Asymmetric formal [1 + 2 + 2]-cycloaddition of diazoamides with enamines and carbonyl compounds

Cycloaddition reaction offers an ideal and powerful method for the construction of cyclic structures with molecular complexity and diversity. The exploration of versatile synthons, especially in situ formed species, for the assembly of poly-functionalized heterocycles in one-pot is an intriguing and challenging area in synthetic chemistry from the perspective of atom economy and bond formation efficiency. Herein, we report an asymmetric formal [1 + 2 + 2]-cycloaddition of readily accessible diazoamides with enamines and carbonyl compounds. This cascade reaction involves a 1,3-dipolar cycloaddition of ketones/aldehydes with the key zwitterionic intermediate that generated in situ through an intermolecular metal carbene transfer to nucleophilic enamines, which offers a direct access to spiro-tetrahydrofurans containing four consecutive stereocenters in high yields and excellent enantioselectivity through chiral copper complex or chiral dirhodium carboxylates catalysis. Cycloaddition reaction offers an ideal and powerful method for the construction of cyclic structures with molecular complexity and diversity. Herein, the authors report an asymmetric formal [1 + 2 + 2]-cycloaddition of diazoamides with enamines and carbonyl compounds, synthesizing spiro-tetrahydrofurans containing four consecutive stereocenters.

• Publication year

  2025

• Venue

  Nature Communications

• Publication date

  2025-11-27

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41467-025-65612-3PMID 41309535PMCID 12660787
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Catalytic Asymmetric Redox-Neutral [3 + 2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

  2024cited by this paper
• Asymmetric Carbene Transformations for the Construction of All-Carbon Quaternary Centers.

  2024cited by this paper
• Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon

  2024cited by this paper
• Asymmetric Synthesis of Remotely Chiral Naphthols and Naphthylamines via Naphthoquinone Methides.

  2023cited by this paper
• Multicomponent Cyclizative 1,2-Rearrangement Enabled Enantioselective Construction of 2,2-Disubstituted Pyrrolinones.

  2023cited by this paper
• Generation and reactivity of unsymmetrical strained heterocyclic allenes

  2023cited by this paper
• Arenes participate in 1,3-dipolar cycloaddition with in situ-generated diazoalkenes

  2023cited by this paper
• Construction of Chiral Quaternary Carbon Centers via Asymmetric Metal Carbene gem-Dialkylation.

  2023cited by this paper
• Mechanistic and structural characterization of an iridium-containing cytochrome reveals kinetically relevant cofactor dynamics

  2023cited by this paper
• Asymmetric [3 + 2] Photocycloaddition of β-Keto Esters and Vinyl Azides by Dual Photoredox/Nickel Catalysis.

  2023cited by this paper
• 1,2,3-Triazole and Its Analogues: New Surrogates for Diazo Compounds.

  2022cited by this paper
• Asymmetric Three-Component Reaction of Enynal with Alcohol and Imine as An Expeditious Track to Afford Chiral α-Furyl-β-amino Carboxylate Derivatives

  2022cited by this paper
• In silico reaction screening with difluorocarbene for N-difluoroalkylative dearomatization of pyridines

  2022cited by this paper
• Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji-Trost of Benzotriazoles with 1,3-Dienes.

  2021cited by this paper
• Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones.

  2021cited by this paper
• Bioorthogonal Reactions Utilizing Nitrones as Versatile Dipoles in Cycloaddition Reactions.

  2021cited by this paper
• Ruthenium-Catalyzed Cycloadditions to Form Five-, Six-, and Seven-Membered Rings.

  2021cited by this paper
• Catalyst-Directed Divergent Catalytic Approaches to Expand Structural and Functional Scaffold Diversity via Metallo-Enolcarbene Intermediates

  2021cited by this paper
• Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

  2021cited by this paper
• Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes.

  2020cited by this paper
• Selective Carbon-Carbon Bond Cleavage of Cyclopropylamine Derivatives.

  2020cited by this paper
• Transition Metal-Catalyzed Selective Carbon-Carbon Bond Cleavage of Vinylcyclopropanes in Cycloaddition Reactions.

  2020cited by this paper
• Creating Stereocenters within Acyclic Systems by C-C Bond Cleavage of Cyclopropanes.

  2020cited by this paper
• The Huisgen Reaction: Milestones of the 1,3‐Dipolar Cycloaddition

  2020cited by this paper
• Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides.

