Gold(I)-catalyzed cycloisomerization reactions of allenes: An exploration of ligand effects and the total synthesis of flinderole B and C
- Author(s): Zeldin, Rachel Motove
- Advisor(s): Toste, F. Dean
- et al.
The modern era of synthetic chemistry can be characterized by increased understanding, development and application of transition metal complexes to traditionally organic transformations. While the field has focused largely on the chemistry of group 4-8 metals (and in particular, rhodium and palladium), there has been growing interest in the past decade in using so-called "coinage metals"--gold, silver and copper--as catalysts for organic reactions.
Gold(I) metal complexes have been shown to effect a range of organic transformations that proceed through π-activation mechanisms, often with greater selectivity than other transition metal complexes. Additionally, in contrast to more established transition metal reactions, gold(I) processes can be conducted at low temperature and in the presence of water and air. Because of their mild conditions and high degree of control, gold(I) reactions are ideal for application to total synthesis. In the first chapter of this text, we discuss the current state of the art of gold(I)-catalysis in the context of complex molecule synthesis.
The reactivity exhibited by gold(I) complexes is highly controlled by choice of catalyst ligand. In the second chapter, we discuss the development of ligand-controlled intramolecular reaction of dienes and allenes to afford selectively either [4+2]- or [4+3] cycloadducts. The purpose of this discussion is two-fold: first, to demonstrate the effect that stabilization of reactive intermediates has on the course of gold(I) reactions, and second, to develop methodologies aimed at constructing novel, complex ring structures.
In the third chapter of this text, we take one of the reactions discovered in the course of our work in diene-allene cycloadditions and apply it to the total synthesis of antimalarial bisindole alkaloids flinderoles B and C. The key step, a gold(I)-catalyzed hydroarylation of an allene using a C2-indole nucleophile, simulatenously installs three of four unique structural motifs of this natural product.