Showing papers in "Synthesis in 2021"
TL;DR: A comprehensive overview of N,N-dimethyl enaminones can be found in this article, where the authors provide a comprehensive overview on the synthetic applications of N-Ndimethyl Enaminones.
Abstract: Enaminones are gaining increasing interest because of their unique properties and their importance in organic synthesis as versatile building blocks. N,N-Dimethyl enaminones offer a better leaving group (a dimethylamine group) than other enaminones, and allow further elaboration via a range of facile chemical transformations. Over the past five years, there have been an increasing number of reports describing the synthetic applications of N,N-dimethyl enaminones. This review provides a comprehensive overview on the synthetic applications of N,N-dimethyl enaminones that have been reported since 2016. 1 Introduction 2 Direct C(sp2)–H α-Functionalization 2.1 Synthesis of α-Sulfenylated N,N-Dimethyl Enaminones 2.2 Synthesis of α-Thiocyanated N,N-Dimethyl Enaminones 2.3 Synthesis of α-Acyloxylated N,N-Dimethyl Enaminones 3 Functionalization Reactions via C=C Double Bond Cleavage 3.1 Synthesis of Functionalized Methyl Ketones 3.2 Synthesis of α-Ketoamides, α-Ketoesters and 1,2-Diketones 3.3 Synthesis of N-Sulfonyl Amidines 4 Construction of All-Carbon Aromatic Scaffolds 4.1 Synthesis of Benzaldehydes 4.2 Synthesis of the Naphthalenes 5 Construction of Heterocyclic Scaffolds 5.1 Synthesis of Five-Membered Heterocycles 5.2 Synthesis of Six-Membered Heterocycles 5.3 Synthesis of Quinolines 5.4 Synthesis of Functionalized Chromones 5.5 Synthesis of Other Fused Polycyclic Heterocycles 6 Conclusions and Perspectives
35 citations
TL;DR: This review article features selected examples on the synthesis of functionalized pyrroles that were reported between 2014 and 2019, and can be broadly classified into four different types: substrates bearing π-systems, substrate bearing carbonyl and other polar groups, and substrates Bearing heterocyclic motifs.
Abstract: This review article features selected examples on the synthesis of functionalized pyrroles that were reported between 2014 and 2019. Pyrrole is an important nitrogen-containing aromatic heterocycle that can be found in numerous compounds of biological and material significance. Given its vast importance, pyrrole continues to be an attractive target for the development of new synthetic reactions. The contents of this article are organized by the starting materials, which can be broadly classified into four different types: substrates bearing π-systems, substrates bearing carbonyl and other polar groups, and substrates bearing heterocyclic motifs. Brief discussions on plausible reaction mechanisms for most transformations are also presented. 1 Introduction 2 From π-Systems 2.1 Alkenes 2.2 1,6-Dienes 2.3 Allenes 2.4 Alkynes 2.5 Propargylic Groups 2.6 Homopropargylic Amines 3 From Carbonyl Compounds 3.1 Aldehydes 3.2 Ketones 3.3 Cyanides and Isocyanides 3.4 Formamides 3.5 β-Enamines 3.6 Dicarbonyl Compounds 4 From Polar Compounds 4.1 Aminols 4.2 Diols 4.3 Organonitro Compounds 5 From Heterocycles 5.1 Munchnones 5.2 Isoxazoles 5.3 Carbohydrates 5.4 trans-4-Hydroxy- l -prolines 5.5 Pyrrolines 6 Summary
34 citations
TL;DR: A review of the recent advances in the field of cycloaddition is given in this article, with a focus on the cyclotrimerization of carbo-and heterocycles.
Abstract: Metal-catalyzed [2+2+2] cycloaddition is a powerful tool that allows rapid construction of functionalized 6-membered carbo- and heterocycles in a single step through an atom-economical process with high functional group tolerance. The reaction is usually regio- and chemoselective although selectivity issues can still be challenging for intermolecular reactions involving the cross-[2+2+2] cycloaddition of two or three different alkynes and various strategies have been developed to attain high selectivities. Furthermore, enantioselective [2+2+2] cycloaddition is an efficient means to create central, axial, and planar chirality and a variety of chiral organometallic complexes can be used for asymmetric transition-metal-catalyzed inter- and intramolecular reactions. This review summarizes the recent advances in the field of [2+2+2] cycloaddition. 1 Introduction 2 Formation of Carbocycles 2.1 Intermolecular Reactions 2.1.1 Cyclotrimerization of Alkynes 2.1.2 [2+2+2] Cycloaddition of Two Different Alkynes 2.1.3 [2+2+2] Cycloaddition of Alkynes/Alkenes with Alkenes/Enamides 2.2 Partially Intramolecular [2+2+2] Cycloaddition Reactions 2.2.1 Rhodium-Catalyzed [2+2+2] Cycloaddition 2.2.2 Molybdenum-Catalyzed [2+2+2] Cycloaddition 2.2.3 Cobalt-Catalyzed [2+2+2] Cycloaddition 2.2.4 Ruthenium-Catalyzed [2+2+2] Cycloaddition 2.2.5 Other Metal-Catalyzed [2+2+2] Cycloaddition 2.3 Totally Intramolecular [2+2+2] Cycloaddition Reactions 3 Formation of Heterocycles 3.1 Cycloaddition of Alkynes with Nitriles 3.2 Cycloaddition of 1,6-Diynes with Cyanamides 3.3 Cycloaddition of 1,6-Diynes with Selenocyanates 3.4 Cycloaddition of Imines with Allenes or Alkenes 3.5 Cycloaddition of (Thio)Cyanates and Isocyanates 3.6 Cycloaddition of 1,3,5-Triazines with Allenes 3.7 Cycloaddition of Aldehydes with Enynes or Allenes/Alkenes 3.8 Totally Intramolecular [2+2+2] Cycloaddition Reactions 4 Conclusion
32 citations
TL;DR: A facile route to polysubstituted 2-pyrones from readily available 2-acylcyclopropane-1-aryl-1 carboxylates mediated by TfOH is reported in this article.
