Abstract

(Principal Investigator's) Due to the """"""""handedness"""""""" of the molecules of life, the development of efficient methods for stereoselective organic synthesis is essential to the expeditious discovery of new therapeutic compounds. This research program focuses on the development of enantioselective nucleophilic catalysts. Because nucleophiles catalyze an enormous array of useful reactions, work in this area provides the opportunity to develop a catalyst (or a small family of catalysts) that will effect a wide range of processes with high levels of enantioselectivity. This investigation is comprised of three areas of research: (1) The development of syntheses of planar-chiral pi complexes of heterocycles with transition metals; (2) The study of the capacity of these planar-chiral complexes to serve as nucleophilic catalysts for a wide array of reactions; (3) The development of enantioselective processes catalyzed by enantiopure planar-chiral pi complexes. It is anticipated that useful new methods for stereoselective organic synthesis will emerge from this investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057034-02
Application #
2857355
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1998-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Ziegler, Daniel T; Fu, Gregory C (2016) Catalytic Enantioselective Carbon-Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C-H Bonds. J Am Chem Soc 138:12069-72
Lee, Sarah Yunmi; Fujiwara, Yuji; Nishiguchi, Atsuko et al. (2015) Phosphine-catalyzed enantioselective intramolecular [3+2] annulations to generate fused ring systems. J Am Chem Soc 137:4587-91
Kalek, Marcin; Fu, Gregory C (2015) Phosphine-Catalyzed Doubly Stereoconvergent ?-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected ?,?-Disubstituted ?-Amino Acid Derivatives. J Am Chem Soc 137:9438-42
Kramer, Søren; Fu, Gregory C (2015) Use of a new spirophosphine to achieve catalytic enantioselective [4 + 1] annulations of amines with allenes to generate dihydropyrroles. J Am Chem Soc 137:3803-6
Ziegler, Daniel T; Riesgo, Lorena; Ikeda, Takuya et al. (2014) Biphenyl-derived phosphepines as chiral nucleophilic catalysts: enantioselective [4+1] annulations to form functionalized cyclopentenes. Angew Chem Int Ed Engl 53:13183-7
Lee, Sarah Yunmi; Neufeind, Stefan; Fu, Gregory C (2014) Enantioselective nucleophile-catalyzed synthesis of tertiary alkyl fluorides via the ?-fluorination of ketenes: synthetic and mechanistic studies. J Am Chem Soc 136:8899-902
Lundgren, Rylan J; Wilsily, Ashraf; Marion, Nicolas et al. (2013) Catalytic asymmetric C-N bond formation: phosphine-catalyzed intra- and intermolecular ?-addition of nitrogen nucleophiles to allenoates and alkynoates. Angew Chem Int Ed Engl 52:2525-8
Lee, Sarah Yunmi; Murphy, Jaclyn M; Ukai, Atsushi et al. (2012) Nonenzymatic dynamic kinetic resolution of secondary alcohols via enantioselective acylation: synthetic and mechanistic studies. J Am Chem Soc 134:15149-53
Zuhl, Andrea M; Mohr, Justin T; Bachovchin, Daniel A et al. (2012) Competitive activity-based protein profiling identifies aza-?-lactams as a versatile chemotype for serine hydrolase inhibition. J Am Chem Soc 134:5068-71
Fujiwara, Yuji; Sun, Jianwei; Fu, Gregory C (2011) Enantioselective Carbon-Sulfur Bond Formation: ? Additions of Aryl Thiols to Allenoates Catalyzed by a Chiral Phosphepine. Chem Sci 2:2196-2198

Showing the most recent 10 out of 39 publications