Copper-Catalyzed Cross-Coupling of Bicyclobutanes with Triftosylhydrazone Leading to Skipped Dienes

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Here, we report a protocol for the synthesis of skipped dienes through cross-coupling bicyclo[1.1.0]butanes with trifluoromethyl triftosylhydrazones. The reaction is run using TpBr3Cu(NCMe) as catalyst to give access library trifluoromethylated (32 examples, ≤98% yield) excellent E/Z selectivity under mild and operationally safe conditions. presented methods proved be compatible various functionalized

Language: Английский

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Generation and Use of Bicyclo[1.1.0]butyllithium under Continuous Flow Conditions

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The bicyclo[1.1.0]butyl scaffold has emerged as a valuable bioisostere in drug discovery programs. Here, we present streamlined approach for the generation of bicyclo[1.1.0]butyllithium and its functionalization with various classes electrophiles one-flow process, eliminating need intermediate isolation. In comparison to traditional batch processes, flow method allows use single organolithium reagent instead two operates at significantly higher temperatures (0 °C versus −78 °C), enhancing both practicality scalability.

Language: Английский

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Copper-Catalyzed Diastereoselective Addition of a [1,1,1]Propellane Dimer to N-tert-Butanesulfinyl Aldimines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

[1,1,1]Propellane is typically used as a building block for the construction of bicyclo[1,1,1]pentanes and cyclobutanes. In this work, diverse chiral bi(methylenecyclobutylidene) complexes were synthesized by diastereoselective addition [1,1,1]propellane dimer to N-tert-butanesulfinyl aldimines in presence copper bipyridine. Density functional theory calculations revealed that both step regeneration catalyst contributed generation favored (Ss,S,S)-diastereomer.

Language: Английский

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Ring-Opening Competes with Peroxidation in Fenchone Low-Temperature Autoignition

The Journal of Physical Chemistry A, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

We report an atypical competition between fenchyl radical β-scission and peroxidation at low temperatures unravel the impacts of strain energy ring substituent location on their respective contributions. Our RRKM modeling reveals that radicals positioned secondary carbons are fastest-scission ones, exhibiting maximum local relief. Dimethyl substituents contribute to increased compared norbornane, hindering bridge scission leading cyclopentene isoprene products. The dimethyl corset generates extra torsional during HO2 elimination from QOOH, while ether formation is favored by electron donation carbonyl group. falloff extent also affected steric hindrance, insofar as it increases stiffness, a lower vibrational partition function low-pressure rate constant. Furthermore, methyl-induced restrictions reactant reorganization found modulate enthalpy–entropy compensation in Korcek reaction hydroperoxide. Unlike our previous stirred reactor experiments, impact reactivity notable under new rapid compression machine (RCM) experiments. present model predicts contrasted selectivities with position, prevailing respectively for F1/F2/F3/F4 F5/F6 radicals. kinetic mechanism accurately experimental IDT but indicates slight first-stage pressure inflection point temperature, which could not be confirmed experimentally. This insight into fenchone ring-opening -closing mechanisms high-pressure oxidation can useful other polycyclic ketones.

Language: Английский

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Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis

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

Published: March 28, 2025

The cycloaddition reactions of bicyclo[1.1.0]butanes with alkenes, imines, nitrones, or aziridines have served as an efficient platform to create conformationally restricted saturated bicyclic scaffolds. However, the use readily available aromatics in such reactions, especially asymmetric manner, remains underexplored. Herein, we report a highly regio- and enantioselective dearomative [2π + 2σ] photocycloaddition reaction between naphthalene derivatives bicyclo[1.1.0]butanes, enabled by Gd(III) catalysis. Bicyclo[1.1.0]butanes naphthalenes adorned diverse array functional groups are well-tolerated under mild conditions, affording enantioenriched pharmaceutically important bicyclo[2.1.1]hexanes 30–96% yields 81–93% ee 12:1 → >20:1 rr. synthetic versatility this is further demonstrated facile removal directing group derivatizations dearomatized product. UV–vis absorption spectroscopy studies suggest involvement excited species process.

Language: Английский

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Substrate-Regulated Divergent Addition of N-Sulfonyl Ketimines to Bicyclo[1.1.0]butanes Enabled by Photoinduced Energy Transfer

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

A substrate-regulated divergent addition of N-sulfonyl ketimines to bicyclo[1.1.0]butanes (BCBs) was developed using a photoinduced energy transfer strategy. The [2π+2σ] cycloaddition BCBs with saccharin-derived cyclic yields benzosultam-fused aza-BCHs good and excellent diastereoselectivity. In contrast, reactions chain produce 1,3-fully substituted cyclobutanes via energy-transfer-induced N-S bond homolysis. ease large-scale synthesis derivatizations products highlight their application potentials.

Language: Английский

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Visible light-mediated dearomative spirocyclization/imination of nonactivated arenes through energy transfer catalysis

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

Published: April 16, 2025

Abstract Aromatic compounds serve as key feedstocks in the chemical industry, typically undergoing functionalization or full reduction. However, partial reduction via dearomative sequences remains underexplored despite its potential to rapidly generate complex three-dimensional scaffolds and existing strategies often require metal-mediated multistep processes suffer from limited applicability. Herein, a photocatalytic radical cascade approach enabling difunctionalization through selective spirocyclization/imination of nonactivated arenes is reported. The method employs bifunctional oxime esters carbonates introduce multiple functional groups single step, forming spirocyclic motifs iminyl functionalities N–O bond cleavage, hydrogen-atom transfer, addition, spirocyclization, radical-radical cross-coupling. reaction constructs up four bonds (C−O, C−C, C−N) simple starting materials. Its broad applicability demonstrated on various substrates, including pharmaceuticals, it compatible with scale-up under flow conditions, offering streamlined synthesizing highly decorated frameworks.

Language: Английский

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Regio- and Diastereoselective Cascade Reactions of Bicyclo[1.1.0]butanes: Access to gem-Difluorinated Carbocyclic Rings

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

gem-Difluorinated carbocyclic rings are attractive motifs in drug development. Herein, we report the transition-metal free cascade reaction of bicyclo[1.1.0]butanes (BCBs) with gem-difluorocyclopropenes for synthesis gem-difluorinated excellent regio- and diastereoselectivity. This method was successfully applied to provide a broad range cyclopentenes cyclopropanes, which could undergo variety difluoromethylene (CF2) retaining transformations.

Language: Английский

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Solvent‐Dependent Divergent Cyclization of Bicyclo[1.1.0]butanes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Bicyclo[1.1.0]butanes (BCBs) have recently garnered significant research interest as versatile precursors for synthesizing potential [n.1.1] bioisosteres and multi-functionalized cyclobutanes in a straightforward atom-economical manner. Here, we report solvent-dependent divergent cyclization of BCBs that provides highly diastereospecific decorated oxygen-containing bicyclo[3.1.1]heptanes (BCHeps), which serve meta-substituted arenes. Additionally, an unprecedented 1,2-difunctionalization reaction mode was explored, thus expanding the chemical space arene functionalized cyclobutanes.

Language: Английский

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Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2‐Amino‐bicyclo[2.1.1]hexenes

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(32)

Published: May 24, 2024

Abstract Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf) 3 ‐catalyzed [3+2] cycloaddition bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding diverse array polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes good excellent yields. These products offer valuable starting materials for the construction novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that reaction involves nucleophilic addition ynamides bicyclo[1.1.0]butanes, followed by an intramolecular cyclization situ generated enolate keteniminium ion. We expect these findings will encourage utilization complex bioisosteres foster further investigation into BCB‐based chemistry.

Language: Английский

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