General and Modular Route to (Halo)alkyl BCP-Heteroaryls Enabled by α-Aminoalkyl Radical-Mediated Halogen-Atom Transfer

ACS Catalysis, Год журнала: 2023, Номер 14(2), С. 619 - 627

Опубликована: Дек. 28, 2023

Synthesis of bicyclo[1.1.1]pentane (BCP) heteroaryls continues to be a part the most important tasks in organic synthesis because they are significant class bioisosteres with universal applications drug discovery. However, substrate scope current multicomponent reactions is limited tertiary alkyl radicals and prefunctionalized (het)arenes due their intrinsic mechanisms, resulting decrease application value. Herein, we report straightforward alternative for (halo)alkyl BCP-heteroaryls from [1.1.1]propellane enabled by α-aminoalkyl radical-mediated halogen-atom transfer (XAT). Carbon derived commonly available precursors such as primary, secondary, halides polyhalides perform additions onto give BCP radicals, which then engage C–H/C–C couplings different heteroarenes. A wide range easily constructed moderate-to-good yields. Late-stage functionalization performed on approved derivatives proceeds good efficiency produce corresponding BCP-heteroaryls. The control experiments density functional theory (DFT) calculations reveal radical nature reaction. This approach not only verifies (XAT) strategy but also provides practical efficient route multifunctionalized BCPs, significantly expands BCP-heteroaryl-type development.

Язык: Английский

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Synthesis of 1-(Halo)alkyl-3-heteroaryl Bicyclo[1.1.1]pentanes Enabled by a Photocatalytic Minisci-type Multicomponent Reaction

ACS Catalysis, Год журнала: 2024, Номер 14(8), С. 6247 - 6258

Опубликована: Апрель 10, 2024

Aryl-substituted bicyclo[1.1.1]pentane (BCP-aryl) derivatives represent the most important bioisosteres of biaryl scaffolds and widely exist in numerous complex pharmaceutical molecules. The current synthetic method limitations using only tertiary radical precursors, prefunctionalized heteroarenes, toxic transition metals, expensive photocatalysts make it urgent to develop a more simple practical protocol. To confront enrich Minisci-type chemistry, herein, we disclose photocatalytic multicomponent reaction for synthesis various (halo)alkyl BCP-aryls [1.1.1]propellane, alkyl halides, unfunctionalized heteroarenes as starting materials. Diverse kinds radicals (primary, secondary, carbons) derived from chlorides, bromides, fluoroalkyl iodides are very compatible this transformation. practicability is additionally boosted by product derivatizations late-stage functionalization pharmaceutically relevant mechanistic studies demonstrate that relay mechanism initiated consecutive photoinduced electron transfer (ConPET) process operation. We anticipate methodology would act useful tool biaryl-type drug derivatives, ultimately resulting great utility discovery program.

Язык: Английский

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Light‐Driven Synthesis and Functionalization of Bicycloalkanes, Cubanes and Related Bioisosteres

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Янв. 5, 2024

Bicycloalkanes, cubanes and their structural analogues have emerged as bioisosteres of (hetero)arenes. To meet increasing demand, the chemical community has developed a plethora novel synthetic methods. In this review, we assess progress made in field light-driven construction functionalization such relevant molecules. We focused on diverse targets, well reaction processes giving access to: (i) [1.1.1]-bicyclopentanes (BCPs); (ii) [2.2.1]-bicyclohexanes (BCHs); (iii) [3.1.1]-bicycloheptanes (BCHeps); (iv) cubanes; other structurally related scaffolds. Finally, future perspectives dealing with identification manifolds to new functionalized bioisosteric units are discussed.

Язык: Английский

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Strain-release transformations of bicyclo[1.1.0]butanes and [1.1.1]propellanes

Tetrahedron Chem, Год журнала: 2024, Номер 9, С. 100070 - 100070

Опубликована: Фев. 28, 2024

Bicyclo[1.1.0]butanes (BCBs) and [1.1.1]propellanes (tricyclo[1.1.1.01,3]pentanes, TCPs) are structurally unique compounds with different chemical properties. Strain-release driven reactions have emerged as an atom- step-economic strategy for the organic synthesis. Using this strategy, a variety of functional ring molecules been efficiently synthesized, including various cyclobutane molecules, bicyclo[2.1.1]hexanes, bicyclo[1.1.1]pentanes, others. More specifically, these strain release-driven include aspects nucleophilic addition, radical electrophilic or transition metal catalysis. This review will discuss recent developments in strain-release transformations bicyclo[1.1.0]butanes [1.1.1]propellanes.