Abstract: A facile route to polysubstituted 2-pyrones from readily available 2-acylcyclopropane-1-aryl-1-carboxylates mediated by TfOH is reported. The strongly donating 1-aryl group is important for directing the C–C bond cleavage of the donor-acceptor cyclopropane ring, which then leads to the formation of the 2-pyrone ring through lactonization.
29 citations
TL;DR: In this paper, a review of the development of copper-mediated carbon-heteroatom bond-forming reactions involving a wide range of substrates has been presented, highlighting the use of various nucleophiles as coupling partners together with reaction optimization.
Abstract: Copper-mediated carbon–heteroatom bond-forming reactions involving a wide range of substrates have been in the spotlight for many organic chemists. This review highlights developments between 2010 and 2019 in both stoichiometric and catalytic copper-mediated reactions, and also examples of nickel-mediated reactions, under modified Chan–Lam cross-coupling conditions using various nucleophiles; examples include chemo- and regioselective N-arylations or O-arylations. The utilization of various nucleophiles as coupling partners together with reaction optimization (including the choice of copper source, ligands, base, and other additives), limitations, scope, and mechanisms are examined; these have benefitted the development of efficient and milder methods. The synthesis of medicinally valuable or pharmaceutically important nitrogen heterocycles, including isotope-labeled compounds, is also included. Chan–Lam coupling reaction can now form twelve different C–element bonds, making it one of the most diverse and mild reactions known in organic chemistry. 1 Introduction 2 Construction of C–N and C–O Bonds 2.1 C–N Bond Formation 2.1.1 Original Discovery via Stoichiometric Copper-Mediated C–N Bond Formation 2.1.2 Copper-Catalyzed C–N Bond Formation 2.1.3 Coupling with Azides, Sulfoximines, and Sulfonediimines as Nitrogen Nucleophiles 2.1.4 Coupling with N,N-Dialkylhydroxylamines 2.1.5 Enolate Coupling with sp3-Carbon Nucleophiles 2.1.6 Nickel-Catalyzed Chan–Lam Coupling 2.1.7 Coupling with Amino Acids 2.1.8 Coupling with Alkylboron Reagents 2.1.9 Coupling with Electron-Deficient Heteroarylamines 2.1.10 Selective C–N Bond Formation for the Synthesis of Heterocycle-Containing Compounds 2.1.11 Using Sulfonato-imino Copper(II) Complexes 2.2 C–O Bond Formation 2.2.1 Coupling with (Hetero)arylboron Reagents 2.2.2 Coupling with Alkyl- and Alkenylboron Reagents 3 C–Element (Element = S, P, C, F, Cl, Br, I, Se, Te, At) Bond Forma tion under Modified Chan–Lam Conditions 4 Conclusions
27 citations
TL;DR: A short review of asymmetric catalysis with transition-metal complexes including asymmetric hydrogenation (AH) and transfer hydrogenation of ketones and imines through dynamic kinetic resolution (DKR) allowing the construction of up to three stereogenic centers is presented in this article.
Abstract: Based on the ever-increasing demand for enantiomerically pure compounds, the development of efficient, atom-economical, and sustainable methods to produce chiral alcohols and amines is a major concern. Homogeneous asymmetric catalysis with transition-metal complexes including asymmetric hydrogenation (AH) and transfer hydrogenation (ATH) of ketones and imines through dynamic kinetic resolution (DKR) allowing the construction of up to three stereogenic centers is the main focus of the present short review, emphasizing the development of new catalytic systems combined to new classes of substrates and their applications as well. 1 Introduction 2 Asymmetric Hydrogenation via Dynamic Kinetic Resolution 2.1 α-Substituted Ketones 2.2 α-Substituted β-Keto Esters and Amides 2.3 α-Substituted Esters 2.4 Imine Derivatives 3 Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution 3.1 α-Substituted Ketones 3.2 α-Substituted β-Keto Esters, Amides, and Sulfonamides 3.3 α,β-Disubstituted Cyclic Ketones 3.4 β-Substituted Ketones 3.5 Imine Derivatives 4. Conclusion
26 citations
TL;DR: The distinct character of ruthenium catalysis for remote C–H activations until March 2021 is demonstrated and important mechanistic insights by experiments and computation are discussed, illustrating the key importance of carboxylate-assisted C-H activation with rutenium(II) complexes.
