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 #
5R01GM060578-13
Application #
8540433
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2000-02-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
13
Fiscal Year
2013
Total Cost
$285,522
Indirect Cost
$84,898
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
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
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
Geier, Michael J; Gagné, Michel R (2014) Diastereoselective Pt catalyzed cycloisomerization of polyenes to polycycles. J Am Chem Soc 136:3032-5
Cochrane, Nikki A; Nguyen, Ha; Gagne, Michel R (2013) Catalytic enantioselective cyclization and C3-fluorination of polyenes. J Am Chem Soc 135:628-31
Geier, Michael J; Gagne, Michel R (2013) A Cyclization/Oxygenation Scheme for the Conversion of Polyenes into C3-Oxygenated Polycycles. Organometallics 32:380-383
Weber, Dieter; Gagne, Michel R (2013) ýý-ýý-Diauration as an alternative binding mode for digold intermediates in gold(i) catalysis. Chem Sci 47:335-338
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
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
Felix, Ryan J; Weber, Dieter; Gutierrez, Osvaldo et al. (2012) A gold-catalysed enantioselective Cope rearrangement of achiral 1,5-dienes. Nat Chem 4:405-9

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