Showing papers in "Organic and Biomolecular Chemistry in 2019"
TL;DR: The utility of catalysts based on Mn, Fe, Co, Ni and Cu to promote a diverse array of important C-C and C-N bond forming reactions is described, including discussion on reaction mechanisms, scope and limitations, and future challenges in this burgeoning area of sustainable catalysis.
Abstract: The review highlights the recent advances (2013-present) in the use of earth-abundant first row transition metals in homogeneous borrowing hydrogen catalysis. The utility of catalysts based on Mn, Fe, Co, Ni and Cu to promote a diverse array of important C–C and C–N bond forming reactions is described, including discussion on reaction mechanisms, scope and limitations, and future challenges in this burgeoning area of sustainable catalysis.
233 citations
TL;DR: This minireview highlights the recent advances in the chemistry of Hantzsch esters in photoredox catalyzed organic synthesis, with particular emphasis placed on reaction mechanisms.
Abstract: Hantzsch esters were often previously used as reductants in thermal catalytic hydrogenation reactions. Over the last few decades, Hantzsch esters have proven to be a useful class of electron donors and proton sources in photoredox catalyzed processes. Moreover, under photoredox catalytic conditions, alkyl-1,4-dihydropyridines can serve as versatile types of alkylation reagents via oxidative fragmentation mechanisms. This minireview highlights the recent advances in the chemistry of Hantzsch esters in photoredox catalyzed organic synthesis, with particular emphasis placed on reaction mechanisms. We hope that this review will inspire further new reaction design and developments with such a class of readily accessible reagents.
175 citations
TL;DR: This mini-review covers recently published reports on the reactivity of diazo compounds under light irradiation.
Abstract: Diazo compounds are among the most important building blocks in organic synthesis. Generally, their photoinitiated, thermal, or transition metal catalyzed decomposition yields the corresponding carbenes or metal carbenoids, which subsequently undergo various transformations. Modern chemistry of diazo compounds is dominated by transition metal catalysis, leaving both catalyzed and non-catalyzed phototransformations of these reagents behind. Recently, photoinitiated reactions of diazo compounds have experienced a revival of interest due to the increased understanding of modern photochemistry. This mini-review covers recently published (year >2000) reports on the reactivity of diazo compounds under light irradiation.
174 citations
TL;DR: This review article highlights the Ugi, Groebke-Blackburn-Bienaymé, Biginelli, Huisgen, Petasis, Gewald, and Asinger reaction-initiated consecutive MCRs.
Abstract: Multicomponent reactions (MCRs) involving a minimum of three reactants or reaction centers are conducted in one pot and with a single operational step This synthetic method has a good pot, atom and step economy in the preparation of diverse and complex molecular scaffolds Consecutive MCRs, also known as sequential or multiple MCRs, by combining two or more MCRs, exhibit even higher synthetic efficiency, product structural diversity, and molecular complexity This review article highlights the Ugi, Groebke-Blackburn-Bienayme, Biginelli, Huisgen, Petasis, Gewald, and Asinger reaction-initiated consecutive MCRs
168 citations
TL;DR: The replacement of para-substituted benzenes with saturated bi- and polycyclic bioisosteres often increases the potency, selectivity and metabolic stability of bioactive compounds, however, the currently remaining challenge for chemists is to rationally design, synthesize and validate the saturated bioisOSTeres for ortho- and meta- Substantial Benzenes.
Abstract: The replacement of para-substituted benzenes with saturated bi- and polycyclic bioisosteres – bicyclo[1.1.1]pentane, bicyclo[2.2.2]octane and cubane, – often increases the potency, selectivity and metabolic stability of bioactive compounds. The currently remaining challenge for chemists, however, is to rationally design, synthesize and validate the saturated bioisosteres for ortho- and meta-substituted benzenes.
162 citations
TL;DR: This review will focus on the recent achievements, mainly including arylation, alkylation, acylation, alkoxycarbonylation, amination, amidation and phosphonation of quinoxalin-2(1H)-ones.