Abstract: Synthetic transformations of otherwise inert C–H bonds have emerged as a powerful tool for molecular modifications during the last decades, with broad applications towards pharmaceuticals, material sciences, and crop protection. Consistently, a key challenge in C–H activation chemistry is the full control of site-selectivity. In addition to substrate control through steric hindrance or kinetic acidity of C–H bonds, one important approach for the site-selective C–H transformation of arenes is the use of chelation-assistance through directing groups, therefore leading to proximity-induced ortho-C–H metalation. In contrast, more challenging remote C–H activations at the meta- or para-positions continue to be scarce. Within this review, we demonstrate the distinct character of ruthenium catalysis for remote C–H activations until March 2021, highlighting among others late-stage modifications of bio-relevant molecules. Moreover, we discuss important mechanistic insights by experiments and computation, illustrating the key importance of carboxylate-assisted C–H activation with ruthenium(II) complexes. 1 Introduction 2 Stoichiometric Remote C–H Functionalizations 3 meta-C–H Functionalizations 4 para-C–H Functionalizations 5 meta-/ortho-C–H Difunctionalizations 6 Conclusions
25 citations
TL;DR: This Short Review is aimed at giving an update in the area of copper-catalyzed C–H functionalization involving nitrogen-centered radicals generated from substrates containing N–F bonds.
Abstract: This Short Review is aimed at giving an update in the area of copper-catalyzed C–H functionalization involving nitrogen-centered radicals generated from substrates containing N–F bonds. These processes include intermolecular Csp3–H bond functionalization, remote Csp3–H bond functionalization via intramolecular hydrogen atom transfer (HAT), and Csp2–H bond functionalization, which might be of potential use in industrial applications in the future. 1 Introduction 2 Intermolecular Csp3–H Functionalization 3 Remote Csp3–H Functionalization 4 Csp2–H Functionalization 5 Conclusion
23 citations
TL;DR: In this paper, the most important enantioselective α-functionalizations of Isoxazol-5-ones and isoxazolidin 5-ones are discussed.
Abstract: Isoxazol-5-ones and isoxazolidin-5-ones represent two important classes of heterocycles, with several applications as bioactive compounds and as versatile building blocks for further transformations. Unlike the parent aromatic isoxazoles, the presence of one or two stereocenters in the ring renders their asymmetric construction particularly important. In this review, starting from the description of general features and differences between these two related compound families, we present an overview on the most important enantioselective synthesis strategies to access these heterocycles. Both chiral metal catalysts and organocatalysts have recently been successfully employed for this task and some of the most promising approaches will be discussed. 1 Introduction 2 Isoxazol-5-ones as Nucleophiles 2.1 Isoxazol-5-ones as C-Nucleophiles 2.2 Isoxazol-5-ones as N-Nucleophiles 2.3 Isoxazol-5-ones as C-Nucleophiles in Cyclization Processes 3 Asymmetric Construction of Isoxazolidin-5-ones 3.1 Enantioselective α-Functionalizations of Isoxazolidin-5-ones 4 Arylideneisoxazol-5-ones in Conjugated Addition 5 Conclusions
23 citations
TL;DR: A short review of palladium-catalyzed bridging C-H activation is presented in this paper, in which an inert proximal C−H bond palladation is promoted by the elementary step of migratory insertion of an alkene, an alkyne or a metal carbene intermediate.
Abstract: Transition-metal-catalyzed direct inert C–H bond functionalization has attracted much attention over the past decades. However, because of the high strain energy of the suspected palladacycle generated via C–H bond palladation, direct functionalization of a C–H bond less than a three-bond distance from a catalyst center is highly challenging. In this short review, we summarize the advances on palladium-catalyzed bridging C–H activation, in which an inert proximal C–H bond palladation is promoted by the elementary step of migratory insertion of an alkene, an alkyne or a metal carbene intermediate. 1 Introduction 2 Palladium-Catalyzed Alkene Bridging C–H Activation 2.1 Intramolecular Reactions 2.2 Intermolecular Reactions 3 Palladium-Catalyzed Alkyne Bridging C–H Activation 3.1 Intermolecular Reactions 3.2 Intramolecular Reactions 4 Palladium-Catalyzed Carbene Bridging C–H Activation 5 Conclusion and Outlook
23 citations
TL;DR: A recent review summarizes recent advances in nucleophilic fluorides preparation can be found in this article, with a focus on peptide synthesis, in challenging esterification and amidation reactions or in transition-metal-catalyzed transformations.
