EFFORTS TOWARD A VERSATILE INTERMEDIATE ALLOWING FOR INVESTIGATION OF OXIDOPYRYLIUM-BASED [5+2] CYCLOADDITIONS EN ROUTE TO TOXICODENANE A AND DERIVATIVES

Publication Date

4-5-2019

Document Type

Poster

Degree Type

Graduate

Department

Chemistry

Mentor

T. Andrew Mitchell

Mentor Department

Chemistry

Abstract

Cycloaddition reactions are valuable synthetic tools, providing efficient reaction pathways toward the formation of complex three-dimensional polycyclic structures from planar precursors. Previously, the Mitchell research group has reported differing reactivity of various acetoxypyranone substrates in the investigation of oxidopyrylium-alkene based [5+2] cycloadditions.2 Cycloadditions proceeding via silyloxypyrones are also efficient routes toward bridged polycyclic ethers, which are common structural motifs found in several types of biologically active compounds.3 Thus, further exploration of oxidopyrylium-based [5+2] cycloaddition pathways will lead to the synthesis of these classes of compounds. Toxicodenane A,4 one example of a bridged polycyclic ether, provides an opportunity to demonstrate the utility of acetoxypyranone-based [5+2] cycloadditions. Major disconnections reveal the possibility of an intramolecular oxidopyrylium [5+2] cycloaddition mediated by a silyl-allene tether as an efficient route toward toxicodenane A beginning from commercially available dimedone. While recent advancements have been made by other groups,5 we propose a total synthesis of toxicodenane A implementing the key oxidopyrylium-based [5+2] cycloaddition to construct the bridged-ether core. 1) (a) Nishiwaki, N. Methods and Applications of Cycloaddition Reactions in Organic Synthesis. Wiley-VCH: Weinheim, 2014. (b) Kobayashi, S.; Jørgensen, K. A. Cycloaddition Reactions in Organic Chemistry. Wiley-VCH: Weinheim, 2002. (c) Carruthers, W. Cycloaddition Reactions in Organic Chemistry, Volume 8 (Tetrahedron Organic Chemistry). Pergamon: Oxford, 1990. 2) (a) Kaufman, R. H.; Law, C. H.; Simanis, J. A..; Woodall, E. L.; Zwick III, C. R.; Wedler, H. B.; Wendelboe, P.; Hamaker, C. G.; Goodell, J. R.; Tantillo, D. J.; Mitchell, T. A. J. Org. Chem. 2018, 83, 9318-9338. (b) Simanis, J. A.; Zwick, C. R.; Woodall, E. L.; Goodell, J. R.; Mitchell, T. A. Heterocycles. 2015, 91, 149-156. (c) Simanis, J. A.; Law, C. M.; Woodall, E. L.; Hamaker, C. G.; Goodell, J. R.; Mitchell, T. A. Chem. Commun. 2014, 50, 9130-9133. (d) Woodall, E. L.; Simanis, J. A.; Hamaker, C. G.; Goodell, J. R.; Mitchell, T. A. Org. Lett. 2013, 15, 3270-3273. 3) (a) Bejcek, L. P.; Murelli, R. P. Tetrahedron 2018, 74, 2501-2521. (b) Liu, X.; Hu, Y.-J.; Fan, J.-H.; Zhao, J.; Li, S.; Li, C.-C. Org. Chem. Front. 2018, 5, 1217-1228. (c) Singh, V.; Krishna, U. M.; Vikrant, Trivedi, G. K. Tetrahedron, 2008, 64, 3405-3428. (d) Ylijoki, K. E. O.; Stryker, J. M. Chem. Rev. 2013, 113, 2244-2266. (e) Nakata, T. Chem. Rev. 2005, 105, 4314-4317. 4) He, J.-B.; Luo, J.; Zhang, L.; Yan, Y.-M.; Cheng, Y.-X. Org. Lett. 2013, 15, 3602-3605. 5) Kobayashi, T.; Yamanoue, K.; Abe, H.; Ito, H. European Journal of Organic Chemistry 2017, 2017 (45), 6693-6699.

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