Scott Eric Denmark
University Of Illinois Urbana-champaign
Project start date: 2010-03-22
Project end date: 2014-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Scott Eric Denmark
ASYMMETRIC LEWIS BASE CATALYSIS IN MAIN GROUP CHEMISTRY
Scott Eric Denmark
University Of Illinois Urbana-champaign, Office Of Sponsored Programs & Research Admin, Champaign, Il 61820
Grant 1R01GM085235-01A1 from National Institute Of General Medical Sciences
Abstract: The primary objectives of this proposal are (1) to demonstrate the concept of Lewis base activation of Lewis acids (Gutmann electron density polarization) as it applies to electrophilic species in Groups 16 and 17 in the Main Group, (2) to develop catalytic variants of classical main group reactions for which catalysis has yet to be realized, (3) to learn the structure/reactivity correlations and the rules for achieving high catalytic activity (turnover frequencies and turnover numbers) for the target reactions, (4) to design chiral Lewis bases that will impart high stereoselectivity and high chemical conversion for the introduction of new carbon and heteroatom substituted stereocenters, and (5) carry out detailed mechanistic (kinetics, spectroscopic, crystallographic, computational) investigations of the newly-invented catalytic reactions described below. The first major effort will be the development of catalytic, enantioselective variants of the most common reactions of electrophilic Group 16 and 17 reagents. Direct functionalization and cyclofunctionalization of alkenes bearing a tethered nucleophile (oxygen, nitrogen, carbon) is a powerful method for creating stereodefined chains, heterocycles and carbocycles. These reactions are efficiently initiated by electrophilic sulfur(II), chlorine(I), bromine(I), and iodine(I) reagents The design of Lewis bases to catalyze and control the constitutional and enantiofacial selectivity will constitute a major component of this program. The synthetic manipulation of the enantiomerically enriched, sulfur-containing products constitutes the second major activity. In addition to well-known functional manipulations, new, stereocontrolled, constructive replacements of the C-S bond that employ transition metal catalyzed coupling and direct ligand coupling reactions will be developed. A third major effort will be the invention, development, and exploration of a new subclass of Lewis base catalyzed reactions that employs higher oxidation state iodine(III) reagents for carbon-carbon bond formation. Catalysis of the ligand coupling reaction of iodonium salts is unprecedented and will be investigated for the construction of enantiomerically enriched ?-aryl, ?-alkenyl, ?-alkynyl, and also potentially ?-aryl substituted ketones and esters. This research proposal aims to develop a fundamentally new class of catalytic reactions of the main group elements, sulfur, chlorine, bromine, and iodine in various oxidation states. The conceptual foundation for the ability of Lewis bases to activate the electrophilic character of these elements has almost unlimited potential. Already, catalysis is involved in the processing of nearly a trillion dollars worth of goods produced annually in the US, and our contribution is for chemical reactions for which there is currently no catalytic process
Keywords: 2, 2`-azobis(2-methylpropionitrile); 2, 2`-azobisisobutyronitrile; AIBN; Acids; Alkenes; Br- element; Bromine; C element; Carbon; Catalysis; Chemicals; Chemistry; Chlorine; Cl element; Constitutional; Coupling; Development; Elements; Esters; Foundations; Frequencies (time pattern); Frequency; Heating; I- element; Intercept; Investigation; Iodine; Ions; Ketones; Kinetic; Kinetics; Learning; Ligands; Methods; N element; N2 element; Nitrogen; O element; O2 element; Olefins; Oxygen; Process; Programs (PT); Programs [Publication Type]; Reaction; Reagent; Research Proposals; S element; Salts; Scheme; Science of Chemistry; Structure; Sulfur; Transition Elements; Variant; Variation; azobis(isobutyronitrile); azobisisobutyronitrile; base; chemical reaction; chlorine gas; design; designing; electron density; oxidation; programs; public health relevance; transition metal
