Auswahl der wissenschaftlichen Literatur zum Thema „C-N bond forming“

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.<br>Includes bibliographical references.<br>New methods for the palladium-catalyzed amination of aryl halides are described. Key to these is the development of new catalysts and reaction conditions for these transformations. Initially, P(o-tol)3 ligated palladium catalysts were investigated but gave way to systems that used chelating phosphine ligands which substantially expanded the scope of the catalytic amination methodology. Palladium catalyst systems based on BINAP ((2,2'-diphenylphosphino)-1, 1 '-binaphthyl) allowed for the transformation of a much wider range of amines and aryl halide substrates, as well as aryl triflates. Of practical significance was that the use of cesium carbonate as a base at 100 °C substantially increased the functional group tolerance of the method. Palladium catalysts supported by novel, bulky, electron-rich phosphine ligands are exceptionally effective in the C-N, C-0, and C-C coupling procedures. For some substrate combinations, these palladium catalysts are effective for the room-temperature catalytic amination of aryl chlorides. These palladium catalysts are also highly effective for Suzuki coupling reactions of aryl bromides and chlorides at room temperature. Suzuki coupling reactions of aryl bromides and aryl chlorides are effective at very low catalyst loadings (0.000001-0.005 mol % Pd for ArBr, 0.02-0.05 mol % for ArCI) at 100 °C, and reactions of hindered aryl halides or boronic acids are effected at moderate catalyst loadings (1 mol % Pd). The high reactivity of these catalysts towards aryl chlorides challenges the conventional dogma that chloride substrates cannot be transformed under mild conditions with palladium catalysts, and significantly expands the pool of substrates available for cross-coupling chemistry.<br>by John P. Wolfe.<br>Ph.D.

In questo lavoro di tesi è riportato l'impiego di alcuni strumenti della Green Chemistry (come la CO2, i liquidi ionici e i dialchilcarbonati) per la messa a punto di metodologie innovative a ridotto impatto ambientale per la formazione di legami C-C, C-N e C-O. Sono state investigate le seguenti reazioni: la metatesi dell'1-ottene catalizzata da sistemi a base di Re ossido, in presenza di CO2 densa come solvente; l'addizione di Michael di nitroalcani e beta-dichetoni a chetoni alfa,beta-insaturi catalizzata da liquidi ionici; la selettiva mono-idrossialchilazione di aniline con la glicerina carbonato, catalizzata da faujasiti; la selettiva bis-N-alchilazione di aniline da parte del dimetilcarbonato prodotto in situ via transesterificazione di carbonati ciclici con metanolo, catalizzata da faujasiti; l'alchilazione di aniline con carbonati ciclici catalizzata da liquidi ionici; la reazione di decarbossilazione dei dialchilcarbonati in presenza di diversi catalizzatori eterogenei; la reazione tra fenolo e glicerina carbonato catalizzata da faujasiti.<br>In this PhD thesis it is presented the use of some Green Chemistry Tools (supercritical carbon dioxide, ionic liquids and dialkylcarbonates) for the set up of new green methodologies for C-C, C-N and C-O bond forming reactions. The following reactions have been investigated: the self-metathesis of 1-octene catalysed by supported Re oxide systems, carried out using dense CO2 as solvent; the Michael addition of nitroalkanes and beta-diketones to alpha,beta-unsaturated ketons catalyzed by task specific phosphonium based ionic liquids; the selective mono-hydroxyalkylation of anilines with glycerol carbonate catalysed by alkali metal exchanged faujasites; the selective bis-N-methylation of anilines carried by dimethylcarbonate prepared in situ via the transesterification of alkylene carbonate with methanol catalysed by alkali metal exchanged faujasites; the alkylation of primary aromatic amines with alkylene carbonates, catalysed by phosphonium based ionic liquids; the decarboxylation reaction of dialkyl carbonates catalyzed by different heterogeneous systems; the reaction of glycerol carbonate with phenol, in the presence of faujasites as catalysts.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006.<br>Vita.<br>Includes bibliographical references.