Development of New Chiral Diaminocarbene Ligands and Their Applications in Copper-catalyzed Reactions PDF Download

Author: Dimitri Hirsch-Weil
Publisher:
ISBN:
Category :
Languages : en
Pages :

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A novel acyclic diaminocarbene-copper complex has been prepared for the first time, conveniently from a chloroamidinium salt and Cu(I)-thiophenecarboxylate. The in situ generated acyclic diaminocarbene-Cu complex was characterized by 13C-NMR experiments using a 13C-labeled carbene precursor. The acyclic diaminocarbene-Cu complex is a highly efficient catalyst for SN2 ...-allylic alkylation with alkyl Grignard reagents, showing high SN2 ... selectivity. C1-symmetric monoisoquinoline based chiral diaminocarbene ligands were envisioned to expand the chiral pool of NHC structures and further optimize previously reported C2-symmetric biisoquinoline carbene ligands. This new ligand was synthesized from readily available chiral phenethylamine. The synthetic scheme allowed easy variation of the ligand structure within the final steps. Both C2 and C1-symmetric carbene ligands could be compared by their respective X-ray structures of Au(I) complexes. Monoisoquinoline based carbene ligand was tested in the copper-catalyzed borylation of ... ... unsaturated amides giving good yields (80-99%) and enantioselectivities (85%) for various substrates.

Author: Montserrat Diéguez
Publisher: CRC Press
ISBN: 1000379000
Category : Science
Languages : en
Pages : 298

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Many new drugs on the market are chiral compounds, that is, they can exist in two non-superimposable mirror-image forms. Asymmetric catalysis encompasses a large variety of processes for obtaining such compounds. The performance of the catalyst in those processes largely depends on the ligand that makes up the catalyst. This book describes the most relevant ligand libraries for some key processes, including an overview of the state of art and the key mechanistic aspects that favor a high catalytic performance. Key Features: The book presents historical content from the time of discovery for each family of ligands. Provides a description of the synthetic route and the ligand library's application in various catalytic asymmetric reactions Suitable as supplementary reading for courses targeting the design, synthesis and application of chiral catalysts, asymmetric catalysis and sustainable production Edited by a distinguished scientist in the field, the book has a diverse audience including research groups in homogeneous catalysis, particularly asymmetric transformations

Author: Junliang Zhang
Publisher: Elsevier
ISBN: 0323852254
Category : Science
Languages : en
Pages : 320

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Chiral Phosphorous Based Ligands in Earth-Abundant Transition Metal Catalysis summarizes the most significant progress in the field of chiral phosphine ligand chemistry and a broad range of earth-abundant transition metal/chiral phosphine ligand-catalyzed enantioselective transformations. The book provides an authoritative and in-depth understanding of important topics about asymmetric catalysis based on earth-abundant transition metals/chiral phosphine ligands, making it ideal for organic chemistry researchers working in the field of asymmetric catalysis, synthetic methodologies and total synthesis. The development of new chiral phosphine ligands to achieve precise stereo control in many earth-abundant transition metal-catalyzed reactions is a very important field in organic synthesis, materials science and medicinal chemistry. The asymmetric synthesis promoted by transition metal/chiral phosphine ligands provides one of the most ideal ways to produce valuable optically active chemicals. Includes a discussion of state-of-the-art asymmetric organic reactions mediated by earth-abundant transition metals and chiral phosphine ligands Features the progress and the prospect of chiral phosphine ligands in asymmetric transition metal catalysis Covers the asymmetric reactivity modes of earth-abundant transition metals and phosphine ligands

Author: Michael P. A. Lyle
Publisher:
ISBN:
Category : Asymmetric synthesis
Languages : en
Pages : 0

