Several new reactions, catalyzed by electrophilic gold complexes, are proposed. A major emphasis is placed on the development of enantioselective C-C and C-X bond constructions. In general, these reactions involve activation of ?-bonds as electrophiles, in some cases activation of nucleophiles, by coordination to cationic gold(I) complexes. A range of enantioselective transformation proceeding via alkyne or allene activation will be investigated. The proposed studies include enantioselective reactions catalyzed by chiral phosphinegold(I) complexes and/or chiral anions. These reactions include enantioselective C-C bond formation through alkyne initiated cyclization cascades or by addition of carbon nucleophiles to allenes. The latter will be applied to the synthesis of the flinderole alkaloids. Enantioselective intermolecular addition of nucleophiles, either directly to the activated ?-bond or to a cationic intermediate, is also proposed. Methods that involve in situ generation of gold(I)-carbenoid intermediates from alkynes and their use in enantioselective cycloaddition reactions will be examined. Additionally, gold(I)-catalyzed enantioselective reactions that proceed through activation of alkynes as nucleophiles will be investigated. Taken together, the proposed reactions encompass both electrophile and nucleophile activation and provide enantioselective entries into a wide range of carbo- and heterocyclic structures. Gold-catalyzed reactions of alkenes are also proposed. These transformations include gold-catalyzed direct addition of nucleophiles to alkenes and gold-catalyzed oxidative difunctionalization of alkenes. In the former, intra- and intermolecular enantioselective addition reactions catalyzed by chiral gold complexes or Bronsted acids generated by coordination of protic species (alcohols) to chiral gold-complexes will be examined. Additionally, gold-catalyzed oxidative functionalization of alkenes, initiated by gold-induced nucleophilic addition to the ?-bond, will be developed. This reaction class includes transformations involving intra- and intermolecular addition of nucleophiles to alkenes and intra- and intermolecular reaction of the resulting gold intermediate with nucleophiles (such as boronic acids).

Public Health Relevance

The proposed program aims to develop new methods for the preparation of structures and compounds of potential importance to medicinal chemistry. To this end, gold-catalyzed methods, including eneatioselective reactions, for synthesis of heterocyclic and carbocyclic structures are proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073932-07
Application #
8487416
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2005-04-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
7
Fiscal Year
2013
Total Cost
$326,775
Indirect Cost
$104,821
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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Levin, Mark D; Kim, Suhong; Toste, F Dean (2016) Photoredox Catalysis Unlocks Single-Electron Elementary Steps in Transition Metal Catalyzed Cross-Coupling. ACS Cent Sci 2:293-301
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Wu, Hongmiao; Zi, Weiwei; Li, Guigen et al. (2015) Gold(I)-Catalyzed Desymmetrization of 1,4-Dienes by an Enantioselective Tandem Alkoxylation/Claisen Rearrangement. Angew Chem Int Ed Engl 54:8529-32
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Navarro, Cristina; Shapiro, Nathan D; Bernasconi, Maurizio et al. (2015) Gold(I)-catalyzed enantioselective [3+2] and [3+3] cycloaddition reactions of propargyl acetals/ketals. Tetrahedron 71:5800-5805
Zi, Weiwei; Wu, Hongmiao; Toste, F Dean (2015) Gold(I)-catalyzed dearomative Rautenstrauch rearrangement: enantioselective access to cyclopenta[b]indoles. J Am Chem Soc 137:3225-8

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