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Extramural Research

Final Report: Water as Solvent for Metal-Mediated Carbon-Carbon Bond Formations

EPA Grant Number: R822668
Title: Water as Solvent for Metal-Mediated Carbon-Carbon Bond Formations
Investigators: Li, Chao-Jun
Institution: Tulane University of Louisiana
EPA Project Officer: Karn, Barbara
Project Period: August 1, 1997 through July 31, 2000
Project Amount: $200,000
RFA: Technology for a Sustainable Environment (1997)
Research Category: Pollution Prevention/Sustainable Development

Description:

Objective:

The use of large quantities of costly organic solvent for industrial scale operations eventually adds to environmental problems. The need to conduct basic research that could eventually lead to the development of pollution prevention-based synthetic methods becomes more and more critical. The long-term objective of this research project was to use water as solvent for various chemical and pharmaceutical syntheses to achieve a win-win situation both for the chemical/pharmaceutical industries and the environment. The specific aim of this project was to establish the foundation of developing the aqueous metal-mediated reaction into a general process that does not use anhydrous organic solvent, avoids the use of protection-deprotections, is applicable to large-scale industry operation, and has a reduced impact on environment due to the use of catalytic amount of metal and/or in-process recycling.

Summary/Accomplishments (Outputs/Outcomes):

Research during this project period on metal-mediated carbon-carbon bond formation in aqueous media has led to extend the scope, synthetic potential, and a better understanding of the reaction. Representative progresses include the following: the study has resulted in the development of a new ring-expansion method that is useful for the synthesis of medium- and large-ring natural products. The expansions also include the synthesis of heterocyclic compounds. The research also developed a regio- and diastereoselective propargylation-allenylation reaction in the media. The reaction has been applied to the synthesis of several biologically important natural products, with the synthesis of one anti-tumor natural product (+)-goniofufurone being completed last year. Several natural products are in satisfactory progress. We also have investigated the potential use of other metals for the aqueous reaction. This led to the observation of completely chemoselective allylation and pinacol coupling for aromatic aldehydes by using manganese as the mediator catalyzed by copper. The research also led to the surprising observation that the classical Barbier-Grignard reaction with magnesium can proceed in water alone or dry THF, but not in THF-water. This shed new light on the mechanism and possibility of extending the scope of this type of reaction. We also have had preliminary success in using electricity as the electron source for effecting carbon-carbon bond formation in water, in which no metal (stoichiometric or catalytic) was used (except the inert electrode).

We have explored a variety of other novel organic transformations and syntheses through the use of water as solvent in our laboratory. Structural transformations through the internal isomerization of functionalities represent the most economical way of organic transformations. We have described a novel reaction in which homoallyl alcohols and allyl alcohols undergo structural reorganization in which both the hydroxyl group and the olefin have been reshuffled in the presence of a catalytic amount of RuCl2(PPh3)3 in water. A novel palladium catalyzed aryl halide-acetylene gas coupling reaction was developed in water. The catalytic reaction has been applied to the synthesis of novel photo/electronic materials. In addition, we also have succeeded in aqueous arylation through a novel rhodium catalyzed reaction in air and water.

In the past 3 years of the support, over 50 journal articles, 1 book, and several book chapters have been published on work related to the support. In the past 2 years of EPA/NCER support, 12 graduate students, 5 undergraduate students, and 5 postdoctoral fellows have worked on projects either directly or indirectly related to this project and have benefited from this support. Eight graduate students have received their Ph.D. and MS degrees during this period on related research. Currently, most of them are employed in pharmaceutical companies or in chemical industries in the country.

