Request pdf coppermediated ch activationcs crosscoupling of heterocycles with thiols we report the synthesis of a series of aryl or alkylsubstituted 2mercaptobenzothiazoles by direct. The coppermediated regioselective ch activation and co bond formation of naphthylamides with arylboronic acids has been developed using water as an oxygen source. Coppermediated amidation of heterocyclic and aromatic ch. H activation and by using a hypervalent iodine reagents as trifluoromethylene. Carbonhydrogen bond functionalization ch functionalization is a type of reaction in which a carbonhydrogen bond is cleaved and replaced with a carbonx bond where x is usually carbon, oxygen, or nitrogen. Mediated cyanation of aryl halides by activation of. The most popular ch activation reactions are catalyzed by transition metals. We also show that the approach can be extended to thiazole, benzimidazole, and indole substrates. Herein, the coppercatalyzed and picolinamideassisted remote pch sulfonylation of 1naphthylamides was realized. A coppermediated aerobic coupling reaction enables direct amidation of heterocycles or aromatics having weakly acidic ch bonds with a variety of nitrogen nucleophiles. In addition, it covers radicalmediated ch activation, fluorination via ch. O bond is subsequently formed at the original position of the amide group in a one.
The kinetic isotope study suggests that ch bond activation is the ratedetermining step. Here, we report a coppercatalyzed radical relay pathway for enantioselective conversion of benzylic ch bonds into benzylic nitriles. Coppermediated direct csp3h and csp2h acetoxylation. The mal and cheng group reported a copper salt mediated methylthiolation of aryl halides using dmso. Copper dioxygen c h bond activation studies have intensified in recent years with interest stemming from pmmo mediated oxidations and reactivity catalyzed by other copper oxygenases. While there is a considerable literature of copper ion promoted organic oxidations 5, 6, we here emphasize more recent efforts to describe copper dioxygen or. Pdf pdcatalyzed ch bond functionalization on the indole and pyrrole nucleus. Synthesis of 2arylindoles by rhodiumcatalyzedcopper.
Ch bond activation in organic synthesis crc press book. Development of novel ch bond transformations and their application to the synthesis of organic functional molecules synlett 2018, 29, 20932107 doi. A greener approach by weerasiri arachchige kushan chandana weerasiri a dissertation submitted to the graduate faculty of auburn university in partial fulfillment of the requirements for the degree of doctor of philosophy auburn, alabama august 2, 2014. Coppercatalyzed direct alkylation of perfluoroarenes. The use of metalbased hydrogen abstracting intermediates enables the control of regioselectivity of ch activation beyond the innate reactivity of ch bonds. This book dedicates a chapter to each of the following catalysts. The h2o18 labelling experiment reveals the incorporat 20th anniversary of the crsi. H bond can be activated and coupled with dicarbonyl or 2. We found that the boronmediated directed ch hydroxylation of nphenylpyrrolidinone 29a in the presence of bbr 3 could provide the desired product 29c with a 79% yield.
Remote ch activation using noxide as a stepping stone h hwang, j kim, j jeong, s chang journal of the american chemical society 6 30, 1077010776, 2014. The cover feature shows a reaction plate where many reactions employing mixture of reagents successfully enable the identification of the most suitable reaction conditions highlighted in green in a straightforward manner. A novel coppermediated chelationassisted ortho ch nitration of heteroarenes has been developed for the first time, which used dioxygen as terminal oxidant and 1,2,3tcp as solvent, leading to the synthesis of nitroaromatics with excellent regioselectivity and in good yields. H bonds and their application in cross coupling chemistry has received a wider interest in recent years. The emphasis is oxygen activation with cu complexes, especially those containing a single copper ion site, and ch bond oxidative cleavage in the context of reactions mediated by monooxygenases 1, 2, cf. Aryl halides with various substituents on the aromatic ring afforded the corresponding aryl nitriles in 3297 % yields 25 examples. Coppermediated intermolecular direct biaryl coupling. Operational stability was enhanced via the introduction. Transition metalcatalyzed modifications of the activated heterocyclic bases of nucleosides as well as dna or rna fragments employing traditional crosscoupling methods have been wellestablished in nucleic acid chemistry. First, the ch activation is mediated by firstrow metal complexes such as metaloxo intermediates instead of organic or inorganic radicals commonly seen in radical reactions. Coppermediated selective ch activation and crossdehydrogenative cn coupling of 2. Request pdf coppermediated ch activation of 1,3,4oxadiazoles with 1,1dibromo1alkenes using peg400 as a solvent medium.
Hydroxide ions on or near the copper surface lower the co 2 reduction and carbon monoxide coco coupling activation energy barriers. Bushuyev,1 chengqin zou,1,4 rafael quinterobermudez, 1yuanjie pang,2 david sinton,2. Ch bond activation in organic synthesis 1st edition. We report the synthesis of a series of aryl or alkylsubstituted 2mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl thiols via coppermediated aerobic ch bond activation in the presence of stoichiometric cui, 2,2. Recent advances in coppermediated chelationassisted. Transition metalcatalyzed direct functionalization of ch bonds has recently emerged as a powerful strategy for the construction of carboncarbon and. Coppercatalyzed c n bond formation through c hn h activation. A catalytic cycle for coppercatalyzed carboxylation of terminal alkynes with co 2 is proposed as shown in fig. Co2 electroreduction to ethylene via hydroxidemediated.
