Showing papers in "Synthesis in 2022"

DABSO – A Reagent to Revolutionize Organosulfur Chemistry

Abstract: The introduction of easy-to-handle SO2 surrogates has transformed the field of sulfur chemistry, enabling methodologies utilizing SO2 to be carried out without specialized apparatus, and paving the way for the development of new procedures. This review highlights some of the varied and significant developments associated with one of the most prominent SO2 surrogates: DABSO.1 Introduction2 DABSO3 Reactions with Nucleophilic Reagents4 Metal-Catalyzed Reactions4.1 Palladium-Catalyzed Reactions4.2 Other Transition-Metal Catalysis5 Radical Reactions5.1 Aryldiazonium Salts5.2 Other Aryl Radical Precursors5.3 Alkyl Radical Precursors6 Conclusion

Catalytic Enantioselective Synthesis of C–N Atropisomeric Heterobiaryls

Abstract: Abstract Molecules containing an atropisomeric C–N biaryl axis are gaining increasing attention in catalytic and medicinal chemistry. Despite this rising interest, relatively few approaches towards their catalytic enantioselective synthesis have been reported. Here we review these approaches, with a focus on the mechanism of asymmetric induction. Some common themes emerge: Brønsted acid catalysed cyclo-condensation and palladium-catalysed ring-closure are the most common and successful approaches. Meanwhile, the more direct but challenging axial C–N bond formation strategy remains in its infancy, with just two reports to-date. We hope this review will inform and inspire other researchers to develop new creative approaches to this important chemical motif. 1 Introduction 2 Cyclo-Condensation 3 Proximal C–N Bond Formation 4 Desymmetrisation of Intact Axes 5 ortho-C–H Functionalisation 6 Cycloaddition 7 Axial C–N Bond Formation 8 Atropisomeric N–N Axes: An Emerging Class of Heterobiaryls 9 Conclusion and Outlook

Organic Nitrating Reagents

Abstract: Nitro compounds are vital raw chemicals that are widely used in academic laboratories and industries for the preparation of various drugs, agrochemicals, and materials. Thus, nitrating reactions are of great importance for chemists and are even taught in schools as one of the fundamental transformations in organic synthesis. Since the discovery of the first nitrating reactions in the 19th century, progress in this field has been constant. Yet, for many years the classical electrophilic nitration approach using a mixture of strong mineral acids dominated the field. However, in recent decades, the attention of researchers has focused on new reactivity and new reagents that can provide access to nitro compounds in a practical and straightforward way under mild reaction conditions. Organic nitrating reagents have played a special role in this field since they have enhanced reactivity. They also allow nitration to be carried out in an ecofriendly and sustainable manner. This review examines the development and application of organic nitrating reagents.1 Introduction2 Organic Nitrating Reagents2.1 Alkyl Nitrites2.2 Nitroalkanes2.3 Alkyl Nitrates2.4 N-Nitroamides2.5 N-Nitropyrazole2.6 N-Nitropyridinium Salts3 Organic Nitrating Reagents Generated In Situ3.1 Acyl Nitrates3.2 Trimethylsilyl Nitrate3.3 Nitro Onium Salts4 Organic Nitronium Salts5 Organic Nitrates and Nitrites5.1 Ammonium Nitrates5.2 Heteroarylium Nitrates5.3 Other Organic Nitrates5.4 Organic Nitrites6 Conclusion and Outlook

Catalyst Engineering through Heterobidentate (N-X type) Ligand Design for Iridium-Catalyzed Borylation

Abstract: Iridium-catalyzed C-H activation and borylation reaction operate under mild conditions which enable easy and atom economical installation of a notably versatile boronate ester group in an arene, heteroarene, or aliphatic molecules. The standard catalytic system for the iridium-catalyzed borylation entails the usage of [Ir(cod)(OMe)]2 as a precatalyst, a bipyridine type ligand and B2pin2 or HBpin as a borylating agent. Initially, a bipyridine ligated trisboryl iridium-complex was generated, which enables borylation reaction and the regioselectivity is mainly governed by the steric of the substituent present on the ring. As a result, monosubstituted and 1,2 –disubstituted arenes give a mixture of isomers. Significant efforts of several research groups have helped to triumph over the selectivity issue for directed proximal C-H borylation by introducing the directing group and newly evolved ligands. This short review aims to summarize the recent elegant discoveries of the directed C(sp2)-H and C(sp3)-H borylation by using heterobidentate ligand (P/N-Si, N-B and N-C) coordinated iridium catalyst.

