Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage.
TL;DR: P palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners--including electrophilic aryl chlorides and tosylates as well as simple arenes in cross-dehydrogenative arylations.
Abstract: The area of transition-metal-catalyzed direct arylation through cleavage of CH bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross-coupling reactions with organometallic reagents In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners—including electrophilic aryl chlorides and tosylates as well as simple arenes in cross-dehydrogenative arylations Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations
Citations
More filters
3,322 citations
TL;DR: This review summarizes the development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations until autumn 2010 and proposes new acronyms, such as CMD (concerted metalationdeprotonation), IES (internal electrophilic substitution), or AMLA (ambiphilic metal ligand activation), which describe related mechanisms.
Abstract: The site-selective formation of carbon-carbon bonds through direct functionalizations of otherwise unreactive carbon-hydrogen bonds constitutes an economically attractive strategy for an overall streamlining of sustainable syntheses. In recent decades, intensive research efforts have led to the development of various reaction conditions for challenging C-H bond functionalizations, among which transition-metal-catalyzed transformations arguably constitute thus far the most valuable tool. For instance, the use of inter alia palladium, ruthenium, rhodium, copper, or iron complexes set the stage for chemo-, site-, diastereo-, and/or enantioselective C-H bond functionalizations. Key to success was generally a detailed mechanistic understanding of the elementary C-H bond metalation step, which depending on the nature of the metal fragment can proceed via several distinct reaction pathways. Traditionally, three different modes of action were primarily considered for CH bond metalations, namely, (i) oxidative addition with electronrich late transition metals, (ii) σ-bond metathesis with early transition metals, and (iii) electrophilic activation with electrondeficient late transition metals (Scheme 1). However, more recent mechanistic studies indicated the existence of a continuum of electrophilic, ambiphilic, and nucleophilic interactions. Within this continuum, detailed experimental and computational analysis provided strong evidence for novel C-H bond metalationmechanisms relying on the assistance of a bifunctional ligand bearing an additional Lewis-basic heteroatom, such as that found in (heteroatom-substituted) secondary phosphine oxides or most prominently carboxylates (Scheme 1, iv). This novel insight into the nature of stoichiometric metalations has served as stimulus for the development of novel transformations based on cocatalytic amounts of carboxylates, which significantly broadened the scope of C-H bond functionalizations in recent years, with most remarkable progress being made in palladiumor ruthenium-catalyzed direct arylations and direct alkylations. These carboxylate-assisted C-H bond transformations were mostly proposed to proceed via a mechanism in which metalation takes place via a concerted base-assisted deprotonation. To mechanistically differentiate these intramolecular metalations new acronyms have recently been introduced into the literature, such as CMD (concerted metalationdeprotonation), IES (internal electrophilic substitution), or AMLA (ambiphilic metal ligand activation), which describe related mechanisms and will be used below where appropriate. This review summarizes the development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations until autumn 2010. Moreover, experimental and computational studies on stoichiometric metalation reactions being of relevance to the mechanism of these catalytic processes are discussed as well. Mechanistically related C-H bond cleavage reactions with ruthenium or iridium complexes bearing monodentate ligands are, however, only covered with respect to their working mode, and transformations with stoichiometric amounts of simple acetate bases are solely included when their mechanism was suggested to proceed by acetate-assisted metalation.
2,820 citations
TL;DR: This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.
Abstract: The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.
2,391 citations
2,317 citations
TL;DR: This critical review covers the recent progresses on the regioselective dehydrogenative direct coupling reaction of heteroarenes, including arylation, olefination, alkynylation, and amination/amidation mainly utilizing transition metal catalysts.
Abstract: The direct functionalization of heterocyclic compounds has emerged as one of the most important topics in the field of metal-catalyzed C–H bond activation due to the fact that products are an important synthetic motif in organic synthesis, the pharmaceutical industry, and materials science. This critical review covers the recent progresses on the regioselective dehydrogenative direct coupling reaction of heteroarenes, including arylation, olefination, alkynylation, and amination/amidation mainly utilizing transition metal catalysts (113 references).
2,062 citations
References
More filters
25 Aug 2004
TL;DR: In this paper, the authors present an approach to the formation of C-X (X = N, O, S) bonds in metal-catalyzed cross-coupling reactions.
