Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

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Chiral Lewis Acid-Catalyzed Intramolecular [2 + 2] Photocycloaddition: Enantioselective Synthesis of Azaarene-Functionalized Azabicyclo[2.1.1]hexanes and Bicyclo[1.1.1]pentanes

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

We present an asymmetric intramolecular [2 + 2] photocycloaddition reaction enabled by a dual catalyst system involving DPZ as photosensitizer and chiral Sc(III) complex, leading to azaarene-functionalized 2-azabicyclo[2.2.1]hexanes (aza-BCHs). The approach efficiently preventing racemization during subsequent nitrogen-deletion skeletal editing of aza-BCHs yield 2-substituted bicyclo[1.1.1]pentanes (BCPs). method achieves high ee broad substrate scope, including the successful formation all-carbon quaternary stereocenters. Furthermore, activation simple azaarene substrates Lewis acids in photocatalysis highlights notable contribution this field.

Language: Английский

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Asymmetric Relay Catalysis Enables Unreactive Allylic Alcohols to Participate in 1,3-Dipolar Cycloaddition of Azomethine Ylides

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Current synthetic transformations occur readily with starting materials that possess both innate reactivity and steric accessibility or functional-group-oriented reactivity. However, achieving reactions inactive feedstock substrates remains significantly challenging normally requires cumbersome prior functional group manipulations. Herein, we report an unprecedented example of catalytic asymmetric 1,3-dipolar cycloaddition azomethine ylides nonactivated alkenes enabled by copper/ruthenium relay catalysis. Key to the success is temporary activation strategy initiated oxidative dehydrogenation inert allylic alcohols into electron-demanding reversed highly reactive enones, which triggers ensuing Cu-catalyzed followed reductive hydrogenation deliver functionalized chiral pyrrolidines construction two C-C bonds four well-defined stereogenic centers in atom-/step-economical redox-neutral manner. This method features mild reaction conditions, operational simplicity, broad substrate scope also characterized formal dynamic kinetic resolution. Mechanistic studies control experiments supported a typical borrowing-hydrogen cascade orthogonally merged revealed superiority reliability catalysis are controlled release but unstable enones impede undesired polymerization. It should be noted up stereoisomers otherwise inaccessible cyclobutanes could prepared through concise late-stage elaborations.

Language: Английский

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

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 15, 2025

Language: Английский

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Skeletal Editing of Isoindolines to Tetralins

Chemistry - A European Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Abstract We present a skeletal editing strategy for transforming isoindolines into tetralins via cascade N‐atom removal deconstruction followed by Diels‐Alder reaction between in situ generated o‐ quinodimethanes and activated alkenes. This approach features broad substrate scope, excellent stereoselectivity, high yields, demonstrating its applicability to complex bioactive compounds natural products. Notably, case studies showcase the efficient construction of challenging spirocyclic bridged systems, underscoring method's versatility potential advancing applications synthetic chemistry.

Language: Английский

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Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 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

Language: Английский

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Nitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A nitrene-mediated aminative N–N–N coupling enables direct triazene 1-oxide synthesis via an aminonitrene–nitrosoarene pathway.

Language: Английский

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

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

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

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 5825 - 5834

Published: March 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.

Language: Английский

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