The study is closely related to the mission of pollution prevention in several aspects: using water as solvent that is nonpolluting for chemical synthesis; saving synthetic steps by avoiding many protection and deprotection processes that contribute to overall synthetic efficiency and a reduction in solvent emission (i.e., in product separation); developing methods with metal being catalytic, recovered, and recycled in-process so that no burden is put on the treatment of aqueous waste; the aqueous reaction is generally more selective in product formation than its counterpart in organic solvent; the aqueous reaction is energy-efficient for using ambient temperature compared to similar reactions in organic solvent using a severely low temperature (e.g., lithium reagent); and the reaction is readily applicable to large-scale manufacturing that, as a result, will help to reduce negative impacts on health and the environment. The present project provides the foundation for catalytic process in water by in-house recycling production systems that will minimize the environmental impact of chemical manufacturing as well as save the resources.


Journal Articles on this Report : 39 Displayed | Download in RIS Format

Other project views: All 86 publications 43 publications in selected types All 39 journal articles

Type Citation Project Document Sources
Journal Article Haberman JX, Li C-J. Indium and zinc mediated one-atom carbocycle enlargement in water. Tetrahedron Letters 1997;38(27):4735-4736, erratum 1997;38(39):6785. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article Haberman JX, Li C-J, Irvin GC, John VT. Aldehyde allylation in liquid carbon dioxide. Green Chemistry 1999;1(6):265-267. R822668 (Final)
  • Abstract: RSC - Abstract
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  • Journal Article Hua X-G, Mague JT, Li C-J. Model studies of (+)-bergenin: a convenient formation of aryl δ-lactones. Tetrahedron Letters 1998;39(38):6837-6840. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article Hua X-G, Li C-J. Synthesis of allene aryl δ-lactones via indium-mediated [4+2] cyclization in water. Main Group Metal Chemistry 1999;22(9):533-537. R822668 (Final)
  • Abstract: De Gruyter-Abstract
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  • Journal Article Huang T, Li C-J. Synthesis of amino acids via a three-component reaction of phenols, glyoxylates and amines. Tetrahedron Letters 2000;41(35):6715-6719. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article Huang T, Li C-J. Synthesis of α-amino γ-lactone via a novel tandem three-component reaction of alkenes, glyoxylates and amines. Tetrahedron Letters 2000;41(50):9747-9751. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article Keh CCK, Li C-J. Indium-mediated organometallic reactions in aqueous media: the nature of the allylindium intermediate--(Note). Chemtracts 1999;12(11):813-816. R822668 (Final)
    not available
    Journal Article Keh CCK, Li C-J. On the mechanism of indium-mediated allylation in water. Chemtracts 1999;12:813. R822668 (Final)
    not available
    Journal Article Li C-J, Meng Y. Grignard-type carbonyl phenylation in water and under an air atmosphere. Journal of the American Chemical Society 2000;122(39):9538-9539 (letter to the editor). R822668 (Final)
  • Abstract: ACS-Citation
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  • Journal Article Li C-J, Meng Y, Yi X-H, Chan T-H. Manganese-mediated reactions in aqueous media: chemoselective allylation and pinacol coupling of aryl aldehydes. Journal of Organic Chemistry 1997;62(25):8632-8633. R822668 (Final)
  • Abstract: ACS-Abstract
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  • Journal Article Li C-J, Zhang W-C. Unexpected Barbier-Grignard allylation of aldehydes with magnesium in water. Journal of the American Chemical Society 1998;120(35):9102-9103. R822668 (Final)
  • Abstract: ACS-Abstract
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  • Journal Article Li C-J, Chen D-L, Lu Y-Q, Haberman JX, Mague JT. Metal-mediated two-atom carbocycle enlargement in aqueous medium. Tetrahedron 1998;54(11):2347-2364. R822668 (Final)
