Abstract

This proposal has as its goal the development of asymmetric catalytic versions of several synthetically important reactions. Efficient catalysts for asymmetric Diels-Alder reactions and aziridination of imines with diazo compounds have been developed with the vaulted biaryl ligands VAPOL and VANOL Future efforts will be directed to determining the scope, mechanism and synthetic applicstions of these existing processes. The information that has already been gained in the study of the Diels-Alder reaction has been used to design new ligands that are tailored for octahedral Lewis acids. Derivatives of the VAPOL ligand will also be explored as a platform for organo-palladium chemistry. If successful, these ligands will be screened for allylic substitutions, cycloisomerizations of enynes, [3 + 2] cycloadditions of TMM complexes and oxy(aza) palladation / carbonylation reactions. The scope of the asymmetric aziridination will be explored with respect to the imine and diazo substrates in both inter- and intramolecular modes. A method is proposed for the first general method for the alkylation of aziridine -2-carboxylates. Methods will explored for the development of a general method for the synthesis of both alpha-amino acids and beta-amino acids from the asymmetric catalytic aziridination reaction. Some of the targets for the aziridination reaction include morphine, the diamine portion of ritonavir, sphingolipids and the antitumor agent FR-900482.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063019-03
Application #
6749050
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2002-06-05
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
3
Fiscal Year
2004
Total Cost
$239,969
Indirect Cost

  Institution

Name
Michigan State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Hu, Gang; Huang, Li; Huang, Rui H et al. (2009) Evidence for a boroxinate based Brønsted acid derivative of VAPOL as the active catalyst in the catalytic asymmetric aziridination reaction. J Am Chem Soc 131:15615-7
Hu, Gang; Holmes, Daniel; Gendhar, Brina Fay et al. (2009) Optically active (aR)- and (aS)-linear and vaulted biaryl ligands: deracemization versus oxidative dimerization. J Am Chem Soc 131:14355-64
Zhang, Yu; Lu, Zhenjie; Desai, Aman et al. (2008) Mapping the active site in a chemzyme: diversity in the N-substituent in the catalytic asymmetric aziridination of imines. Org Lett 10:5429-32
Zhang, Yu; Desai, Aman; Lu, Zhenjie et al. (2008) Catalytic asymmetric aziridination with borate catalysts derived from VANOL and VAPOL ligands: scope and mechanistic studies. Chemistry 14:3785-803
Rabalakos, Constantinos; Wulff, William D (2008) Enantioselective organocatalytic direct Michael addition of nitroalkanes to nitroalkenes promoted by a unique bifunctional DMAP-thiourea. J Am Chem Soc 130:13524-5
Newman, Cory A; Antilla, Jon C; Chen, Pei et al. (2007) Regulation of orthogonal functions in a dual catalyst system. Subservient role of a nonchiral Lewis acid in an asymmetric catalytic heteroatom Diels-Alder reaction. J Am Chem Soc 129:7216-7
Lu, Zhenjie; Zhang, Yu; Wulff, William D (2007) Direct access to N-H-aziridines from asymmetric catalytic aziridination with borate catalysts derived from vaulted binaphthol and vaulted biphenanthrol ligands. J Am Chem Soc 129:7185-94
Patwardhan, Aniruddha P; Pulgam, V Reddy; Zhang, Yu et al. (2005) Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377. Angew Chem Int Ed Engl 44:6169-72
Patwardhan, Aniruddha P; Lu, Zhenjie; Pulgam, V Reddy et al. (2005) Novel ozone-mediated cleavage of the benzhydryl protecting group from aziridinyl esters. Org Lett 7:2201-4
Yu, Su; Rabalakos, Constantinos; Mitchell, William D et al. (2005) New synthesis of vaulted biaryl ligands via the Snieckus phenol synthesis. Org Lett 7:367-9

Showing the most recent 10 out of 11 publications