Abstract: The direct C3-functionalization of quinoxalin-2(1H)-ones via C–H bond activation has recently attracted considerable attention, due to their diverse biological activities and chemical properties. This review will focus on the recent achievements, mainly including arylation, alkylation, acylation, alkoxycarbonylation, amination, amidation and phosphonation of quinoxalin-2(1H)-ones. Their mechanisms are also discussed.
133 citations
TL;DR: In the last few years, organic dyes have been utilized as an attractive alternative to transition metal catalyzed photocatalysis as discussed by the authors, which has been widely applied as a photocatalyst in organic synthesis due to its low cost and easy accessibility.
Abstract: In the last few years, organic dyes have been utilized as an attractive alternative to transition metal catalyzed photocatalysis. Rose Bengal, an organic dye has been widely applied as a photocatalyst in organic synthesis due to its low cost and easy accessibility. In this review, we summarize the key photophysical properties of the dye and its synthetic applications in the formation of C-C and C-X (N, O, S, P, Si, and Se) bonds.
97 citations
TL;DR: Sulfur polymer composites released nutrients in a controlled fashion, resulting in less wasted fertiliser and better health for potted tomato plants when compared to free NPK.
Abstract: Sulfur polymer composites were prepared by the reaction of canola oil and elemental sulfur in the presence of the NPK fertiliser components ammonium sulfate, calcium hydrogen phosphate, and potassium chloride. These composites released nutrients in a controlled fashion, resulting in less wasted fertiliser and better health for potted tomato plants when compared to free NPK.
93 citations
TL;DR: In this review, recent applications of a stereoselective aza-Michael reaction as an efficient tool for the asymmetric synthesis of naturally occurring nitrogen-containing heterocyclic scaffolds and their usefulness to pharmacology are reviewed and summarized.
Abstract: The prevalence of nitrogen containing heterocycles in natural products and pharmaceuticals is a doubtless fact. In this review, recent applications of a stereoselective aza-Michael reaction as an efficient tool for the asymmetric synthesis of naturally occurring nitrogen-containing heterocyclic scaffolds and their usefulness to pharmacology are reviewed and summarized. The available data are for the first time classified according to types of heterocyclic products and subdivided in accordance with synthetic methodologies used as key stereocontrolling steps (diastereoselective or enantioselective reactions, single bond-forming or cascade reactions, etc.). This classification is convenient for organic chemists and for researchers working in the areas of natural product synthesis and medicinal chemistry. Specific attention is paid to organocatalytic asymmetric versions of the aza-Michael reaction developed over the past decade.
90 citations
TL;DR: Difluoromethylation of alkenes, isonitriles and aryl bromides promoted by photoredox catalysis is described together with a non-catalytic photoinduced system.
Abstract: Recently, photoinduced radical difluoromethylation has emerged as a step-economical synthetic method of CHF2-containing compounds. In this article, difluoromethylation of alkenes, isonitriles and aryl bromides promoted by photoredox catalysis is described together with a non-catalytic photoinduced system. Representative reactions will be discussed for each highlighted difluoromethylating reagent. In addition, related monofluoromethylation with their corresponding monofluoromethylating reagents is also discussed.
83 citations
TL;DR: The progress achieved in this area inspires us to develop new strategies, including the combination of photocatalysis with other catalytic modes and the design and synthesis of multifunctional chiral photocatalysts in an attempt to incorporate chirality into the photo-mediated chemical transformations.
Abstract: Asymmetric visible-light photocatalysis has recently drawn considerable attention of the scientific community owing to its unique activation modes and significance for the enantioselective green synthesis. In this review, the recent advances in the visible-light-triggered enantioselective synthesis, classified by different catalytic strategies, are summarized. The progress achieved in this area inspires us to develop new strategies, including the combination of photocatalysis with other catalytic modes and the design and synthesis of multifunctional chiral photocatalysts, in an attempt to incorporate chirality into the photo-mediated chemical transformations.
TL;DR: An up-to-date summary of fluorogenic probes applied to super-resolution imaging of cellular structures and several excellent reviews summarize recent developments in SRM techniques, labeling techniques or different aspects of small synthetic fluorophores are summarized.
