Studies towards the total synthesis of (±)- Lycoramine : II. Development of the retro-aza-Claisen rearrangement to synthesize medium sized N-substituted heterocycles : III. Studies towards the total synthesis of (-)- Nakadomarin A

Thesis (Ph. D.)--University of Rochester. Dept. of Chemistry, 2010.I. Studies Towards the Total Synthesis of (±)-Lycoramine The tricyclic core of the amaryllidaceae alkaloids was prepared in a convergent synthesis via an intramolecular Heck/phenol capture sequence. The versatile cascade reaction allows for a rapid assembly of numerous key intermediates that can be elaborated to give the necessary framework for the completion of the total synthesis of lycoramine. II. Development of the Aza-Retro-Claisen Rearrangement to Synthesize - Medium Sized N-Substituted Heterocycles An efficient synthesis of medium-sized heterocyclic rings was achieved using a one-pot aza-Wittig/retro-aza-Claisen sequence of vinyl cyclobutanecarboxaldehydes derived from simple allylic carbonates. A range of Staudinger reagents in the aza-Wittig reaction were used to allow for a variety of Nsubstituted products to be obtained. The rearrangement is thermodynamically controlled though ring strain relief of the cyclobutane and resonance stabilization of the resulting vinylogous sufonamide. III. Studies Towards the Total Synthesis of (-)-Nakadomarin A The total synthesis of Nakadomarin A was pursued. An efficient asymmetric synthesis of a key bicyclic lactam precursor was completed based on previous research efforts. A series of model studies were completed in order to help understand the behavior of a 3-aza-6-π-electrocyclic ring closure; a key steps in our synthetic strategy. In addition to the model studies, a variety of synthetic routes toward the completion of 2,4-substituted furfural cinnamaldehydes were undertaken, which was applied towards the completion of the synthetic effort