Modular oxazoline ligands: Synthesis and application in asymmetric catalysis

The development of catalytic enantioselective reactions is important to the synthesis of single enantiomer of organic molecules. Recently, several groups including ours have studied the design and utility of modular catalysts in this area. Typically, such catalysts contain modules that can be varied independently and assembled easily. Simplified access to catalyst analogs enables the rapid optimization of yield and ee.; To explore the utility of modular ligands, an oxazoline ring with a pendant amino group was chosen. The choice of oxazoline as the core scaffold was based on the fact that metal complexes of oxazolines have been shown to be powerful catalysts for mechanistically unrelated reaction. Additionally, amine functionalized oxazolines can be assembled from the appropriately protected chiral alpha-amino acids and beta-amino alcohos. Further, the scaffold can be diversified by functionalizing the pendant amino group. Several combinations of synthetic methods and protecting groups on the amino acid were evaluated. This has led to the identification of two protocols for the synthesis of amine functionalized oxazolines.; An oxazoline scaffold displaying two hydrogen bond donating arms in the form of a tertiary alcohol and a sulfonamide was chosen for further exploration. With this scaffold, the hydrogen bond promoted hetero Diels-Alder reaction was studied. After screening several analogs, an oxazoline with a pendant camphorsulfonamide was identified as the optimal catalyst, giving ee's up to 92% for this important reaction. Further studies aimed at elucidating the role of all the structural features are in progress.