Recent Advances in the Synthesis and Medicinal Chemistry of SF 5 and SF 4 Cl Compounds

Abstract: This Short Review covers the most important advances published in the literature during the last five years, concerning the synthesis, chemical modification and applications of SF5- and SF4Cl-compounds in medicinal/bioorganic chemistry and materials science.

Recent Advances in Thianthrenation/Phenoxathiination Enabled Site-Selective Functionalization of Arenes

Abstract: Site-selective functionalization of simple arenes remains a paramount challenge due to the similarity of multiple C–H bonds in the same molecule with similar steric environment and electronic properties. Recently, the site-selective thianthrenation/phenoxathiination of arenes has become an attractive solution to reach this challenging goal and it has been applied in the late-stage functionalization of various bioactive molecules. This short review aims to summarize recent advances in the site-selective C–H functionalization of arenes via aryl thianthrenium salts, as well as mechanistic insights in the remarkable site-selectivity obtained in thianthrenation step.1 Introduction2 Site-Selective Thianthrenation of Arenes and Mechanistic Insight3 Thianthrenation-Enabled Site-Selective Functionalization of Arenes3.1 Thianthrenation-Enabled C(sp 2)–C Bond Formation Reaction3.2 Thianthrenation-Enabled C(sp 2)–X Bond Formation Reaction4 Conclusion and Outlook

Recent Advances in C–F Bond Activation of Acyl Fluorides Directed toward Catalytic Transformations by Transition Metals, N-Heterocyclic Carbenes, or Phosphines

Abstract: Studies on the activation of carbon–fluorine bonds have been reported intensively in recent years. Among them, acyl fluorides have been utilized as versatile reagents for acylation, arylation, and even fluorination. In this review, we focus on acyl fluorides as compounds with carbon-fluorine bonds and review recent advances in strategies for the activation of their C-F bonds, including 1) transition metal catalysis, 2) N-heterocyclic carbene (NHCs) catalysis, 3) organophosphine catalysis, and 4) classical nucleophilic substitution reactions.

Formation of a Naphthalene Framework by Rhodium(III)-Catalyzed Double C–H Functionalization of Arenes with Alkynes: Impact of a Supporting Ligand and an Acid Additive

Abstract: Abstract An efficient protocol has been developed for the synthesis of larger condensed arenes from aromatic hydrocarbons and internal alkynes. This protocol uses readily available [CpRhI2]n as a catalyst and Cu(OAc)2 as an oxidant and proceeds smoothly through undirected double C–H activation. The addition of trifluoroacetic acid has a crucial positive impact on the reaction selectivity and the yields of the target products. In contrast to the previously reported catalytic systems, the new conditions allow the use of both dialkyl- and diarylacetylenes with the same high efficiency.

Current Advances in Meerwein-type Radical Alkene Functionalizations

Abstract: Alkene functionalizations via Meerwein arylations are becoming increasingly attractive, especially since a variety of mild and sustainable methods for aryl radical generation are available today. This entails a broad spectrum of substrates and radical scavengers, as well as convenient synthetic routes to relevant precursors for further transformations. The present review focuses on recent advances in Meerwein-type alkene functionalizations and gives insights into the key mechanistic details of the respective reactions.1 Introduction2 Hydroarylation and Carboarylation3 Carboamination, Carbooxygenation, and Carbothiolation4 Carbohalogenation5 Conclusion and Outlook

Recent advances to mediate reductive processes of nitroarenes using single electron transfer-, organomagnesium-, or organozinc reagents

Abstract: Recent advances in the development of reductive reactions of nitroarenes using organomagnesium-, organozinc-, and single electron transfer reagents is discussed within this review. The review is divided into the following sections: 1 Introduction 2 Organomagnesium-mediated reductive reactions 3 Organozinc- and zinc-mediated reductive reactions 4 Iodine-catalyzed redox cyclizations 5 Titanium(III)-mediated reductive cyclizations 6 Sulfur-mediated reductive reactions 7 Alkoxide-mediated reductive reactions 8 4,4'-Bipyridine-mediated reductive reactions 9 Visible light-driven reductive amination reactions 10 Electrochemical reductive reactions 11 Conclusion