<br>Chapter 1. The first detailed study of the palladium-catalyzed amination of aryl nonaflates is reported. Use of bulky electron-rich monophosphinobiaryl ligands or BINAP allow for the catalytic amination of electron-rich and -neutral aryl nonaflates with both primary and secondary amines. Using XantPhos, the catalytic amination of a variety of functionalized aryl nonaflates resulted in excellent yields of anilines; even 2-carboxymethyl aryl nonaflate is effectively coupled with a primary alkyl amine. Moderate yields were obtained when coupling halo-aryl nonaflates with a variety of amines, where in most cases the aryl nonaflate reacted in preference to the aryl halide. Overall, aryl nonaflates are an effective alternative to aryl triflates in palladium-catalyzed C-N bond-forming processes due to their increased stability under the reaction conditions. Chapter 2. A catalyst comprised of a Pd precatalyst and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl is explored in C-N bond-forming processes. This catalyst displayed unprecedented stability and scope allowing, for the first time, the coupling of substrates bearing a carboxylic acid or a primary amide.<br>(cont.) Also, the more bulky catalyst system Pd/2-tert-butylphosphino-2',4',6'-triisopropylbiphenyl was found to be effective for the Narylation of 2-aminoheterocycles and weakly basic HN-heterocycles: pyrazole and indazole. The chemoselectivity for amination using these catalysts was explored where the rough order of reactivity for amines is: aryl amines >> primary and secondary alkyl amines > 2-aminoheterocycles > primary amides - HN-heterocycles. Chapter 3. The palladium-catalyzed Suzuki-Miyaura coupling of haloaminoheterocycles and functionalized organoboronic acids using a highly active and stable monophosphinobiaryl ligand, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, efficiently produced aminoheterocyclic biaryl derivatives. This same catalyst was effective in coupling 2-haloaminoaryl compounds with 2-formyl or 2-acetylphenyl boronic acids, providing the fused heterocyclic compounds phenanthridine, benzo[c][1 ,8]naphthridine and benzo[c][1,5]naphthridine in excellent yields. Chapter 4. A water-soluble monophosphinobiaryl ligand, sodium -dicyclohexylphosphino-2',6'-dimethoxybiphenyl-3'-sulfonate, was synthesized by electrophilic sulfonation of the lower-aromatic ring of 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl.<br>(cont.) This ligand was utilized in the palladium-catalyzed Suzuki-Miyaura reaction of water-soluble aryl/heteroaryl halides and organoboronic acids. The catalyst displays unprecedented reactivity and stability for Suzuki-Miyaura reactions conducted in water. Chapter 5. A water-soluble monophosphinobiaryl ligand, sodium 2'-(dicyclohexyl-osphanyl)-2,6-diisopropyl-biphenyl-4-sulfonate, was synthesized by a proposed electrophilic ipso-substitution/reverse Friedel-Crafts alkylation of the lower-aromatic ring on 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl. This ligand was utilized in the palladium-catalyzed Heck alkynylation (copper-free Sonogashira coupling) of hydrophobic and hydrophilic aryl halides and terminal alkynes conducted in an aqueous acetonitrile solvent system. For the first time, an electron-deficient terminal alkyne, propiolic acid, was successfully coupled with aryl bromides. We also demonstrated that this catalyst is useful in the reaction of benzyl chlorides and terminal alkynes to provide benzyl alkynes in good yields. We show that by using an excess amount of base (> 1.0 equiv.) and higher reaction temperatures ( 80 °C), base-catalyzed isomerization to the corresponding aryl allenes can be achieved in a one-pot process.<br>by Kevin W. Anderson.<br>Ph.D.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.<br>Cataloged from PDF version of thesis. Volume 1 (page 1 to page 510) ; Volume 2 (page 511 to 881). Duplicated pages for pages 195 to 240 are bound after page 881.<br>Includes bibliographical references.<br>Part I. Palladium-Catalyzed Carbon-Carbon Bond Forming Cross-Couplings Chapter 1. Ligand-Controlled Palladium-Catalyzed Regiodivergent Suzuki-Miyaura Cross-Coupling of Allylboronates and Aryl Halides An orthogonal set of catalyst systems based on the use of two biarylphosphine ligands has been developed for the Suzuki-Miyaura coupling of 3,3-disubstituted and 3-monosubstituted allylboronates with (hetero)aryl halides. These methods allow for the regiodivergent preparation of either the ct- or the [gamma]-isomeric coupling product with high levels of site selectivity using a common allylboron building block. Preliminary investigations have demonstrated the feasibility of an enantioselective variant for the [gamma]-selective cross-coupling using chiral monodentate biarylphosphine ligands. Chapter 2. Palladium-Catalyzed Completely Linear-Selective Negishi Coupling of 3,3-Disubstituted Organozinc Reagents with Aryl and Vinyl Electrophiles A palladium-catalyzed general and completely linear-selective Negishi coupling of 3,3- disubstituted allyl organozinc reagents with (hetero)aryl and vinyl electrophiles has been developed. This method provided an effective means for accessing highly functionalized aromatic and heteroaromatic compounds bearing prenyl-type side chains. The utility of the current protocol was further illustrated in the concise synthesis of the anti-HIV natural product siamenol. Chapter 3. Palladium-Catalyzed Highly Selective Negishi Cross-Coupling of Secondary Alkylzinc Reagents with Aryl and Heteroaryl Halides The palladium-catalyzed Negishi cross-coupling of secondary alkylzinc reagents and heteroaryl halides with high levels of regioisomeric retention has been described. The development of a series of biarylphosphine ligands has led to the identification of an improved catalyst for the coupling of electron-deficient heterocyclic substrates. Preparation and characterization of oxidative addition complex (L)Pd(Ar)(Br) provided insight into the unique reactivity of palladium catalysts based on CPhos-type biarylphosphine ligands in facilitating challenging reductive elimination processes. Chapter 4. Mechanistic Studies on the Aryl-Trifluoromethyl Reductive Elimination from Pd(II) Complexes Based on Biarylphosphine Ligands A series of monoligated (L)Pd(Ar)(CF₃) (L = dialkyl biarylphosphine) have been prepared and studied in an effort to shed light on the mechanism of the aryl-trifluoromethyl reductive elimination from these systems. Combined experimental and computational investigations revealed unique reactivity and binding modes of (L)Pd(Ar)(CF₃) complexes derived from BrettPhos-type biarylphosphines. In contrast to a variety of C-C and C-heteroatom bond forming reductive eliminations, kinetic measurements showed this Ar-CF₃ reductive elimination is largely insensitive to the electronic nature of the to-be-eliminated aryl substituent. Furthermore, the aryl group serves as the nucleophilic coupling partner in this reductive elimination process. The structure-reactivity relationship of biarylphosphine ligands was also investigated, uncovering distinct roles of the ipso-arene and alkoxy interactions in affecting these reductive elimination reactions. Part II. Copper-Catalyzed Carbon-Carbon and Carbon-Nitrogen Bond Formation via Olefin Functionalization Chapter 5. Copper-Catalyzed ortho C-H Cyanation of Vinylarenes A copper-catalyzed regioselective ortho C-H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper-catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction. This mechanism has been validated through density functional theory calculations. Computational studies revealed that the high level of ortho selectivity in the electrophilic cyanation event originates from a unique six-membered transition state that minimizes unfavorable steric repulsions. Chapter 6. Regio- and Stereospecific 1,3-Allyl Group Transfer Triggered by a Copper-Catalyzed Borylation/ortho-Cyanation Cascade A copper-catalyzed borylation/cyanation/allyl group transfer cascade has been developed. This process features an unconventional copper-catalyzed electrophilic dearomatization followed by the subsequent regio- and stereospecific 1,3-transposition of the allyl fragment enabled by the aromatization-driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with high levels of stereochemical purity. Chapter 7. Copper-Catalyzed Asymmetric Hydroamination of Unactivated Internal Olefins: an Effective Means to Access Highly Enantioenriched Aliphatic Amines Catalytic assembly of enantiopure aliphatic amines from abundant and readily available precursors has long been recognized as a paramount challenge in synthetic chemistry. We describe a mild and general copper-catalyzed hydroamination that effectively converts unactivated internal olefins-an important yet unexploited class of abundant feedstock chemicals-into highly enantioenriched [alpha]-branched amines (>/= 96% ee) featuring two minimally differentiated aliphatic substituents. This method provides a powerful means to access a broad range of advanced, highly functionalized enantioenriched amines of interest in pharmaceutical research and other areas.<br>by Yang Yang.<br>Ph. D. in Organic Chemistry