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 #
5R01GM058160-15
Application #
8304964
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
2012-08-01
Budget End
2013-07-31
Support Year
15
Fiscal Year
2012
Total Cost
$616,420
Indirect Cost
$233,696
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
Cheung, Chi Wai; Buchwald, Stephen L (2014) Palladium-catalyzed hydroxylation of aryl and heteroaryl halides enabled by the use of a palladacycle precatalyst. J Org Chem 79:5351-8
Vinogradova, Ekaterina V; Müller, Peter; Buchwald, Stephen L (2014) Structural reevaluation of the electrophilic hypervalent iodine reagent for trifluoromethylthiolation supported by the crystalline sponge method for X-ray analysis. Angew Chem Int Ed Engl 53:3125-8
Zhu, Ye; Buchwald, Stephen L (2014) Ligand-controlled asymmetric arylation of aliphatic ?-amino anion equivalents. J Am Chem Soc 136:4500-3
Ernst, Johannes B; Tay, Nicholas E S; Jui, Nathan T et al. (2014) Regioselective synthesis of benzimidazolones via cascade C-N coupling of monosubstituted ureas. Org Lett 16:3844-6
Su, Mingjuan; Hoshiya, Naoyuki; Buchwald, Stephen L (2014) Palladium-catalyzed amination of unprotected five-membered heterocyclic bromides. Org Lett 16:832-5
Zhu, Shaolin; Buchwald, Stephen L (2014) Enantioselective CuH-catalyzed anti-Markovnikov hydroamination of 1,1-disubstituted alkenes. J Am Chem Soc 136:15913-6
Bruno, Nicholas C; Niljianskul, Nootaree; Buchwald, Stephen L (2014) N-substituted 2-aminobiphenylpalladium methanesulfonate precatalysts and their use in C-C and C-N cross-couplings. J Org Chem 79:4161-6
Park, Nathaniel H; Teverovskiy, Georgiy; Buchwald, Stephen L (2014) Development of an air-stable nickel precatalyst for the amination of aryl chlorides, sulfamates, mesylates, and triflates. Org Lett 16:220-3
Cheung, Chi Wai; Surry, David S; Buchwald, Stephen L (2013) Mild and highly selective palladium-catalyzed monoarylation of ammonia enabled by the use of bulky biarylphosphine ligands and palladacycle precatalysts. Org Lett 15:3734-7
DeBergh, J Robb; Niljianskul, Nootaree; Buchwald, Stephen L (2013) Synthesis of aryl sulfonamides via palladium-catalyzed chlorosulfonylation of arylboronic acids. J Am Chem Soc 135:10638-41

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