Download or read book Synthesis of Chiral Nonracemic C2 symmetric 2 2 bipyridines and Their Evaluation as Ligands in Copper catalyzed Asymmetric Reactions written by Brendan John Whelan and published by . This book was released on 2010 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis concerns the synthesis and evaluation of a series of new chiral nonracemic C2-symmetric 2,2'-bipyridines for use as ligands in catalytic asymmetric reactions. The 2,2'-bipyridines were prepared using a divergent synthetic strategy which employed an asymmetric dihydroxylation reaction of a 2-chloropyrindine as the key step. The resultant chiral diol was condensed with a series of symmetrical ketones to afford chiral acetals which were converted into the requisite ligand series. These ligands were evaluated in the asymmetric copper(I)-catalyzed cyclopropanation reaction of styrene and ethyldiazoacetate. The major Trans-cyclopropane products were isolated in good yield and very high enantioselectivities were achieved (up to 94% ee). These are amongst the highest enantioselectivities reported for chiral 2,2'-bipyridyl ligands. The most effective ligand, an adamantanone derivative, was evaluated in the copper(I)-catalyzed asymmetric allylic oxidation of cyclic alkenes with Tert-butyl peroxybenzoate. High enantioselectivities were also obtained in these reactions (up to 91% ee).

Download or read book Design Synthesis and Evaluation of Chiral Nonracemic Ligands and Catalysts for Asymmetric Synthesis written by Michael P. A. Lyle and published by . This book was released on 2005 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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).