Abstract: Fluorogenic probes efficiently reduce non-specific background signals, which often results in highly improved signal-to-noise ratios. Although this implies improved resolution, fluorogenic probes in the context of super-resolution microscopy are somewhat overlooked. Several excellent reviews summarize recent developments in SRM techniques, labeling techniques or different aspects of small synthetic fluorophores, however there is no comprehensive review on fluorogenic probes suitable for super-resolution microscopy. Herein we wish to fill this gap by providing the readers with an up-to-date summary of fluorogenic probes applied to super-resolution imaging of cellular structures.
TL;DR: This present review focuses on the most recent developments on Co-catalysed C(sp2)-H and C( sp3)-H functionalizations.
Abstract: Ready availability, low cost and low toxicity of cobalt salts have redirected the attention of researchers away from noble metals, such as Pd, Rh, and Ir, towards Co in the field of C–H functionalization. In this context, the examples of Co-catalysed functionalization have exponentially grown over the last few decades. This present review focuses on the most recent developments on Co-catalysed C(sp2)–H and C(sp3)–H functionalizations. Included is also a comprehensive overview of enantioselective transformations.
TL;DR: The present review gives an overview over non-toxic cyanation agents and cyanide sources used in the synthesis of structurally diverse products containing the nitrile function.
Abstract: The present review gives an overview over non-toxic cyanation agents and cyanide sources used in the synthesis of structurally diverse products containing the nitrile function. Nucleophilic as well as electrophilic agents/systems that transfer the entire CN-group were taken in consideration. Reactions in which a preexisting carbon functionality is transformed into a nitrile function by addition of nitrogen are however not covered here.
TL;DR: DNA-encoded libraries represent an exciting and powerful modality for high-throughput screening and some important directions that would make the technology even more powerful are suggested.
Abstract: DNA-encoded libraries represent an exciting and powerful modality for high-throughput screening. In this article, we highlight recent important advances in this field and also suggest some important directions that would make the technology even more powerful.
TL;DR: These CDPS-containing DKP pathways provide intriguing models of metabolic pathway evolution across related and divergent microorganisms, and open doors to synthetic biology approaches for generation of DKP combinatorial libraries.
Abstract: Microorganisms are remarkable chemists, with enzymes as their tools for executing multi-step syntheses to yield myriad natural products. Microbial synthetic aptitudes are illustrated by the structurally diverse 2,5-diketopiperazine (DKP) family of bioactive nonribosomal peptide natural products. Nonribosomal peptide synthetases (NRPSs) have long been recognized as catalysts for formation of DKP scaffolds from two amino acid substrates. Cyclodipeptide synthases (CDPSs) are more recently recognized catalysts of DKP assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. CDPS-encoding genes are typically found in genomic neighbourhoods with genes encoding additional biosynthetic enzymes. These include oxidoreductases, cytochrome P450s, prenyltransferases, methyltransferases, and cyclases, which equip the DKP scaffold with groups that diversify chemical structures and confer biological activity. These tailoring enzymes have been characterized from nine CDPS-containing biosynthetic pathways to date, including four during the last year. In this review, we highlight these nine DKP pathways, emphasizing recently characterized tailoring reactions and connecting new developments to earlier findings. Featured pathways encompass a broad spectrum of chemistry, including the formation of challenging C–C and C–O bonds, regioselective methylation, a unique indole alkaloid DKP prenylation strategy, and unprecedented peptide-nucleobase bond formation. These CDPS-containing pathways also provide intriguing models of metabolic pathway evolution across related and divergent microorganisms, and open doors to synthetic biology approaches for generation of DKP combinatorial libraries. Further, bioinformatics analyses support that much unique genetically encoded DKP tailoring potential remains unexplored, suggesting opportunities for further expansion of Nature's biosynthetic spectrum. Together, recent studies of DKP pathways demonstrate the chemical ingenuity of microorganisms, highlight the wealth of unique enzymology provided by bacterial biosynthetic pathways, and suggest an abundance of untapped biosynthetic potential for future exploration.