Abstract: Acyl fluorides are valuable intermediates in organic synthesis. They are increasingly employed in peptide synthesis, in challenging esterification and amidation reactions or in transition-metal-catalyzed transformations. This review summarizes recent advances in their preparation. 1 Introduction 2 Nucleophilic Fluorination 2.1 α-Fluoroamine Reagents 2.2 Sulfur-Based Reagents 2.3 Metal Catalysts 2.4 Phosphorus-Based Reagents 2.5 N,N′-Dicyclohexylcarbodiimide/HF·Pyridine 2.6 Uranium Hexafluoride 2.7 Bromine Trifluoride 3 Radical Fluorination 4 Conclusion
TL;DR: A comprehensive review of the acceptorless dehydrogenation of primary alcohols to carboxylates can be found in this article, where a number of transition-metal compounds have been used as catalysts for the process.
Abstract: Oxidation of primary alcohols to carboxylic acids is a fundamental transformation in organic chemistry, yet despite its simplicity, extensive use, and relationship to pH, it remains a subject of active research for synthetic organic chemists. Since 2013, a great number of new methods have emerged that utilize transition-metal compounds as catalysts for acceptorless dehydrogenation of alcohols to carboxylates. The interest in this reaction is explained by its atom economy, which is in accord with the principles of sustainability and green chemistry. Therefore, the methods for the direct synthesis of carboxylic acids from alcohols is ripe for a modern survey, which we provide in this review. 1 Introduction 2 Thermodynamics of Primary Alcohol Oxidation 3 Oxometalate Oxidation 4 Transfer Dehydrogenation 5 Acceptorless Dehydrogenation 6 Electrochemical Methods 7 Outlook
TL;DR: A short review of the recent emergence of organosodium chemistry can be found in this article, motivated by the requirements of modern synthetic chemistry for sustainability, and powered by the use of sodium dispersion, a form of sodium that is commercially available, easy to handle and has a large active surface area.
Abstract: This short review describes the recent emergence of organosodium chemistry, motivated by the requirements of modern synthetic chemistry for sustainability, and powered by the use of sodium dispersion, a form of sodium that is commercially available, easy to handle, and has a large active surface area. We present recent methods for the preparation of organosodium compounds using sodium dispersion, and their applications to synthesis. Sodium amides and phosphides are also briefly discussed. 1 Introduction 2 Sodium Dispersion 3 Preparation of Organosodium Compounds 3.1 Two-Electron Reduction of Aryl Halides 3.2 Halogen–Sodium Exchange 3.3 Directed Metalation 3.4 Cleavage of C–C and C–Heteroatom Bonds 4 Synthetic Applications 4.1 Reduction in Combination with a Proton Source 4.1.1 Bouveault–Blanc Reduction 4.1.2 Birch Reduction 4.1.3 Reductive Deuteration 4.1.4 Chemoselective Cleavage of Amides and Nitriles 4.2 Difunctionalization of Alkenes and Alkynes 5 Sodium Amides and Phosphides 6 Conclusions and Outlook
TL;DR: This review will showcase the different photomediated phosphorylation procedures available for converting C–H bonds into C–P(V) bonds by unlocking radical mechanisms and providing interesting redox pathways.
Abstract: Organophosphorus compounds have numerous useful applications, from versatile ligands and nucleophiles in the case of trivalent organophosphorus species to therapeutics, agrochemicals and material additives for pentavalent species. Although phosphorus chemistry is a fairly mature field, the construction of C–P(V) bonds relies heavily on either prefunctionalized substrates such as alkyl or aryl halides, or requires previously oxidized bonds such as C=N or C=O, leading to potential sustainability issues when looking at the overall synthetic route. In light of the recent advances in photochemistry, using photons as a reagent can provide better alternatives for phosphorylations by unlocking radical mechanisms and providing interesting redox pathways. This review will showcase the different photomediated phosphorylation procedures available for converting C–H bonds into C–P(V) bonds. 1 Introduction 1.1 Organophosphorus Compounds 1.2 Phosphorylation: Construction of C–P(V) Bonds 1.3 Photochemistry as an Alternative to Classical Phosphorylations 2 Ionic Mechanisms Involving Nucleophilic Additions 3 Mechanisms Involving Radical Intermediates 3.1 Mechanisms Involving Reactive Carbon Radicals 3.2 Mechanisms Involving Phosphorus Radicals 3.2.1 Photoredox: Direct Creation of Phosphorus Radicals 3.2.2 Photoredox: Indirect Creation of Phosphorus Radicals 3.2.3 Dual Catalysis 3.3 Photolytic Cleavage 4 Conclusion and Outlook
TL;DR: The catalytic asymmetric hydrogenation of prochiral olefins is one of the most widely studied and utilized transformations in asymmetric synthesis as discussed by the authors, which induces chirality in a broad range of substrates and is widely relevant for both industrial applications and academic research.
