Radical strain-release photocatalysis for the synthesis of azetidines

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(11), P. 1223 - 1231

Published: Aug. 14, 2024

The increasing popularity of four-member rings in drug discovery has prompted the synthetic chemistry community to advance and reinvent old strategies craft these structures. Recently, strain-release concept been used build complex architectures. However, although there are many for accessing small carbocyclic derivatives, synthesis azetidines remains underdeveloped. Here we report a photocatalytic radical strategy densely functionalized from azabicyclo[1.1.0]butanes. protocol operates with an organic photosensitizer, which finely controls key energy-transfer process distinct types sulfonyl imines. intermediates intercepted by azabicyclo[1.1.0]butanes via process, providing access difunctionalized single step. This is revealed combination spectroscopic optical techniques density functional theory calculations. power generality this method illustrated various azetidine targets, including derivatives celecoxib naproxen. Four-membered have become popular motifs discovery, prompting develop more expedite approaches scaffolds. Here, authors

Language: Английский

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Isolation and Reactivity of Arylnickel(II) Complexes in Nickel-Catalyzed Borylation of Aryl Fluorosulfates

JACS Au, Journal Year: 2024, Volume and Issue: 4(4), P. 1646 - 1653

Published: March 25, 2024

Aryl fluorosulfates have emerged as versatile SuFExable substrates, harnessing the reactivity of S-F bond. In this study, we unveil their alternative synthetic utility in nickel-catalyzed borylation via C-O bond activation. This method highlights mild reaction conditions, a broad substrate scope, and moderate functional group tolerance, rendering it practical appealing approach for synthesizing diverse array aryl boronate esters. Furthermore, computational analysis sheds light on pathways, uncovering participation LNi(0) LNi(II)ArX species. insight is supported by

Language: Английский

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Synthesis of 1‐azabicyclo[2.1.1]hexanes via formal single electron reduction of azabicyclo[1.1.0]butanes under photochemical conditions

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(44)

Published: July 22, 2024

Abstract C(sp 3 )‐rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen‐containing in high demand. Herein, we report a general synthesis of 1‐azabicyclo[2.1.1]hexanes (1‐aza‐BCH) via formal cycloaddition azabicyclo[1.1.0]butanes (ABB) with styrenes under photochemical conditions. To overcome the challenging direct single electron reduction ABBs, designed polar‐radical‐polar relay strategy leverages fast acid‐mediated ring‐opening ABBs form bromoazetidines, which undergo efficient debrominative radical formation initiate reaction. The reaction is applicable broad range ABB‐ketones demonstrate 1‐aza‐BCH products can be further functionalized larger saturated, conformationally rigid heterocycles.

Language: Английский

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In Situ SERS Monitoring and Heterogeneous Catalysis Verification of Pd-Catalyzed Suzuki–Miyaura Reaction via Bifunctional “Black Raspberry-like” Plasmonic Nanoreactors

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

Published: March 3, 2025

Constructing materials that possess both catalytic properties and surface plasmonic active structures presents an essential requirement in the field of situ surface-enhanced Raman spectroscopy (SERS) monitoring. In this work, we developed a novel black raspberry-like bifunctional nanoreactor platform (HPRS@Au–Pd) with enhanced activity (EF = 3.11 × 109) excellent performance (e.g., |K| 1.72 10–2 s–1 for 4-BTP). This enables sensitive real-time monitoring Suzuki reactions, providing efficient stable system mechanistic investigations. By fitting first-order kinetic model, quantitatively analyzed reaction kinetics haloarenes on Pd NPs, revealing direct involvement surface-bound NPs process. Furthermore, 4MPBA-blocking experiments using devoid functional groups demonstrated absence from dissolved species, conclusively supporting heterogeneous nature reaction. work extends applicability conclusion regarding catalysis to broader range substrates, offering valuable insights into design optimization dual-functional nanoreactors. Beyond versatility opens avenues applications other showcasing its potential advanced studies

Language: Английский

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Modular Synthesis of 3,3-Disubstituted Azetidines via Azetidinylation Reagents

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

Published: March 19, 2025

Azetidines represent an attractive and emerging design option in medicinal chemistry owing to their small size polar nature, as well potential significantly impact the physicochemical properties of drug molecules. However, traditional methods for synthesis 3,3-disubstituted azetidines usually require higher step counts or exhibit poor functional group compatibility. Herein, we report a modular strategy based on azetidinylation reagents. The practicality this method is further exemplified by use readily available starting materials, mild reaction conditions, very broad substrate scope.

