-Diels-Alder reaction to afford diastereomerically enriched piperidinones is discussed in chapter one. The design of novel ligands based on N-sulfinyl imine chirality is reported in chapter two. This report chronicles the development of the bis(tert-butanesulfinyl)imidoamidine (siam) ligands and describes their utility in the copper(II) catalyzed asymmetric Diels-Alder reaction. This work represents the first application of the sulfinyl moiety in ligands for asymmetric catalysis and, for certain substrates, affords the highest enantioselectivities yet reported for a copper catalyzed Diels-Alder reaction. In the final chapter, the preparation of N-sulfinyl amidines and the investigation of their rhodium complexes is addressed.