Carboxylate-assisted transition-metal-catalyzed C-H bond functionalizations: mechanism and scope.
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.
Citations
More filters
2,317 citations
TL;DR: This critical review summarizes and discusses endeavours towards the development of mild C-H activation methods and wishes to trigger more research towards this goal.
Abstract: Functionalizing traditionally inert carbon–hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C–H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C–H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C–H functionalization (84 references).
2,137 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
TL;DR: The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials.
Abstract: Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene substrates bearing nitrogen and oxygen directing groups are covered in their coupling with unsaturated partners such as alkenes and alkynes. The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials. Comparisons and contrasts between rhodium(III) and palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of structures accessible is demonstrated with various recent examples, with a proposed mechanism for each transformation being briefly summarized (critical review, 138 references).
1,899 citations
TL;DR: This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry, and are more atom- and step-economical than previous methods.
Abstract: The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry.
1,838 citations
References
More filters
TL;DR: This is the first comprehensive review encompassing the large body of work in this field over the past 5 years, and will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium.
Abstract: 1.1 Introduction to Pd-catalyzed directed C–H functionalization
The development of methods for the direct conversion of carbon–hydrogen bonds into carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds remains a critical challenge in organic chemistry. Mild and selective transformations of this type will undoubtedly find widespread application across the chemical field, including in the synthesis of pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. Traditional approaches for the formation of such functional groups rely on pre-functionalized starting materials for both reactivity and selectivity. However, the requirement for installing a functional group prior to the desired C–O, C–X, C–N, C–S, or C–C bond adds costly chemical steps to the overall construction of a molecule. As such, circumventing this issue will not only improve atom economy but also increase the overall efficiency of multi-step synthetic sequences.
Direct C–H bond functionalization reactions are limited by two fundamental challenges: (i) the inert nature of most carbon-hydrogen bonds and (ii) the requirement to control site selectivity in molecules that contain diverse C–H groups. A multitude of studies have addressed the first challenge by demonstrating that transition metals can react with C–H bonds to produce C–M bonds in a process known as “C–H activation”.1 The resulting C–M bonds are far more reactive than their C–H counterparts, and in many cases they can be converted to new functional groups under mild conditions.
The second major challenge is achieving selective functionalization of a single C–H bond within a complex molecule. While several different strategies have been employed to address this issue, the most common (and the subject of the current review) involves the use of substrates that contain coordinating ligands. These ligands (often termed “directing groups”) bind to the metal center and selectively deliver the catalyst to a proximal C–H bond. Many different transition metals, including Ru, Rh, Pt, and Pd, undergo stoichiometric ligand-directed C–H activation reactions (also known as cyclometalation).2,3 Furthermore, over the past 15 years, a variety of catalytic carbon-carbon bond-forming processes have been developed that involve cyclometalation as a key step.1b–d,4
The current review will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium. Palladium complexes are particularly attractive catalysts for such transformations for several reasons. First, ligand-directed C–H functionalization at Pd centers can be used to install many different types of bonds, including carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon linkages. Few other catalysts allow such diverse bond constructions,5,6,7 and this versatility is predominantly the result of two key features: (i) the compatibility of many PdII catalysts with oxidants and (ii) the ability to selectively functionalize cyclopalladated intermediates. Second, palladium participates in cyclometalation with a wide variety of directing groups, and, unlike many other transition metals, promotes C–H activation at both sp2 and sp3 C–H sites. Finally, the vast majority of Pd-catalyzed directed C–H functionalization reactions can be performed in the presence of ambient air and moisture, making them exceptionally practical for applications in organic synthesis.
While several accounts have described recent advances, this is the first comprehensive review encompassing the large body of work in this field over the past 5 years (2004–2009). Both synthetic applications and mechanistic aspects of these transformations are discussed where appropriate, and the review is organized on the basis of the type of bond being formed.
5,179 citations
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: The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier.
Abstract: The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.
3,855 citations
TL;DR: A review of palladium-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle can be found in this paper.
Abstract: Pick your Pd partners: A number of catalytic systems have been developed for palladium-catalyzed CH activation/CC bond formation. Recent studies concerning the palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed.
In the past decade, palladium-catalyzed CH activation/CC bond-forming reactions have emerged as promising new catalytic transformations; however, development in this field is still at an early stage compared to the state of the art in cross-coupling reactions using aryl and alkyl halides. This Review begins with a brief introduction of four extensively investigated modes of catalysis for forming CC bonds from CH bonds: PdII/Pd0, PdII/PdIV, Pd0/PdII/PdIV, and Pd0/PdII catalysis. A more detailed discussion is then directed towards the recent development of palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle. Despite the progress made to date, improving the versatility and practicality of this new reaction remains a tremendous challenge.
3,533 citations
TL;DR: N-Heterocyclic carbenes have become universal ligands in organometallic and inorganic coordination chemistry as mentioned in this paper, and they not only bind to any transition metal, be it in low or high oxidation states, but also to main group elements such as beryllium, sulfur, and iodine.
Abstract: N-Heterocyclic carbenes have become universal ligands in organometallic and inorganic coordination chemistry. They not only bind to any transition metal, be it in low or high oxidation states, but also to main group elements such as beryllium, sulfur, and iodine. Because of their specific coordination chemistry, N-heterocyclic carbenes both stabilize and activate metal centers in quite different key catalytic steps of organic syntheses, for example, C-H activation, C-C, C-H, C-O, and C-N bond formation. There is now ample evidence that in the new generation of organometallic catalysts the established ligand class of organophosphanes will be supplemented and, in part, replaced by N-heterocyclic carbenes. Over the past few years, this chemistry has been the field of vivid scientific competition, and yielded previously unexpected successes in key areas of homogeneous catalysis. From the work in numerous academic laboratories and in industry, a revolutionary turning point in oraganometallic catalysis is emerging.
3,388 citations