Download or read book C2 and C3 Symmetric Chiral Bis and Tris phosphines in Asymmetric Catalysis written by Zhiming Xu and published by . This book was released on 2017 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapter 1. Effect of linker length on selectivity and cooperative reactivity in platinum-catalyzed asymmetric alkylation of bis(phenylphosphino)alkanes. The selectivity of catalytic asymmetric transformations of bifunctional symmetrical substrates often depends on the linker between the two reactive sites. If the catalyst controls the selectivity of reactions at both sites, the rac product will be formed in high enantiomeric ratio (er) via asymmetric amplification. Substrate control may augment this selectivity (positive cooperativity) or detract from it (negative cooperativity). We investigated the effect of linker length on the selectivity of catalytic asymmetric alkylation of the bis(secondary phosphines) PhHP-(CH2)[subscript n]PHPh (n = 2-6, 1a-e) with benzyl bromide using the base NaOSiMe3 and the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl). The two alkylations of bis(secondary phosphines) 1b-e with longer linker lengths (n = 3-6) showed identical selectivity, within experimental error. This catalyst control resulted in asymmetric amplification of rac-2. In contrast, the selectivity of the first alkylation of ethano-bridged 1a was lower than that in 1b-e (negative cooperativity), but the selectivity of the second alkylation increased due to positive cooperativity. I developed an efficient synthesis of the intermediate PhHP(CH2)2PPh(CH2Ph) (3a), which was required for determination of the selectivity of both steps in Pt-catalyzed alkylation of 1a. Possible mechanistic explanations for the observed dependence of selectivity on linker length are discussed in this chapter. Chapter 2. Selective formation of a C3-symmetric P-stereogenic tris(phosphine) via platinum-catalyzed asymmetric alkylation of a tris(secondary phosphine). C2-symmetric bis(phosphines) are the most common and successful ligands for metal-catalyzed reactions. Considering the great success of C2-symmetric ligands in asymmetric catalysis, C3-symmetric chiral tris(phosphines) were proposed to be useful in octahedral complexes, creating three homotopic sites. However, very little is known about C3-symmetric tris(phosphines) and their applications, mostly because of the lack of synthetic routes. We used Pt-catalyzed asymmetric alkylation to prepare enantiomerically enriched C3-symmetric, P-stereogenic tripodal tris(phosphines) from the tris(secondary phosphine) MeC(CH2PHPh)3 (5 a racemic mixture of C1- and C3-symmetric diastereomers) and a benzl bromide, utilizing the Pt((R,R)-Me-Duphos)(Ph)(Cl) catalyst precursor and a base. Pt-catalyzed alkylation of MeC(CH2PHPh)3 (5) with 2-cyanobenzyl bromide gave a mixture of tris(phosphines) MeC(CH2PPh(CH2Ar))3 (6) enriched in C3-6; oxidation of 6 by sulfur or H2O2 formed phosphine sulfide S-6 and oxide O-6. Hydrogen bonding between O-6 and the chiral amino acid (S)-Fmoc-Trip(BOC)-OH leads to the formation of new diastereomers. By integrating the 31P NMR spectra, I measured the dr and er values. Tris(phosphine) 6 was formed with a disatereomeric ratio (dr - C3/C1) of 2.1(2) and enantiomeric ratios of 54(10) and 3.8(7) for C3-3 and C1-3 respectively, which showed that the selectivity of the triple alkylation was not the same at each site (substrate control). Chapter 3. Screening racemic catalysts provides information on selectivity and mechanism in platinum-mediated asymmetric alkylation of bis- and tris(secondary phosphines). Screening racemic catalysts for transformations of symmetrical bifunctional substrates can provide information on the selectivity of an enantiopure catalyst. This idea was extended to Pt-catalyzed asymmetric alkylation of the bis(secondary phosphines) PhHP(CH2)3PHPh and PhHPCH2CMe2CH2PHPh and the tris(phosphine) MeC(CH2PHPh)3 with benzyl bromides using the catalyst precursors Pt(Me-DuPhos)(Ph)(CI) and Pt(BenzP*)(Ph)(CI). Depending on the catalyst and the substrate, these reactions occured under catalyst control without dissociation of the substrate, or under substrate control with or without substrate dissociation. The resulting structure-selectivity relationships provided mechanistic information. Chapter 4. Synthesis of new chiral bis(phospholane) metal-pincer complexes. Metal pincer complexes have received great attention in recent years as robust catalyst precursors. However, chiral metal pincer complexes for application in asymmetric catalysis are rare. Dialkylphospholane groups have an outstanding track record in asymmetric catalysis (commercial DuPhos and BPE ligands) and their steric properties can be easily controlled by tuning the alkyl substituents on the phospholane ring. These donors have similar steric and electronic properties to the common used bulky dialkylphosphine groups (P(t-Bu)2, P(i-Pr)2, etc.). Optimization of the synthesis of chiral PCP ligands bearing such phospholane groups and investigation of their coordination chemistry are discussed in this chapter.

Download or read book Nickel catalyzed Asymmetric Cross couplings of Secondary Allylic Chlorides and Planar chiral Compounds in Asymmetric Synthesis written by Sunghee Son and published by . This book was released on 2008 with total page 185 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Part I, nickel-catalyzed asymmetric carbon-carbon bond-forming reactions are described. A nickel/Pybox system effectively catalyzes regio- and enantioselective cross-couplings between racemic secondary allylic chlorides and readily available alkylzinc halides. This method is applied to generate two stereo centers in a formal total synthesis of fluvirucinine A1. In Part II, the use of planar-chiral compounds as ligands or catalysts in organic synthesis is described. A C2-symmetric planar-chiral bipyridine is an efficient ligand for copper-catalyzed asymmetric [4+1]-cycloadditions between enones and diazoacetates to form 2,3-dihydrofurans. The highly substituted dihydrofurans are not only obtained in good stereoselectivity but also readily converted to other useful molecules. This method is applied to the first catalytic enantioselective synthesis of a deoxy-C-nucleoside. The synthesis of new C2-symmetric planar-chiral catalysts is described. The diastereoslective functionalization of ferrocene using a chiral directing group enables the formation of a number of amines in enantiopure form. These catalysts are tested as several asymmetric catalysts.