Abstract: The catalytic asymmetric hydrogenation of prochiral olefins is one of the most widely studied and utilized transformations in asymmetric synthesis. This straightforward, atom economical, inherently direct and sustainable strategy induces chirality in a broad range of substrates and is widely relevant for both industrial applications and academic research. In addition, the asymmetric hydrogenation of enamides has been widely used for the synthesis of chiral amines and their derivatives. In this review, we summarize the recent work in this field, focusing on the development of new catalytic systems and on the extension of these asymmetric reductions to new classes of enamides. 1 Introduction 2 Asymmetric Hydrogenation of Trisubstituted Enamides 2.1 Ruthenium Catalysts 2.2 Rhodium Catalysts 2.3 Iridium Catalysts 2.4 Nickel Catalysts 2.5 Cobalt Catalysts 3 Asymmetric Hydrogenation of Tetrasubstituted Enamides 3.1 Ruthenium Catalysts 3.2 Rhodium Catalysts 3.3 Nickel Catalysts 4 Asymmetric Hydrogenation of Terminal Enamides 4.1 Rhodium Catalysts 4.2 Cobalt Catalysts 5 Rhodium-Catalyzed Asymmetric Hydrogenation of Miscellaneous Enamides 6 Conclusions
TL;DR: Ru(II)-catalyzed enantioselective C–H functionalization reactions of sulfoximines with sulfoxonium ylides are described, which furnished the S-chiral products in 76:24–92:8 er.
Abstract: Ru(II)-catalyzed enantioselective C–H functionalization reactions of sulfoximines with sulfoxonium ylides are described. The combination of [RuCl2(p-cymene)]2 and a pseudo-C
2-symmetric binaphthyl monocarboxylic acid furnished the S-chiral products in 76:24–92:8 er.
TL;DR: In this article, the authors highlight the recent advances made on transition-metal (Ni, Cu, Fe, Co or Cr) catalyzed C-X (X = C, N, H, O, B, or Si) bond formation as well as syntheses of ketones, amino acids, alcohols, ethers and difluoromethyl derivatives via radical decarboxylation of carboxylic acids or their derivatives.
Abstract: Aliphatic carboxylic acids are abundant in natural and synthetic sources and are widely used as connection points in many chemical transformations. Radical decarboxylative functionalization promoted by transition-metal catalysis has achieved great success, enabling carboxylic acids to be easily transformed into a wide variety of products. Herein, we highlight the recent advances made on transition-metal (Ni, Cu, Fe, Co or Cr) catalyzed C–X (X = C, N, H, O, B, or Si) bond formation as well as syntheses of ketones, amino acids, alcohols, ethers and difluoromethyl derivatives via radical decarboxylation of carboxylic acids or their derivatives, including, among others, redox-active esters (RAEs), anhydrides, and diacyl peroxides. 1 Introduction 2 Ni-Catalyzed Decarboxylative Functionalizations 3 Cu-Catalyzed Decarboxylative Functionalizations 4 Fe-Catalyzed Decarboxylative Functionalizations 5 Co- and Cr-Catalyzed Decarboxylative Functionalizations 6 Conclusions
TL;DR: This review presents strategies towards the synthesis of α-, β-, γ-, δ- and e-lactams using IMCRs or IMCRS/post-transformation reactions reported in the literature between 2000 and 2020.
Abstract: Lactams are very important heterocycles as a result of their presence in a wide range of bioactive molecules, natural products and drugs, and also due their utility as versatile synthetic intermediates. Due to these reasons, numerous efforts have focused on the development of effective and efficient methods for their synthesis. Compared to conventional two-component reactions, multicomponent reactions (MCRs), particularly isocyanide-based MCRs, are widely used for the synthesis of a range of small heterocycles including lactam analogues. Despite their numerous applications in almost every field of chemistry, as yet there is no dedicated review on isocyanide-based multicomponent reactions (IMCRs) concerning the synthesis of lactams. Therefore, this review presents strategies towards the synthesis of α-, β-, γ-, δ- and e-lactams using IMCRs or IMCRs/post-transformation reactions reported in the literature between 2000 and 2020. 1 Introduction 2 Developments in Lactam Synthesis 2.1 α-Lactams 2.2 β-Lactams 2.3 γ-Lactams 2.3.1 General γ-Lactams 2.3.2 Benzo-Fused γ-Lactams 2.3.3 Spiro γ-Lactams 2.3.4 α,β-Unsaturated γ-Lactams 2.3.5 Polycyclic Fused γ-Lactams 2.4 δ-Lactams 2.5 e-Lactams 3 Conclusions
TL;DR: In this article, the authors present a review of the catalytic enantioselective synthesis of chiral pyrazolones with a tetrasubstituted stereocenter at C-4.
Abstract: Pyrazolone [2,4-dihydro-3H-pyrazol-4-one] represents one of the most important five-membered nitrogen heterocycles which is present in numerous pharmaceutical drugs and molecules with biological activity. Recently, many catalytic methodologies for the asymmetric synthesis of chiral pyrazolones have been established with great success, specially, for the synthesis of pyrazolones bearing a tetrasubstituted stereocenter at C-4. This review summarizes these excellent research studies since 2018, including representative examples and some mechanistic pathways explaining the observed stereochemistry. 1 Introduction 2 Catalytic Enantioselective Synthesis of Chiral Pyrazolones with a Full Carbon Tetrasubstituted Stereocenter at C-4 3 Catalytic Enantioselective Synthesis of Chiral Pyrazolones with a Quaternary Carbon Stereocenter at C-4 bearing a Heteroatom 4 Catalytic Enantioselective Synthesis of Chiral Spiropyrazolones 5 Conclusion
TL;DR: In this paper, a review of recent developments in this area is presented, with an emphasis on C-C bond constructions involving radical intermediates generated through photoredox processes.
