Catalytic Functionalization of C(sp²)H and C(sp³)H Bonds by Using Bidentate Directing Groups

Angewandte Chemie International Edition, Год журнала: 2013, Номер 52(45), С. 11726 - 11743

Опубликована: Сен. 17, 2013

C-H bonds are ubiquitous in organic compounds. It would, therefore, appear that direct functionalization of substrates by activation would eliminate the multiple steps and limitations associated with preparation functionalized starting materials. Regioselectivity is an important issue because molecules can contain a wide variety bonds. The use directing group largely overcome regiocontrol allowing catalyst to come into proximity targeted A functional groups have been evaluated for as transformation In 2005, Daugulis reported arylation unactivated C(sp(3))-H using 8-aminoquinoline picolinamide bidentate groups, Pd(OAc)2 catalyst. Encouraged these promising results, number transformations since developed systems based on groups. this Review, recent advances area discussed.

Язык: Английский

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The Cross‐Dehydrogenative Coupling of CH Bonds: A Versatile Strategy for CC Bond Formations

Angewandte Chemie International Edition, Год журнала: 2013, Номер 53(1), С. 74 - 100

Опубликована: Ноя. 8, 2013

Abstract Over the last decade, substantial research has led to introduction of an impressive number efficient procedures which allow selective construction CC bonds by directly connecting two different CH under oxidative conditions. Common these methodologies is generation reactive intermediates in situ activation both bonds. This strategy was introduced group Li as cross‐dehydrogenative coupling (CDC) and discloses waste‐minimized synthetic alternatives classic rely on use prefunctionalized starting materials. Review highlights recent progress field C C formations provides a comprehensive overview existing employed methodologies.

Язык: Английский

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Mild metal-catalyzed C–H activation: examples and concepts

Chemical Society Reviews, Год журнала: 2016, Номер 45(10), С. 2900 - 2936

Опубликована: Янв. 1, 2016

C–H Activation reactions that proceed under mild conditions are more attractive for applications in complex molecule synthesis. Mild transformations reported since 2011 reviewed and the different concepts strategies have enabled their mildness discussed.

Язык: Английский

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Carboxylate-Assisted Ruthenium-Catalyzed Alkyne Annulations by C–H/Het–H Bond Functionalizations

Accounts of Chemical Research, Год журнала: 2013, Номер 47(2), С. 281 - 295

Опубликована: Фев. 4, 2013

To improve the atom- and step-economy of organic syntheses, researchers would like to capitalize upon chemistry otherwise inert carbon–hydrogen (C–H) bonds. During past decade, remarkable progress in organometallic has set stage for development increasingly viable metal catalysts C–H bond activation reactions. Among these methods, oxidative functionalizations are particularly attractive because they avoid use prefunctionalized starting materials. For example, annulations that involve sequential heteroatom–H cleavages allow modular assembly regioselectively decorated heterocycles. These structures serve as key scaffolds natural products, functional materials, crop protecting agents, drugs. While other have devised rhodium or palladium complexes alkyne annulations, my laboratory focused on application significantly less expensive, yet highly selective ruthenium complexes.This Account summarizes evolution versatile ruthenium(II) alkynes via C–H/N–H, C–H/O–H, C–H/N–O cleavages. achieve functionalizations, we needed understand detailed mechanism crucial metalation with importance carboxylate assistance this process. As a consequence, our recent efforts resulted widely applicable methods preparation differently arenes heteroarenes, providing access among others isoquinolones, 2-pyridones, isoquinolines, indoles, pyrroles, α-pyrones. Most reactions used Cu(OAc)2·H2O, which not only acted oxidant but also served essential source acetate carboxylate-assisted ruthenation manifold. Notably, ruthenium(II)-catalyzed occurred under an ambient atmosphere air cocatalytic amounts Cu(OAc)2·H2O. Moreover, substrates displaying N–O bonds "internal oxidants" syntheses isoquinolones isoquinolines. Detailed experimental mechanistic studies provided strong support catalytic cycle relies initial ruthenation, followed by coordinative insertion alkyne, reductive elimination, reoxidation thus formed ruthenium(0) complex.

Язык: Английский

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The medicinal chemist's toolbox for late stage functionalization of drug-like molecules

Chemical Society Reviews, Год журнала: 2015, Номер 45(3), С. 546 - 576

Опубликована: Окт. 28, 2015

The advent of modern C-H functionalization chemistries has enabled medicinal chemists to consider a synthetic strategy, late stage (LSF), which utilizes the bonds drug leads as points diversification for generating new analogs. LSF approaches offer promise rapid exploration structure activity relationships (SAR), generation oxidized metabolites, blocking metabolic hot spots and preparation biological probes. This review details toolbox intermolecular with proven applicability drug-like molecules, classified by regioselectivity patterns, gives guidance on how systematically develop strategies using these patterns other considerations. In addition, number examples illustrate have been used impact actual discovery chemical biology efforts.

