This research proposal describes the development of an efficient asymmetric catalysis based on the new chemistry of N-O compounds. The research will be directed towards three goals. ? The first goal will be to design a metal catalyst for a truly useful and practical asymmetric oxidation of olefinic alcohols, alkenes, sulfides, and phosphines. The method heavily depends on our previous observations of vanadium asymmetric epoxidation catalyst for which unique hydroxamic acid libraries were developed. We intend to synthesize a number of new hydroxamic acid ligand libraries and evaluate them for enantioselectivity and reactivity in vanadium-catalyzed asymmetric epoxidation. ? The second theme will focus on selective synthesis of new hydroxyamino and aminooxy carbonyl compounds. Using simple nitroso starting materials in the presence of Lewis acid catalysts, various carbonyl compounds could be converted to new hydroxyamino and aminooxy derivatives. Furthermore, with this approach, asymmetric catalytic introduction of oxygen and nitrogen functional groups alpha to carbonyl compounds will be obtained and used as a key synthetic reaction useful for chiral natural and unnatural product synthesis. ? The third effort will be to develop new asymmetric protonation in alcoholic solvents using metal catalysts with hydroxamic acid and related N-O ligand libraries. Efficient asymmetric protonation of racemic carbonyl compounds is an important synthetic transformation, which has not been developed to a useful level. ? Overall, all of these goals are expected to result in not only the development of highly efficient catalytic asymmetric synthesis but also the development of new methods and concepts that should provide a number of useful organic synthesis endeavors as well as new entry into various N-O compounds, which biologically are a highly important class of molecules. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM068433-02
Application #
6795583
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2003-09-01
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$314,888
Indirect Cost
Name
University of Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Wang, Chuan; Luo, Lan; Yamamoto, Hisashi (2016) Metal-Catalyzed Directed Regio- and Enantioselective Ring-Opening of Epoxides. Acc Chem Res 49:193-204
Nakashima, Erika; Yamamoto, Hisashi (2015) Continuous flow of nitroso Diels-Alder reaction. Chem Commun (Camb) 51:12309-12
Luo, Lan; Yamamoto, Hisashi (2015) Synthesis of virtually enantiopure aminodiols with three adjacent stereogenic centers by epoxidation and ring-opening. Org Biomol Chem 13:10466-70
Wang, Chuan; Yamamoto, Hisashi (2015) Gadolinium-Catalyzed Regio- and Enantioselective Aminolysis of Aromatic trans-2,3-Epoxy Sulfonamides. Angew Chem Int Ed Engl 54:8760-3
Wang, Chuan; Yamamoto, Hisashi (2015) Nickel-catalyzed regio- and enantioselective aminolysis of 3,4-epoxy alcohols. J Am Chem Soc 137:4308-11
Wang, Chuan; Yamamoto, Hisashi (2014) Tungsten-catalyzed asymmetric epoxidation of allylic and homoallylic alcohols with hydrogen peroxide. J Am Chem Soc 136:1222-5
Wang, Chuan; Yamamoto, Hisashi (2014) Tungsten-catalyzed regio- and enantioselective aminolysis of trans-2,3-epoxy alcohols: an entry to virtually enantiopure amino alcohols. Angew Chem Int Ed Engl 53:13920-3
Luo, Lan; Yamamoto, Hisashi (2014) Iron(II)-Catalyzed Asymmetric Epoxidation of Trisubstituted ?,?-Unsaturated Esters. European J Org Chem 2014:7803-7805
Wang, Chuan; Yamamoto, Hisashi (2014) Tungsten-catalyzed regioselective and stereospecific ring opening of 2,3-epoxy alcohols and 2,3-epoxy sulfonamides. J Am Chem Soc 136:6888-91
Saadi, Jakub; Yamamoto, Hisashi (2013) ?-Siloxy-?-haloketones through highly diastereoselective single and double mukaiyama aldol reactions. Chemistry 19:3842-5

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