Abstract: Chiral amines are key substructures of biologically active natural products and drug candidates. The advent of photoredox catalysis has changed the way synthetic chemists think about building these substructures, opening new pathways that were previously unavailable. New developments in this area are reviewed, with an emphasis on C–C bond constructions involving radical intermediates generated through photoredox processes. 1 Introduction 2 Radical–Radical Coupling of α-Amino Radicals 2.1 Radical–Radical Coupling Involving Amine Oxidation 2.2 Radical–Radical Coupling Involving Imine Reduction 2.3 Couplings Involving both Amine Oxidation and Imine Reduction 3 Addition Reactions of α-Amino Radicals 3.1 Conjugate Additions of α-Amino Radicals 3.2 Addition of α-Amino Radicals to Heteroaromatic Systems 3.3 Cross Coupling via Additions to Transition Metal Complexes 4 Radical Addition to C=N Bonds Using Photoredox Catalysis 4.1 Intramolecular Radical Addition to C=N Bonds 4.2 Intermolecular Radical Addition to C=N Bonds 5 Conclusion
TL;DR: The use of iron catalysis to enable reactions with diazo compounds has emerged as a valuable tool to forge carbon-carbon or carbon-heteroatom bonds as mentioned in this paper, and a short review will showcase and highlight the recent advances in iron-mediated reactions of DIAZ compounds.
Abstract: The use of iron catalysis to enable reactions with diazo compounds has emerged as a valuable tool to forge carbon–carbon or carbon–heteroatom bonds. While diazo compounds are often encountered with toxic and expensive metal catalysts, such as Rh, Ru, Pd, Ir, and Cu, a resurgence of Fe catalysis has been observed. This short review will showcase and highlight the recent advances in iron-mediated reactions of diazo compounds. 1 Introduction 2 Insertion Reactions 2.1 Insertion into B–H Bonds 2.2 Insertion into Si–H Bonds 2.3 Insertion into N–H Bonds 2.4 Insertion into S–H bonds 3 Ylide Formation and Subsequent Reactions 3.1 Doyle–Kirmse Rearrangement 3.2 [1,2]-Stevens and Sommelet–Hauser Rearrangements 3.3 Olefination Reactions 3.4 Cycloaddition Reactions 3.5 gem-Difluoroalkenylation 4 Three-Component Reactions 5 Miscellaneous 6 Conclusion
TL;DR: In this article, the most important transition-metal-catalyzed cross-coupling reactions realized in the period 2000 to 2020 are summarized and compared to other transition metal catalysts, such as nickel, palladium, and iron.
Abstract: Transition-metal-catalyzed cross-coupling of organohalides, ethers, sulfides, amines, and alcohols (and derivatives thereof) with Grignard reagents, known as the Kumada–Tamao–Corriu reaction, can be used to prepare important intermediates in the synthesis of numerous biologically active compounds. The most frequently used transition metals are nickel, palladium, and iron, but there are several examples for cross-coupling reactions catalyzed by copper, cobalt, manganese, chromium, etc. salts and complexes. The aim of this review is to summarize the most important transition-metal-catalyzed cross-coupling reactions realized in the period 2000 to 2020. 1 Introduction 2 Nickel Catalysis 3 Palladium Catalysis 4 Iron Catalysis 5 Catalysis by Other Transition Metals 5.1 Cobalt Catalysis 5.2 Copper Catalysis 5.3 Manganese Catalysis 5.4 Chromium Catalysis 6 Conclusion
TL;DR: A review of recent developments in manganese-catalyzed reducing transformations can be found in this paper, where a clear and concise overview of the catalyst structures and substrate transformations is provided.
Abstract: Recent developments in manganese-catalyzed reducing transformations—hydrosilylation, hydroboration, hydrogenation, and transfer hydrogenation—are reviewed herein. Over the past half a decade (i.e., 2016-present), more than 115 research publications have been reported in these fields. Novel organometallic compounds and new reduction transformations have been discovered and further developed. Significant challenges that had historically acted as barriers for the use of manganese catalysts in reduction reactions are slowly being broken down. This review will hopefully assist in developing this research with a clear and concise overview of the catalyst structures and substrate transformations published so far.
TL;DR: 4-substituted 1-aryl-3-arylidenepyrrolidine-2,5-diones of defined regiochemistry and geometrical configuration are delivered to be studied as Michael acceptors capable of inhibiting thioredoxin reductase, a promising cancer target.
