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Angewandte Chemie (International Ed. in... Sep 2017The development of a new decarboxylative cross-coupling method that affords terminal and substituted alkynes from various carboxylic acids is described using both...
The development of a new decarboxylative cross-coupling method that affords terminal and substituted alkynes from various carboxylic acids is described using both nickel- and iron-based catalysts. The use of N-hydroxytetrachlorophthalimide (TCNHPI) esters is crucial to the success of the transformation, and the reaction is amenable to in situ carboxylic acid activation. Additionally, an inexpensive, commercially available alkyne source is employed in this formal homologation process that serves as a surrogate for other well-established alkyne syntheses. The reaction is operationally simple and broad in scope while providing succinct and scalable avenues to previously reported synthetic intermediates.
Topics: Alkynes; Decarboxylation; Esters; Molecular Structure; Nickel; Phthalimides; Thalidomide
PubMed: 28636185
DOI: 10.1002/anie.201705107 -
Chemical Reviews Oct 2018The hallmark of nucleophilic phosphine catalysis is the initial nucleophilic addition of a phosphine to an electrophilic starting material, producing a reactive... (Review)
Review
The hallmark of nucleophilic phosphine catalysis is the initial nucleophilic addition of a phosphine to an electrophilic starting material, producing a reactive zwitterionic intermediate, generally under mild conditions. In this Review, we classify nucleophilic phosphine catalysis reactions in terms of their electrophilic components. In the majority of cases, these electrophiles possess carbon-carbon multiple bonds: alkenes (section 2), allenes (section 3), alkynes (section 4), and Morita-Baylis-Hillman (MBH) alcohol derivatives (MBHADs; section 5). Within each of these sections, the reactions are compiled based on the nature of the second starting material-nucleophiles, dinucleophiles, electrophiles, and electrophile-nucleophiles. Nucleophilic phosphine catalysis reactions that occur via the initial addition to starting materials that do not possess carbon-carbon multiple bonds are collated in section 6. Although not catalytic in the phosphine, the formation of ylides through the nucleophilic addition of phosphines to carbon-carbon multiple bond-containing compounds is intimately related to the catalysis and is discussed in section 7. Finally, section 8 compiles miscellaneous topics, including annulations of the Hüisgen zwitterion, phosphine-mediated reductions, iminophosphorane organocatalysis, and catalytic variants of classical phosphine oxide-generating reactions.
Topics: Alcohols; Alkenes; Alkynes; Catalysis; Molecular Structure; Phosphines
PubMed: 30260217
DOI: 10.1021/acs.chemrev.8b00081 -
Annual Review of Chemical and... Jun 2022Natural products are a diverse class of biologically produced compounds that participate in fundamental biological processes such as cell signaling, nutrient... (Review)
Review
Natural products are a diverse class of biologically produced compounds that participate in fundamental biological processes such as cell signaling, nutrient acquisition, and interference competition. Unique triple-bond functionalities like isonitriles and alkynes often drive bioactivity and may serve as indicators of novel chemical logic and enzymatic machinery. Yet, the biosynthetic underpinnings of these groups remain only partially understood, constraining the opportunity to rationally engineer biomolecules with these functionalities for applications in pharmaceuticals, bioorthogonal chemistry, and other value-added chemical processes. Here, we focus our review on characterized biosynthetic pathways for isonitrile and alkyne functionalities, their bioorthogonal transformations, and prospects for engineering their biosynthetic machinery for biotechnological applications.
Topics: Alkynes; Biological Products; Biosynthetic Pathways
PubMed: 35236086
DOI: 10.1146/annurev-chembioeng-092120-025140 -
Chemical Reviews Jun 2021At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this... (Review)
Review
At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this concept has had diverse impact over a broad range of chemical and biological research due to the spatiotemporal control, high selectivity, and excellent product yields afforded by the combination of light and click chemistry. While the reactions designated as "photoclick" have many important features in common, each has its own particular combination of advantages and shortcomings. A more extensive realization of the potential of this chemistry requires a broader understanding of the physical and chemical characteristics of the specific reactions. This review discusses the features of the most frequently employed photoclick reactions reported in the literature: photomediated azide-alkyne cycloadditions, other 1,3-dipolarcycloadditions, Diels-Alder and inverse electron demand Diels-Alder additions, radical alternating addition chain transfer additions, and nucleophilic additions. Applications of these reactions in a variety of chemical syntheses, materials chemistry, and biological contexts are surveyed, with particular attention paid to the respective strengths and limitations of each reaction and how that reaction benefits from its combination with light. Finally, challenges to broader employment of these reactions are discussed, along with strategies and opportunities to mitigate such obstacles.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Photochemistry
PubMed: 33835796
DOI: 10.1021/acs.chemrev.0c01212 -
Organic & Biomolecular Chemistry Apr 2021Biomimetic natural product synthesis is generally straightforward and efficient because of its established feasibility in nature and utility in comprehensive synthesis,... (Review)
Review
Biomimetic natural product synthesis is generally straightforward and efficient because of its established feasibility in nature and utility in comprehensive synthesis, and the cost-effectiveness of naturally derived starting materials. On the other hand, nonbiomimetic strategies can be an important option in natural product synthesis since (1) nonbiomimetic synthesis offers more flexibility and can demonstrate the originality of chemists, and (2) the structures of derivatives accessible by nonbiomimetic synthesis can be considerably different from those that are synthesised in nature. This review summarises nonbiomimetic total syntheses of indole alkaloids using alkyne chemistry for constructing core structures, including ergot alkaloids, monoterpene indole alkaloids (mainly corynanthe, aspidosperma, strychnos, and akuammiline), and pyrroloindole and related alkaloids. To clarify the differences between alkyne-based strategies and biosynthesis, the alkynes in nature and the biosyntheses of indole alkaloids are also outlined.