Synthesis of P- and S-Stereogenic Compounds via Enantioselective C−H Functionalization

Abstract: Transition metal-catalyzed enantioselective C−H functionalization has emerged as an efficient and powerful strategy to access various chiral molecules. Recently, this strategy also provided a complementary pathway to the construction of P- and S-stereogenic compounds. In this short review, we summarize the development and applications of various catalytic systems, including Pd(II)/MPAA, Pd(0)/trivalent phosphorus chiral ligand, chiral CpxM(III) (M = Rh, Ir), half-sandwich d6 Ir(III) and Ru(II) with chiral carboxylic acid (CCA) ligand, Ir(I)/chiral bidentate boryl ligand, and Ir(I)/chiral cation, in the access of these chiral compounds via enantioselective C−H functionalization.

Research progress on N-heterocyclic carbene catalyzed reactions for synthesizing ketones through radical mechanism

Abstract: Recently NHC-catalyzed radical cross-coupling reactions have sprung up, which provided an efficient method to access ketones from aldehydes or carboxylic acid derivatives with sp3-hybridized carbon radical precursors. It has indirectly solved the limitation of coupling partners scope in NHC umpolung catalysis of aldehydes. In this short review, we present some of the recent advances in NHC-catalyzed radical reactions, with a focus on the construction of C-C(CO) bond.

Povarov Reaction: A Versatile Method to Synthesize Tetrahydroquinolines, Quinolines and Julolidines

Abstract: Multicomponent Povarov reaction is a powerful approach for the construction of N-heterocyclic containing substances. By using Povarov reaction, in addition to accessing tetrahydroquinolines, quinolines and julolidines in a single step, it is possible to form, respectively, two new Csp3-Csp3 and one Csp3-Nsp3 bonds, two new Csp2-Csp2 and one Csp2-Nsp2 bonds and four Csp3-Csp3 and two Csp3-Nsp1 bonds. This review article reports the main features of the Povarov reaction such as its mechanism, the scope of such reaction concerning to different catalysts and substrates used on it as well as the stereoselective versions of Povarov reaction

Silver-Catalyzed One-Pot Biarylamination of Quinones with Arylamines: Access to N-Arylamine-Functionalized p-Iminoquinone Derivatives

Abstract: Concise one-pot biarylamination of quinones with arylamines was developed to synthesize N-arylamine-functionalized p-iminoquinones derivatives. The approach employed AgOAc as the catalyst and (NH4)2S2O8 as the oxidant in the presence of 3-chlorophenylboronic acid, giving a series of N-arylamine-functionalized p-iminoquinone derivatives in moderate to good yields whereas reaction in the absence of the 3-chlorophenylboronic acid, gave a series of N-arylamine-functionalized 1,4-naphthoquinone derivatives. This catalytic approach represents a step-economic and convenient strategy for the difunctionalization of quinones.

Recent Progress on Transition-Metal-Mediated Reductive C(sp3)‒O Bond Radical addition and Coupling Reactions

Abstract: In this mini review, we summarized the recent development of thermo-driven C(sp3)‒O bond radical scission methods and their applications in the construction of C(sp3)‒C bonds via conjugate additions with activated double bonds and reductive coupling mediated by economic 3d metals, in particular nickel. We assort the review based on the approaches of C(sp3)‒O bond radical scission in three folds (see below). Upon creation of the radical intermediates, subsequent transformation into C(sp3)‒C bonds that enables C(sp3)‒O cross-electrophile coupling with carbon electrophiles are discussed in depth. 1. Direct SET to C(sp3)‒O bond 2. Radical scission of activated C(sp3)‒O bonds via SET to the protecting groups 3. In situ activation of alcohols 4. Summary and outlook

State-of-the-Art Advances in Enantioselective Transition-Metal-Mediated Reactions of Silacyclobutanes

Abstract: Studies on the enantioselective transformation of silacyclobutanes (SCBs) have become an emerging topic in the recent decade, due to the feature of high ring strain, and manageable Si-C bond cleavage and formation. This short review summarized the remarkable achievements in the asymmetric transition-metal-mediated reaction of silacyclobutanes and benzosilacyclobutaenes, resulting in carbon- or silicon-stereogenic organosilanes with functional substituents.