Relevance: This research proposal aims to develop a fundamentally new class of catalytic reactions of the main group elements, sulfur, chlorine, bromine, and iodine in various oxidation states. The conceptual foundation for the ability of Lewis bases to activate the electrophilic character of these elements has almost unlimited potential. Already, catalysis is involved in the processing of nearly a trillion dollars worth of goods produced annually in the US, and our contribution is for chemical reactions for which there is currently no catalytic process
Project start date: 2010-03-22
Project end date: 2014-01-31
Budget start date: 22-MAR-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
1R01GM085235-01A1 (2010): $359030
CROSS-COUPLING REACTIONS OF ORGANOSILANOLS
Scott Eric Denmark
Department/ Educational Institution Type:
Grant 5R01GM063167-08 from National Institute Of General Medical Sciences
Abstract: The basic objectives of this application are the development and application of a newly invented silicon- based carbon-carbon bond forming reaction that proceeds via a silyloxmetallic intermediate. This programis divided into three sections the first and major effort will be methodological exploration of the new process, the second will be the investigation of the mechanism, and the third will be the application of the reaction to the synthesis of selected targets that illustrate the power of the technology. The methodological program is the most extensive and is subdivided into many projects. The first involves the development of new and general methods for the introduction of the silanol (or its surrogate) into organic structures using direct installation, cross- and ring closing metathesis and other ring forming processes. The second and most ambitious part of the methodological study is the exploration and development of the various structural scenarios in which the silicon cross coupling process can function, for example cyclopropyl-, oxiranyl-, aliyl-, alkenyi- aryl-, heteroaryl-, and bifunctional bissiyl dienes. Included in this section will be the examination of the scope of organic electro-philic components that will serve as partners in the cross-coupling reaction such as chlorides and triflates. The extension of the silyloxmetallic intermediate to transmetalation to other metals such as mercury copper and gold will be investigated. The opportunities for catalysis of the transmetalation from silicon to palladium will be studies. The parallels between mercury and gold offer excellent opportunity to use silanols to generate rare organogold(lll) compounds which can be intercepted by conjugate acceptors. The section on mechanistic studies will focus on structurally and kinetically characterizing the silyloxy- metaltic intermediates. A key focus will be to identify the elementary steps in the transmetalation. A major effort will be the development of functionalized ligands to effect nucleopnilic catalysis of transmetalation. The synthesis targets to be tackled belong to a wide range of natural product families. The selection of synthetic challenges is mostly driven by the successes achieved in the methodological section. Synthetic approaches to isodomoic acid H, hepatitis C viral inihibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed
Keywords: Acids; Address; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Antiviral Agents; Antiviral Drugs; Antivirals; Au element; base; Biological; Biological Factors; C element; Carbon; Carbonates; Catalysis; Chloride; Chloride Ion; Chlorides; Cl- element; Copper; Coupling; Cu element; Denmark; Development; diene; Epoxides; Epoxy Compounds; Evaluation; Factor, Biologic; Family; Goals; Gold; HCV infection; Hepatitis C; Hepatitis C virus infection; hepatitis non A non B; hepatitis nonA nonB; Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted; Hg element; Indole Alkaloids; Intercept; Investigation; Investigators; Kinetic; Kinetics; Left; Ligands; Mercury; Metals; Methodological Studies; Methods; Miscellaneous Antibiotic; NANBH; Natural Products; Nature; non A non B hepatitis; non A, non B hepatitis; non-A non-B hepatitis; non-A, non-B hepatitis; oximidine II; Palladium; Parenterally-Transmitted Non-A, Non-B Hepatitis; Pd element; Polyenes; Process; programs; Programs (PT); Programs [Publication Type]; PT-NANBH; Reaction; Research Personnel; Researchers; Role; Scheme; Si element; silane; Silanes; silanol; Silicon; social role; Structure; success; Survey Instrument; Surveys; Technology; Viral
Project start date: 2001-04-01
Project end date: 2010-12-31
Budget start date: 1-JAN-2009
Budget end date: 31-DEC-2010
5R01GM063167-08 (2009): $272605
3R01GM063167-08S1 (2009): $76633