N–O Bond Activation by Energy Transfer Photocatalysis

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(17), P. 2526 - 2541

Published: Aug. 20, 2022

ConspectusA radical shift toward energy transfer photocatalysis from electron under visible-light photoirradiation is often due to the greener prospects of atom and process economy. Recent advances in embrace unique strategies for direct small-molecule activation sometimes extraordinary chemical bond formation absence additional/sacrificial reagents. Selective requires careful selection substrates photocatalysts a perfect match with respect their triplet energies while having incompatible redox potentials prevent competitive pathways. Substrates containing labile N–O bonds are potential targets generating reactive key intermediates via access variety functionalized molecules. Typically, differential densities N O heteroatoms have been exploited generation either N- or O-centered by pathway. However, latest developments involve homolysis generate both radicals subsequent utilization diverse organic transformations, also sacrificial In this Account, we highlight our contributions field intermediates, coverage useful mechanistic insights. More specifically, well-designed bond-containing such as 1,2,4-oxadiazolines, oxime esters, N-indolyl carbonates, N-enoxybenzotriazoles were successfully utilized versatile transformations involving selective over high state energy. Direct N-, O-, C-centered (if decarboxylation follows) was achieved cross-couplings rearrangement processes. particular, open-shell nitrogen including N(sp2) N(sp3) nitrenes, utilized. Notably, diversified identical through control reaction conditions. 1,2,4-Oxadiazolines converted into spiro-azolactams iminyl presence 1O2, benzimidazoles, sulfoximines external sulfoxide reagent nitrene inert Besides, esters underwent intramolecular C(sp3)–N radical–radical coupling intermolecular combined transfer–hydrogen strategy. Furthermore, series electrochemical photophysical experiments well computational studies performed substantiate proposed energy-transfer-driven We hope that Account will serve guide rational design processes further bonds.

Language: Английский

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Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Language: Английский

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Amino‐λ³‐iodane‐Enabled Electrophilic Amination of Arylboronic Acid Derivatives

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 26, 2024

Abstract In this report, we describe the use of amino‐λ 3 ‐iodanes in electrophilic amination arylboronic acids and boronates. Iodine(III) reagents with transferable amino groups, including one an NH 2 group, were synthesized used amination, allowing synthesis a wide range primary secondary (hetero)arylamines. Mechanistic studies by DFT calculations indicate that reaction proceeds through process from tetravalent borate complex B−N dative bond.

Language: Английский

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Recent advances in Chan–Lam coupling reaction

Catalysis Science & Technology, Journal Year: 2024, Volume and Issue: 14(9), P. 2320 - 2351

Published: Jan. 1, 2024

Chan–Lam coupling has evolved as a shining star among C–heteroatom reactions because of its greener open flask chemistry and tremendous possibilities in terms substrate bank, catalyst varieties, unlocking nature friendly conditions, etc.

Language: Английский

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Decarboxylative stereoretentive C–N coupling by harnessing aminating reagent

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 6, 2024

Abstract In recent decades, strategies involving transition-metal catalyzed carbon-carbon or carbon-heteroatom bond coupling have emerged as potent synthetic tools for constructing intricate molecular architectures. Among these, decarboxylative carbon-nitrogen formation using abundant carboxylic acids their derivatives has garnered notable attention accessing alkyl- arylamines, one of key pharmacophores. While several amination methods been developed, the involvement a common carboradical intermediate currently poses challenges in achieving stereospecific transformation toward chiral alkylamines. Herein, we present base-mediated, stereoretentive amidation by harnessing 1,4,2-dioxazol-5-one reactive and robust amidating reagent under transition-metal-free ambient conditions, encompassing all types primary, secondary tertiary acids, thereby providing access to important pharmacophore, α-chiral amines. This method exhibits high functional group tolerance, convenient scalability, ease applicability 15 N-isotope labeling, thus accentuating its utilities. Experimental computational mechanistic investigations reveal sequence elementary steps: i) nucleophilic addition carboxylate dioxazolone, ii) rearrangement form dicarbonyl N-hydroxy intermediate, iii) conversion hydroxamate, followed Lossen-type rearrangement, finally, iv) reaction situ generated isocyanate with leading C–N manner.