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Li C-J, Meng Y, Yi X-H, Ma J, Chan T-H. Manganese-mediated carbon-carbon bond formation in aqueous media: chemoselective allylation and pinacol coupling of aryl aldehydes. Journal of Organic Chemistry 1998;63(21):7498-7504. R822668 (Final)
  • Abstract from PubMed
  • Abstract: ACS - Abstract
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  • Journal Article Li C-J, Chan T-H. Organic syntheses using indium-mediated and catalyzed reactions in aqueous media. Tetrahedron 1999;55(37):11149-11176. R822668 (Final)
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Li C-J, Chen D-L. Eight-membered thiocycloether via indium-mediated ring enlargement. Synlett 1999;1999(6):735-736. R822668 (Final)
  • Abstract: Thieme-Abstract
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  • Journal Article Li J, Li C-J. Synthesis of oxepanes via indium chloride mediated and tin chloride catalyzed Prins-type cyclization. Heterocycles 2000;53(8):1691-1695. R822668 (Final)
  • Abstract: Heterocycles - Abstract
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  • Journal Article Li J, Li C-J. Synthesis of tetrahydropyran derivatives via a novel indium trichloride mediated cross-cyclization between epoxides and homoallyl alcohols. Tetrahedron Letters 2001;42(5):793-796. R822668 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Mague JT, Hua X-G, Li C-J. An unexpected product of an indium-mediated carbon-carbon coupling:2-(1-phenyl-1,3-butadien-2-yl)benzoic acid. Acta Crystallographica Section C-Crystal Structure Communication 1998;54(Pt 12):1934-1936. R822668 (Final)
  • Abstract: International Union of Crystallography-Abstract
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  • Journal Article Tian H-Y, Chen Y-J, Wang D, Zeng C-C, Li C-J. Calix[6]arene derivatives bearing sulfonate and alkyl groups as surfactants in Sc(OTf)3-catalyzed Mukaiyama aldol reactions in water. Tetrahedron Letters 2000;41(15):2529-2532. R822668 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Tian H-Y, Chen Y-J, Wang D, Bu Y-P, Li C-J. The effects of aromatic and aliphatic anionic surfactants on Sc(OTf)3-catalyzed Mukaiyama aldol reaction in water. Tetrahedron Letters 2001;42(10):1803-1805. R822668 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Venkatraman S, Li C-J. Carbon-carbon bond formation via palladium-catalyzed reductive coupling in air. Organic Letters 1999;1(7):1133-1135. R822668 (Final)
    R828129 (2002)
  • Abstract: ACS-Abstract
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  • Journal Article Venkatraman S, Li C-J. The effect of crown-ether on the palladium-catalyzed Ullmann-type coupling mediated by zinc in air and water. Tetrahedron Letters 2000;41(25):4831-4834. R822668 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Venkatraman S, Li C-J. Rhodium catalyzed conjugated addition of unsaturated carbonyl compounds by triphenylbismuth in aqueous media and under an air atmosphere. Tetrahedron Letters 2001;42(5):781-784. R822668 (Final)
  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Viswanathan GS, Yang J, Li C-J. A novel stereoselective cyclization to functionalized dihydropyrans. Organic Letters 1999;1(7):993-995. R822668 (Final)
  • Abstract: ACS - Abstract
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  • Journal Article Wang D, Chen D, Haberman JX, Li C-J. Ruthenium-catalyzed isomerization of homoallylic alcohols in water. Tetrahedron 1998;54(20):5129-5142. R822668 (Final)
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Wang D, Li C-J. Mono-allylation of diols through ruthenium-catalyzed reaction with homoallyl alcohols. Synthetic Communications 1998;28(3):507-515. R822668 (Final)
  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Yang J, Viswanathan GS, Li C-J. Highly effective synthesis of 4-halo-tetrahydropyrans via a highly diastereoselective in situ Prins-type cyclization reaction. Tetrahedron Letters 1999;40(9):1627-1630. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article Yang J, Li C-J. Indium-trichloride mediated synthesis of 4,4-dichlorotetrahydropyrans. Synlett 1999;1999(6):717-718. R822668 (Final)
  • Abstract: Thieme-Abstract