Abstract: The use of readily available 1-aryl-3-arylidenepyrrolidine-2,5-diones in high yielding direct diazo-transfer reactions and subsequent involvement of the resulting diazo compounds in RhII-catalyzed O–H, S–H, and N–H insertion reactions delivered 4-substituted 1-aryl-3-arylidenepyrrolidine-2,5-diones of defined regiochemistry and geometrical configuration. These products are intended to be studied as Michael acceptors capable of inhibiting thioredoxin reductase, a promising cancer target.
TL;DR: In this paper, a review of the recent trends and modifications frequently used in the synthesis of derivatives of benzimidazole such as the Phillips-Ladenburg and Weidenhagen reactions, as well as entirely new methods of synthesis, involving oxidative cyclization, cross-coupling, ring distortion strategy, and rearrangements carried out under environmentally benign conditions.
Abstract: Benzimidazole is an important heterocycle that is widely researched and utilized by the pharmaceutical industry and is one of the five most commonly used five-membered aromatic heterocyclic compounds approved by the US Food and Drug Administration. In view of their wide-ranging bioactivities, systems containing benzimidazole as one of the moieties occupy a special place among other benzimidazole derivatives. Since 2010, many improved synthetic strategies have been developed for the construction of hetaryl- and arylbenzimidazole molecular scaffolds under environmentally benign conditions. This review emphasizes the recent trends and modifications frequently used in the synthesis of derivatives of benzimidazole such as the Phillips–Ladenburg and Weidenhagen reactions, as well as entirely new methods of synthesis, involving oxidative cyclization, cross-coupling, ring distortion strategy, and rearrangements carried out under environmentally benign conditions. 1 Introduction 2 From 1,2-Diaminobenzenes with Various One-Carbon Unit Suppliers 2.1 Phillips–Ladenburg Reaction 2.1.1 With (Het)arenecarboxylic Acids 2.2.2 With (Het)arenecarboxylic Acid Derivatives 2.2 Weidenhagen Reaction 2.2.1 With (Het)arenecarbaldehydes or (Het)aryl Methyl Ketones 2.2.2 With Primary Alcohols 2.2.3 With Primary Alkylamines 2.2.4 With 2-Methylazaarenes 2.2.5 With Other One-Carbon Fragment Suppliers 3 From 2-Haloacetanilides and Amines 4 From Amidines 5 From Tetrahydroquinazolines 6 Mamedov Rearrangement 7 Conclusions and Outlook
TL;DR: Recently, significant developments have been made using non-heme-type transition-metal catalysts as mentioned in this paper, which can be introduced to not only simple hydrocarbons but also complex natural products.
Abstract: C–H bonds are ubiquitous and abundant in organic molecules. If such C–H bonds can be converted into the desired functional groups in a site-, chemo-, diastereo-, and enantio-selective manner, the functionalization of C–H bonds would be an efficient tool for step-, atom- and redox-economic organic synthesis. C–H oxidation, as a typical C–H functionalization, affords hydroxy and carbonyl groups, which are key functional groups in organic synthesis and biological chemistry, directly. Recently, significant developments have been made using non-heme-type transition-metal catalysts. Oxygen functional groups can be introduced to not only simple hydrocarbons but also complex natural products. In this paper, recent developments over the last fourteen years in non-heme-type complex-catalyzed C–H oxidations are reviewed. 1 Introduction 2 Regio- and Chemo-Selective C–H Oxidations 2.1 Tertiary Site-Selective C–H Oxidations 2.2 Secondary Site-Selective C–H Oxidations 2.3 C–H Oxidations of N-Containing Molecules 2.4 C–H Oxidations of Carboxylic Acids 2.5 Chemo- and Site-Selective Methylenic C–H Hydroxylations 3 Enantioselective C–H Oxidations 3.1 Desymmetrizations through C–H Oxidations 3.2 Enantiotopic Methylenic C–H Oxygenations 4 Conclusion
TL;DR: The Heck-type reaction between unactivated alkenes and alkyl electrophlies is considered as one of the most ingenious and widely used methods for constructing C-C bonds as mentioned in this paper.
Abstract: The Mizoroki–Heck reaction is considered as one of the most ingenious and widely used methods for constructing C–C bonds. This reaction mainly focuses on activated olefins (styrenes, acrylates, or vinyl ethers) and aryl/vinyl (pseudo) halides. In comparison, the studies on unactivated alkenes and alkyl electrophiles are far less due to the low reactivity, poor selectivity, as well as competitive β-H elimination. In the past years, a growing interest has thus been devoted and significant breakthroughs have been achieved in the employment of unactivated alkenes and alkyl electrophiles as the reaction components, and this type of coupling is called as Heck-type or Heck-like reaction, which distinguishes from the traditional Heck reaction. Herein, we give a brief summary on Heck-type reaction between unactivated alkenes and alkyl electrophlies, covering its initial work, recent advancements, and mechanistic discussions. 1 Introduction 2 Intramolecular Heck-Type Reaction of Unactivated Alkenes and Alkyl Electrophiles 2.1 Cobalt-Catalyzed Intramolecular Heck-Type Reaction 2.2 Palladium-Catalyzed Intramolecular Heck-Type Reaction 2.3 Nickel-Catalyzed Intramolecular Heck-Type Reaction 2.4 Photocatalysis and Multimetallic Protocol for Intramolecular Heck-Type Reaction 3 Intermolecular Heck-Type Reaction of Unactivated Alkenes and Alkyl Electrophiles 3.1 Electrophilic Trifluoromethylating Reagent as Reaction Partners 3.2 Alkyl Electrophiles as Reaction Partners 4 Oxidative Heck-Type Reaction of Unactivated Alkenes and Alkyl Radicals 5 Conclusions and Outlook
TL;DR: In this article, a review summarizes the advances made on the synthesis and functionalization of furans via gold catalysis during the period between 2016 and 2020, and a separate section is dedicated to the tandem gold-catalyzed synthesis of Furans.