Language: Английский

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Iron-Catalyzed Intermolecular C–N Cross-Coupling Reactions via Radical Activation Mechanism

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14599 - 14607

Published: June 30, 2023

A concept for intermolecular C-N cross-coupling amination has been discovered using tetrazoles and aromatic aliphatic azides with boronic acids under iron-catalyzed conditions. The follows an unprecedented metalloradical activation mechanism that is different from traditional metal-catalyzed reactions. scope of the reaction demonstrated by employment a large number tetrazoles, azides, acids. Moreover, several late-stage aminations short synthesis drug candidate have showcased further synthetic utility. Collectively, this should wide applications in context medicinal chemistry, discovery, pharmaceutical industries.

Language: Английский

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Late-Stage Isotopic Exchange of Primary Amines

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24367 - 24374

Published: Oct. 27, 2023

Stable isotopes such as 2H, 13C, and 15N have important applications in chemistry drug discovery. Late-stage incorporation of uncommon via isotopic exchange allows for the direct conversion complex molecules into their valuable isotopologues without requiring a de novo synthesis. While synthetic methods exist hydrogen carbon atoms less abundant isotopes, corresponding method accessing 15N-primary amines from naturally occurring 14N-analogues has not yet been disclosed. We report an approach to access 15N-labeled primary late-stage using simple benzophenone imine source. By activating α-1 α-2° Katritzky pyridinium salts α-3° redox-active imines, we can engage alkyl deaminative amination. The imines proceed radical-polar crossover mechanism, whereas are engaged copper catalysis electron donor–acceptor complex. is general variety amines, including multiple compounds, results complete selective labeling.

Language: Английский

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Stereospecific Enzymatic Conversion of Boronic Acids to Amines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19160 - 19167

Published: July 3, 2024

Boronic acids and esters are highly regarded for their safety, unique reactivity, versatility in synthesizing a wide range of small molecules, bioconjugates, materials. They not exploited biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon–boron bonds rare. We wish to combine the advantages boronic molecular assembly with biocatalysis, which offers potential unsurpassed selectivity efficiency. Here, we introduce an engineered protoglobin nitrene transferase catalyzes new-to-nature amination using hydroxylamine. Initially targeting aryl acids, show enzyme produce array anilines high yields total turnover numbers (up 99% yield >4000 TTN), water boric acid as only byproducts. also demonstrate is effective bench-stable esters, hydrolyze situ corresponding acids. Exploring enzyme's capacity enantioselective catalysis, found racemic alkyl ester affords enantioenriched amine, transformation achieved chemocatalysts. The formation exclusively unrearranged product during radical clock reaction's stereospecificity support two-electron process akin 1,2-metallate shift mechanism. developed enables new routes chiral amines.

Language: Английский

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Photomediated reductive coupling of nitroarenes with aldehydes for amide synthesis

Chemical Science, Journal Year: 2022, Volume and Issue: 13(32), P. 9361 - 9365

Published: Jan. 1, 2022

In view of the widespread significance amide functional groups in organic synthesis and pharmaceutical studies, an efficient practical synthetic protocol that avoids use stoichiometric activating reagents or metallic reductants is highly desirable. A straight-forward pathway to access amides from abundant chemical feedstock would offer a strategic advantage complex amides. We herein disclose direct reductive amidation reaction using readily available aldehydes nitroarenes enabled by photo-mediated hydrogen atom transfer catalysis. It production toxic waste. While represent classic class electrophilic synthons, corresponding nucleophilic acyl radicals could be directly accessed photo catalysis, enabling polarity inversion. Our method provides orthogonal strategy conventional couplings, tolerating substituents such as free alcohols sensitive amines carbonyl formyl groups. The utilization this demonstrated late-stage modification biologically active molecules drug leflunomide lidocaine.

Language: Английский

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Advancement of vinylene carbonate as a coupling partner in metal-catalyzed C–H functionalization

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(22), P. 5717 - 5734

Published: Jan. 1, 2023

Vinylene carbonate (VC) has emerged as a promising coupling partner to participate in various attractive C–H conversions and implement an increasing number of novel reactions. In this review, we provide summary the advancements achieved metal-catalyzed functionalization using VC.

Language: Английский

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