Strain-Release Photocatalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(38), С. 20716 - 20732

Опубликована: Сен. 15, 2023

The concept of strain in organic compounds is as old modern chemistry and was initially introduced to justify the synthetic setbacks along synthesis small ring systems (pars construens strain). In last decades, chemists have developed an arsenal strain-release reactions destruens strain) which can generate─with significant driving force─rigid aliphatic that act three-dimensional alternatives (hetero)arenes. Photocatalysis added additional dimension processes by leveraging energy photons create chemical complexity under mild conditions. This perspective presents latest advancements photocatalysis─with emphases on mechanisms, catalytic cycles, current limitations─the unique architectures be produced, possible future directions.

Язык: Английский

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Silver‐Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Окт. 12, 2023

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles bicyclobutane precursors is described. The strain-release operates under mild conditions, tolerating wide range functional groups. It capable forming with up four contiguous quaternary carbon centers, achieving yields 99 %. In addition, scale-up experiment synthetic transformations cycloadducts further highlighted utility.

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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Metal-Free Photoinduced Acylboration of [1.1.1]Propellane via Energy Transfer Catalysis

ACS Catalysis, Год журнала: 2023, Номер 13(14), С. 9542 - 9549

Опубликована: Июль 5, 2023

Highly strained 1,3-disubstituted bicyclo[1.1.1]pentanes (BCPs) have been established as bioisosteres of para-disubstituted benzene because they impart valuable pharmacokinetic properties. Herein, we demonstrate an energy transfer-mediated protocol for acylboration [1.1.1]propellanes that allows the direct construction various carbonyl species, such carbamoyl-, carboxyl-, and acyl-, in tandem with synthetically versatile pinacol boronate (Bpin) groups onto BCP substructure under simple reaction conditions. Moreover, drug-like molecules containing boronates are further submitted to late-stage functionalization events. Several important transformations Bpin functional group boronates, including photoinduced cross-coupling reactions BCP-BF3K, derived from BCP-Bpin, were successfully performed showcase synthetic utility. Additionally, diverse elaborate mechanistic investigations provide insights, a plausible mechanism is proposed.

Язык: Английский

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A General and Practical Route to Functionalized Bicyclo[1.1.1]Pentane‐Heteroaryls Enabled by Photocatalytic Multicomponent Heteroarylation of [1.1.1]Propellane

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(24)

Опубликована: Апрель 15, 2023

Abstract 1‐Aryl‐substituted bicyclo[1.1.1]pentanes (BCPs) are an important class of BCP derivatives with widespread application in drug development. Most syntheses these materials require multiple chemical steps via electrophiles or nucleophiles derived from [1.1.1]propellane. Although one‐step, multicomponent radical cross‐coupling reactions could provide a more sustainable and rapid route to access diverse heteroarylated BCPs, current approaches limited tertiary alkyl radicals, leading decrease their practical value. In this study, conceptually different approach enabled by heteroarylation [1.1.1]propellane functionalized BCPs is described. Importantly, protocol compatible primary‐, secondary‐, aliphatic as well various fluoroalkyl sources, thus enabling library generation sought‐after for

Язык: Английский

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“Alkene-to-Alkene” Difunctionalization of Enaminones for the Synthesis of Polyfunctionalized Alkenes by Transition-Metal-Free C–H and C–N Bond Transformation

Organic Letters, Год журнала: 2023, Номер 25(47), С. 8451 - 8456

Опубликована: Ноя. 16, 2023

The three-component reactions of enaminones, disulfides, and alcohols for the synthesis polyfunctionalized alkenes have been realized via C-H C-N bond transformation on enaminones. proceed in a novel "alkene-to-alkene" difunctionalization mode without using any transition metal. application alkene products divergent sulfenyl heteroaryls, including sulfenylated pyrazoles, pyrimidines, isoxazoles, simple annulation has also verified.

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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Photoinduced C(sp³)−H Bicyclopentylation Enabled by an Electron Donor–Acceptor Complex‐Mediated Chemoselective Three‐Component Radical Relay

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

Опубликована: Апрель 10, 2024

The photoredox electron donor-acceptor (EDA) complex-mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application two-component reactions. However, EDA complex-promoted multi-component reactions are not well developed with only a limited number examples have been reported. Herein, we report photoinduced and highly chemoselective three-component arylalkylation [1.1.1]propellane, which allows direct functionalization C(sp

Язык: Английский

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Intermolecular Formal [2π + 2σ] Cycloaddition of Enol Silyl Ethers with Bicyclo[1.1.0]butanes Promoted by Lewis Acids

Organic Letters, Год журнала: 2024, Номер 26(30), С. 6309 - 6313

Опубликована: Июль 23, 2024

Silyl enol ethers react with bicyclo[1.1.0]butanes (BCBs) through Yb(OTf)

Язык: Английский

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