Studies towards the total synthesis of neoliacinic acid

QD Chemistry

Nuter, Frederick ; Clark, J.S.

University:University of Glasgow

Department:School of Chemistry

关键词: Organic Chemistry, Organic synthesis, Synthesis of natural compound;   

Others  :  http://theses.gla.ac.uk/2841/1/2011NuterPhD.pdf

来源: University of Glasgow

【 摘 要 】

This thesis is concerned with studies towards the total synthesis of the natural product neoliacinic acid using metal carbenoid methodology. The work described herein shows the most recent contribution to this field from our research group. Chapter 1 provides an introduction to metal carbenoids, their preparation and uses in organic synthesis. Cyclopropanation reaction, C-H insertion and oxonium ylide formation and their subsequent rearrangements are discussed in detail.The target molecule is described followed by previous synthetic attempts toward neoliacinic acid. The Clark group strategy toward neoliacinic acid is explained with a retrosynthetic analysis using two metal-carbenoid transformations: intramolecular C-H insertion and oxonium ylide formation followed by [2,3]-sigmatropic rearrangement.Chapter 2 describes efforts towards the total synthesis of the target molecule from commercially chiral pool materials. A synthetic route is described in which construction of the two precursors required for metal carbenoid formation is followed by the application of the two key reactions to build the oxabicyclic core of the natural product. Efforts to generate an advanced intermediate containing the third ring (the lactone) including all six stereocentres present in the natural product are detailed. Finally, various options for completion of the synthesis as future work are discussed.