TL;DR: Advances in hypervalent iodine chemistry have put the field on the precipice of a second golden age; the first being pioneered in the 1990s and more recently, the development of hyperValent iodine-guided electrophilic substitution, arylations using hyper valent iodine, and photoredox reactions with hypervalents have shown great progress in the area of C-C bond formation.
Abstract: Advances in hypervalent iodine chemistry have put the field on the precipice of a second golden age; the first being pioneered in the 1990s. During that period, C–C bond forming reactions would be published but rarely with the intended goal of developing a C–C bond forming methodology. More recently, the development of hypervalent iodine-guided electrophilic substitution, arylations using hypervalent iodine, and photoredox reactions with hypervalent iodine have shown great progress in the area of C–C bond formation.
TL;DR: A clear overview of chemical warfare agents is offered to organic chemists not specialized in this field by introducing the main CWAs and their relevant simulants legally usable in academic laboratories and presenting a selection of recent and soft neutralisation methods.
Abstract: Despite international prohibition, some ill-intentioned states and organisations have shown their will and capacity to run chemical weapon programs, and the number of incidents involving chemical warfare agents (CWA) has significantly increased in recent years. Herein, we aimed to offer a clear overview of chemical warfare agents to organic chemists not specialized in this field by (1) introducing the main CWAs and their relevant simulants legally usable in academic laboratories and (2) presenting a selection of recent and soft neutralisation methods, such as organocatalysis and continuous flow, and materials such as metal–organic frameworks and polyoxometalates. These modern approaches offer potential future alternatives to “heavy” decontamination methods.
TL;DR: In this paper, the authors summarized some interesting cascade reaction based synthesis designs leading to complex indole polycycles including some biologically intriguing and natural product inspired indole frameworks, and then they proposed a cascade reaction-based approach to build various molecular scaffolds.
Abstract: Indole polycycles are common structural frameworks of biologically intriguing small molecules of natural and synthetic origin and therefore remain interesting and challenging synthetic targets. Cascade reactions wherein a number of reactions occur in a sequential manner in the same reaction apparatus are highly efficient chemical processes which quickly build up molecular complexity. Synthetic approaches based on cascade reactions are highly useful as they tend to avoid multiple reaction work-up steps as well as purifications of all intermediary products. Therefore, in the last decade, a number of cascade reaction based approaches to build various molecular scaffolds of biological interest have been reported. However, a relatively smaller number of cascade reaction based synthetic strategies have targeted the indole polycycles. In this article, we have summarized some interesting cascade reaction based synthesis designs leading to complex indole polycycles including some biologically intriguing and natural product inspired indole frameworks.
TL;DR: An overview of the broad spectrum of chemical reactivity of dhAAs, with special emphasis on recent efforts to adapt such transformations for biomolecules such as natural products, peptides, and proteins.
Abstract: α,β-Dehydroamino acids (dhAAs) are noncanonical amino acids that are found in a wide array of natural products and can be easily installed into peptides and proteins. dhAAs exhibit remarkable synthetic flexibility, readily undergoing a number of reactions, such as polar and single-electron additions, transition metal catalyzed cross-couplings, and cycloadditions. Because of the relatively mild conditions required for many of these reactions, dhAAs are increasingly being used as orthogonal chemical handles for late-stage modification of biomolecules. Still, only a fraction of the chemical reactivity of dhAAs has been exploited in such biorthogonal applications. Herein, we provide an overview of the broad spectrum of chemical reactivity of dhAAs, with special emphasis on recent efforts to adapt such transformations for biomolecules such as natural products, peptides, and proteins. We also discuss examples of enzymes from natural product biosynthetic pathways that have been found to catalyze many similar reactions; these enzymes provide mild, regio- and stereoselective, biocatalytic alternatives for future development. We anticipate that the continued investigation of the innate reactivity of dhAAs will furnish a diverse portfolio dhAA-based chemistries for use in chemical biology and drug discovery.
