Alkene Amidooxysulfonylation: Development & Application to the Common Daphniphyllum Alkaloid Core

The electrophile addition (AdE) reaction of alkenes to form 1,2-bifunctional products is among the more widely studied processes in the field of organic chemistry, reflecting its value as a means to rapidly install chemical complexity. Despite long-standing interest in this type of reaction, the oxyamination, or addition of nitrogen and oxygen-based groups, of alkenes remains a challenging transformation. This thesis describes the development of a synthetic method for the amidooxysulfonylation of alkenes, employing hypervalent iodine reagents. A discussion of the application of this method to the synthesis of bicyclic alkaloid natural product targets follows. Chapter 1 opens with a review of the chemistry of O-alkyl hydroxamates and the nitrenium ions, or equivalent species, accessed through the N-oxidation of these substrates. Details of the development of a versatile method for the amidooxysulfonylation of unsaturated O-alkyl hydroxamates employing hypervalent iodine reagents are then discussed. In Chapters 2 and 3, the application of this methodology to the preparation of the functionalized core structures of two alkaloid families, namely those belonging to the Daphniphyllum and Delphinium groups, is described. More specifically, the A/B/C-ring system of (-)-himalensine A and the A/E/F-ring system of (+)-methyllycaconitine are prepared. In the final chapter, we described the development and implementation of a synthetic strategy for the selective diastereoselective preparation of 4-substituted 1,2-trans-cyclohexyldiamines, and the application of this method to the synthesis of a functional CyDTPA-based metal chelator for use in PET imaging.