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Activities & Awards
Camille Dreyfus Teacher-Scholar Award, 2005
NSF CAREER Award, 2004
Henry Eyring Assistant Professorship 2004
Alfred P. Sloan Award, 2006
Research Interests
The development of metal-mediated reactions has greatly expanded the synthesis of small molecules and polymeric materials.
These complexes possess the profound ability to permit transformations
that are otherwise energetically prohibited.
Toward this end, our group hybridizes classical synthetic chemistry with state-of-the-art instrumentation to discover new metal-mediated reactions. Efforts focus on reaction optimization,
mechanism elucidation, and constructing small and large
molecules rich in structure and function.
Catalytic Activation of Heterocumulenes
An attractive method for the rapid construction of the heterocyclic core of numerous biologically active pharmacophores is the cycloaddition or rearrangement of unsaturated substrates. Unfortunately, such cycloadditions are often not thermally allowed and existing alternatives show poor functional group compatibility. However, reactions which require prohibitively harsh conditions (high temperatures, high pressures) may become practical (room temperature, atmospheric pressures) when a transition metal catalyst is employed. We have built a research program centered around the development of a general Ni-based cycloaddition catalyst system (Scheme 1). Ultimately, we found that our Ni/NHC system is quite a versatile catalyst – one that allows for facile cycloaddition to prepare highly functionalized pyrones, pyridones, pyrans, and pyridines in excellent yields from readily available starting materials (e.g. CO 2, isocyanates, carbonyls and nitriles, respectively).
Ni-Catalyzed Rearrangements: Rapid Entry to Carbocycles
An atom-efficient protocol for preparing cyclopentenes, a common carbocyclic building block and structural motif in many biological systems, is the rearrangement of vinylcyclopropanes (VCPs). We recently reported that our Ni/imidazolylidene system catalyzes the isomerization of a variety of activated and unactivated VCPs under mild conditions to afford the respective cyclopentenes (eq 1).
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We have also discovered this methodology can be extended to the rearrangement of cyclopropylen-ynes to afford two different carbocycles. We have recently developed reaction conditions whereby a cyclopentane-based carbocycle can be formed selectively and in good yields (eq 2). Studies toward understanding the mechanism and developing an asymmetric variant are in progress.
CO 2 Sequestering Agents
As a corollary to our primary investigations, we found that the imidazolylidene ligands reversibly react with CO2 to afford zwitterionic imidazolylidene carboxylates. We are investigating the stability and reactivity of these carboxylates such that further applications of these compounds can be realized. For example, the incorporation of imidazolylidenes into polymeric materials may function as CO2 sequestering and/or delivery agents.
Selected Publications
- J. Louie, J. E. Gibby, M. V. Farnworth, T. N. Tekavec "Efficient Nickel-Catalyzed [2+2+2] Cycloaddition of CO 2 and Diynes" J. Am. Chem. Soc. 2002, 124 , 15188-15189.
- H. A. Duong, T. N. Tekavec, A. M. Arif, J. Louie "Reversible Carboxylations of N-Heterocyclic Carbenes" Chem. Comm. 2004 , 1 , 112-113 .
- G. Zuo, J. Louie "Highly Active Nickel Catalysts for the Isomerization of Unactivated Vinyl Cyclopropanes to Cyclopentenes" Angew. Chem. Int. Ed. 2004 , 43 , 2777-2779; “Hot Paper” Web Release 03/24/2004.
- T. N. Tekavec, A. M. Arif, J. Louie "Regioselectivity in Nickel-Catalyzed Cycloadditions between CO2 and Diynes" Tetrahedron 2004 , 60,7431-7437.
- H. A. Duong, M. J. Cross, J. Louie "Nickel-Catalyzed Cycloadditions of Alkynes and Isocyanates" J. Am. Chem. Soc 2004 , 126, 11438-11439.
- H. A. Duong, M. J. Cross, J. Louie "N-heterocyclic carbenes as highly efficient catalysts for the cyclotrimerization of isocyanates" Org. Lett. 2004 , 6, 4679-4681 .
- M. M. McCormick, H. A. Duong, G. Zuo, J. Louie "A Nickel-Catalyzed Route to Pyridines" J. Am. Chem. Soc. 2005, 127,
5030-5031.
- G. Zuo, J. Louie "Selectivity in Nickel-Catalyzed Rearrangements of Cyclopropylen-ynes" J. Am. Chem. Soc. 2005, 127, 5798-5799.
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