Download or read book Chiral Bisoxazoline Ligands in Catalytic Asymmetric Allylic Oxidation written by Davoud Asgari and published by LAP Lambert Academic Publishing. This book was released on 2009-09 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Synthesis and Catalytic Properties of Chiral C2 Symmetric Ligands for Asymmetric Synthesis written by Kevin B. Albertson and published by . This book was released on 1999 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Applications of C2 symmetric Bis azaferrocenes in Asymmetric Copper catalyzed Reactions written by Michael Man-chu Lo and published by . This book was released on 2002 with total page 423 pages. Available in PDF, EPUB and Kindle. Book excerpt: (Cont.) The Kinugasa reaction, which is the copper-mediated reaction between nitrones and terminal alkynes, is an underexplored synthetic pathway to 2-azetidinones. Using a bis(azaferrocene) as the ligand, we have successfully improved the Kinugasa reaction in the following aspects: (1) the reaction is catalytic in copper; (2) the reaction gives high cis diastereoselectivity; and, (3) the reaction is highly enantioselective with a variety of nitrones and alkynes. Combined with a subsequent epimerization, our enantioselective process represents the first general, catalytic system for the Kinugasa reaction, which provides stereoselective access to all four of the possible isomers.

Download or read book Design and Synthesis of Chiral Ligands and Their Applications in Transition Metal catalyzed Asymmetric Reactions written by Wei Li and published by . This book was released on 2012 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Catalytic Desymmetrization of D2d symmetric Proprochiral Tetrasubstituted Biphenyl Compounds written by Jeremey Tyson Gunderson and published by . This book was released on 2009 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many D2d̳-symmetric 2,2',6,6'-tetrasubstituted biphenyls are readily prepared via net oxidative dimerization of appropriate 1,3-disubstituted benzenes. Conversion of such proprochiral compounds to useful C2-symmetric chiral biphenyls requires formal replacement of two substituents on opposing aryl ring units with alternate groups. This under exploited desymmetrization tactic has been demonstrated for the generation of scalemic biaryls using stoichiometric chiral reagent control, but no reports concerning its realization by a (potentially) more efficient asymmetric catalytic approach have appeared. Accordingly, two different possible strategies for achieving a catalytic enantioselective biaryl synthesis based on D2d to C2 desymmetrization were investigated: (a) enzyme catalyzed hydrolysis of tetraester derivatives of 2,2'-biresorcinol, and (b) transition metal catalyzed substitution from 2,2',6,6'- tetrabromobiphenyl. In pursuit of the first approach, 2,2'- biresorcinol was prepared from 1,3-dimethoxybenzene via nbutyllithium initiated ortho-directed lithiation, followed by iron(III) chloride mediated oxidative coupling of the aryllithium, and then (in a separate step) demethylation of the resulting 2,2',6,6'-tetramethoxybiphenyl with excess boron tribromide. Tetraacetate and tetravalerate esters of 2,2'-biresorcinol were subsequently synthesized and their hydrolysis with the following four distinct esterases was examined: Pseudomonas cepacia lipase (PCL), porcine liver esterase (PLE), Candida antarctica lipase B (CAL B), and bovine pancreas acetone powder (a source of bovine cholesterol esterase). Turn-over was not observed in any case; however, a majority of the enzymes studied successfully hydrolyzed model test substrates such as phenyl valerate, phenyl acetate, and mono- and diesters of resorcinol. For the second approach, a significant new one-pot synthesis of 2,2',6,6'-tetrabromobiphenyl was realized from 1,3- dibromobenzene via lithium diisopropylamide mediated ortholithiation followed again by oxidative coupling with iron(III) chloride (66% yield). Palladium catalyzed cross-coupling reactions (comprising Kumada, Negishi, and Sonogashira subtypes) were evaluated from 2,2',6,6'-tetrabromobiphenyl and 1,3- dibromobenzene. The latter model substrate revealed that a degree of control was possible, in that monosubstitution could be readily achieved; however, reactions from the pivotal D2d-symmetric 2,2',6,6'-tetrasubstituted substrate typically gave either no reaction (reflecting the high steric hindrance of the starting material) or else complex intractable mixtures of various polysubstituted products.

