Development of Selective and Catalytic Arylation Methods for Sp2 and Sp3 C-H Bonds in Complex Organic Molecules PDF Download
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Author: Bengü Sezen
Publisher:
ISBN:
Category :
Languages : en
Pages : 926
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Author: Bengü Sezen
Publisher:
ISBN:
Category :
Languages : en
Pages : 926
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Author: Jin Xie
Publisher: Springer
ISBN: 3662494965
Category : Science
Languages : en
Pages : 91
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Book Description
This book highlights major achievements made in the last five years concerning sustainable C(sp3)-H bond functionalization and offers a promising and emerging tool-kit for organic synthesis. The book is divided into three chapters demonstrating key advances in C(sp3)-H bond functionalization. Chapter 1 reviews transition-metal-catalyzed C(sp3)-H bond functionalization using different directing groups, while Chapter 2 addresses the new methods of transition-metal-catalyzed and metal-free C(sp3)-H bond functionalization without directing groups, in addition to briefly highlighting redox-neutral C(sp3)-H bond functionalization. In closing, Chapter 3 examines visible-light photoredox catalysis, an emerging and highly sustainable C(sp3)-H bond functionalization strategy. The book offers an intriguing and useful reference guide for a broad readership working and/or interested in the fields of organic, organometallic, and green chemistry.
Author: Marc Taillefer
Publisher: Springer
ISBN: 3642405460
Category : Science
Languages : en
Pages : 233
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Palladium-Catalyzed sp2C–N Bond Forming Reactions: Recent Developments and Applications. Metal-catalyzed C(sp2)-N bond formation.- Recent Developments in Recyclable Copper Catalyst Systems for C−N Bond Forming Cross-Coupling Reactions Using Aryl Halides and Arylboronic Acids. Assembly of N-containing heterocycles via Pd and Cu-catalyzed C-N bond formation reactions. Copper-Catalyzed C(aryl)-N Bond Formation.
Author: Sophie Rousseaux
Publisher:
ISBN:
Category : Arylation
Languages : en
Pages :
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Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for "palladium-catalyzed cross couplings in organic synthesis", and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.
Author: Su Yong Go
Publisher: Springer Nature
ISBN: 9819989949
Category :
Languages : en
Pages : 185
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Author: Dung Le Golden
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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C-H functionalization reactions are among the most useful and synthetically applicable approaches to access structurally complex organic molecules, including pharmaceuticals and agrochemicals. While methods promoting functionalization and cross coupling of C(sp2)-H bonds have found broad applications, a growing number of reactions have focused on functionalizing C(sp3)-H bonds to incorporate three-dimensionality and expand the chemical space. Radical C-H functionalization reactions initiated by hydrogen-atom transfer and proceeding via radical intermediates introduce strategic opportunities to functionalize C(sp3)-H bonds. In addition to the commonly seen radical-chain and biomimetic radical-rebound mechanisms, radical-relay reactions provide the basis for versatile C-H cross-coupling methods with diverse partners. This thesis discloses our recent development of radical-relay and radical-chain (hetero)benzylic C(sp3)-H functionalization and their synthetic utility in accessing three-dimensional chemical space. Chapter 2 discussed our recent development of a copper-catalyzed benzylic C-H esterification reaction enabled by a "photochemical redox buffering" strategy using tert-butyl peroxybenzoate as the oxidant. Copper(I)/peroxide (or Kharasch-Sosnovsky-typed) reactions historically require excess of C-H substrates and forcing reaction conditions, leading to poor synthetic applicability. Copper(I) catalysts interact rapidly with peroxide-based oxidants, resulting in a pool of inactive copper(II) species, which are incapable of activating oxidants. Our recent efforts in copper/NFSI-catalyzed radical relay functionalization and cross coupling of benzylic C(sp3)-H bonds revealed a ''redox buffering'' strategy enabling the controlled regeneration of copper(I). For copper/NFSI systems, we