Coppermediated ch activation of 1,3,4oxadiazoles with 1. Recently, ch amination via a transitionmetal catalyzed ch activation process has attracted considerable attention and has been proven to be a useful method for preparing amine molecules. Mechanistic investigations indicate a mechanism involving a fourcentered transition state, with simultaneous. Coppercatalyzedmediated halogenation of the csp 2h bond halogenation of the arene csp 2h bond. Providing comprehensive insight into the use of copper in crosscoupling reactions, coppermediated crosscoupling reactions provides a complete uptodate collection of the available reactions and catalytic systems for the formation of carbonheteroatom and carboncarbon bonds. Venkatachalam rajeshkumar, selvaraj chandrasekar, govindasamy sekar. This ch activation transformation proceeds smoothly for the construction of the isoindolin1one scaffold under mild conditions with less equivalents of copper salts and a.
Mediated nucleophilic addition and intramolecular ch activationcn or cc bond formation. Copperdioxygen complex mediated ch bond oxygenation. Copperdioxygen ch bond activation studies have intensified in recent years with interest stemming from pmmomediated oxidations and reactivity catalyzed by other copper oxygenases. Some ch activation reactions have been shown to proceed much more ef. Copper mediated selective c h activation and crossdehydrogenative cn coupling of 2. Direct methods for stereoselective functionalization of sp3hybridized carbonhydrogen csp3h bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals.
The term usually implies that a transition metal is involved in the ch cleavage process. We report the synthesis of a series of aryl or alkylsubstituted 2mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl thiols via copper mediated aerobic ch bond activation in the presence of stoichiometric cui, 2,2. Electrochemistry co electroreduction to ethylene via. Although these methods involve ch activation of one of the coupling partners, the efficient and direct synthesis of 1,2,3,4tetrahydroquinolines remains a challenge. Elaboration of copperoxygen mediated ch activation. H bond activation of small organic molecules, for example, formamide c. Copper and coppernheterocyclic carbenecatalyzed ch. In the synthesis of aryl halides employing the conventional electrophilic halogenation of arenes, the site selectivity was a main challenge and mixed haloarene products were frequently obtained. Achieving pcarh site selectivity is one of the major challenges in direct carbonhydrogen ch functionalization reactions. First, we show that, for the wide range of catalysts that proceed via a radical intermediate, a unifying framework for predicting ch activation barriers using a single universal descriptor can be established. This reaction has high functional group tolerance and is not affected by steric hindrance.
This essential reference covers a broad scope of coppermediated reactions, their variations, key advances. Regioselective introduction of heteroatoms at the c8 position of quinoline noxides. Ch bond halogenation catalyzed or mediated by copper. The reaction proceeds in excellent yield, even in gram scale, and the directing group can be removed after the reaction.
Generation of benzyne from benzoic acid using ch activation. Coppermediated regioselective ch etherification of. Greaneya a eastchem, school of chemistry, university of edinburgh, kings buildings, west mains rd, edinburgh, uk tel. Ch bond activation, functionalized reaction, cc bond formation, nickel catalysts table of contents 1. Pdf palladium and copper catalysis in regioselective, intermolecular. A copper mediated terminal positionselective csp3h acetoxylation using a bidentate directing group and agoac as an oxidant was achieved. Cupricsuperoxo mediated intermolecular ch activation.
Distinct approach for the alkynylation of 1,3,4oxadiazoles the. Kinetic studies indicate a firstorder dependence on both the cucomplex and bnah with a deuterium kinetic isotope effect kie of 12. Electrochemistry co 2 electroreduction to ethylene via hydroxidemediated copper catalysis at an abrupt interface caothang dinh, 1 thomas burdyny,2 md golam kibria,1 ali seifitokaldani, christine m. Aryl nitriles were efficiently synthesized through copper. The synthetic utility of this method was further examined by sequential functionalizations and the efficient synthesis of the pharmaceutically. These reactions provide efficient access to many biologically important skeletons, including ones with the potential to serve as inhibitors of hmts. Transition metalcatalyzed functionalization of ch bonds has been used as a powerful. Second, we combine this scaling approach with a thermodynamic analysis of active site formation to provide a map of methane activation. In 2010, the qing group reported the first example of the copper mediated ch methylthiolation of 2phenyl pyridines using dmso as the methylthio reagent in the presence of k 2 s 2 o 8 as the oxidant. However, direct use of arenes and alkanes via a twofold oxidative ch bond activation strategy to access chemoselective csp2. H bond activation in the presence of stoichiometric cui, 2,2. Dcsign mediated internalisation of glycosylated extracellular vesicles from schistosoma mansoni increases activation of monocytederived dendritic cells. While there is a considerable literature of copperion promoted organic oxidations 5, 6, we here emphasize more recent efforts to describe copperdioxygen or.
A novel and convenient copper ii bromide and 1,8diazabicyclo5. Norbornenemediated ortho ch functionalization mechanistic considerations in the development and use of azine, diazine and azole noxides in palladiumcatalyzed direct arylation palladium and copper catalysis in regioselective, intermolecular coupling of ch and chal bonds pdcatalyzed ch bond functionalization on the. Pdf mechanistic study of coppercatalyzed ch hydroxylationcs. Coppermediated ch activationcs crosscoupling of heterocycles with thiols. Copperiimediated 2quinoxalinol salens in alcohol oxidation and ch activation. Reactions classified by the term typically involve the hydrocarbon first to react with. Pdf a coppermediated terminal positionselective csp3h acetoxylation using a. The amide directing group is detached simultaneously under the reaction conditions through c. Catalyst and additivefree sp2 ch acetoxylation of diversely substituted. It is known that copper acetylide is the key intermediate for coppercatalyzed ch activation of terminal alkynes and the cuc bond is active for co 2 insertion 18, 3941, 48. Pdf modification of purine and pyrimidine nucleosides by. In an effort to develop such a method in an efficient and sustainable manner, chem21 researchers developed a simple copperii catalysed method for the synthesis of. S1 generation of benzyne from benzoic acid using ch activation alastair a.
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