This program has as its objectives the discovery, development, and application of selective catalytic reactions of use in organic synthesis. In particular, we seek to identify catalysts for asymmetric reactions of broad synthetic utility, to elucidate the reaction mechanisms of these reactions, and to illustrate their utility through their application in the efficient synthesis of useful building blocks and complex targets. The ultimate goal of this effort is to advance the field of organic synthesis through the development of truly practical catalysts that will find application in both industry and academia for the enantioselective synthesis of biologically important compounds. Four major projects are outlined in this application. We propose to develop novel multimeric metal catalysts that operate on the basis of cooperative reactivity. This will be accomplished through the preparation of conformationally constrained oligomeric complexes wherein the relative orientation of catalyst units can be tuned through conformational control of the linker units. We will also explore the possibility of generating synthetically accessible self-assembling multimeric catalysts that display cooperative reactivity. In a second project, we plan to test a new hypothesis for asymmetric catalysis wherein two different chiral catalyst complexes function cooperatively to catalyze nucleophile- electrophile addition reactions. The goal of this effort is to establish whether reinforced stereoinduction and reactivity effects may open the door to valuable new reactions. A third project is focused on the investigation of the mechanism and scope of a novel class of non-metal catalysts. We recently applied a parallel library approach to the discovery of extraordinarily general non-metal-containing catalysts for imine hydrocyanation. Preliminary studies indicate both a fascinating enzyme-like mechanism of action of these novel catalysts, and a highly promising level of generality in other synthetically useful reactions. In a fourth area of effort, we plan to investigate new classes of chiral catalyst systems, and two new research directions are described. One involves the design of effective chiral imidazolium carbene ligand systems for late-transition metal catalyzed reactions. A second is focused on the discovery of self-assembling biomimetic oxidation catalysts, and their development into synthetically useful systems for enantioselective epoxidation of alkenes with hydrogen peroxide.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Lees, Robert G
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Harvard University
Schools of Arts and Sciences
United States
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Wendlandt, Alison E; Vangal, Prithvi; Jacobsen, Eric N (2018) Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction. Nature 556:447-451
Zhou, Biying; Haj, Moriana K; Jacobsen, Eric N et al. (2018) Mechanism and Origins of Chemo- and Stereoselectivities of Aryl Iodide-Catalyzed Asymmetric Difluorinations of ?-Substituted Styrenes. J Am Chem Soc 140:15206-15218
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Banik, Steven M; Mennie, Katrina M; Jacobsen, Eric N (2017) Catalytic 1,3-Difunctionalization via Oxidative C-C Bond Activation. J Am Chem Soc 139:9152-9155
Park, Yongho; Harper, Kaid C; Kuhl, Nadine et al. (2017) Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions. Science 355:162-166
Turek, Amanda K; Hardee, David J; Ullman, Andrew M et al. (2016) Activation of Electron-Deficient Quinones through Hydrogen-Bond-Donor-Coupled Electron Transfer. Angew Chem Int Ed Engl 55:539-44
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