Development of functionalized spiroligomers for metal-binding and asymmetric catalysis

Abstract

This thesis describes the synthesis of functionalized spiroligomers and their applications in metal binding, metal-mediated catalysis, and organocatalysis. By synthesizing a family of functionalized bis-amino acids achieved from reductive alkylation, the Schafmeister group has developed access to highly functionalized and shape programmable structures named “spiroligomers.” The rigid backbones of spiroligomers are good at organizing the orientations of functional groups on their side chains. This property enables them as promising candidates for catalysts. Firstly we synthesized a few spiroligomer dimers presenting metal-binding groups such as terpys and bipys. With the right orientation of metal binding groups controlled by adjusting the stereocenter of the spiroligomer, macrocyclic “square” complexes with metals were obtained. The crystal structures of these intriguing complexes were solved. This work rendered the first structurally, spectroscopically and electronically characterized metal-spiroligomer complexes as well as the first crystal structure of spiroligomer. Secondly, the question of whether metal-binding spiroligomers are able to catalyze certain reactions became our major concern. We developed a binuclear copper catalyst that could accelerate a phosphate ester rearrangement, and that demonstrated that when the two copper binding terpyridine groups were best able to approach each other, they accelerated the rearrangement more than 1,000 times faster than the background reaction. Other molecules that did not properly organize the two copper atoms demonstrate considerably slower reaction rates. At last, catalysts based on spiroligomers without metals are also of interests. By displaying two hydrophobic groups in various directions on a monomeric spiroligomer (also can be regarded as a proline derivative), we observed variable activities and enantioselectivities in the catalysis of asymmetric Michael addition (up to 94% ee at -40 °C for one organocatalyst).