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The work described in this thesis concerns the design, synthesis and evaluation of new chiral nonracemic ligands and catalysts for use in asymmetric reactions. A series of chiral nonracemic chloroacetals were prepared from 2-chloro-4- methyl-6,7-dihydro-5H-[l]pyrindine-7-one and a variety of C2-symmetric and chiral nonracemic 1,2-ethanediols (R = Me, i-Pr and Ph). These chloroacetals were further elaborated, in a modular fashion, to provide a series of chiral ligands and catalysts. A new class of C2-symmetric 2,2'-bipyridyl ligands were prepared in one step fiom the chloroacetals via a nickel(0)-mediated homo-coupling reaction. These ligands were then evaluated as chiral directors in copper@)-catalyzed asymmetric cyclopropanation reactions of styrene and diazoesters (up to 44% ee). A chiral pyridine N-oxide and a C2-symmetric 2,2'-bipyridyl N, N'-dioxide were also prepared by direct oxidation of the corresponding pyridine and the 2,2'-bipyridine, respectively. These chiral N-oxides were evaluated as chiral catalysts in desymmeterization reactions of cis-stilbene oxide (up to 20% ee). A series of pyridylphosphine ligands (P, N-ligands) were subsequently prepared in two steps from the chloroacetals via a Suzuki coupling reaction with orthofluorophenylboronic and on subsequent displacement of the fluoride with the potassium anion of diphenylphosphine. These ligands were then evaluated in palladium-catalyzed asymmetric allylic substitution reactions of racemic 3-acetoxy-l,3-diphenyl-1-propene with dimethyl malonate. Optimization of the reaction conditions resulted in the formation of the alkylated product in excellent yield (91%) and in high enantiomeric excess (90%). A related chiral nonracemic and C2-symmetric 2,2'-bipyridyl ligand was prepared from 2-chloro-4-methyl-5H-[llpyrindine. This pyrindine was prepared from a common intermediate that was used in the synthesis of the first generation of ligands. The chirality of this second generation ligand was installed by a Sharpless asymmetric dihydroxylation reaction (90% ee). The subsequently elaborated 2,2'-bipyridyl ligand (enriched to>99% ee) was then evaluated in copper(1)-catalyzed asymmetric cyclopropanation reactions of alkenes and diazoesters. In the case of the reaction of para-fluorostyrene and tert-butyl diazoacetate, the corresponding cyclopropane was formed in good diastereoselectivity (92:8) and in excellent enantioselectivity (99% ee). This ligand was also evaluated in copper(I1)-catalyzed asymmetric Friedel-Crafts alkylation reactions of various substituted indoles (up to 90% ee) and in copper(1)- catalyzed asymmetric allylic oxidation reactions of cyclic alkenes with tert-butyl peroxybenzoate (up to 9 1 % ee).

Author: Gwilherm Evano
Publisher: John Wiley & Sons
ISBN: 1118690478
Category : Science
Languages : en
Pages : 682

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Providing comprehensive insight into the use of copper in cross-coupling reactions, Copper-Mediated Cross-Coupling Reactions provides a complete up-to-date collection of the available reactions and catalytic systems for the formation of carbon-heteroatom and carbon-carbon bonds. This essential reference covers a broad scope of copper-mediated reactions, their variations, key advances, improvements, and an array of academic and industrial applications that have revolutionized the field of organic synthesis. The text also discusses the mechanism of these transformations, the use of copper as cost-efficient alternative to palladium, as well as recently developed methods for conducting copper-mediated reactions with supported catalysts.

Author: Nootaree Niljianskul
Publisher:
ISBN:
Category :
Languages : en
Pages : 635

