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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM060578-10
Application #
7983067
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Hagan, Ann A
Project Start
2000-02-01
Project End
2014-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
10
Fiscal Year
2010
Total Cost
$298,866
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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
Geier, Michael J; Gagné, Michel R (2014) Diastereoselective Pt catalyzed cycloisomerization of polyenes to polycycles. J Am Chem Soc 136:3032-5
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
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
Geier, Michael J; Dadkhah Aseman, Marzieh; Gagné, Michel R (2014) Anion-Dependent Switch in C-X Reductive Elimination Diastereoselectivity. Organometallics 33:4353-4356
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
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
Geier, Michael J; Gagne, Michel R (2013) A Cyclization/Oxygenation Scheme for the Conversion of Polyenes into C3-Oxygenated Polycycles. Organometallics 32:380-383
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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