Novel transformations in the Stevens rearrangement of ammonium ylides and their application toward synthesis of alkaloid natural products

The Stevens rearrangement, or Stevens [1,2]-shift, of ammonium ylides has emerged as a powerful method for accessing nitrogen heterocycles. Mechanistically, the Stevens [1,2]-shift proceeds through a radical pair held in proximity via a solvent cage. The presented studies demonstrate the effectiveness of this rearrangement in rapidly accessing pyrrolizidine, indolizidine, and quinolizidine alkaloid ring systems.; Pyrrolizidines are a family of alkaloids that have been found to be potent inhibitors of glucosidase I and have other interesting biological properties as well. Using azetidines, we have developed a novel approach to the pyrrolizidine ring system based on the Stevens [1,2]-shift of a spirocyclic ylide. This methodology resulted in the efficient synthesis of the natural products turneforcidine and platynecine. The indolizidine ring system was also successfully accessed using a similar ring-expansion. A short route to 3-carboxyproline derivatives through an intermolecular version of this chemistry is also discussed. These compounds are of importance as rigid aspartic acid analogues.; Synthetic interest in polyhydroxylated quinolizidines has grown in recent years since these molecules have been identified as potential glycosidase inhibitors. The synthesis of an unnatural dihydroxylated quinolizidine using a novel silyl-directed Stevens rearrangement of ammonium ylides and subsequent Fleming-Tamao oxidation is described. In the key transformation, ring-expansion proceeds with excellent retention of configuration at the migrating center in the case of phenyldimethylsilyl substituted substrate. This work offers a unique application of Beak's asymmetric lithiation methodology.; Marine ladder toxins consist of some of the largest natural products known to man. These molecules contain within them a repeating cyclic ether backbone that has been the basis of several iterative approaches towards them. Presented are initial efforts at using the Stevens rearrangement of oxonium ylides in an iterative approach to polycyclic ethers. Results from this chemistry prompted another study. Also presented is the synthesis of a few acyclic ether substrates that were used in a collaborative project designed at exploring the effect of catalyst on competing Stevens [1,2]-shifts and the [2,3]-shift as well as activated C-H insertion pathways.