The long-standing focus of the Montgomery group has been the discovery and development of new transition metal-catalyzed reactions that enable the efficient assembly of bioactive structures. These efforts include the design and synthesis of new classes of transition metal catalysts, the discovery of new metal-catalyzed processes as enabling tools for organic synthesis, mechanistic and kinetic study of catalytic processes, and total synthesis of complex molecules. Our laboratory played a pioneering role in developing the area of nickel-catalyzed reductive coupling methods involving reactive pi-components, and we have provided mechanistic understanding and numerous preparative advances in this field. Recent work has focused on developing a broad array of regiodivergent catalytic transformations, where two or more product regioisomers may be obtained through careful control of catalyst structure and reaction conditions. Additionally, new catalytic cycloaddition and C-H activation processes are currently being developed.
Our laboratory has recently initiated a program in the development of innovative catalytic methods for glycoside bond construction. A new class of carbohydrate-derived reagents, termed sugar silanes, was devised in our laboratory and enables sequential reductive conversions paired with an intramolecular glycosylation process. A newer collaborative interest is the development of biocatalysts as general tools in synthetic chemistry, particularly for the functionalization of unactivated C-H bonds. Our recent studies demonstrate that carefully designed substrate modifications enable improvements and/or reversals in site-selectivity of oxidations of a broad array of unnatural substrates using engineered cytochrome P450 enzymes.
Our general approach to research encompasses identifying novel catalyst structures that accomplish unprecedented chemical transformations, rigorously characterizing the mechanisms by which the processes occur, and optimizing the efficiency and selectivity of the processes developed. Attention is then placed on complex synthetic applications including natural product synthesis, assembly of novel glycosylated structures, and preparation of unnatural motifs designed to probe questions in biology and medicinal chemistry.
Jackson, E. P.; Montgomery, J. “Regiocontrol in Catalytic Reductive Couplings Through Alterations of Silane Rate Dependence,” J. Am. Chem. Soc. 2015, 137, 958-963.
Walk, J. T.; Buchan, Z. A.; Montgomery, J. “Sugar Silanes: Versatile Reagents for Stereocontrolled Glycosylation via Intramolecular Aglycone Delivery,” Chem. Sci. 2015, 6, 3448-3453.
Jackson, E. P.; Malik, H. A.; Sormunen, G. J.; Baxter, R. D.; Liu, P.; Wang, H.; Shareef, A. R.; Montgomery, J. “Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings,” Acc. Chem. Res. 2015, 48, 1736-1745.
Miller, Z. D.; Dorel, R.; Montgomery, J. “Regiodivergent and Stereoselective Hydrosilylation of 1,3-Disubstituted Allenes” Angew. Chem. Int. Ed. 2015, 54, 9088-9091.
Nett, A. J.; Zhao, W.; Zimmerman, P.; Montgomery, J. “Highly Active Nickel Catalysts for C-H Functionalization Identified Through Analysis of Off-Cycle Intermediates” J. Am. Chem. Soc. 2015, 137, 7636-7639.
Narayan, A. R. H.; Jiménez-Osés, G.; Liu, P.; Negretti, S.; Zhao, W.; Ramabhadran, R. O.; Furan, L. R.; Li, Z.; Yang, Y.-F.; Gilbert, M. M.; Podust, L. M.; Montgomery, J.; Houk, K. N.; Sherman D. H. “Enzymatic Hydroxylation of an Unactivated Methylene C-H Bond Guided by Molecular Dynamics Simulations,” Nat. Chem. 2015, 7, 653-660.