Topics: Alkynes; Indole Alkaloids; Molecular Structure; Stereoisomerism
PubMed: 33908430
DOI: 10.1039/d0ob02577a -
Journal of the American Chemical Society May 2018The merger of open- and closed-shell elementary organometallic steps has enabled the selective intermolecular addition of nucleophilic radicals to unactivated alkynes. A...
The merger of open- and closed-shell elementary organometallic steps has enabled the selective intermolecular addition of nucleophilic radicals to unactivated alkynes. A range of carboxylic acids can be subjected to a CO extrusion, nickel capture, migratory insertion sequence with terminal and internal alkynes to generate stereodefined functionalized olefins. This platform has been further extended, via hydrogen atom transfer, to the direct vinylation of unactivated C-H bonds. Preliminary studies indicate that a Ni-alkyl migratory insertion is operative.
Topics: Alkenes; Alkylation; Alkynes; Decarboxylation; Molecular Structure
PubMed: 29664294
DOI: 10.1021/jacs.8b02834 -
Angewandte Chemie (International Ed. in... Jul 2021A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in...
A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine. The kinetics are on par with those of the fastest strain-promoted azide-alkyne cycloaddition reactions, the products regioselectively formed, the components sufficiently stable and easily installed, and the reaction suitable for cellular labeling.
Topics: Alkynes; Amination; Azides; Cycloaddition Reaction; Molecular Structure
PubMed: 34019705
DOI: 10.1002/anie.202104863 -
Bioconjugate Chemistry Nov 2023The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists... (Review)
Review
The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide-alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based pretargeting.
Topics: Click Chemistry; Radiochemistry; Azides; Radiopharmaceuticals; Cycloaddition Reaction; Alkynes
PubMed: 37737084
DOI: 10.1021/acs.bioconjchem.3c00286 -
Molecules (Basel, Switzerland) Feb 2023Dichalcogenides (disulfides and diselenides), as reactants for organic transformations, are important and widely used because of their potential to react with... (Review)
Review
Dichalcogenides (disulfides and diselenides), as reactants for organic transformations, are important and widely used because of their potential to react with nucleophiles, electrophilic reagents, and radical precursors. In recent years, in combination with photochemical technology, the application of dichalcogenides as stable radical reagents has opened up a new route to the synthesis of various sulfur- and selenium-containing compounds. In this paper, synthetic strategies for disulfides and diselenides and their applications with photochemical technology are reviewed: (i) Cyclization of dichalcogenides with alkenes and alkynes; (ii) direct selenylation/sulfuration of C-H/C-C/C-N bonds; (iii) visible-light-enabled seleno- and sulfur-bifunctionalization of alkenes/alkynes; and (iv) Direct construction of the C(sp)-S bond. In addition, the scopes, limitations, and mechanisms of some reactions are also described.
Topics: Sulfur; Selenium Compounds; Disulfides; Technology; Alkenes; Alkynes
PubMed: 36838986
DOI: 10.3390/molecules28041998 -
Chemical Reviews Jun 2021Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on... (Review)
Review
Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on multiple scientific disciplines, and its implementation within the nucleic acid field has enabled researchers to generate a wide variety of tools with application in biology, biochemistry, and biotechnology. Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds. Application of AAC chemistry to nucleic acids allows labeling, ligation, and cyclization of oligonucleotides efficiently and cost-effectively relative to previously used chemical and enzymatic techniques. In this review, we provide a guide to inexperienced and knowledgeable researchers approaching the field of click chemistry with nucleic acids. We discuss in detail the chemistry, the available modified-nucleosides, and applications of AAC reactions in nucleic acid chemistry and provide a critical view of the advantages, limitations, and open-questions within the field.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Nucleic Acids; Thermodynamics
PubMed: 33443411
DOI: 10.1021/acs.chemrev.0c00928