C(sp3)–C(sp3) bond formation through nitrogen deletion of secondary amines using O-diphenylphosphinylhydroxylamine

Nature Synthesis, Год журнала: 2024, Номер 3(7), С. 913 - 921

Опубликована: Июнь 7, 2024

Язык: Английский

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Site‐Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines**

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(8)

Опубликована: Янв. 5, 2024

Abstract The introduction of trifluoromethyl groups into organic molecules is paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp 2 )−CF 3 bonds have been well established, the advancement practical comprehensive approaches forming remains considerably restricted. In this work, we describe an efficient site‐specific deaminative trifluoromethylation reaction aliphatic primary amines to afford corresponding alkyl compounds. proceeds at room temperature with readily accessible N ‐anomeric amide (Levin's reagent) bench‐stable bpyCu(CF ) (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. protocol features mild conditions, good functional group tolerance, moderate yields. Remarkably, method can be applied direct, late‐stage natural products bioactive molecules. Experimental mechanistic studies were conducted, a radical mechanism proposed, wherein dual roles Grushin's reagent elucidated.

Язык: Английский

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N‐(Sulfonio)Sulfilimine Reagents: Non‐Oxidizing Sources of Electrophilic Nitrogen Atom for Skeletal Editing

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(25)

Опубликована: Апрель 16, 2024

The one-pot synthesis of λ

Язык: Английский

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Evidence for Dearomatizing Spirocyclization and Dynamic Effects in the Quasi-stereospecific Nitrogen Deletion of Tetrahydroisoquinolines

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(26), С. 17719 - 17727

Опубликована: Июнь 20, 2024

Selectivity in organic chemistry is generally presumed to arise from energy differences between competing selectivity-determining transition states. However, cases where static density functional theory (DFT) fails reproduce experimental product distributions, dynamic effects can be examined understand the behavior of more complex reaction systems. Previously, we reported a method for nitrogen deletion secondary amines which relies on formation isodiazene intermediates that subsequently extrude dinitrogen with concomitant C-C bond via caged diradical. Herein, detailed mechanistic analysis 1-aryl-tetrahydroisoquinolines presented, suggesting this system previously determined diradical mechanism undergoes dynamically controlled partitioning both normal 1,5-coupling and an unexpected spirocyclic dearomatized intermediate, converges expected indane by unusually facile 1,3-sigmatropic rearrangement. This not reproduced DFT but supported quasi-classical molecular dynamics calculations unifies several unusual observations system, including partial chirality transfer, nonstatistical isotopic scrambling at ethylene bridge, isolation species related heterocyclic series, observation introduction 8-substituent dramatically improves enantiospecificity.

Язык: Английский

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Molecular Skeleton Editing for New Drug Discovery

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(16), С. 13509 - 13511

Опубликована: Авг. 12, 2024

Язык: Английский

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Precision single-atom editing: new frontiers in nitrogen insertion and substitution for the generation of N-heterocycles

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(14), С. 4041 - 4053

Опубликована: Янв. 1, 2024

This paper primarily focuses on the editing of nitrogen atoms, encompassing insertion N, substitution C with and utilization 15 N in place 14 for construction N-heterocycles.

Язык: Английский

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Palladium-catalyzed selective alkoxycarbonylation of different alcohols toward the direct synthesis of cyclobutanecarboxylates

Journal of Catalysis, Год журнала: 2025, Номер unknown, С. 115956 - 115956

Опубликована: Янв. 1, 2025

Язык: Английский

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Enantioselective total synthesis of lycoposerramine congeners through late-stage nitrogen deletion

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 15, 2025

Язык: Английский

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Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

ConspectusN-Heterocycles are essential in pharmaceutical engineering, materials science, and synthetic chemistry. Recently, skeletal editing, which involves making specific point changes to the core of a molecule through single-atom insertion, deletion, or transmutation, has gained attention for its potential modify complex substrates. In this context, insertion nitrogen atoms into carbocycles form N-heterocycles emerged as significant research focus modern chemistry owing novel logic. This distinctive retrosynthetic approach enables late-stage modification molecular skeletons provides different pathway synthesizing multiply substituted N-heterocycles. Nevertheless, atom proven challenging because inherent inertness carbon-based difficulty cleaving C-C bonds. Therefore, selective editing remains growing field Account primarily highlights contributions our laboratory active acknowledges key from other researchers. It is organized two sections based on type carbocycle. The first section explores cycloalkenes. Recent Co-catalyzed oxidative azidation strategies have enabled cyclobutenes, cyclopentenes, cyclohexenes, facilitating synthesis polysubstituted pyridines, been conventionally pyridine cross-coupling. subsequent discovery realm arenes. site-selective stable arenes We developed method intramolecular benzene rings 2-amino biaryls by suppressing competing C-H process using paddlewheel dirhodium catalyst. addition, address issues we employed arenols substrates, could act controlling elements editing. reported Cu-catalyzed arenols, proceeds dearomative azidation/aryl migration process, enabling incorporation Inspired result, recently extended reaction model Fe-catalyst facilitate ring contraction nitrogen-inserted product, achieving carbon-to-nitrogen transmutation arenols. Various polyaromatic effectively undergo desired atom's presenting considerable various applications Account, present an overview achievements reactions, with scopes, mechanistic features, applications. anticipate that will provide valuable insights propel development innovative methodologies both N-heterocycle synthesis.

Язык: Английский

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N-Atom Deletion Involving Rearrangement of Sulfamoyl Azides or Triazanium Salts

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

ConspectusAmines are frequent structural components in natural products, pharmaceuticals, ligands, and catalysts, making their synthesis transformation essential to organic chemistry. While C-N bond formation has become a well-established reliable synthetic strategy, the selective cleavage of bonds remains relatively underexplored. This challenge arises from low heterolytic nucleofugality nitrogen, property that limits practical application cleavage. gap underscores significant area methodology need further development. In this context, N atom deletion─defined as removal nitrogen via cleavage, while preserving integrity remaining framework─has emerged promising approach for skeletal editing. Since Levin's landmark 2021 report, deletion gained attention its potential precisely modify molecular skeletons. Building on editing concepts advanced by Levin Sarpong, particularly strategies modifying cyclic frameworks, we recognized critical developing mild efficient methods enable manipulation systems.This Account summarizes our research since 2017, focusing two approaches with distinct mechanisms: rearrangement sulfamoyl azides conversion triazanium intermediates. Initially, explored optimized thermal derived secondary amines, discovering viable strategy deletion. 2024, introduced an O-diphenylphosphinyl hydroxylamine (DPPH)-promoted deletion, involving generation novel Both polar aliphatic amines into nonpolar scaffolds applicable both linear molecules systems varying sizes. The DPPH-based approach, particular, demonstrated exceptional effectiveness sterically hindered substrates reaction conditions no anhydrous or oxygen-free environments. mechanisms methods─both isodiazene radical intermediates─were elucidated through rigorous experimental investigation. Additionally, observed rapid hydro(deutero)deamination products when primary were exposed DPPH.Beyond role typical crucial approach. Though limitations, it transforms challenging task constructing C-C more manageable sequence: following removal. We have applied hydrocarbon cages, pharmaceuticals. hope work will stimulate interest encourage incorporation methodologies, thereby expanding utility across diverse areas

Язык: Английский

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