Download or read book Part I the Synthesis of the Advanced Intermediates for Bengamides written by Wei Fu and published by . This book was released on 2001 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Copper II catalyzed Asymmetric Method Development of Silyl containing Spirocarbamate and Spiropyrrolidine Oxindoles and Phosphoric Acid catalyzed Asymmetric Synthesis of Spirotetrahydro beta carbolines written by Benjamin Henry Shupe and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Herein I describe my research that was performed in the Franz Group while working toward the completion of a PhD at the University of California, Davis. My research has focused on developing new synthetic methods to access enantioenriched nitrogen-containing spirooxindoles. Chapter 1 contains an overview of the previous literature that provides a background for my research. This chapter includes an overview of biologically active spirooxindoles, Lewis acid-catalyzed allylsilane annulations, the Tamao-Fleming reaction, stereoselective methodology to access nitrogen containing spirooxindoles, enantioselective copper-catalyzed reactions and the use of Sodium Tetrakis[(3,5-trifluoromethyl)phenyl]borate (NaBArF) as a loosely coordinating counter ion to increase the Lewis acidity of metal complexes. Chapter 2 presents research resulting from collaborative efforts with Joseph Badillo and Abel Silva to develop a chiral binaphthyl phosphoric acid-catalyzed Pictet Spengler reaction between isatin and tryptamine to access enantioenriched spiroindolones with up to 99% yield and 98:2 er. We discovered that two different binaphthyl phosphoric acids with opposite axial chirality ((S)-2,4,6-triisopropylphenyl and (R)-9-anthracenyl) afford the same enantiomer of product. This chapter uses a stereochemical model to rationalize this phenomena. Ongoing research with this methodology will extend the scope of the reaction to isotryptamine scaffolds in order to access additional spirocycles. Chapter 3 discusses the synthesis of N-aryl and N-Boc iminooxindoles and the Lewis acid-catalyzed addition of pi-nucleophiles to these electrophiles. Initial studies showed that the addition of methallyltrimethylsilane to N-Boc iminooxindole was significantly more reactive than N-aryl iminooxindoles to access 3-amino-3-allyloxindoles. The Lewis acid-catalyzed addition of trimethylallylsilane to N-Boc iminooxindoles led to the discovery of novel silyl-containing spirocarbamate oxindoles via a [beta]-silyl trapping pathway (up to 91% yield and up to 80:20 dr). This reaction can be catalyzed by metal chloride complexes with NaBArF). Additional work in collaboration with Brittany Armstrong led to the development of the enantioselective synthesis of spirocarbamates (75% conv., up to 99:1 er and >95:5 dr) using CuCl2/BArF catalyst system with a phenyl-bisoxazoline ligand. We discovered that accessing these compounds with high stereoselectivity required increasing the quantity of 4Å molecular sieves. Spirocarbamate oxindoles were also screened in a molecular docking study with Mouse double minute 2 homolog (MDM2), which led to the design and synthesis of a series of compounds that are currently being evaluated for their biological activity. Chapter 4 continues the work presented in Chapter 3 by investigating the addition of enantioenriched crotylsilanes to N-Boc iminooxindoles. It was discovered that both CuCl2 and Montmorillonite K10 can catalyze crotylsilane addition to N-Boc iminooxindoles in the presence of NaBArF to provide enantioenriched spiropyrrolidine as a single isomer by a [3+2] annulation pathway. Spiropyrrolidine oxindoles were further functionalized to add additional hydrogen bond donating groups to be investigated as potential organocatalysts. I utilized these derivatized-spiropyrrolidine oxindoles to attempt forming carbon-carbon bonds but this scaffold has been unsuccessful at catalyzing any reaction. Chapter 5 presents investigation for the transformation of a carbon-silicon bond to a carbon-nitrogen bond in order to access chiral amines from silyl groups. The strategy that I investigated for this transformation was designed based on mechanistic analysis that parallels the Tamao-Fleming reaction utilizing amphiphilic amine reagents. While this work is ongoing, preliminary results show that the nitrogen-silicon bond is labile under these reaction conditions. Reactions were also investigated for the conversion of silicon-hydrogen bonds to silicon-carbon bonds.