TL;DR: The responsiveness of such vesicles to various external stimuli and their applications in drug delivery are highlighted and the outstanding performance of pillar[n]arene-based supramolecular vesicle would definitely enrich the family of supramolcular vESicles and promote the development of dynamic supramolescular materials.
Abstract: Supramolecular vesicles have attracted considerable attention due to their advantages of facile construction, high-cargo-loading capacity, and good biocompatibility. Pillar[n]arenes are a unique family of supramolecular macrocycles, exhibiting excellent features and broad applications due to their intrinsic topology and high functionality. In the past decade, the construction of pillar[n]arene-based supramolecular vesicles has been continuously attempted and developed rapidly. In this review, we mainly summarize the significant advancements of such supramolecular vesicles in the last three years. By showing some representative examples, the design strategies, construction methods, and potential applications of these dynamic nanocarriers are discussed in detail. In particular, the responsiveness of such vesicles to various external stimuli and their applications in drug delivery are highlighted. The outstanding performance of pillar[n]arene-based supramolecular vesicles would definitely enrich the family of supramolecular vesicles and promote the development of dynamic supramolecular materials.
TL;DR: The results of in vitro studies reveal that Lyso-BTC is lysosome-targeted and could be applied for the detection of viscosity changes inLysosomes caused by chloroquine treatment and confirm that Lys-BTC could be employed to monitor lysOSomal viscosities changes in living cells.
Abstract: Lysosomes, as the cellular recycling center, are filled with numerous hydrolases that can degrade most cellular macromolecules. Studies have shown that the abnormality of viscosity in lysosomes will disrupt the normal function of lysosomes. Herein, a D-π-A structure near-infrared fluorescent probe containing N,N-dimethylamino benzene as an electron donor, benzothiozole as an electron acceptor, and a vinyl group as a π unit, Lyso-BTC, is explored for fluorescence imaging of lysosomes and detection of lysosomal viscosity changes. Lyso-BTC exhibits a large Stokes shift (∼180 nm), NIR emission (685 nm), good biocompatibility, excellent photostability, and fluorescence response to viscosity. Moreover, the results of in vitro studies reveal that Lyso-BTC is lysosome-targeted and could be applied for the detection of viscosity changes in lysosomes caused by chloroquine treatment. These results confirm that Lys-BTC could be employed to monitor lysosomal viscosity changes in living cells.
TL;DR: A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described, which exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin (1H)ones in good yields.
Abstract: A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described. This protocol employs cheap and readily available phenyliodine(III) dicarboxylates as the alkylation reagents to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones in good yields.
TL;DR: The present review, classified according to the types of synthetic methods involved, encompasses all recent developments in the field of transition-metal-free iodine(iii)-catalyzed/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.
Abstract: Late stage functionalization (LSF) through direct X-H manipulations (X = C, N) enables synthetic chemists to accelerate the diversification of natural products, agrochemicals and pharmaceuticals allowing rapid access to novel bioactive molecules without resorting to arduous de novo synthesis. LSF does not only allow tapping of the hitherto unexplored chemical space but also renders the synthetic sequence more straightforward, atom economical and cost-effective. In this regard, the recent decade has witnessed the emergence of hypervalent iodine(iii) reagents as a powerful synthetic tool owing to their easy availability, mild reaction conditions, remarkable oxidizing properties and high functional group tolerance. Iodine(iii) reagents have tremendous applications in the regio- and chemo-selective late-stage functionalization of a diverse variety of heterocycles through an exciting range of transformations, such as oxidative amination, cross-dehydrogenative coupling (CDC), fluoroalkylation, azidation, halogenation and oxidation. The present review, classified according to the types of synthetic methods involved, encompasses all these recent developments in the field of transition-metal-free iodine(iii)-catalyzed/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.
TL;DR: This review highlights the developments in palladium-catalyzed allylic C-H functionalization from early 2014 to the present date.
