Electrophile ≈ Electrophile
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The Halogen Bond Open
The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In thi…
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Applications of the Conceptual Density Functional Theory Indices to Organic Chemistry Reactivity Open
Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literat…
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Cyclic (Alkyl)(amino)carbenes (CAACs): Recent Developments Open
Discovered in 2005, cyclic (alkyl)(amino)carbenes (CAACs) are among the most nucleophilic (σ donating) and also electrophilic (π‐accepting) stable carbenes known to date. These properties allow them to activate a variety of small molecules…
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The unique fluorine effects in organic reactions: recent facts and insights into fluoroalkylations Open
Fluoroalkylation reaction, featuring the transfer of a fluoroalkyl group to a substrate, is a straightforward and efficient method for the synthesis of organofluorine compounds. In fluoroalkylation reactions, fluorine substitution can dram…
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Silyl Radical Activation of Alkyl Halides in Metallaphotoredox Catalysis: A Unique Pathway for Cross-Electrophile Coupling Open
A strategy for cross-electrophile coupling has been developed via the merger of photoredox and transition metal catalysis. In this report, we demonstrate the use of commercially available tris(trimethylsilyl)silane with metallaphotoredox c…
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Photoredox-Mediated Routes to Radicals: The Value of Catalytic Radical Generation in Synthetic Methods Development Open
Photoredox catalysis has experienced a revitalized interest from the synthesis community during the past decade. For example, photoredox/Ni dual catalysis protocols have been developed to overcome several inherent limitations of palladium-…
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Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to S<sub>N</sub>1 and S<sub>N</sub>2 Processes Open
Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (SN1 and SN2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-bas…
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Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions Open
Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; howeve…
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Definition of the chalcogen bond (IUPAC Recommendations 2019) Open
This recommendation proposes a definition for the term “chalcogen bond”; it is recommended the term is used to designate the specific subset of inter- and intramolecular interactions formed by chalcogen atoms wherein the Group 16 element i…
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Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions Open
Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the th…
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Nickel-Catalyzed Dicarbofunctionalization of Alkenes Open
1,2-Dicarbofunctionalization of alkenes has emerged as an efficient synthetic strategy for preparing substituted molecules by coupling readily available alkenes with electrophiles and/or nucleophiles. Nickel complexes serve as effective ca…
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CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition Open
In organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors and carbonyl compounds. Recently, our group and others hav…
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Mechanisms of Nickel-Catalyzed Coupling Reactions and Applications in Alkene Functionalization Open
Nickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox potentials. These properties enable Ni catalysts to accommodate and stabili…
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Decarboxylative Cross-Electrophile Coupling of <i>N</i>-Hydroxyphthalimide Esters with Aryl Iodides Open
A new method for the decarboxylative coupling of alkyl N-hydroxyphthalimide esters (NHP esters) with aryl iodides is presented. In contrast to previous studies that form alkyl radicals from carboxylic acid derivatives, no photocatalyst, li…
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Iodine(III) Reagents in Radical Chemistry Open
The chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as…
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Metal-Catalyzed Carboxylation of Organic (Pseudo)halides with CO<sub>2</sub> Open
The recent years have witnessed the development of metal-catalyzed reductive carboxylation of organic (pseudo)halides with CO2 as C1 source, representing potential powerful alternatives to existing methodologies for preparing carboxylic ac…
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Redox Signaling by Reactive Electrophiles and Oxidants Open
The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous …
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Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross Couplings via C–N Bond Activation Open
We developed a strategy to harness alkyl amines as alkylating agents via C-N bond activation. This Suzuki-Miyaura cross coupling of alkylpyridinium salts, readily formed from primary amines, is the first example of a metal-catalyzed cross …
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Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening Open
Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversib…
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Reductive radical-polar crossover: traditional electrophiles in modern radical reactions Open
The concept of reductive radical-polar crossover (RRPCO) reactions has recently emerged as a valuable and powerful tool to overcome limitations of both radical and traditional polar chemistry.
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Synthesis of Diiron(I) Dithiolato Carbonyl Complexes Open
Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(μ-SR)2(CO)x centers at the active si…
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Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions Open
A cyclic catalyst to pair up sugars Linking sugar molecules together to make complex carbohydrates is a geometrical challenge. For a six-carbon sugar such as glucose, there are six different possible linkage sites and also two possible con…
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“Inverse Drug Discovery” Strategy To Identify Proteins That Are Targeted by Latent Electrophiles As Exemplified by Aryl Fluorosulfates Open
Drug candidates are generally discovered using biochemical screens employing an isolated target protein or by utilizing cell-based phenotypic assays. Both noncovalent and covalent hits emerge from such endeavors. Herein, we exemplify an "I…
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Advances in covalent kinase inhibitors Open
This comprehensive review details recent advances, challenges and innovations in covalent kinase inhibition within a 10 year period (2007–2018).
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Chemo- and Regioselective Lysine Modification on Native Proteins Open
Site-selective chemical conjugation of synthetic molecules to proteins expands their functional and therapeutic capacity. Current protein modification methods, based on synthetic and biochemical technologies, can achieve site selectivity, …
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Transition Metal (Ni, Cu, Pd)-Catalyzed Alkene Dicarbofunctionalization Reactions Open
Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditious…
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Rational Engineering of a Flavoprotein Oxidase for Improved Direct Oxidation of Alcohols to Carboxylic Acids Open
The oxidation of alcohols to the corresponding carbonyl or carboxyl compounds represents a convenient strategy for the selective introduction of electrophilic carbon centres into carbohydrate-based starting materials. The O2-dependent oxid…
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The Chemical Reactivity of Anthocyanins and Its Consequences in Food Science and Nutrition Open
Owing to their specific pyrylium nucleus (C-ring), anthocyanins express a much richer chemical reactivity than the other flavonoid classes. For instance, anthocyanins are weak diacids, hard and soft electrophiles, nucleophiles, prone to de…
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1,4-Dihydropyridines as Alkyl Radical Precursors: Introducing the Aldehyde Feedstock to Nickel/Photoredox Dual Catalysis Open
A Ni/photoredox dual catalytic cross-coupling is disclosed in which a diverse range of (hetero)aryl bromides are used as electrophiles, with 1,4-dihydropyridines serving as precursors to Csp3-centered alkyl radical coupling partners. The r…
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Enantioselective Electroreductive Coupling of Alkenyl and Benzyl Halides via Nickel Catalysis Open
An electrochemically-driven enantioselective nickel-catalyzed reductive cross-coupling of alkenyl bromides and benzyl chlorides is reported. The reaction forms products bearing allylic stereogenic centers with good enantioselectivity under…