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The research presented in this dissertation is aimed at the development of novel methodologies for carbon-heteroatom cross-coupling reactions catalyzed by late-transition metals. Both palladium and copper are central to the field of transition metal-catalysis and are integral to the catalyst systems developed as part of our continual advancement in cross-coupling reactions. The first part of this thesis focuses on the use of palladium catalysts to form carbon-sulfur bonds directed towards aryl sulfonamide synthesis. The second part of the thesis describes the recent development in the copper(!) hydride mediated formation of carbon-nitrogen bonds via hydroamination of olefins. Part I. Chapter 1. Palladium-Catalyzed Chlorosulfonylation of Arylboronic Acids Using a biaryl phosphine ligand platform, the first palladium-catalyzed cross-coupling reaction of phenyl chlorosulfate with arylboronic acids was achieved. In this context, the arylsulfonyl chloride products serve as useful precursors to a variety of sulfonyl functional groups, such as aryl sulfonamides, aryl sulfones, and arenesulfonate esters. In particular, this method allows for the preparation of a number of arylsulfonyl chlorides that are not accessible via electrophilic aromatic substitution pathways and under mild reaction conditions. Additionally, this methodology points to an unprecedented selectivity for the phenylchlorosulfate electrophiles used in the cross-coupling reactions. Part II. Chapter 2. Enantio- and Regioselective Copper-Catalyzed Hydroamination of Styrenes and the Extension of the Methodology towards Anti-Markovnikov Hydroamination of Terminal Aliphatic Alkenes The development of a copper-mediated strategy towards the hydroamination of styrene derivatives is reported. In this system, the reaction proceeds regioselectively and enantioselectively to generate [alpha]-branched amines. The system can transform a wide variety of substituted styrenes, including trans-, cis-, and [beta]-disubstituted styrenes. In addition, our extension to copper-catalyzed hydroamination reactions of unactivated aliphatic olefins is reported. Using terminal aliphatic alkenes, the copper-catalyzed hydroamination reactions proceed with anti-Markovnikov regioselectivity. Preliminary results point to the application of this methodology towards [beta]-chiral amine synthesis via the hydroamination of I, 1-disubstituted alkenes. Chapter 3. [alpha]-Aminosilane Synthesis via Copper-Catalyzed Hydroamination of Vinylsilanes The copper-catalyzed hydroamination of vinylsilanes is described. This regioselective reaction generates a-chiral aminosilanes in high yields and enantioselectivities. The method is compatible with differentially substituted vinylsilanes and allows access to many valuable chiral organosilicon compounds. Chapter 4. Synthesis of [gamma]-Chiral Amines via Copper-Catalyzed Hydroamination of 3,3- Disubstituted Allylic Alcohols and 3,3-Disubstituted Allylic Benzoates An investigation into the copper-catalyzed hydroamination of allylic alcohols and allylic benzoates is reported. The reaction proceeds via a [beta]-alkoxy elimination, setting a stereogenic center at the 3-postion to generate [gamma]-chiral amine products. The reaction is more efficient using allylic benzoates. This method is completely regioselective and is applicable to aliphatic allylic benzoates as well as aromatic allylic benzoates. Additionally, we demonstrated that this strategy is applicable towards an allylic epoxide substrate to generate [delta]-chiral amine.

Author: Davoud Asgari
Publisher: LAP Lambert Academic Publishing
ISBN: 9783838312507
Category :
Languages : en
Pages : 164

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The Past three decades have witnessed a major development in asymmetric catalysis in organic synthesis. New and powerful catalysts have been designed and developed which exhibit levels of enantioselectivity previously considered beyond reach for non-enzymatic processes. Nitrogen-based transition metal ligands such as bisoxazoline ligands have emerged as an efficient class of ligands in an increasing number of asymmetric transformations including cyclopropanation, aziridination, Diels-Alder reaction, reduction, aldol reaction, ene reactions, allylic oxidation, and etc. This book reviews the synthesis and applications of bisoxazoline-metal complexes in a variety of asymmetric transformations and then describes the design and synthesis of a novel class of C2-symmetric biarylbisoxazoline ligands and their application in copper catalyzed asymmetric allylic oxidation of olefins. Potential applications for chiral cycloalkenols derived from allylic oxidation are great. A clear example is the conversion of (S)-cyclohexenyl benzoate to the key aldehyde-methyl ester intermediate for the synthesis of inflammation mediator leukotriene B4.

