This program focuses on the development of new catalytic methods for selective functionalization of C-H bonds in complex organic substrates of biological interest. The ability to transform selectively a preset C-H bond to a new C-C bond carries significant consequences for the practice of organic synthesis. The previous funding period established a vital and productive research program. In the process, we demonstrated that selective C-H bond activation and functionalization can be achieved in complex organic substrates and that these processes can be made catalytic in the transition metal. Also, our research showed that C-H bond transformations offer exciting strategic opportunities in synthesis. The next funding period will continue these efforts with particular emphasis on the development of new C-H to C-C transformations in the context of heterocyclic compounds (both saturated heterocycles and heteroarenes). Heterocycles are indispensable structural units frequently found in biologically active compounds, including natural products, protein ligands, and pharmaceuticals. New synthetic methods in this area are of high importance to life sciences, medicine, and health. New chemical transformations not only facilitate access to desired compounds of biological and medicinal interest, but also shape the very process of molecular design. In specific terms, the future projects include C-H arylation of saturated heterocycles (1-arylation of amines equipped with a new directing group;sp3 C-H bonds), direct C-H arylation of complex azole heteroarenes (sp2 C-H bonds). Also, two new approaches to cross-coupling of sp3 C-H bonds and alkenes (1-alkylation of saturated heterocycles) will be pursued: first, the intermolecular transition metal-catalyzed alkylation;and second, Lewis acid catalyzed intramolecular cyclization. These new methods will not only impact the synthesis of specific target molecules, but also will reshape the synthetic strategies for preparation of series of compounds. Selective C-H Bond Functionalization in Complex Organic Synthesis Resubmission Renewal Application, GM 60326 New methods for the preparation of research probes, medicinal agents, and new pharmaceuticals will be developed. Such research tools will increase the rate of understanding and potential treatment of human diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Schwab, John M
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Columbia University (N.Y.)
Other Domestic Higher Education
New York
United States
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Joo, Jung Min; Guo, Pengfei; Sames, Dalibor (2013) C-H bonds as ubiquitous functionality: preparation of multiple regioisomers of arylated 1,2,4-triazoles via C-H arylation. J Org Chem 78:738-43
Vadola, Paul A; Carrera, Ignacio; Sames, Dalibor (2012) C-H bond functionalization via hydride transfer: formation of ýý-arylated piperidines and 1,2,3,4-tetrahydroisoquinolines via stereoselective intramolecular amination of benzylic C-H bonds. J Org Chem 77:6689-702
Guo, Pengfei; Joo, Jung Min; Rakshit, Souvik et al. (2011) C-H arylation of pyridines: high regioselectivity as a consequence of the electronic character of C-H bonds and heteroarene ring. J Am Chem Soc 133:16338-41
Joo, Jung Min; Toure, B Barry; Sames, Dalibor (2010) C-H bonds as ubiquitous functionality: a general approach to complex arylated imidazoles via regioselective sequential arylation of all three C-H bonds and regioselective N-alkylation enabled by SEM-group transposition. J Org Chem 75:4911-20
McQuaid, Kevin M; Long, Jonathan Z; Sames, Dalibor (2009) C-H bond functionalization via hydride transfer: synthesis of dihydrobenzopyrans from ortho-vinylaryl akyl ethers. Org Lett 11:2972-5
McQuaid, Kevin M; Sames, Dalibor (2009) C-H bond functionalization via hydride transfer: Lewis acid catalyzed alkylation reactions by direct intramolecular coupling of sp3 C-H bonds and reactive alkenyl oxocarbenium intermediates. J Am Chem Soc 131:402-3
Goikhman, Roman; Jacques, Teresa L; Sames, Dalibor (2009) C-H bonds as ubiquitous functionality: a general approach to complex arylated pyrazoles via sequential regioselective C-arylation and N-alkylation enabled by SEM-group transposition. J Am Chem Soc 131:3042-8
Vadola, Paul A; Sames, Dalibor (2009) C-H bond functionalization via hydride transfer: direct coupling of unactivated alkynes and sp(3) C-H bonds catalyzed by platinum tetraiodide. J Am Chem Soc 131:16525-8
Gribkov, Denis V; Pastine, Stefan J; Schnurch, Michael et al. (2007) Ruthenium catalyzed decarbonylative arylation at sp3 carbon centers in pyrrolidine and piperidine heterocycles. J Am Chem Soc 129:11750-5
Wang, Xiang; Gribkov, Denis V; Sames, Dalibor (2007) Phosphine-free palladium-catalyzed C-H bond arylation of free (N-H)-indoles and pyrroles. J Org Chem 72:1476-9

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