The design and execution of reliable complexity enhancing chemical transformations continues to be a goal at the forefront of synthesis. Since transition metal catalysts increase efficiency and enable new routes to complex molecules, their utility will continue to grow. This proposal outlines a research plan for developing a broad class of metal catalyzed reactions that utilize electrophilic metal catalysts (Pt, Au) to initiate, propagate, and terminate cation-olefin reactions (CORs), the principal C-C bond (and ring) forming reaction in terpene biosynthesis. The first Specific Aim focuses on the development of asymmetric catalysts for the dehydrogenative cation-olefin cyclization reaction, with a special emphasis on alkene terminated examples. The second Specific Aim takes this concept one step further by oxidatively intercepting the intermediate Pt-C3 organometallic to generate C3-oxygenated products, which are common bio-active compounds. The third specific aim investigates the mechanism of common Gold(I) catalyzed reactions to support new approaches to asymmetric catalysis and cyclization/cross-coupling.
This project will develop new approaches to the synthesis of complex carbocyclic structures. The emphasis is on discovering synthetic catalysts that mimic the outcome of terpene cyclase enzymes in biosynthesis. Success will provide access to natural bioactive compounds and non-natural analogs thereof.
|McCulley, Christina H; Geier, Michael J; Hudson, Brandi M et al. (2017) Biomimetic Platinum-Promoted Polyene Polycyclizations: Influence of Alkene Substitution and Pre-cyclization Conformations. J Am Chem Soc 139:11158-11164|
|Roselli, Christina A; Gagné, Michel R (2016) Gold(i)-catalyzed addition of aldehydes to cyclopropylidene bearing 6-aryl-1,5-enynes. Org Biomol Chem 14:11261-11265|
|Felix, Ryan J; Munro-Leighton, Colleen; Gagné, Michel R (2014) Electrophilic Pt(II) complexes: precision instruments for the initiation of transformations mediated by the cation-olefin reaction. Acc Chem Res 47:2319-31|
|Geier, Michael J; Gagné, Michel R (2014) Diastereoselective Pt catalyzed cycloisomerization of polyenes to polycycles. J Am Chem Soc 136:3032-5|
|Zheng, Hongchao; Felix, Ryan J; Gagné, Michel R (2014) Gold-catalyzed enantioselective ring-expanding cycloisomerization of cyclopropylidene bearing 1,5-enynes. Org Lett 16:2272-5|
|Zheng, Hongchao; Adduci, Laura L; Felix, Ryan J et al. (2014) Gold-catalyzed diastereoselective cycloisomerization of alkylidene-cyclopropane-bearing 1,6-diynes. Angew Chem Int Ed Engl 53:7904-7|
|Sokol, Joseph G; Cochrane, Nikki A; Becker, Jennifer J et al. (2013) Catalytic platinum-initiated cation-olefin reactions with alkene terminating groups. Chem Commun (Camb) 49:5046-8|
|Gutierrez, Osvaldo; Harrison, Jason G; Felix, Ryan J et al. (2013) Carbonium vs. carbenium ion-like transition state geometries for carbocation cyclization - how strain associated with bridging affects 5-exo vs. 6-endo selectivity. Chem Sci 4:|
|Felix, Ryan J; Gutierrez, Osvaldo; Tantillo, Dean J et al. (2013) Gold(I)-catalyzed formation of bicyclo[4.2.0]oct-1-enes. J Org Chem 78:5685-90|
|Cochrane, Nikki A; Nguyen, Ha; Gagne, Michel R (2013) Catalytic enantioselective cyclization and C3-fluorination of polyenes. J Am Chem Soc 135:628-31|
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