have identified that certain nucleophiles (i.e. cyanides and arylboronic acids) can promote the reduction of CuII to CuI, whereas nucleophiles like alcohols and azoles requires additional chemical reductants (i.e. dialkylphosphites) to promote ''redox buffering.'' To address the issues with copper/peroxide system, we have developed a 2,2'-biquinoline/copper-catalyzed reaction under photoirradiation to promote benzylic esterification using limiting C-H substrates. Mechanistic interrogation revealed that light promoted carboxylate-to-copper charge transfer enables the regeneration of copper(I) catalyst, similar to the aforementioned ''redox buffering'' approach. Chapter 3 disclosed our recently developed chlorination/ diversification sequence of heterobenzylic C(sp3)-H bonds in 3-alkylpyridines via radical chain. Alkylpyridines are important and prevalent classes of substrates in medicinal chemistry with the (hetero)benzylic C-H bonds having similar bond dissociation energies to alkylarenes. However, copper/NFSI-catalyzed reactions are unsuccessful in accessing these C-H bonds due to the deleterious reactivity between the pyridyl nitrogen atom and NFSI. While chlorination of 2- and 4-alkylpyridines can be achieved using a polar activation strategy, heterobenzylic C-H bonds of 3-alkylpyridines are more amenable to radical-based chlorination. Experimental and density functional theory identified an N-chlorosulfonamide reagent for selective chlorination at the heterobenzylic C-H site. Subsequent diversification of heterobenzyl chlorides with a broad scope of nucleophiles enabled facile access to complex cross-coupled products. This method should find broad application for building block modification and library synthesis in drug discovery. Chapter 4 detailed our investigation in copper/NFSI-catalyzed fluorination of benzylic C-H bonds followed by diversification with various nucleophiles. Redox buffering promoted by addition of boron-based reductants enabled successful fluorination with limiting C-H substrates. Benzyl fluorides were subsequently subjected to nucleophilic displacement catalyzed by Lewis acidic additives, affording C-O, C-N, and C-C bond formations. This method inspired later developments of other radical halogenation/diversification methods to functionalize (hetero)benzylic C-H bonds. Chapter 5 disclosed our development of a copper/NFSI-catalyzed cross couplings of benzylic C(sp3)-H bonds and azoles enabled by redox buffering. In addition to excellent benzylic selectivity, N-site selectivity of azoles was achieved by modifying the reaction conditions. Diverse N-H heterocycles were compatible coupling partners, including pyrazoles, purines, and sultams. The ability to access both regioisomers of azoles via a cross coupling array validated the synthetic utility of this method in pharmaceutical research. Collectively, radical (hetero)benzylic C(sp3)-H functionalization contributed to a growing number of methods in accessing more three-dimensional chemical space. Mechanistic insights from these reactions will enable further development of more synthetically useful methodologies. Additionally, the synthetic applications should allow chemists to assemble compound libraries with higher complexity and expand the accessible chemical space.
Author: Su Yong Go
Publisher: Springer
ISBN: 9789819989935
Category : Science
Languages : en
Pages : 0
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Book Description
This book addresses novel C(sp3)-C(sp2) and C(sp3)-heteroatom bond-forming reactions. Two strategies are given in the book using photoredox or electrochemical methods. The first strategy describes that the hydroalkylation of alkynes via photoredox-mediated Ni/Ir dual catalysis produces trisubstituted alkenes as versatile synthetic building blocks for the synthesis of pharmaceutical agents and natural products. High regioselectivity and E/Z-selectivity were achieved by introducing silyl groups that can provide steric and electronic effects to these selectivities with extensive opportunities for post-functionalization. The second strategy enables the development of C(sp3)-heteroatom bond-forming reactions through the electrochemical activation of C(sp3)-B bonds. The bonding of heteroatoms to carbon atoms has been an enduring subject of investigation for organic chemists. The function of most molecules is mainly determined by heteroatoms attached to the carbon atom, althoughthe backbone structure of organic compounds comprises carbon fragments.
