The ability to prepare functionalized organic molecules rationally and predictably, whether individually or in libraries, is central to organic synthesis, medicinal chemistry and the pharmaceutical industry.
The aims of this work are to develop new and/or improved methods for the formation of carbon-carbon and carbon-fluorine bonds. Included in this work are methods directed to the construction of sp3C-sp2C bonds both in racemic form and with absolute stereocontrol. We are also proposing to develop new methods for the preparation of selectively fluorinated organic molecules and those that are selectively substituted with fluorocarbon groups. Further, fundamental mechanistic information gained from this work will help to understand the mechanism of the processes that are being developed in order to increase the rate of improvement of the techniques that we are studying. The development of new methods for organic synthesis is key to the development of the field of organic chemistry as a whole. These reactions are of critical importance to the pharmaceutical industry. Methods for the selective fluorination of complex molecules are of great significance for positron emission tomography (PET) for imaging applications. The chemistry we are proposing has the possibility to improve access to selectively labeled compounds for PET applications. Cross-coupling methods for carbon-carbon bond formation are regularly used by those in the pharmaceutical industry for the preparation of analogues with increased potency and reduced side effects. Moreover, the methods can be employed for the preparation of quantities of new substances for preclinical and clinical testing and for the actual manufacture of a pharmaceutical agent. The techniques that are being developed allow for these important functions to be carried out in a more rapid and efficient fashion than previously possible. Moreover, they allow for the preparation of new substances, which have previously been inaccessible. These new compounds have the possibilities of having physiological properties of great importance in medicinal chemistry and the pharmaceutical industry.

Public Health Relevance

The chemistry we are proposing has the possibility to improve access compounds of importance in biomedical research in both academia and industry. An additional aspect application to selectively labeled compounds for PET applications. The cross-coupling methods we are developing for carbon-carbon bond formation are regularly used by those in the pharmaceutical industry for the preparation of analogues with increased potency and reduced side effects.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01GM046059-23
Application #
8628947
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Liu, Richard Y; Yang, Yang; Buchwald, Stephen L (2016) Regiodivergent and Diastereoselective CuH-Catalyzed Allylation of Imines with Terminal Allenes. Angew Chem Int Ed Engl 55:14077-14080
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Vincent, Benjamin M; Langlois, Jean-Baptiste; Srinivas, Raja et al. (2016) A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance. Cell Chem Biol 23:978-991
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Yang, Yang; Perry, Ian B; Buchwald, Stephen L (2016) Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration. J Am Chem Soc 138:9787-90
Wang, Yi-Ming; Buchwald, Stephen L (2016) Enantioselective CuH-Catalyzed Hydroallylation of Vinylarenes. J Am Chem Soc 138:5024-7
Ye, Yuxuan; Takada, Takashi; Buchwald, Stephen L (2016) Palladium-Catalyzed Fluorination of Cyclic Vinyl Triflates: Effect of TESCF3 as an Additive. Angew Chem Int Ed Engl 55:15559-15563
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