Part 1. Biomimetic synthesis of trans, syn, trans-fused polyoxepanes: Remarkable substituent effects on the endo-regioselective oxacyclization of polyepoxides. Part 2. Carbon terminating nucleophiles in combination with the tandem oxacyclization of polyepoxides: Progress toward the total synthesis of abudinol B.

摘要

Part 1. Biomimetic synthesis of trans, syn, trans-Fused polyoxepanes: Remarkable substituent effects on the endo-regioselective oxacyclization of polyepoxides. Substituent effects in the Lewis acid-promoted, biomimetic oxacyclization of polyepoxides were studied. Oxacyclization reactions with 2,3-disubstituted epoxides revealed the necessity for a regiocontrol element at C-3 to achieve endo-selectivity.*; Further work demonstrated 2,3-epoxysilanes to serve as a removable surrogate to achieve anti-stereoselectivity and endo-regioselectivity in the oxacyclization reaction. The 3-silyl substituted oxepanes were able to be protiodesilylated.*; 6,7-Epoxysilanes were shown to direct endo-oxacyclization to yield 7-trimethylsilyl dioxepane. However, 7-silylated dioxepanes could not be protiodesilylated or functionalized under a variety of conditions.*; Internally trans-disubstituted epoxides proved to be viable substrates in the biomimetic endo-regioselective oxacyclization method. The method was extended to both tri- and tetraepoxide substrates to give di- and trioxepanes, respectively.*; These oxacyclization results are evidence for nucleophile-driven regiocontrol, where the regiochemistry of epoxide addition is due to minimization of ring strain in the formation of bicyclic intermediates.; These findings greatly expand the scope of the biomimetic oxacyclization methodology so that naturally occurring, non-terpene derived polycyclic ethers can now be efficiently prepared by our approach.; Part 2. Carbon terminating nucleophiles in combination with the tandem oxacyclization of polyepoxides: Progress toward the total synthesis of abudinol B. An alternative biosynthetic hypothesis of the marine natural product abudinol B has been proposed. We have demonstrated the use of carbon terminating nucleophiles in combination with the oxacyclization of diepoxides to give bicyclic products. Both silyl enol ethers and allylic silanes were viable terminating nucleophiles in the reaction. However, the reaction efficiency was greater with the more nucleophilec silyl enol ether. The bicyclic oxacyclization product has the same connectivity and relative stereochemistry as the D, E-ring system of abudinol B.*; Application of carbon terminating nucleophiles in combination with the tandem oxacyclization of polyepoxides can provide a biomimetic synthesis of abudinol B.; *Please refer to dissertation for diagrams.