An approach to catalytic asymmetric electrocyclization
Smith, Martin D.
University of Cambridge
Department of Chemistry
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Kothari, A. (2010). An approach to catalytic asymmetric electrocyclization (doctoral thesis).
Chapter 1 outlines the development of a catalytic electrocyclic process and its exploitation in asymmetric synthesis. Since Woodward and Hoffmann delineated a rationale for the mechanism and stereochemistry of these reactions they have become powerful synthetic tools. The aim of this project was to investigate catalytic asymmetric 6π electrocyclizations that will enable the rapid synthesis of highly functionalized molecules. We have demonstrated that the transient hexatriene precursors for [1,6]-electrocyclization are difficult to synthesize. When possible the central cis-alkene prefers to exist in a trans-configured geometry, while the free ketone undergoes an essentially irreversible oxo-electrocyclization. However the precursors for [1,5]-electrocyclization could be assembled via the Suzuki or Stille reactions. We have established a methodology for [1,5]-electrocyclization using chiral phase-transfer catalysis. These reactions afford the electrocyclized products in excellent yield and diastereoselectivity with enantiomeric excess up to 68 %. These transformations offer a glimpse of the potential of electrocyclic reactions. In chapter 2, the effects of cyclic backbones on the secondary structures of γ-peptides were evaluated. Two series of abiotic γ-peptides were synthesized with five and six-membered cyclic backbones. We have demonstrated that intra-residue nearest-neighbour hydrogen bonds may be favoured when the flexibility of the ring constraint can permit their formation. These cyclic backbone containing γ-peptides have been shown to populate a bend-ribbon conformation in the solution and solid phase by NMR and X-ray crystallography respectively.
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