Recent Advances in Transition-Metal-Catalyzed Asymmetric Functionalization of Enamides

Abstract: Abstract Enamides, as prefunctionalized electron-rich heteroatom-substituted alkenes represent a powerful platform to synthesize useful nitrogen-containing natural products and bioactive molecules. This review discloses recent progress in the transition-metal-catalyzed enantioselective functionalization of enamides, including the Heck reaction, hydrofunctionalization, and difunctionalization, with a focus on the general scope, current limitations, stereochemical reaction control, and mechanistic aspects. 1 Introduction 2 Asymmetric Heck Reaction of Enamides 3 Asymmetric Hydrofunctionalization of Enamides 3.1 Nickel Catalysis 3.2 Copper Catalysis 3.3 Rhodium Catalysis 3.4 Iridium Catalysis 4 Asymmetric Difunctionalization of Enamides 4.1 Palladium Catalysis 4.2 Nickel Catalysis 4.3 Copper Catalysis 5 Summary and Outlook

Acrylamide-based Pd-Nanoparticle Carriers as Smart Catalyst for the Suzuki-Miyaura Cross-Coupling of Amino Acids

Abstract: Polyacrylamide-based waterborne microgels were prepared with copolymerized carboxylic acid and tertiary amine moieties. The colloidal gels were loaded with palladium nanoparticles and utilized for the Suzuki-Miyaura cross-coupling of amino acids and peptides. The thermoresponsive properties of the prepared microgels were characterized by means of photon correlation spectroscopy (PCS) at solvent conditions of the catalytic reaction. The localization and morphology of the incorporated nanoparticles were characterized with transmission electron microscopy (TEM). Palladium-catalyzed Suzuki-Miyaura cross-coupling of Nα-Boc-4 iodophenylalanine and Nα-Boc-7-bromotryptophan with phenylboronic acid was carried out under ambient atmosphere in water at 20 °C, 37 °C and 60 °C, respectively. The properties of the thermoresponsive microgel showed a strong influence on the reactivity and selectivity towards the respective substrate. For the amine containing microgels a recyclability for up to four cycles without loss in activity could be realized. Furthermore, the systems showed good catalytic activity regarding Suzuki-Miyaura cross-coupling of halogenated amino acids in selected tri- and tetrapeptides.

An Alternative to the Arbuzov Reaction: Generation and Transformation of α-Dialkyl-Substituted Methylphosphonate Carbanions via an SET Reduction Process

Abstract: With B-alkyl Suzuki cross coupling as the strategy, 1-alkyl substituted ethenylphosphonates could be efficiently accessed via palladium-catalyzed reactions of α-phosphonovinyl tosylate with B-alky-9-BBN. Using α-alkyl ethenylphosphonates as the radical acceptors, visible-light-driven photocatalytic Giese-type and cyclopropanation reactions based on reductive radical-polar crossover have been successfully developed. The redox-neutral photocatalysis serves as a viable strategy for the preparation of various 1,1-dialkyl substituted methylphosphonates and 1-alkylcyclopropylphosphonates.

Photochemical activation of sulfur hexafluoride – a tool for fluorination and pentafluorosulfanylation reactions

Abstract: The photoactivation of notoriously inert sulfur hexafluoride represents a challenge for photochemistry. This short review summarizes recently published efforts and the corresponding photochemical mechanisms for switching between the fluorination and pentafluorosulfanylation reactivity of organic substrates: 1 Introduction, 2 Sulfur hexafluoride (SF6), 3 The pentafluorosulfanyl (SF5) group, 4 Photoredox catalytic activation of SF6, 5 Conclusions.