Author: Qi-Lin Zhou
Publisher: John Wiley & Sons
ISBN: 3527635211
Category : Technology & Engineering
Languages : en
Pages : 670

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Catalytic asymmetric synthesis has been one of the most active research areas in chemistry (Nobel Prize in 2001). The development of efficient chiral catalysts plays a crucial role in asymmetric catalysis. Although many chiral ligands/catalysts have been developed in the past decades, the most efficient catalysts are derived from a few core structures, called "privileged chiral catalysts". This ultimate "must have" and long awaited reference for every chemist working in the field of asymmetric catalysis starts with the core structure of the catalysts, explaining why a certain ligand or catalyst is so successful. It describes in detail the history, the basic structural characteristics, and the applications of these "privileged catalysts". This novel presentation provides readers with a much deeper insight into the topic and makes it a must-have for organic chemists, catalytic chemists, chemists working with/on organometallics, chemists in industry, and libraries. From the contents: * BINAP * Bisphosphacycles - From DuPhos and BPE to a Diverse Set of Broadly Applied Ligands * Josiphos Ligands: From Discovery to Technical Applications * Chiral Spiro Ligands * Chiral Bisoxazoline Ligands * PHOX Ligands * Chiral Salen Complexes * BINOL * TADDOLate Ligands * Cinchona Alkaloids * Proline Derivatives

Author: Evelyn Louise Rosen
Publisher:
ISBN:
Category :
Languages : en
Pages : 286

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Book Description
With the ever expanding utility of transition metal catalysis, there has been a thrust both to develop catalysts with unique selectivites or activites, and to understand the factors which govern these characteristics at both a fundamental and practical level. Olefin metathesis has become an essential reaction for the synthesis of small molecules in addition to polymeric materials. We have pursued two distinct ligand classes based on diaminocarbenes with novel architectures to address specific limitations within this useful class of reactions: 1) limited access to polymeric materials with controlled microstructures and 2) poor stereoselectivity in Ru-catalyzed cross-metathesis (CM) reactions. Numerous phosphines and N-heterocyclic carbenes (NHCs) have been used as ligands for Ru metathesis catalysts, and the resulting activity is very sensitive to their steric and electronic nature. We envisioned that we could take advantage of this dependence by developing a catalyst with tunable ligand donicity. Redox-switchable ligands can lead to catalysts whose selectivity and/or activity are dependent upon the ligand oxidation state. Towards this purpose, we have developed a ligand which incorporates a 1,1'-disubstituted ferrocene moiety into the backbone of a diaminocarbene (FcDAC). Upon ligation of FcDAC to various transition metals, we were able to use cyclic voltammetry and a spectroelectrochemical FT-IR experiment to show electronic communication between FcDAC and the coordinated metal. We then pursued Ru metathesis catalysts incorporating these ligands. The ring-opening metathesis polymerization of 1,5-cyclooctadiene was studied using [(FcDAC)(PPh3)Cl2Ru=(3-phenylindenylid-2-ene)] as the catalyst. Chemical redox reactions were used to establish the ability of FcDAC to impart redox-tunable properties to Ru metathesis catalysts. A new ligand class pioneered in our group, N-aryl, N-alkyl acyclic diaminocarbenes (ADCs), was also studied in various Ru metathesis catalysts. To our delight, these catalysts showed lower E : Z ratios than analogous NHC ligands in two representative CM reactions. We also investigated the conformational diversity of these differentially substituted ADCs given their ability to rotate about their C-N bonds, in particular, to determine how this might influence their donicity. Complexes of the type [(ADC)Ir(COD)Cl] and [(ADC)Ir(CO)2Cl] were studied, given the wealth of structural and spectral data available for analogous compounds incorporating related ligand classes. Different conformations resulted depending on the N-substituents and the nature of the metal complex. Interestingly, the electron donating ability of ADC ligands was found to depend on their conformation, as evidenced by FT-IR and cyclic voltammetry. This established a new avenue for tuning the donor properties of differentially substituted ADC ligands. The unique properties of these novel ligand classes were demonstrated in Ru metathesis catalysts. However, on a broader level, these ligands are expected to have utility in diverse catalytic applications.

