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-nitrogen and carbon-oxygen bonds. Included in this work is the development of new strategies and techniques for the preparation of complex heterocycles, which are the building blocks of medicinal chemistry and the pharmaceutical industry, via cross-coupling methodology. Further, 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. Cross-coupling methods for carbon-heteroatom 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. Further these techniques are used by researchers in both academia and industry in a variety of areas of bioorganic and materials research including in the formation of new sensory materials.

Public Health Relevance

The cross-coupling methods we are developing for carbon-heteroatom 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058160-16
Application #
8519465
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
1998-09-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
16
Fiscal Year
2013
Total Cost
$592,349
Indirect Cost
$225,727
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
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
Ruiz-Castillo, Paula; Buchwald, Stephen L (2016) Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions. Chem Rev 116:12564-12649
Friis, Stig D; Pirnot, Michael T; Buchwald, Stephen L (2016) Asymmetric Hydroarylation of Vinylarenes Using a Synergistic Combination of CuH and Pd Catalysis. J Am Chem Soc 138:8372-5
Corcoran, Emily B; Pirnot, Michael T; Lin, Shishi et al. (2016) Aryl amination using ligand-free Ni(II) salts and photoredox catalysis. Science 353:279-83
King, Sandra M; Buchwald, Stephen L (2016) Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates. Org Lett 18:4128-31
Shi, Shi-Liang; Wong, Zackary L; Buchwald, Stephen L (2016) Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols. Nature 532:353-6
Pirnot, Michael T; Wang, Yi-Ming; Buchwald, Stephen L (2016) Copper Hydride Catalyzed Hydroamination of Alkenes and Alkynes. Angew Chem Int Ed Engl 55:48-57
Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L (2016) A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination. Nat Chem 8:144-50
Arrechea, Pedro Luis; Buchwald, Stephen L (2016) Biaryl Phosphine Based Pd(II) Amido Complexes: The Effect of Ligand Structure on Reductive Elimination. J Am Chem Soc 138:12486-93
Park, Nathaniel H; Vinogradova, Ekaterina V; Surry, David S et al. (2015) Design of New Ligands for the Palladium-Catalyzed Arylation of α-Branched Secondary Amines. Angew Chem Int Ed Engl 54:8259-62

Showing the most recent 10 out of 143 publications