Flow hydrogenation of 1,3,5-trinitrobenzenes over Cu-based catalysts as an efficient approach for the preparation of phloroglucinol derivatives

Abstract: An environmentally friendly and safe synthesis of phloroglucinol and its derivatives through the flow hydrogenation of 1,3,5-trinitrobenzenes on heterogeneous copper catalysts is reported. It was found that hydrogenation of 1,3,5-trinitrobenzene, 2,4,6-trinitrotoluene 2,4,6-trinitroxylene and 2,4,6-trinitromesitylene in methanol over Cu-Al mixed oxides derived from layered double hydroxides provides the selective formation of the corresponding triaminobenzenes, which were isolated from the reaction mixture in the form of double salts with sulfuric acid stable in storage. The subsequent hydrolysis in aqueous solution gives phloroglucinol derivatives in good yields (75–82%).

Survey of New, Small-Molecule Isatin-Based Oxindole Hybrids as Multi-Targeted Drugs for the Treatment of Alzheimer’s Disease

Abstract: Abstract In the last decade, our group has been very active at developing and assaying complex libraries of scaffolds with a focus on their potential to identify bioactive drug candidates for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Attention has been focused on isatin-based oxindole scaffolds, for which promising results concerning butyrylcholinesterase (BuChE) inhibitory activity have previously been obtained. Considering some published reports and detailed analysis of the pharmacophores of commercially available drugs for AD (powerful cholinesterase (ChE) inhibitors), we performed a strategic structural modification of the isatin core and generated a new family of isatin-based oxindole hybrids (27 new compounds) possessing crucial key functional units in their framework. The syntheses were accomplished using multiple approaches, including simple N-alkylation reactions, copper-catalyzed amination reactions, and click chemistry. The resulting library was evaluated on ChE and MAO enzymes, both of which are involved in the pathophysiology of neurodegeneration. IC50 values of 1.6 and 2.6 μM (BuChE assays), were achieved for the best inhibitors.

Synthesis of Peptide N-Acylpyrroles via Anodically Generated N,O-Acetals

Abstract: An electrochemical approach to peptide C-terminal N-acylpyrroles is described from readily accessible C-terminal hydroxyproline-containing peptides, prepared via standard Fmoc solid-phase peptide synthesis (Fmoc-SPPS). Following electrochemical decarboxylation, the reactive hydroxyproline-derived N,O-acetal intermediate is aromatized under mild acidic conditions, which enable concomitant deprotection of amino acid side-chain protecting groups. The resulting peptide N-acylpyrrole is amenable to late-stage peptide modifications, including reduction with NaBH4 to deliver a valuable C-terminal peptide aldehyde motif.

Developments in the alkynyltrifluoromethylations of alkenes and alkynes

Abstract: As a consequence of the expanding relevance of fluorine-containing organic molecules in drug research, the synthesis of organofluorine scaffolds has received high significance in synthetic organic chemistry. Trifluoromethylative difunctionalizations of carbon–carbon multiple bonds, with the simultaneous introduction of a CF3 group and another function, have considerable potential. Considering the high importance of carbon–carbon bond-forming reactions in organic synthesis, carbotrifluoromethylations and, in particular, alkynyltrifluoromethylations are considered to be increasing areas of synthetic chemistry. Alkynyltrifluoromethylation is a narrow segment and a relatively new approach in synthetic chemistry, however it has not been reviewed so far. Therefore, our goal in the current minireview is to summarize the recent developments of alkynyltrifluoromethylation reactions taking into consideration several main aspects, such as (a) alkynyltrifluoromethylation reactions of alkenes including (i) reactions involving intramolecular alkynyl migration and (ii) intermolecular transformations as well as (b) alkynyltrifluoromethylation reactions of alkynes.