Author: Yujing Zhou (Ph. D.)
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Chapter 2. Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates The direct asymmetric copper hydride (CuH)-catalyzed coupling of [alpha],[beta]-unsaturated carboxylic acids to aryl alkenes is developed to access chiral [alpha]-aryl dialkyl ketones. A variety of substrate substitution patterns, sensitive functional groups and heterocycles are tolerated in this reaction, which significantly expands the range of accessible products compared to existing hydroacylation methodology. Although mechanistic studies are ongoing, we propose that CuH-catalyzed silylation of unsaturated acids occurs to access a uniquely effective acyl electrophilic coupling partner. Chapter 3. CuH-Catalyzed Asymmetric Reduction of [alpha],[beta]-Unsaturated Carboxylic Acids to [beta]-Chiral Aldehydes The copper hydride (CuH)-catalyzed enantioselective reduction of [alpha],[beta]-unsaturated carboxylic acids to saturated aldehydes is reported. This protocol provides a new method to access a variety of [beta]-chiral aldehydes in good yields, with high levels of enantioselectivity and broad functional group tolerance. A reaction pathway involving a ketene intermediate is proposed based on preliminary mechanistic studies and density functional theory calculations. Chapter 4. CuH-Catalyzed Asymmetric Reductive Amidation of [alpha],[beta]-Unsaturated Carboxylic Acids The direct enantioselective copper hydride (CuH)-catalyzed synthesis of [beta]-chiral amides from [alpha],[beta]-unsaturated carboxylic acids and secondary amines under mild reaction conditions is reported. The method utilizes readily accessible carboxylic acids, and tolerates a variety of functional groups at [beta]-position including several heteroarenes. A subsequent iridium-catalyzed reduction to [gamma]-chiral amines can be performed in the same flask without purification of the intermediate amides. Chapter 5. CuH-Catalyzed Asymmetric Hydroamidation of Vinylarenes A CuH-catalyzed enantioselective hydroamidation reaction of vinylarenes has been developed using readily accessible 1,4,2-dioxazol-5-ones as electrophilic amidating reagents. This method provides a straightforward and efficient approach to synthesize chiral amides in good yields with high levels of enantiopurity under mild conditions. Moreover, this transformation tolerates substrates bearing a broad range of functional groups. Chapter 6. Enantioselective Allylation Using Allene, a Petroleum Cracking Byproduct Allene (C3H4) gas is produced and separated on million-metric-ton scale per year during petroleum refining but is rarely employed in organic synthesis. Meanwhile, the addition of an allyl group (C3H5) to ketones is among the most common and prototypical reactions in synthetic chemistry. Herein, we report that the combination of allene gas with inexpensive and environmentally benign hydrosilanes, such as PMHS, can serve as a replacement for stoichiometric quantities of allylmetal reagents, which are required in most enantioselective ketone allylation reactions. This process is catalyzed by copper catalyst and commercially available ligands, operates without specialized equipment or pressurization, and tolerates a broad range of functional groups. Furthermore, the exceptional chemoselectivity of this catalyst system enables industrially relevant C3 hydrocarbon mixtures of allene with methylacetylene and propylene to be applied directly. Based on our strategy, we anticipate the rapid development of methods that leverage this unexploited feedstock as an allyl anion surrogate. Chapter 7. Synthesis of Pyrroles through the CuH-Catalyzed Coupling of Enynes and Nitriles Herein, we describe an efficient method to prepare polysubstituted pyrroles via a copper-hydride (CuH)- catalyzed enyne-nitrile coupling reaction. This protocol accommodates both aromatic and aliphatic substituents and a broad range of functional groups, providing a variety of N-H pyrroles in good yields and with high regioselectivity. We propose that the Cu-based catalyst promotes both the initial reductive coupling and subsequent cyclization steps. Density functional theory (DFT) calculations were performed to help elucidate the reaction mechanism.