Phosphate Tether-Mediated Metathesis Studies and Application Towards Natural Product Synthesis

Abstract

Over the past decade, work in our lab has focused on phosphate tether-mediated desymmetrization of C2-symmetric 1,3-anti-dienediol via ring-closing metathesis (RCM) to afford P-stereogenic bicyclo[4.3.1]phosphates. However, efforts in this direction relied solely on phosphate tether-mediated coupling of allylic alcohol cross partners with 1,3-anti-dienediol synthons leading to the formation of simple bicyclo[4.3.1]phosphates and their applications in natural product synthesis. The objective of this dissertation work is to advance the phosphate tether-mediated methods to include the construction of complex bicyclo[n.3.1]phosphates via ring-closing metathesis (RCM). The RCM study, discussed in detail in Chapter 2, highlights the synthetic potential of phosphates as a temporary tethers in facilitating the coupling of complex fragments to produce novel P-stereogenic bicyclic phosphate scaffolds. Chapter 3 describes the development of phosphate tether-mediated one-pot and two-pot sequential metathesis/reduction protocols towards the stereodivergent synthesis of complex polyols. The potential application of phosphate tether-mediated reactions en route to the synthesis of the C9–C25 fragment of spirastrellolide B is discussed in Chapter 4.