ORGANIC, INORGANIC, AND POLYMER CHEMISTRY
Professor and Henry Eyring Fellow
B.S. University of California, Los Angeles 1993
Office: 3116 HEB-N
Activities & Awards
- ACS Arthur C. Cope Scholar Award 2007
- Alfred P. Sloan Award 2006
- ACS/Dreyfus PROGRESS “Rising Stars” Lectureship, 2005-6
- Camille and Henry Dreyfus Teacher-Scholar Award, 2005-2010
- NSF Faculty Early CAREER Development Award, 2004-2009
- Henry Erying Assistant Professorship 2004
- Fellow of the American Association for the Advancement of Science, 2012
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. CO2, 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). 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.
CO2 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.
K. Zhang, M. Conda-Sheridan, S. Cooke, J. Louie “N-Heterocyclic Carbene Bound Ni(I)-Complexes and Their Roles in Catalysis” Organometallics 2011, 30, 2546-2552.
K. Zhang, J. Louie “Rhodium-Catalyzed Decarboxylative Cycloaddition Route to Substituted Anilines” J. Org. Chem. 2011, 76, 4686-4691.
P. Kumar, D. M. Troast, R. Cella, J. Louie “Ni-Catalyzed Ketene Cycloaddition: A System that Resists the Formation of Decarbonylation Side Products” J. Am. Chem. Soc. 2011, 133, 7719-7721; C & E News May 9, 2011.
B. R. D’Souza, T. K. Lane, J. Louie “Iron Catalyzed Cycloaddition of Cyanoalkynes and Alkynes” Org. Lett. 2011, 13, 2936-2939.
R. M. Stolley, M. T. Maczka,† J. Louie “Nickel-Catalyzed Cycloaddition of Diynes and Cyanamides” Eur. J. Org. Chem. 2011, 20-21, 3815-3824; Invited Contribution to a Special Edition Honoring Women in Chemistry.
P. Kumar, S. Prescher,† J. Louie “A Serendipitous Discovery of a Nickel-Catalyst for Cycloaddition of Diynes with Unactivated Nitriles” Angew. Chem. Int. Ed. 2011, 50, 10694-10698.
P. Kumar, J. Louie “Double the Fun: Nickel-Catalyzed Cycloaddition via Two Sequential C-H Activations” Angew. Chem. Int. Ed. 2011, 50, 10768-10769; Invited Highlight.
B. R. Van Ausdall, N. F. Pols,† V. A. Kincaid,† A. M. Aarif, J. Louie “NHC•CO2-bound MBPh4 Complexes (M = Li, Na) and their Relevance in Transcarboxylation Reactions” J. Org. Chem. 2011, 76, 8413-8420.
A. Thakur, K. Zhang, J. Louie “Suzuki-Miyaura Coupling if Hetero-aryl Boronic Acids and Vinyl Chlorides” Chem. Comm. 2012, 48, p203-205.
R. M. Stolley, W. X. Guo,† J. Louie “Palladium-Catalyzed Cross-Coupling of Cyanamides” Org. Lett. 2012, 14, 322-325; C & E News December 19, 2011.
P. Kumar, J. Louie “A Single Step Approach to Highly Substituted Piperidines Via Ni-Catalyzed β-Carbon Elimination” Org. Lett. 2012, 14, 2026-2029.