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Research Summary
Our interests center on the development of C-H bond activation reagents and catalysts for complex organic synthesis. C-H bond activation represents a chemical process of broad scientific and technological potential. The ability to transform ubiquitous but inert C-H bonds to other functional groups has far-reaching implications, ranging from oxidation of simple alkanes to the synthesis of complex organic molecules.
We are developing a program directed toward selective C-H bond functionalization of complex, multifunctional substrates. This plan represents uncharted territory as C-H functionalization has previously been achieved mostly in simple substrates. Despite significant advances in this area, most transition metal complexes capable of C-H bond activation are intolerant to functional groups and have a strong preference for the activation of aryl and other activated C-H bonds. Assuming the possibility of overcoming such constraints, novel and unique strategies for the assembly of complex organic molecules can be envisioned. General solutions to this problem will ultimately require the integration of several chemical disciplines, including organometallic chemistry, synthetic chemistry, and molecular recognition. Currently, we seek to achieve this goal via coordination-directed C-H bond activation. Thus, a suitable heteroatomic function is utilized to activate and direct a metal complex to a specific alkane region of the substrate in such a way as to prevent interference of other functional groups. This logic has been supported by our recent results. The total synthesis of the natural product rhazinilam was accomplished via selective C-H bond functionalization (see references). Recently, we have developed a catalytic system capable of selective hydroxylation of a-amino acids in water. We will continue to further develop this approach in the context of complex molecule assembly. Toward these ends we will pursue both the rational design of catalysts and high throughput screening methods.
We also focus on the development of new fluorogenic probes in order to detect chemical reactions with high sensitivity. Fluorogenic substrates are designed to change their fluorescent profile during the bond-making and -breaking events. These probes are currently used in the high throughput screening of solid-supported catalysts. Furthermore, the study of molecular interactions and chemical reactions in living cells through the use of such probes will also be pursued.
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SP3 C-H Bond Arylation Directed by Amidine Protecting Group: Alpha-arylation of Pyrrolidines and Piperidines, Stefan J. Pastine, Denis V. Gribkov, and Dalibor Sames, Journal of the American Chemical Society ASAP DOI: 10.1021/ja064481j (2006)
Synthesis of Luminescent Heterometallic bis-Lanthanide Complexes via Selective, Sequential Metallation Matthew S. Tremblay and Dalibor Sames, Chemical Communications, 4116 – 4118 (2006)
Fluorogenic Metabolic Probes for Direct Activity Readout of Redox Enzymes: Selective Measurement of Human AKR1C2 in Living Cells, Dominic J. Yee, Vojta Balsanek, David R. Bauman, Trevor M. Penning, and Dalibor Sames, Proceedings of the National Academy of Sciences,103, 13304 – 13309 (2006)
Phosphorylation State-Responsive Lanthanide Peptide Conjugates: A Luminescence Switch Based on Reversible Complex Reorganization, Matthew S. Tremblay, Qing Zhu, Angel A. Marti, Joanne Dyer, Marlin Halim, Steffen Jockusch, Nicholas J. Turro, and Dalibor Sames. Organic Letters 8, 2723 – 2726 (2006)
Catalytic C-H Arylation of SEM- Protected Azoles with Palladium Complexes of NHCs and Phosphines, B. Barry Toure, Benjamin S. Lane, and Dalibor Sames, Organic Letters, 81979 – 1982 (2006)
C-H Bond Functionalization in Complex Organic Synthesis, Kamil Godula and Dalibor Sames, Science, 312, 67 – 72 (2006)
Fluoromorphic Substrates for Fatty Acid Metabolism: Highly Sensitive Probes for Mammalian Medium-Chain Acyl-CoA Dehydrogenase, Mary K. Froemming and Dalibor Sames, Angewandte Chemie, International Edition, 45, 637 – 642 (2006)
Room Temperature Intramolecular Hydro-O- alkylation of Aldehydes: sp3 C-H Functionalization via a Lewis Acid-Catalyzed Tandem 1,5- Hydride Transfer/Cyclization, Stefan J. Pastine and Dalibor Sames, Organic Letters, 7 (24), 5429 – 5431 (2005)
Room Temperature Hydroalkylation of Electron-Deficient Olefins: sp3 C-H Functionalization via a Lewis Acid- Catalyzed Intramolecular Redox Event, Stefan J. Pastine, Kevin M. McQuaid, and Dalibor Sames, Journal of the American Chemical Society 127 (35), 12180 – 12181 (2005)
A New Fluorogenic Transformation: Development of an Optical Probe for Coenzyme Q, Matthew S. Tremblay and Dalibor Sames, Organic Letters 7 (12), 2417 – 2420 (2005)
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