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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Unimolecular Fragment Coupling and Single Carbon Atom Doping as Tools for Structural Reprogramming

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

Опубликована: Март 13, 2025

ConspectusOver the past decade, precise deletion or insertion of atom(s) within a molecular skeleton has emerged as powerful strategy for constructing and diversifying complex molecules. This approach is particularly valuable in organic synthesis, where subtle structural changes can dramatically impact reactivity, stability, function, making it highly relevant to medicinal chemistry material science.Our research focuses on two key reprogramming concepts: unimolecular fragment coupling (UFC) single carbon atom doping (SCAD). These innovative strategies enable efficient modifications that go beyond conventional functional group interconversions reactions, offering new synthetic opportunities chemists.UFC involves selective elimination from skeleton, followed by recombination remaining fragments form bonds. A advantage this intramolecular process its superior chemoselectivity stereoselectivity compared traditional intermolecular reactions. prime example our nickel(0)/N-heterocyclic carbene (NHC)-mediated decarbonylation simple diaryl ketones, yielding biaryls via C–C bond activation. offers an alternative cross-coupling reactions leveraging intrinsic connectivity substrate, enabling more direct atom-economical transformations. We extended concept catalytic amides acylsilanes, further broadening scope UFC include diverse carbonyl-containing precursors.Expanding this, we developed decarboxylative aryl carbamates, nickel(0) catalyst supported polystyrene-anchored bisphosphine ligand facilitates oxidative addition C(aryl)–O extrusion CO2. method provides practical sustainable route while generating CO2 byproduct. Inspired decarboxylation reaction, explored deisocyanative UFC, late-stage removal amide functionalities. allows serve transient directing protecting groups, significantly enhancing utility versatility UFC-based strategies.On other hand, SCAD atomic into without loss leading dramatic changes. successfully applied α,β-unsaturated using NHC one-carbon unit. Remarkably, transformation forms four bonds at center one step, lactams acyclic precursors. skeletal modification unlocks pathways cyclic frameworks with minimal steps.Together, introduce paradigm editing, providing tools rapid controlled framework modifications. By reprogramming, these methodologies expand toolbox chemists, accelerating molecule synthesis streamlining access novel architectures. Account highlights contributions field, demonstrating their potential drive both fundamental discoveries applications chemical synthesis.

Язык: Английский

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Late-Stage N-Atom Deletion of Multisubstituted 2-Azabicyclo[2.1.1]Hexanes

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 5825 - 5834

Опубликована: Март 25, 2025

Rigid three-dimensional scaffolds such as 2-azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) serve unique saturated isosteres of arenes, offering distinct substitution patterns due to their differing molecular exit vectors. This study introduces a skeletal editing strategy that efficiently transforms multisubstituted aza-BCHs into BCPs via an O-diphenylphosphinylhydroxylamine-promoted N-atom deletion process. method effectively addresses the challenge creating sterically hindered (2°)C–C(3°) bonds by removing nitrogen atom encased within bulky alkyl groups, reconstructing strained aza-BCH structure more BCP without generating undesired ring-opening diene byproducts. The used can be prepared from modified intermolecular [3 + 2] cycloaddition between bicyclo[1.1.0]butanes imines, making this practical. approach achieves remarkable efficiency, with yields up 99% scalability decagram quantities. resulting carboxylates further functionalized through decarboxylation, highlighting potential for programmed divergent synthesis BCPs. broad substrate scope high functional group tolerance protocol emphasize its versatility, it particularly valuable late-stage contained peptides, natural products, pharmaceuticals.

Язык: Английский

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A Highly Efficient Cross‐Coupling Mode via the Release of Small Molecules: Transition Metal‐Catalyzed Unimolecular Fragment Coupling (UFC)

ChemCatChem, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Abstract As a recently developed redox‐neutral coupling reaction, transition‐metal‐catalyzed unimolecular fragment (UFC) has been extensively investigated over the past decade. In comparison to conventional cross‐coupling reactions, cross‐electrophilic (XEC) and cross‐dehydrogenative (CDC) protocols eliminate need for stoichiometric organometallic reagents, reductants, or oxidants. Additionally, it produces only minimal molecular by‐products formation of series C−C bonds C−X with high atom efficiency. This review presents summary classification research progress made decade in this field. The is classified into four main categories, decarbonylation, decarboxylation, desulfonylation, deisocyanation, according type small molecule that liberated from reaction system. facilitates implementation more practical, straightforward, expedient operations. It noteworthy employs carbonyl compounds (aldehydes, ketones, carboxylic acid derivatives, etc.), sulfones, amides, which are typically inexpensive accessible, as substrates. groundbreaking synthetic approach since yielded plethora outcomes novel avenues related fields, while also offering benefits other fields.

Язык: Английский

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Catalytic Decarbonylation of Unstrained Diaryl Ketone Moieties to 2,2′-Bipyridyls Enabled by Electron-Deficient Pd Ensembles

Опубликована: Май 28, 2024

Although decarbonylation of carbonyl compounds have attracted much attention for the direct molecular transformations universal moieties into useful compounds, reports on catalytic diaryl ketones are scarce. In this study, we successfully developed a unstrained ketone in bearing bidentate directing groups to obtain 2,2′-bipyridyls using CeO2-supported Cu–Pd alloy nanoparticle catalyst. The catalyst characterization and series control experiments revealed that was efficiently catalyzed by Pd(0) ensembles, which became electron-deficient upon alloying with small amount Cu(0) species.

Язык: Английский

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KO^tBu-Catalyzed Synthesis of Isoindole Derivatives from N-Benzyl Amides Bearing an Ortho Alkynyl Group via 1,2-Acyl Shift

Organic Letters, Год журнала: 2024, Номер 26(26), С. 5587 - 5591

Опубликована: Июнь 24, 2024

In this study, we present the catalytic conversion of benzylamides featuring an ortho alkynyl moiety into 1-acylisoindole derivatives via a 1,2-acyl shift. Remarkably, transformation proceeds without need for transition-metal catalysts; instead, KO

Язык: Английский

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