Hydroxylamines: From Synthetic Intermediates to Synthetic Targets

ConspectusSynergy between the teaching and research activities of a University should be a source of new ideas, each informing the other. A classroom discussion gave rise to our concept of using hydroxylamines as a form of "tethered nitrogen" for alkaloid synthesis. The "tether" temporarily connects a nucleophilic nitrogen atom to the substrate, rendering an intermolecular reaction intramolecular, thus providing stereo- and regiochemical control for C-N bond formation. In the context of the synthesis of 1,3-amino alcohols, this necessitated the synthesis of isoxazolidines. This concept led to the exploration of methods for the synthesis of these heterocycles beyond the well-established 1,3-dipolar cycloadditions. The first two methods developed based upon this concept were palladium catalyzed cyclocarbonylation and silver catalyzed allene cyclization. These new methods were applied to two syntheses of sedamine and the synthesis of three