Author: Derek Schipper
Publisher:
ISBN:
Category : Aromatic compounds
Languages : en
Pages :
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Part 1: Transition-metal-catalyzed direct transformations of aromatic C-H bonds are emerging as valuable tools in organic synthesis. These reactions are attractive because of they allow for inherently efficient construction of organic building blocks by minimizing the pre-activation of substrates. Of these processes, direct arylation has recently received much attention due to the importance of the biaryl core in medicinal and materials chemistry. Also, alkyne hydroarylation has garnered interest because it allows for the atom-economical synthesis of functionalized alkenes directly from simple arenes and alkynes. Described in this thesis are number of advancements in these areas. First, palladium catalyzed direct arylation of azine N-oxides using synthetically important aryl triflates is described. Interesting reactivity of aryl triflates compared to aryl bromides was uncovered and exploited in the synthesis of a compound that exhibits antimalarial and antimicrobial activity. Also reported is the efficient, direct arylation enabled (formal) synthesis of six thiophene based organic electronic materials in high yields using simple starting materials. Additionally, the site-selective direct arylation of both sp2 and sp3 sites on azine N-oxide substrates is described. The arylation reactions are carried out in either a divergent manner or a sequential manner and is applied to the synthesis of the natural products, Papaverine and Crykonisine. Mechanistic investigations point towards the intimate involvement of the base in the mechanism of these reactions. Next, the rhodium(III)-catalyzed hydroarylation of internal alkynes is described. Good yields are obtained for a variety of alkynes and arenes with excellent regioselectivity for unsymmetrically substituted alkynes. Mechanistic investigations suggest that this reaction proceeds through arene metalation with the cationic rhodium catalyst, which enables challenging intermolecular reactivity. Part 2: Access to single enantiomer compounds is a fundamental goal in organic chemistry and despite remarkable advances in enantioselective synthesis, their preparation remains a challenge. Kinetic resolution of racemic products is an important method to access enantioenriched compounds, especially when alternative methods are scarce. Described in this thesis is the resolution of tertiary and secondary alcohols, which arise from ketone and aldehyde aldol additions. The method is technically simple, easily scalable, and provides tertiary and secondary alcohols in high enantiomeric ratios. A rationale for the unique reactivity/selectivity associated with (1S,2R)-N-methylephedrine in the resolution is proposed. Organocatalysis is a rapidly developing, powerful field for the construction of enantioenriched organic molecules. Described here is a complimentary class of organocatalysis using simple aldehydes as temporary tethers to perform challenging formally intermolecular reactions at room temperature. This strategy allows for the enantioselective, intermolecular cope-type hydroamination of allylic amines with hydroxyl amines. Also, interesting catalytic reactivity for dichloromethane is revealed.
Author: Liqin Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 184
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During this thesis, we were interested in the sp2 and sp3 C-H bond activation catalyzed by palladium catalysts for the preparation of (hetero)aryl-aryls and biaryls. This method is considered as cost effective and environmentally attractive compared to the classical couplings such as Suzuki, Heck, or Negishi. First we described the palladium-catalyzed direct C2-arylation of benzothiophene in the absence of phosphine ligand with high selectivity. We also demonstrated that it is possible to active both C2 and C5 C-H bonds for access to 2,5-diarylated compounds in one step, and also to non-symmetrically substituted 2,5-diarylpyrroles via sequential C2 arylation followed by C5 arylation. We also studied the reactivity of polychlorobenzenes via palladium-catalyzed C-H activation. We finally examined the palladium-catalysed selective sp2 and sp3 C-H bond activation of guaiazulene. The selectivity depends on the solvent and base: sp2 C2-arylation (KOAc in ethylbenzene), sp2 C3-arylation (KOAc in DMAc) and sp3 C4-Me arylation (CsOAc/K2CO3 in DMAc). Through this method, a challenging sp3 C-H bond was activated.
Author: Nicholas Armada
Publisher:
ISBN:
Category :
Languages : en
Pages : 51
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Book Description
Convenient catalytic methodologies that can facilitate the formation of C-C bonds are undoubtedly of great interest in synthetic organic chemistry. Recent reports in literature have showcased hybrid catalytic methods that couple Ni-redox catalysis and photocatalysis to enable C-H activation of tetrahydrofuran (THF) and subsequent cross-coupling with aryl halides in appreciable yields and under relatively mild reaction conditions.1-2 However, these studies used expensive, heavy metal-containing photocatalysts and both report difficulty obtaining low-specificity across their scopes of aryl-halides. The following report will shed light on a class of photo-excitable small organic molecules that – in conjunction with a catalytic Ni-redox cycle – can be used to catalyze C-C cross-coupling reactions between THF and aryl chlorides, bromides, and iodides with yields comparable to the aforementioned reports. After screening several organic molecules with suspected photoactivity and optimization of the reaction conditions, several benzophenone derivatives were found to catalyze the cross-coupling reaction in yields up to 97%. Mechanistic investigations suggest that this reaction proceeds through a tandem catalytic pathway that involves a photocatalyzed hydrogen atom transfer/proton-coupled electron transfer (HAT/PCET) process and a Ni-mediated oxidative addition/reductive elimination cross-coupling process.
