Ring Expansion toward Fused Diazabicyclo[3.1.1]heptanes through Lewis Acid Catalyzed Highly Selective C−C/C−N Bond Cross‐Exchange Reaction between Bicyclobutanes and Diaziridines

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 13, 2024

Abstract The synthesis of bicyclic scaffolds has garnered considerable interest in drug discovery because their ability to mimic benzene bioisosteres. Herein, we introduce a new approach that utilizes Lewis acid (Sc(OTf) 3 )‐catalyzed σ‐bond cross‐exchange reaction between the C−C bond bicyclobutanes and C−N diaziridines produce multifunctionalized medicinally interesting azabicyclo[3.1.1]heptane derivatives. proceeds well with different broad range aryl‐ as alkenyl‐, but also alkyl‐substituted (up 98 % yield). Conducting scale‐up experiment exploring synthetic transformations cycloadducts emphasized practical application synthesis. Furthermore, zinc‐based chiral catalytic system was developed for enantioselective version this 96 ee ).

Язык: Английский

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Synthetically Relevant Post-Transition State Bifurcation Leading to Diradical and Zwitterionic Intermediates: Controlling Nonstatistical Kinetic Selectivity through Solvent Effects

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

A post-transition state surface intersection (PTSSI) between radical and zwitterionic states that causes a bifurcation in the reaction pathway was discovered through density functional theory calculations on potential energy surfaces ab initio molecular dynamics simulations of cycloadditions bicyclobutane triazolinedione (BCB-TAD). It predicted changes to solvent polarity would enable control over dynamic selectivity this system; indeed, experimental evidence supported prediction. This work not only provides new insights into an unusual type bifurcation, but also demonstrates how nonstatistical effects for such reactions can be manipulated rationally increase yields synthetically useful reactions.

Язык: Английский

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Lewis Acid Catalyzed (4π+2σ) Annulation of Bicyclobutanes with Dienol Ethers for the Synthesis of Bicyclo[4.1.1]octanes

Опубликована: Март 5, 2024

Bicyclic carbocycles containing a high fraction of Csp3 have become highly attractive synthetic targets because the multiple applications they found in medicinal chemistry. The formal cycloaddition bicyclobutanes (BCB) has recently been extensively explored for construction both bicyclohexanes and bicycloheptanes. Adopting this approach synthesis medium-sized bridged instead remained more limited. We report herein (4π+2σ) BCB ketones with silyl dienol ethers. reaction occurred presence aluminium triflate as Lewis acid catalyst. Upon acidic hydrolysis enol ether intermediates, rigid bicyclo[4.1.1]octanes (BCOs) diketones could be easily accessed good to very yields. This convenient scalable procedure was tolerant towards range aromatic aliphatic substituents on substrates dienes. obtained BCO products smoothly functionalized through reduction cross-coupling reactions.

Язык: Английский

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Synthesis of Cyclobutanes and Cyclobutenes by Strain-Release-Driven Ring-Opening of Bicyclo[1.1.0]butanes

Synthesis, Год журнала: 2024, Номер 56(24), С. 3829 - 3848

Опубликована: Авг. 23, 2024

Abstract Cyclobutanes and cyclobutenes exhibit intriguing structures demonstrate significant biological activities diverse synthetic applications. This review aims to summarize recent progress in strain-release-driven ring-opening reactions of bicyclo[1.1.0]butanes (BCBs) synthesize these four-membered carbon rings. It outlines the strategies, regio- stereoselectivity, scope reactions, mechanistic implications catalytic process, providing a supplementary perspective existing reviews. 1 Introduction 2 Thermally Driven Nucleophilic Ring-Opening 3 Rearrangement Isomerization Reaction 4 Light-Driven 5 Transition-Metal/Lewis Acid Catalyzed 6 Conclusion Outlook

Язык: Английский

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Recent Progress in (3+3) Cycloadditions of Bicyclobutanes to Access Bicyclo[3.1.1]heptane Derivatives

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Abstract The synthesis of bicyclo[3.1.1]heptane (BCHeps) derivatives, which serve as three-dimensional (3D) bioisosteres benzenes and are the core skeleton several terpene natural products, is garnering growing interest. (3+3) cycloadditions bicyclobutanes (BCBs) represent an attractive method for efficiently accessing (hetero)BCHep skeletons with 100% atom economy. Herein, we give a brief summary recent achievements in this approach diverse BCHep emphasizing our progress initial palladium-catalyzed vinyl oxiranes. 1 Introduction 2 Radical Cycloaddition Reaction 3 Polar 4 Palladium-Catalyzed Enantioselective 5 Conclusion

Язык: Английский

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Enantioselective dearomative formal (3+3) cycloadditions of bicyclobutanes with aromatic azomethine imines: access to fused 2,3-diazabicyclo[3.1.1]heptanes

Chemical Science, Год журнала: 2024, Номер 15(46), С. 19488 - 19495

Опубликована: Янв. 1, 2024

We present the first enantioselective dearomative (3+3) cycloadditions of bicyclobutanes (BCBs) utilizing a chiral Lewis acid catalyst and bidentate chelating BCB substrates.

Язык: Английский

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Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Дек. 3, 2024

The high percentage of sp

Язык: Английский

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Synthesis of constrained bicycloalkanes through bibase-promoted brook rearrangement/radical-polar crossover cyclization

Chemical Science, Год журнала: 2024, Номер 15(28), С. 11092 - 11098

Опубликована: Янв. 1, 2024

A concise protocol for the synthesis of constrained bicycloalkanes has been developed, using easily obtainable α-silyl alcohols and alkenes through a bibase-promoted brook rearrangement/radical-polar crossover cyclization (RPCC) process.

Язык: Английский

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Recent Advances in Radical Coupling Reactions Directly Involving Bicyclo[1.1.1]pentane (BCP)

Topics in Current Chemistry, Год журнала: 2025, Номер 383(1)

Опубликована: Янв. 18, 2025

Язык: Английский

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

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 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

Язык: Английский

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