Language: Английский

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Harnessing Oxetane and Azetidine Sulfonyl Fluorides for Opportunities in Drug Discovery

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Four-membered heterocycles such as oxetanes and azetidines represent attractive emergent design options in medicinal chemistry due to their small polar nature potential significantly impact the physiochemical properties of drug molecules. The challenging preparation these derivatives, especially a divergent manner, has severely limited combination with other medicinally biologically important groups. Consequently, there is substantial demand for mild effective synthetic strategies access new oxetane azetidine derivatives molecular scaffolds. Here, we report development use sulfonyl fluorides (OSFs) (ASFs), which behave precursors carbocations an unusual defluorosulfonylation reaction pathway (deFS). small-ring are activated under thermal conditions (60 °C), generated reactive intermediates couple broad range nucleophiles. Oxetane heterocyclic, -sulfoximine, -phosphonate prepared, several do not have comparable carbonyl analogs, providing chemical motifs elements discovery. Alternatively, SuFEx anionic accesses oxetane-sulfur(VI) derivatives. We demonstrate utility novel OSF ASF reagents through synthesis 11 showcasing subsequent diversification facile inclusion into programs. Moreover, propose application linker incorporation pendant groups suitable common conjugation reactions. Productive deFS reactions E3 ligase recruiters pomalidomide related provide degrader PROTAC linkers.

Language: Английский

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Access to 3‐Azetidines via Halogenation of Titanacyclobutanes

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(10), P. 2214 - 2219

Published: March 20, 2024

Abstract Azetidines are valuable nitrogenous heterocycles. Herein, we disclose a strategy for the modular assembly of 3‐azetidines and related spirocyclic congeners featuring all‐carbon quaternary centers. This approach leverages titanacyclobutanes generated from ketones or alkenes. Halogenation these organotitanium species gives rise to functionalized alkyl dihalides that can be subsequently captured by amines afford azetidine building blocks. facilitated synthesis small molecule anti‐tuberculosis drug. It also enabled access carbon‐13 isotopologs diazaspiro[3.3]heptane fragments challenging prepare any other means.

Language: Английский

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State-of-the-Art Strategies for Lewis Acid-Catalyzed Strain-Release Cycloadditions of Bicyclo[1.1.0]butanes (BCBs)

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(23), P. 6942 - 6957

Published: Jan. 1, 2024

This review primarily focuses on the latest developments in Lewis acid-catalyzed strain-release cycloaddition reactions of BCBs.

Language: Английский

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Biocatalytic hydroxylation tertiary C-H bonds for synthesis of chiral tertiary alcohols by cytochrome P450

Molecular Catalysis, Journal Year: 2023, Volume and Issue: 553, P. 113791 - 113791

Published: Dec. 23, 2023

Language: Английский

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Ketone-Derived Pro-aromatic Reagents for Radical Group Transfer Reactions and Deconstructive Functionalizations

Synlett, Journal Year: 2023, Volume and Issue: 35(10), P. 1072 - 1088

Published: Oct. 24, 2023

Abstract The recent prominence of ketones as handles for sp3-rich radicals has expanded the paradigm synthetic utility ketones, putting ubiquitous functional group once again into spotlight in years. One emerging strategy arose through ketone-derived pro-aromatic reagents form dihydrobenzothiazoline (BTZ), dihydroquinazolinone (DHQZ), dihydropyrazole (DHP), and dihydro-1,2,4-triazole (DHT) key intermediates aromaticity-promoted C–C bond homolytic fission. formed sp3-radicals could then participate various radical functionalizations, including alkylations, arylations, olefination, alkynylation, silylations, amination, thiolation, deuteration, among others, either photocatalytic, thermal, or oxidative conditions. In this review, we highlight implications advances using these transfer reactions deconstructive functionalization. 1 Introduction 2 Aromatization-Driven Bond Scission Ketones 3 Photochemical Reactions Ketone-Derived Pro-aromatic Reagents 4 Non-photochemical 5 Conclusion Future Outlook

Language: Английский

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