  2020cited by this paper
• Gold(I)-catalyzed intramolecular cyclization/intermolecular cycloaddition cascade as a fast track to polycarbocycles and mechanistic insights

  2020cited by this paper
• Mechanistic Studies of Transition-Metal-Catalyzed [2 + 2 + 2] Cycloaddition Reactions.

  2020cited by this paper
• Cu-catalyzed Asymmetric Dearomative [3 + 2] Cycloaddition Reaction of Benzazoles with Aminocyclopropanes

  2019cited by this paper
• Catalytic Enantioselective Construction of Spiro Quaternary Carbon Stereocenters

  2019cited by this paper
• Catalytic Enantioselective Ynamide Additions to Isatins: Concise Access to Oxindole Alkaloids.

  2019cited by this paper
• Selectivity Switch in a Rhodium(II) Carbene Triggered Cyclopentannulation: Divergent Access to Three Polycyclic Indolines.

  2019cited by this paper
• Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis.

  2018cited by this paper
• 2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides.

  2018cited by this paper
• Asymmetric Synthesis of Tetrahydroindolizines by Bimetallic Relay Catalyzed Cycloaddition of Pyridinium Ylides.

  2018cited by this paper
• Cycloaddition reactions of enoldiazo compounds.

  2017cited by this paper
• Switchable regioselectivity in amine-catalysed asymmetric cycloadditions

  2017cited by this paper
• Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds.

  2016cited by this paper
• Asymmetric Cooperative Catalysis in a Three-Component Reaction: Mechanism and Origin of Enantio- and Diastereoselectivities.

  2016cited by this paper
• Rh(II)‐Catalyzed Chemoselective Synthesis of 3‐Substituted Oxindoles by C(sp2)−H and C(sp2)−N Functionalization of β‐Enaminoesters

  2016cited by this paper
• Alkaloids and Isoprenoids Modification by Copper(I)-Catalyzed Huisgen 1,3-Dipolar Cycloaddition (Click Chemistry): Toward New Functions and Molecular Architectures.

  2016cited by this paper
• Diversity-oriented synthesis yields novel multistage antimalarial inhibitors

  2016cited by this paper
• Asymmetric Construction of Spirooxindoles by Organocatalytic Multicomponent Reactions Using Diazooxindoles.

  2015cited by this paper
• Recent advances of catalytic asymmetric 1,3-dipolar cycloadditions.

  2015cited by this paper
• Side arm strategy for catalyst design: modifying bisoxazolines for remote control of enantioselection and related.

  2014cited by this paper
• Dynamic kinetic asymmetric [3 + 2] annulation reactions of aminocyclopropanes.

  2014cited by this paper
• Gold-Containing and Gold-Generated 1,n-Dipoles as Useful Platforms Toward Cycloadditions and Cyclizations

  2012cited by this paper
• Design of chiral bis-phosphoric acid catalyst derived from (R)-3,3'-di(2-hydroxy-3-arylphenyl)binaphthol: catalytic enantioselective Diels-Alder reaction of α,β-unsaturated aldehydes with amidodienes.

  2011cited by this paper
• Dynamic one-pot three-component catalytic asymmetric transformation by combination of hydrogen-bond-donating and amine catalysts.

  2011cited by this paper
• Organocatalytic Synthesis of Spiro[pyrrolidin-3,3′-oxindoles] with High Enantiopurity and Structural Diversity.

  2010cited by this paper
• Domino reactions of rhodium(II) carbenoids for alkaloid synthesis.

  2009influential reference
• Organocatalytic synthesis of spiro[pyrrolidin-3,3'-oxindoles] with high enantiopurity and structural diversity.

  2009cited by this paper
• Nonlinear effects in asymmetric catalysis.

  2009cited by this paper
• Catalytic enantioselective synthesis of tetrahydrofurans: a dynamic kinetic asymmetric [3 + 2] cycloaddition of racemic cyclopropanes and aldehydes.

  2009cited by this paper
• Asymmetric organocatalytic three-component 1,3-dipolar cycloaddition: control of stereochemistry via a chiral Brønsted acid activated dipole.

  2008cited by this paper
• Enantioselective copper-catalyzed 1,3-dipolar cycloadditions.

  2008cited by this paper
• Recent Developments in Asymmetric Cyclopropanation

  2008cited by this paper
• A planning strategy for diversity-oriented synthesis.

  2004cited by this paper

• No citing papers are available for this paper.