Download or read book Synthesis of Novel Chiral Ligands for Catalytic Asymmetric Reactions written by and published by . This book was released on 2006 with total page 640 pages. Available in PDF, EPUB and Kindle. Book excerpt: A series of N-salicyl-beta-aminoalcohol ligands had been synthesized by three component Mannich type reaction followed by ring opening of oxazolidine derivatives with hydroxylamine hydrochloride. The reactions provided a series of chiral N-salicyl-beta-aminoalcohol ligands in high yields (84-92%) without any racemization. These synthesized compounds were evaluated as ligands for catalytic asymmetric Strecker reactions. N-Benzhydrylaldimines derived from aromatic and aliphatic aldehydes reacted withTMSCN in the presence of 10 mol% of Ti-ligand complex to give the alpha-aminonitriles in excellent yields and in up to >98% ee. In addition, the catalyst loading was successfully reduced to 2.5 mol% which is very effective and extremely simple for large scale synthesis. The presence of 2-propanol is essential to ensure good conversion and reaction rate. The absolute configuration of all products derived from the (S)-ligand was confirmed to be S. Racemization of alpha-aminophenylacetonitriles is catalyzed by weak acids such as silica (SiO[subscript 2]) or even methanol. However, the racemization can be suppressed by addition of either a base such as triethylamine (NEt[subscript 3]) or strong acid such as hydrochloric acid (HCI). Importantly, optically active alpha-aminoacetonitriles can be easily converted to arylglycines by complete hydrolysis with minimal racemization. (>80% and >90% ee). A transition state model to explain the enantioselectivity of the reaction is proposed. The present chiral catalysts showed their catalytic ability in not only asymmetric strecker reaction but also asymmetric Pudovic reaction as well as asymmetric Michael addition.

Download or read book Chiral Diazaligands for Asymmetric Synthesis written by Marc Lemaire and published by Springer. This book was released on 2010-02-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The use of phosphine derivatives has historically induced the tremendous development of catalysis (both non-asymmetric and asymmetric). Although the chemistry of amines is more documented, the use of nitrogen-containing ligands only appeared recently. Nevertheless, during the last ten years, the results describing chiral diamine preparations and their uses in asymmetric catalysis and synthesis are increasing faster than their phosphorus counterparts. The reader will find in this volume the most recent methods for the synthesis of chiral diamines as well as their applications in asymmetric catalysis of CC bond formation. Particular attention will be given to spartein and derivatives of such diamines. Recently, the particular properties and the chemistry of amines allowed to obtain catalysts easy to separate and recycle and new types of ligands such as diaminocarbenes, ureas and thioureas. Finally, the complexing properties of some diamines allowed the formation of complexes with chirality "at the metal " which is of major theoretical interest and presents numerous potential applications.

Download or read book Design and Synthesis of Chiral Ligands for Copper Catalysed Asymmetric Synthesis written by Chris Mark Topping and published by . This book was released on 1998 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthesis of Transition Metal N heterocyclic Carbene Complexes and Applications in Catalysis written by Michael Holtz-Mulholland and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Asymmetric Synthesis of C2 symmetric Bimorpholines and Their Application as Chiral Ligands in the Transfer Hydrogenation of Aromatic Ketones written by Kadri Kriis and published by . This book was released on 2003 with total page 85 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Asymmetric Synthesis of Chiral Bipyridine based Ligands for Use in Asymmetric Catalysis written by David A. Regan and published by . This book was released on 2008 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: