The development of efficient new chemical processes has an impact on a wide array of disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology). Catalysts can provide access to unique modes of reactivity, and they can furnish less expensive and more environmentally friendly methods for creating new molecules. During the next grant period, this program will explore the development of enantioselective processes catalyzed by planar-chiral derivatives of 4-(dimethylamino)pyridine (DMAP) and by chiral phosphines. A diverse array of reactions (e.g., kinetic resolutions of alcohols and amines, annulations, couplings of ketenes with acylating agents, and 3 additions) will be examined. Achieving the objectives of this program will facilitate access to important families of compounds in highly enantioenriched form. Mechanistic studies will play a significant role in this project. This research area offers an exciting opportunity to have a substantial impact on synthetic chemistry, as well as to enrich our understanding of chemical reactivity.

Public Health Relevance

In order to probe many biological questions and to develop new therapeutic compounds, there is a need to be able to synthesize organic molecules efficiently and to control the chirality ("handedness") of the target compounds. This proposal is directed at addressing both of these challenges.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057034-15
Application #
8208132
Study Section
Special Emphasis Panel (ZRG1-BCMB-B (03))
Program Officer
Lees, Robert G
Project Start
1998-01-01
Project End
2012-05-31
Budget Start
2012-01-01
Budget End
2012-05-31
Support Year
15
Fiscal Year
2012
Total Cost
$127,238
Indirect Cost
$43,202
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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
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
Bachovchin, Daniel A; Mohr, Justin T; Speers, Anna E et al. (2011) Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors. Proc Natl Acad Sci U S A 108:6811-6
Fujiwara, Yuji; Fu, Gregory C (2011) Application of a new chiral phosphepine to the catalytic asymmetric synthesis of highly functionalized cyclopentenes that bear an array of heteroatom-substituted quaternary stereocenters. J Am Chem Soc 133:12293-7
Denmark, Scott E; Burk, Matthew T (2010) Lewis base catalysis of bromo- and iodolactonization, and cycloetherification. Proc Natl Acad Sci U S A 107:20655-60
Wilson, Jonathan E; Sun, Jianwei; Fu, Gregory C (2010) Stereoselective phosphine-catalyzed synthesis of highly functionalized diquinanes. Angew Chem Int Ed Engl 49:161-3
Sinisi, Riccardo; Sun, Jianwei; Fu, Gregory C (2010) Phosphine-catalyzed asymmetric additions of malonate esters to {gamma}-substituted allenoates and allenamides. Proc Natl Acad Sci U S A 107:20652-4
Sun, Jianwei; Fu, Gregory C (2010) Phosphine-catalyzed formation of carbon-sulfur bonds: catalytic asymmetric synthesis of gamma-thioesters. J Am Chem Soc 132:4568-9

Showing the most recent 10 out of 33 publications