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  • Journal Article Yang X-F, Li C-J. Diastereoselective synthesis of multisubstituted thiacyclohexanes via cation-olefin cyclizations. Tetrahedron Letters 2000;41(9):1321-1325. R822668 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Yang X-F, Mague JT, Li C-J. Diastereoselective synthesis of polysubstituted tetrahydropyrans and thiacyclohexanes via indium trichloride mediated cyclizations. Journal of Organic Chemistry 2001;66(3):739-747. R822668 (Final)
  • Abstract from PubMed
  • Abstract: ACS-Abstract
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  • Journal Article Yi X-H, Meng Y, Li C-J. Indium mediated reactions in water:synthesis of β-hydroxyl esters, Tetrahedron Letters 1997;38:4731-4734, Corrigendum. Tetrahedron Letters 1997;38(39):6785. R822668 (Final)
  • Full-text: ScienceDirect-Full Text PDF
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  • Abstract: ScienceDirect-Errata
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  • Journal Article Yi X-H, Haberman JX, Li C-J. Metal-mediated Barbier-type carbonyl allylation under solvent-free conditions. Synthetic Communications 1998;28(16):2999-3009. R822668 (Final)
  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Yi X-H, Meng Y, Hua X-G, Li C-J. Regio- and diastereoselective allenylation of aldehydes in aqueous media: total synthesis of (+)-goniofufurone. Journal of Organic Chemistry 1998;63(21):7472-7480. R822668 (Final)
  • Abstract from PubMed
  • Abstract: ACS - Abstract
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  • Journal Article Yi X-H, Meng Y, Li C-J. Indium-mediated highly diastereoselective allenylation in aqueous medium: total synthesis of (+)-goniofufurone. Chemical Communications 1998;(4):449-450. R822668 (Final)
  • Abstract: RSC-Abstract
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  • Journal Article Zhang W-C, Li C-J. Magnesium in water: simple and effective for pinacol-coupling. Journal of the Chemical Society-Perkin Transactions 1 1998;(19):3131-3132. R822668 (Final)
  • Abstract: RSC-Abstract
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  • Journal Article Zhang W-C, Li C-J. Magnesium-mediated carbon-carbon bond formation in aqueous media: Barbier-Grignard allylation and pinacol coupling of aldehydes. Journal of Organic Chemistry 1999;64(9):3230-3236. R822668 (Final)
  • Abstract: ACS-Abstract
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  • Journal Article Zhang W-C, Viswanathan GS, Li C-J. Scandium triflate catalyzed in situ Prins-type cyclization: formations of 4-tetrahydropyranols and ethers. Chemical Communications 1999;(3):291-292. R822668 (Final)
  • Abstract: RSC-Abstract
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  • Journal Article Zhang W-C, Li C-J. Diastereoselective synthesis of 2,4-disubstituted tetrahydropyranols and ethers via a Prins-type cyclization catalyzed by scandium triflate. Tetrahedron 2000;56(16):2403-2411. R822668 (Final)
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Zhang W-C, Li C-J. A direct retro-Barbier fragmentation. Journal of Organic Chemistry 2000;65(18):5831-5833. R822668 (Final)
  • Abstract from PubMed
  • Abstract: ACS-Abstract
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  • Supplemental Keywords:

    media, air, ambient air, atmosphere, water, drinking water, watersheds, groundwater pollution, green chemistry, sustainable development, alternatives, clean technologies, innovative technology, renewable, waste reduction, waste minimization, environmentally conscious manufacturing., RFA, Scientific Discipline, Sustainable Industry/Business, Chemical Engineering, Environmental Chemistry, Sustainable Environment, Technology for Sustainable Environment, Economics and Business, cleaner production, waste minimization, waste reduction, aqueous processing, environmentally benign solvents, carbon bond formation, alternative materials, catalysts, anhydrous organic solvents, metal recovery, recycling, pollution prevention, green chemistry

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    Chao-Jun Li, Ph.D. Exit

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