Abstract: This review highlights the developments in palladium-catalyzed allylic C–H functionalization from early 2014 to the present date. π-Allylpalladium chemistry emphasizes the research originating from less appealing stoichiometric Pd(II) based allylic C–H activation to the present day green, step- and atom-economical and sustainable strategy, wherein the allylic hydrogen atom becomes the “leaving group”. This constitutes a direct C–H activation method, which is essentially catalytic in the presence of a terminal oxidant to regenerate the Pd(II)-species from Pd(0). The availability of chiral ligands, under oxidative conditions, has paved the way to realize asymmetric oxidative Tsuji–Trost allylic alkylations.
TL;DR: An efficient protocol through photocatalytic decarboxylation coupling reactions of quinoxalin-2(1H)-ones with N-hydroxyphthalimide ester was developed and provides an alternative way to obtain various valuable corresponding products in moderate-to-good yields.
Abstract: An efficient protocol to synthesize 3-alkylated quinoxalin-2(1H)-ones through photocatalytic decarboxylation coupling reactions of quinoxalin-2(1H)-ones with N-hydroxyphthalimide ester was developed. The control experiment showed that a radical was involved in this transformation. This approach provides an alternative way to obtain various valuable corresponding products in moderate-to-good yields.
TL;DR: In this review of the recent developments in organophotocatalyzed C-H bond functionalization reactions, visible light photoredox reactions have recently emerged as one of the most efficient and highly selective processes for the direct introduction of a functionality into organic molecules.
Abstract: Over the last decade, a variety of methodologies for the direct functionalization of C-H bonds have been developed. Among others, visible light photoredox reactions have recently emerged as one of the most efficient and highly selective processes for the direct introduction of a functionality into organic molecules. Easy reaction setups, as well as mild reaction conditions, make this approach superior to other methodologies applying transition metals or strong oxidants, in terms of both costs and substrate and functional group tolerance. In this review, the recent developments in organophotocatalyzed C-H bond functionalization reactions are presented.
TL;DR: This review comprehensively highlights the (2015-2019) article that focuses on the synthesis of carbazoles derived from an indole-template through transition-metal catalyzed C-H functionalization, metal-free cyclization, three-component reaction, and electrophilic iodocyclizations.
Abstract: Carbazoles are privileged nitrogen heterocycles that are present in a wide range of natural products, pharmaceuticals, and functional materials. Due to their wide application, various synthetic strategies are available in the literature using substituted amines or indoles as a substrate. Thus, this review comprehensively highlights the (2015-2019) article that focuses on the synthesis of carbazoles derived from an indole-template through transition-metal catalyzed C-H functionalization, metal-free cyclization, three-component reaction, and electrophilic iodocyclizations. The synthetic strategies described in this review provided diversely substituted carbazoles and few of them have profound pharmacological activity.
TL;DR: A practical method has been developed for the conversion of alkenes to β-keto/hydroxyl sulfones by their reaction with sulfonyl hydrazides under metal-free conditions and the key features of this reaction include readily available reagents, mild reaction conditions and broad substrate scope.
Abstract: A practical method has been developed for the conversion of alkenes to β-keto/hydroxyl sulfones by their reaction with sulfonyl hydrazides under metal-free conditions. This reaction proceeds through the oxidative addition of alkenes by sulfonyl radicals that are generated by visible-light induced oxidation of sulfonyl hydrazides. Notaly the reaction uses O2 as the terminal oxidant, instead of metal catalysts or oxidants like TBHP, leading to H2O and N2 as the clean by-products. The key features of this reaction include readily available reagents, mild reaction conditions and broad substrate scope.
TL;DR: A new generation of reagents (ArSO2SRf) as efficient sources of SCF3, SCF2H and more generally SRf groups are designed, considerably extending the portfolio of tools for the direct introduction of SRf moieties.
Abstract: In recent years, a renewal of interest was shown to the quest for new synthetic solutions to directly introduce emergent fluorinated groups (SRf) onto molecules. In this context, a new generation of reagents (ArSO2SRf) as efficient sources of SCF3, SCF2H and more generally SRf groups, was designed. Hence, potent solutions were developed for the synthesis of SRf-containing molecules, compounds of interest for drug and agrochemical research. This review highlights the recent advances made in the synthesis and the use of this new class of reagents, considerably extending the portfolio of tools for the direct introduction of SRf moieties.