Activation Modes in Asymmetric Anion-Binding Catalysis

Abstract: Abstract Over the past two decades, enantioselective anion-binding catalysis has emerged as a powerful strategy for the induction of chirality in organic transformations. The stereoselectivity is achieved in a range of different reactions by using non-covalent interactions between a chiral catalyst and an ionic substrate or intermediate, and subsequent formation of a chiral contact ion pair upon anion binding. This strategy offers vast possibilities in catalysis and the constant development of new reactions has led to various substrate activation approaches. This review provides an overview on the different activation modes in asymmetric anion-binding catalysis by looking at representative examples and recent advances made in this field. 1 Introduction 2 Electrophile Activation by Single Anion-Binding Catalysis 2.1 Prior In Situ Charged Electrophiles 2.2 Neutral Electrophile Activation via Anion Abstraction 2.2.1 Anion Abstraction via an SN1 Mechanism 2.2.2 Anion Abstraction via an SN2 Mechanism 3 Nucleophile Activation and Delivery 4 Bifunctional and Cooperative Co-catalysis Strategies 4.1 Amine Groups for Bifunctional and Cooperative Catalysis 4.2 Brønsted Acid Co-catalysis 4.3 Lewis Acid Co-catalysis 4.4 Lewis Base Co-catalysis 4.5 Nucleophilic Co-catalysis for Activation of Electrophiles 4.6 Cooperative Metal and Anion-Binding Catalysis 4.7 Combination of Photoredox and Anion-Binding Catalysis 5 Anion-π Catalysis 6 Conclusion

Transition-Metal-Catalyzed Enantioselective Synthesis of Indoles from 2-Alkynylanilines

Abstract: Optically active indole derivatives are ubiquitous in natural products and widely recognized as privileged components in pharmacologically relevant compounds. Therefore, developing catalytic asymmetric approaches for constructing indole derivatives is highly desirable. In this short review, transition-metal-catalyzed enantioselective synthesis of indoles from 2-alkynylanilines is summarized. 1 Introduction 2 Aminometalation triggered asymmetric cross-coupling reaction/insertion 2.1 Asymmetric Cross-Coupling Reaction 2.2 Asymmetric insertion of C=O, C=C and C≡N bonds 3 Asymmetric relay catalysis 4 Conclusion

Recent Metal-Catalyzed Methods for Thioether Synthesis

Abstract: This review summarizes the more recent methods for the synthesis of thioethers using homogeneous metals as catalysts. The thioether moiety can be found in numerous compounds for pharmaceutical, agricultural or material applications and it is therefore important to develop new, efficient methods for their synthesis. The recent efforts in this field focus on the use of non-precious metal catalysts, as well as on the development of new bond-forming processes. 1 Introduction 2 Cross-couplings 3 C-H Activation 4 Hydrothiolation 5 Carbothiolation 6 Miscelaneous 7 Conclusion

Recent Developments in Transannular Reactions

Abstract: Transannular reactions have shown a remarkable performance for the construction of polycyclic scaffolds from medium- or large sized cyclic molecules in an unconventional manner. Recent examples of transannular reactions reported from 2011 have been reviewed, emphasizing the excellent performance of this approach when accessing the target compounds. This review also highlights how this methodology provides an alternative approach to other commonly used methodologies for the construction of cyclic entities such as cyclization or cycloaddition reactions

Advances in the synthesis of enterobactin, artificial analogues and enterobactin-derived antimicrobial drug conjugates and imaging tools for infection diagnosis

Abstract: Iron is an essential growth factor for bacteria, but although highly abundant in nature, its bioavailability during infection in the human host or the environment is limited. Therefore, bacteria produce and secrete siderophores to ensure their supply with iron. The tris-catecholate siderophore enterobactin and its glycosylated derivatives, the salmochelins, play a crucial role for iron acquisition in several bacteria. As these compounds can serve as carrier molecules for the design of antimicrobial siderophore drug conjugates as well as siderophore-derived tool compounds for the detection of infections with bacteria, their synthesis and the design of artificial analogues is of interest. In this review, we give an overview on the synthesis of enterobactin, biomimetic as well as totally artificial analogues and related drug-conjugates covering up to 12/2021.

(3+2) Cycloadditions of Vinyl Sulfonyl Fluorides with Ethyl Diazoacetate or Azides: Metal-Free Synthesis of Pyrazole and Triazole Scaffolds via SO2 Elimination

Abstract: A (3+2) cycloaddition reaction between substituted vinyl sulfonyl fluorides and ethyl diazoacetate or azides for the rapid construction of pyrazole or triazole cores via Michael addition and SO2 gas elimination is developed. Trimethylsilyl azide or organic azide selectively attacks at the β-carbon of vinyl sulfonyl fluoride rather than at the S(VI) center and generates C-substituted or C,N-disubstituted triazole. In contrast, vinyl sulfonyl fluorides react with ethyl diazoacetate to generate pyrazoles in good to high yields.