Язык: Английский

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Multicomponent Synthesis of Alkyl BCP-Heteroaryls via Electron Donor–Acceptor Complex Photoactivation under Mild Conditions

The Journal of Organic Chemistry, Год журнала: 2025, Номер 90(4), С. 1683 - 1696

Опубликована: Янв. 17, 2025

In the vanguard of sustainable chemistry, pursuit efficient pathways for synthesis alkyl bicyclo[1.1.1]pentane-heteroaryls has captured attention scientific vanguard. We herein report a groundbreaking and eco-conscious multicomponent coupling reaction that paves way alkylation heteroarylation [1.1.1]propellane, process uniquely enabled by photochemical prowess an electron donor–acceptor (EDA) complex. This method is distinguished its minimalist yet powerful approach: devoid transition metals, additives, photosensitizers. Its universality further exemplified seamless compatibility broad spectrum halides heteroarenes under standardized conditions, heralding new era synthetic versatility. The method's practicality underscored capacity late-stage modification pharmaceuticals, offering transformative tool enhancement existing drug molecules. Moreover, facile derivatization synthesized products underscores adaptability potential diverse applications. Our mechanistic studies have elucidated underlying radical-relay pathway, pinpointing pivotal role EDA complex in initiating transformation. discovery not only enriches our fundamental understanding but also opens avenues strategic optimization.

Язык: Английский

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Photochemistry in Medicinal Chemistry and Chemical Biology

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(6), С. 4322 - 4345

Опубликована: Март 8, 2024

Photochemistry has emerged as a transformative force in organic chemistry, significantly expanding the chemical space accessible for medicinal chemistry. Light-induced reactions enable efficient synthesis of intricate structures and have found applications throughout different stages drug discovery development processes. Moreover, photochemical techniques provide innovative solutions biology, allowing precise spatiotemporal activation targeted delivery. In this Perspective, we highlight already numerous remarkable even more promising future photochemistry chemistry biology.

Язык: Английский

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Transition-metal-, oxidant- and additive-free multi-component synthesis of alkyl heteroaryl BCPs enabled by visible-light-induced phosphine-catalyzed halogen-atom transfer

Organic Chemistry Frontiers, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

This study describes a pioneering visible-light-induced phosphine-catalyzed halogen-atom transfer (XAT) strategy that heralds new era in the difunctionalization of [1.1.1]propellane.

Язык: Английский

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Metal- and photocatalyst-free three-component strategy to prepare benzylalcohol-, aldehyde-substituted BCP building blocks

Green Chemistry, Год журнала: 2024, Номер 26(9), С. 5531 - 5537

Опубликована: Янв. 1, 2024

A mild one-step, light-promoted, three-component radical-coupling reaction of [1.1.1]propellane to afford difunctionalized benzylalcohol-, aldehyde-substituted BCPs in the absence metals, photocatalysts or external oxidants was reported.

Язык: Английский

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Stereoselective Synthesis of Highly Functionalized Bicyclo[2.1.0]pentanes by Sequential [2 + 1] and [2 + 2] Cycloadditions

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

This study describes a method for the stereoselective synthesis of highly functionalized bicyclo[2.1.0]pentanes (housanes). The approach utilizes two-step sequence, silver- or gold-catalyzed cyclopropenation alkynes followed by an intermolecular [2 + 2] photocycloaddition reaction with electron-deficient alkenes. is established aryldiazoacetates. A regioselective cycloaddition cyclopropane was developed using blue LED irradiation, commercially available photocatalyst as triplet-sensitizer, and low temperature (−40 °C). diastereoselective, when enantioenriched cyclopropenes are used, it proceeds enantioretention.

Язык: Английский

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Iodopentafluorosulfanylation of [1.1.1]propellane and further functionalizations

Science China Chemistry, Год журнала: 2023, Номер 66(10), С. 2871 - 2877

Опубликована: Авг. 24, 2023

Язык: Английский

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