Abstract: Preface.List of Contributors.1 Mechanistic Aspects of Metal-Catalyzed C,C- and C,X-Bond-Forming Reactions (Antonio M. Echavarren and Diego J. Cardenas).1.1 Mechanisms of Cross-Coupling Reactions.1.2 Formation of C,C-Bonds in the Palladium-Catalyzed alpha-Arylation of Carbonyl Compounds and Nitriles.1.3 Key Intermediates in the Formation of C-X (X = N, O, S) bonds in Metal-Catalyzed Reactions 251.3.1 Reductive Elimination of C-N, C-O, and C-S Bonds From Organopalladium(II) Complexes.1.4 Summary and Outlook.Abbreviations.References.2 Metal-Catalyzed Cross-Coupling Reactions of Organoboron Compounds with Organic Halides (Norio Miyaura).2.1 Introduction.2.2 Advances in the Synthesis of Organoboron Compounds.2.3 Reaction Mechanism.2.4 Reaction Conditions.2.5 Side Reactions.2.6 Reactions of B-Alkyl Compounds.2.7 Reactions of B-Alkenyl Compounds.2.8 Reactions of B-Aryl Compounds.2.9 Reactions of B-Allyl and B-Alkynyl Compounds.2.10 Reactions Giving Ketones.2.11 Dimerization of Arylboronic Acids.2.12 N-, O-, and S-Arylation.Abbreviations.References.3 Organotin Reagents in Cross-Coupling Reactions (Terence N. Mitchell).3.1 Introduction.3.2 Mechanism and Methodology.3.3 Natural Product Synthesis.3.4 Organic Synthesis.3.5 Polymer Chemistry.3.6 Inorganic Synthesis.3.7 Conclusions.3.8 Experimental Procedures.Abbreviations.References.4 Organosilicon Compounds in Cross-Coupling Reactions (Scott E. Denmark and Ramzi F. Sweis).4.1 Introduction.4.2 Modern Organosilicon-Cross-Coupling.4.3 Mechanistic Studies in Silicon-Cross-Coupling.4.4 Applications to Total Synthesis.4.5 Summary and Outlook.4.6 Experimental Procedures.Abbreviations.References.5 Cross-Coupling of Organyl Halides with Alkenes: The Heck Reaction (Stefan Brase and Armin de Meijere).5.1 Introduction.5.2 Principles.5.3 Cascade Reactions and Multiple Couplings.5.4 Related Palladium-Catalyzed Reactions.5.5 Enantioselective Heck-Type Reactions.5.6 Syntheses of Heterocycles, Natural Products and Other Biologically Active Compounds Applying Heck Reactions.5.7 Carbopalladation Reactions in Solid-Phase Syntheses.5.8 The Heck Reaction in Fine Chemicals Syntheses.5.9 Conclusions.5.10 Experimental Procedures.Acknowledgments.Abbreviations and Acronyms.References.6 Cross-Coupling Reactions to sp Carbon Atoms (Jeremiah A. Marsden and Michael M. Haley).6.1 Introduction.6.2 Alkynylcopper Reagents.6.3 Alkynyltin Reagents.6.4 Alkynylzinc Reagents.6.5 Alkynylboron Reagents.6.6 Alkynylsilicon Reagents.6.7 Alkynylmagnesium Reagents.6.8 Other Alkynylmetals.6.9 Concluding Remarks.6.10 Experimental Procedures.Acknowledgments.Abbreviations and Acronyms.References.7 Carbometallation Reactions (Ilan Marek, Nicka Chinkov, and Daniella Banon-Tenne).7.1 Introduction.7.2 Carbometallation Reactions of Alkynes.7.3 Carbometallation Reactions of Alkenes.7.4 Zinc-Enolate Carbometallation Reactions.7.5 Carbometallation Reactions of Dienes and Enynes.7.6 Carbometallation Reactions of Allenes.7.7 Conclusions.7.8 Experimental Procedures.Acknowledgments.References.8 Palladium-Catalyzed 1,4-Additions to Conjugated Dienes (Jan-E. Backvall).8.1 Introduction.8.2 Palladium(0)-Catalyzed Reactions.8.3 Palladium(II)-Catalyzed Reactions.References.9 Cross-Coupling Reactions via PI-Allylmetal Intermediates (Uli Kazmaier and Matthias Pohlman)9.1 Introduction.9.2 Palladium-Catalyzed Allylic Alkylations.9.3 Allylic Alkylations with Other Transition Metals.9.4 Experimental Procedures.Abbreviations.References.10 Palladium-Catalyzed Coupling Reactions of Propargyl Compounds (Jiro Tsuji and Tadakatsu Mandai).10.1 Introduction.10.2 Classification of Pd-Catalyzed Coupling Reactions of Propargyl Compounds.10.3 Reactions with Insertion into the sp2 Carbon Bond of Allenylpalladium Intermediates (Type I).10.4 Transformations via Transmetallation of Allenylpalladium Intermediates and Related Reactions (Type II).10.5 Reactions with Attack of Soft Carbon and Oxo Nucleophiles