Язык: Английский

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A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

Chemical Society Reviews, Год журнала: 2018, Номер 47(17), С. 6603 - 6743

Опубликована: Янв. 1, 2018

The present review is devoted to summarizing the recent advances (2015-2017) in field of metal-catalysed group-directed C-H functionalisation. In order clearly showcase molecular diversity that can now be accessed by means directed functionalisation, whole organized following directing groups installed on a substrate. Its aim comprehensive reference work, where specific group easily found, together with transformations which have been carried out it. Hence, primary format this schemes accompanied concise explanatory text, are ordered sections according their chemical structure. feature typical substrates used, products obtained as well required reaction conditions. Importantly, each example commented respect most important positive features and drawbacks, aspects such selectivity, substrate scope, conditions, removal, greenness. targeted readership both experts functionalisation chemistry (to provide overview progress made last years) and, even more so, all organic chemists who want introduce way thinking for design straightforward, efficient step-economic synthetic routes towards molecules interest them. Accordingly, should particular also scientists from industrial R&D sector. overall goal promote application reactions outside research dedicated method development establishing it valuable archetype contemporary R&D, comparable role cross-coupling play date.

Язык: Английский

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Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups

Organic Chemistry Frontiers, Год журнала: 2015, Номер 2(9), С. 1107 - 1295

Опубликована: Янв. 1, 2015

In this review, a summary of transition metal-catalyzed C–H activation by utilizing the functionalities as directing groups is presented.

Язык: Английский

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Cobalt-Catalyzed C–H Activation

ACS Catalysis, Год журнала: 2015, Номер 6(2), С. 498 - 525

Опубликована: Ноя. 24, 2015

Catalytic C–H activation has emerged as a powerful tool for sustainable syntheses. In the recent years, notable success was achieved with development of cobalt-catalyzed functionalizations either in situ generated or single-component cobalt-complexes under mild reaction conditions. Herein, progress field organometallic is reviewed until November 2015.

Язык: Английский

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Substrate Activation Strategies in Rhodium(III)-Catalyzed Selective Functionalization of Arenes

Accounts of Chemical Research, Год журнала: 2015, Номер 48(4), С. 1007 - 1020

Опубликована: Апрель 6, 2015

The possibility of developing new methods for the efficient construction organic molecules via disconnections other than traditional functional group transformations has driven interest in direct functionalization C-H bonds. ubiquity bonds makes such attractive, but they also pose several challenges. first is reactivity and selectivity To achieve this, directing groups (DGs) are often installed that can enhance effective concentration catalyst, leading to thermodynamically stable metallacyclic intermediates. However, presence a pendant product undesirable unnecessary. This may account limitation applications reactions more common general uses. Thus, development removable or functionalizable desirable. Another key problem resulting M-C bond be low, which limit scope coupling partners hence reaction patterns activation reactions. While Cp*Rh(III)-catalyzed arenes was reported only 7 years ago, significant progress been made this area past few years. We began our studies 2010, we others have demonstrated diversified catalytic realized using Cp*Rh(III) complexes with high reactivity, stability, compatibility. Account describes efforts solve some these challenges Rh(III) catalysis. fulfilled design arene substrates by taking advantage nucleophilicity, electrophilicity, oxidizing potential, properties participating ligand when coupled relatively reactive unsaturated as alkenes alkynes. These situ funtionalizable roles DG allowed extensive chemical manipulation initial product, especially diverse array heterocycles. In polar partners, Rh(III)-C(aryl) showed higher both an organometallic reagent nucleophilic aryl source. were accordingly activated virtue umpolung, ring strain, rearomatization. All possible integration compatibility Rh(III)-C into systems. date achieved under rhodium addition, means stoichiometric reactions, gained mechanistic insights interactions between Rh-C opened avenues future

Язык: Английский

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Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions

Angewandte Chemie International Edition, Год журнала: 2013, Номер 52(47), С. 12256 - 12267

Опубликована: Окт. 22, 2013

Abstract The methyl group is one of the most commonly occurring carbon fragments in small‐molecule drugs. This simplest alkyl fragment appears more than 67 % top‐selling drugs 2011 and can modulate both biological physical properties a molecule. Review focuses on so‐called magic effects binding potency, where seemingly mundane change CH to CMe improves IC 50 value drug candidate 100‐fold. discussion followed by survey recent advances synthetic chemistry that allow direct methylation C(sp 2 )H 3 bonds. It our hope relevance meager discovery as presented herein will inspire reports new reactions.

Язык: Английский

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