| Part I of this dissertation presents an account of the method development of the segment-coupling Prins cyclization utilizing acyclic and cyclic α-acetoxy ethers. The scope and limitations of this reaction has been investigated. The method involves esterification of a homoallylic alcohol, reductive acetylation of the ester to provide α-acetoxy ethers (Prins precursors), and cyclization on treatment with a Lewis acid to produce a tetrahydropyran with up to three new stereocenters. This investigation establishes the stereoselectivity and regioselectivity for a number of synthetically useful segment-coupling Prins cyclizations.; Part II presents a discussion of our mechanistic investigation of the Prins cyclization. The 2-oxonia Cope rearrangement is a competitive pathway in Prins cyclizations, and in our activated substrate, the rearrangement is faster than the cyclization. With our version of the Prins cyclization, the segment-coupling strategy, we have overcome two main limitations that are inherent to the classic Prins cyclization: side-chain exchange products and partial racemization by reversible 2-oxonia Cope rearrangements. We validate these two very important synthetic advantages through two syntheses of (−)-centrolobine.; Part III presents a full account of studies which have culminated in the first total synthesis of the diarylheptanoid, calyxin F. A highly convergent approach was developed, and the fully protected carbon skeleton was rapidly synthesized in 5 steps. The key reaction employed was the Prins cyclization/Friedel-Crafts alkylation reaction that sets two C–C bond in the newly formed tetrahydropyran with excellent diastereoselectivity. |