on the sp-Carbon of Allenylpalladium Intermediates (Type III).10.6 Experimental Procedures.Abbreviations.References.11 Carbon-Carbon Bond-Forming Reactions Mediated by Organozinc Reagents (Paul Knochel, M. Isabel Calaza, and Eike Hupe).11.1 Introduction.11.2 Methods of Preparation of Zinc Organometallics.11.3 Uncatalyzed Cross-Coupling Reactions.11.4 Copper-Catalyzed Cross-Coupling Reactions.11.5 Transition Metal-Catalyzed Cross-Coupling Reactions.11.6 Conclusions.11.7 Experimental Procedures.Abbreviations.References.12 Carbon-Carbon Bond-Forming Reactions Mediated by Organomagnesium Reagents (Paul Knochel, Ioannis Sapountzis, and Nina Gommermann).12.1 Introduction.12.2 Preparation of Polyfunctionalized Organomagnesium Reagents via a Halogen-Magnesium Exchange.12.3 Conclusions.12.4 Experimental Procedures.References.13 Palladium-Catalyzed Aromatic Carbon-Nitrogen Bond Formation (Lei Jiang and Stephen L. Buchwald).13.1 Introduction.13.2 Mechanistic Studies.13.3 General Features.13.4 Palladium-Catalyzed C-N Bond Formation.13.5 Vinylation.13.6 Amination On Solid Support.13.7 Conclusion.13.8 Representative Experimental Procedures.References.14 The Directed ortho-Metallation (DoM) Cross-Coupling Nexus. Synthetic Methodology for the Formation of Aryl-Aryl and Aryl-Heteroatom-Aryl Bonds (Eric J.-G. Anctil and Victor Snieckus).14.1 Introduction.14.2 The Aim of this Chapter.14.3 Synthetic Methodology derived from the DoM-Cross-Coupling Nexus.14.4 Applications of DoM in Synthesis.14.5 Conclusions and Prognosis.14.6 Selected Experimental Procedures.Abbreviations.References and Notes.15 Palladium- or Nickel-Catalyzed Cross-Coupling with Organometals Containing Zinc, Aluminum, and Zirconium: The Negishi Coupling (Ei-ichi Negishi, Xingzhong Zeng, Ze Tan, Mingxing Qian, Qian Hu, and Zhihong Huang).15.1 Introduction and General Discussion of Changeable Parameters.15.2 Recent Developments in the Negishi Coupling and Related Pd- or Ni-Catalyzed Cross-Coupling Reactions.15.3 Summary and Conclusions.15.4 Representative Experimental Procedures.References.Index.
4,387 citations
TL;DR: Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal.
Abstract: Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.
3,830 citations
3,281 citations
TL;DR: A number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, but the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps.
Abstract: The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century 1 organic chemists have sought to develop new and more efficient aryl -aryl bond-forming methods. Although there exist a variety of routes for the construction of aryl -aryl bonds, arguably the most common method is through the use of transition-metalmediated reactions. 2-4 While earlier reports focused on the use of stoichiometric quantities of a transition metal to carry out the desired transformation, modern methods of transitionmetal-catalyzed aryl -aryl coupling have focused on the development of high-yielding reactions achieved with excellent selectivity and high functional group tolerance under mild reaction conditions. Typically, these reactions involve either the coupling of an aryl halide or pseudohalide with an organometallic reagent (Scheme 1), or the homocoupling of two aryl halides or two organometallic reagents. Although a number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps. In particular, the obligation to use coupling partners that are both activated is wasteful since it necessitates the installation and then subsequent disposal of stoichiometric activating agents. Furthermore, preparation of preactivated aryl substrates often requires several steps, which in itself can be a time-consuming and economically inefficient process.
3,204 citations
TL;DR: Privileged substructures are believed to achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns.
Abstract: Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.
2,620 citations