Abstract: This review summarizes the advances made on the synthesis and functionalization of furans via gold catalysis during the period between 2016 and 2020. A separate section is dedicated to the tandem gold-catalyzed synthesis and functionalization of furans. 1 Introduction 2 Gold-Catalyzed Synthesis of Furans 2.1 Cycloisomerizations of Alkynyl and Cumulenyl Alcohols 2.2 Cycloisomerizations of Alkynyl and Allenyl Ketones 2.3 Reactions with External Oxidants 2.4 Miscellaneous 3 Gold-Catalyzed Functionalization of Furans 3.1 Cycloadditions 3.2 Furan Ring Decorations 3.3 Reactions Involving Furan Ring Opening 4 Gold-Catalyzed Tandem Synthesis and Functionalization of Furans 4.1 Cycloisomerizations Followed by Gold-Catalyzed Cycloaddition 4.2 Cycloisomerizations to a Gold 1,3- or 1,4-Dipole and Intermolecular Annulation 4.3 Cycloisomerizations to a Gold Carbene and Intermolecular Trapping 5 Conclusion
TL;DR: A review of the application of the Horner-Wadsworth-Emmons (HWE) olefinations in total syntheses of structurally different natural products covering 2015 to 2020 can be found in this paper.
Abstract: The Horner–Wadsworth–Emmons (HWE) reaction is one of the most reliable olefination reaction and can be broadly applied in organic chemistry and natural product synthesis with excellent selectivity. Within the last few years HWE reaction conditions have been optimized and new reagents developed to overcome challenges in the total syntheses of natural products. This review highlights the application of HWE olefinations in total syntheses of structurally different natural products covering 2015 to 2020. Applied HWE reagents and reactions conditions are highlighted to support future synthetic approaches and serve as guideline to find the best HWE conditions for the most complicated natural products. 1 Introduction and Historical Background 2 Applications of HWE 2.1 Cyclization by HWE Reactions 2.2.1 Formation of Medium- to Larger-Sized Rings 2.2.2 Formation of Small- to Medium-Sized Rings 2.3 Synthesis of α,β-Unsaturated Carbonyl Groups 2.4 Synthesis of Substituted C=C Bonds 2.5 Late-Stage Modifications by HWE Reactions 2.6 HWE Reactions on Solid Supports 2.7 Synthesis of Poly-Conjugated C=C Bonds 2.8 HWE-Mediated Coupling of Larger Building Blocks 2.9 Miscellaneous 3 Summary and Outlook
TL;DR: Recently, the emergence of photoredox-mediated single-electron transmetalation has evoked an ideal paradigm for selectively manipulating C(sp3)-C(sp 3) cross-coupling with the unprecedented application of native C (sp3) functionalities instead of organometallic reagents.
Abstract: Transition-metal-catalyzed carbon–carbon cross-coupling reactions represent a significant achievement in modern synthetic chemistry and they have become indispensable tools for the construction of organic molecules. Despite the important progress in this area, methods for coupling two C(sp3)-hybridized alkyl fragments remain elusive. To date, existing methods have largely relied on using organometallic reagents as the nucleophilic coupling partners, thereby inevitably limiting the compatibility of functional groups. Although cross-electrophile coupling may alleviate the pain somewhat, it is necessary to add a stoichiometric amount of a reductant to complete the catalytic cycle. Recently, the emergence of photoredox-mediated single-electron transmetalation has evoked an ideal paradigm for selectively manipulating C(sp3)–C(sp3) cross-coupling with the unprecedented application of native C(sp3) functionalities instead of organometallic reagents, thus opening a new window for C(sp3)–C(sp3) bond creation. This short review highlights the recent advances in this exciting subfield. 1 Introduction 2 Nickel/Photoredox-Catalyzed C(sp3)–C(sp3) Cross-Coupling 3 Palladium/Photoredox-Catalyzed C(sp3)–C(sp3) Cross-Coupling 4 Copper/Photoredox-Catalyzed C(sp3)–C(sp3) Cross-Coupling 5 Direct C(sp3)–H Alkylation via Metallaphotoredox-Mediated Hydrogen Atom Transfer 6 Conclusion and Perspectives