Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines

Chemical Reviews, Год журнала: 2024, Номер 124(3), С. 1122 - 1246

Опубликована: Янв. 2, 2024

Dearomatization reactions have become fundamental chemical transformations in organic synthesis since they allow for the generation of three-dimensional complexity from two-dimensional precursors, bridging arene feedstocks with alicyclic structures. When those processes are applied to pyridines, quinolines, and isoquinolines, partially or fully saturated nitrogen heterocycles formed, which among most significant structural components pharmaceuticals natural products. The inherent challenge lies low reactivity heteroaromatic substrates, makes dearomatization process thermodynamically unfavorable. Usually, connecting event irreversible formation a strong C–C, C–H, C–heteroatom bond compensates energy required disrupt aromaticity. This aromaticity breakup normally results 1,2- 1,4-functionalization heterocycle. Moreover, combination these subsequent tandem stepwise protocols allows multiple heterocycle functionalizations, giving access complex molecular skeletons. aim this review, covers period 2016 2022, is update state art nucleophilic dearomatizations showing extraordinary ability dearomative methodology indicating their limitations future trends.

Язык: Английский

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Fine‐Tuning Substrate–Catalyst Halogen–Halogen Interactions for Boosting Enantioselectivity in Halogen‐Bonding Catalysis

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(35)

Опубликована: Май 25, 2023

A new approach towards highly enantioselective halogen-bonding catalysis has been developed. To circumvent the intrinsic issues of nature halogen-bond (XB) and resultant unresolved limitations in asymmetric catalysis, fine-tuned halogen-halogen interactions between substrate XB-donor were designed to preorganize catalyst's cavity boost enantiocontrol. The present strategy exploits both electron cloud (Lewis base site) sigma (σ)-hole site halogen substituent substrates form a tight catalyst-substrate-counteranion chiral complex, thus enabling controlled induction high levels chirality transfer. Remarkable enantioselectivities up 95 : 5 e.r. (90 % ee) have achieved model dearomatization reaction halogen-substituted (iso)quinolines with tetrakis-iodotriazole multidentate anion-binding catalysts.

Язык: Английский

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Catalytic Asymmetric Dearomative [2 + 2] Photocycloaddition/Ring-Expansion Sequence of Indoles with Diversified Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(33), С. 23457 - 23466

Опубликована: Июль 12, 2024

Developing novel strategies for catalytic asymmetric dearomatization (CADA) reactions is highly valuable. Visible light-mediated photocatalysis demonstrated to be a powerful tool activate aromatic compounds further synthetic transformations. Herein, dearomative [2 + 2] photocycloaddition/ring-expansion sequence of indoles with simple alkenes was reported, providing facile access enantioenriched cyclopenta[

Язык: Английский

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Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 16982 - 16989

Опубликована: Июнь 13, 2024

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed naphthalene with PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This features application Gd/PyBox complex, which regulates reactivity selectivity simultaneously, in excited-state catalysis. A wide range functional groups is compatible this protocol, giving highly enantioenriched bridged polycycles excellent yields (up to 96%) >20:1 chemoselectivity, dr, >99% ee). The synthetic utility demonstrated by 2 mmol scale reaction, removal directing group, diversifications products. Preliminary mechanistic experiments are performed elucidate mechanism.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Anion Recognition-Directed Supramolecular Catalysis with Functional Macrocycles and Molecular Cages

Accounts of Chemical Research, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

ConspectusThe development of supramolecular chemistry has provided a variety host molecules and noncovalent tools for boosting catalytic processes, stimulating the emergence advance catalysis, among which macrocyclic cage-like compounds have attracted great attention due to their possession an enzyme-mimetic cavity recognition ability. While privileged scaffolds such as crown ethers, cyclodextrins, cucurbiturils, calixarenes, metal-coordinated cages been widely used, skeletons usually do not contain directional binding site; activation mainly rely on cation-associated interactions or hydrophobic effects. In this context, recent anion drawn our developing recognition-directed approach by using tailor-made functionalized macrocycles cages. Anions are important existing species in both biological chemical systems play role regulating structure function enzymes. We envisioned that taking advantage anions, including rich variety, diverse geometry, multiple interaction sites, sophisticated cooperation can be manipulated confined directing efficient selective catalysis.Following concept, we initiated study introducing typical thiourea H-bonding groups design synthesize series bis-thiourea macrocycles, especially chiral incorporating linkers. Taking obtained strong, cooperative binding, macrocycle-enabled counteranion trapping strategy was developed, afforded greatly enhanced efficiency excellent stereocontrol acid-catalyzing reactions. Furthermore, inspired sulfate-induced dimerization assembly, built substrate-induced assembly system, enabling induced-fit network enantioselective catalysis. addition, recognition-driven chirality gearing with more trithiourea cage revealed, could provide basis implementing anion-triggered allosteric catalysis within induced helical space. Not limited hydrogen bonding, emerging anion-π were largely exploited. A triazine-based prism containing three V-shaped electron-deficient π-cavities constructed, properties studied. Based established driving highly paved way push toward practical useful catalyst design.These results demonstrated anion-recognition direction serve powerful, versatile It is feasible only employing exogenous anions (e.g., counteranion) handle but also regulation anionic active intermediates/transition states, from use conventional recognition.

Язык: Английский

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Chalcogen- and Halogen-Bond-Donating Cyanoborohydrides Provide Imine Hydrogenation

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(5), С. 2916 - 2925

Опубликована: Фев. 19, 2024

Sulfonium, selenonium, telluronium, and iodonium cyanoborohydrides have been synthesized, isolated, fully characterized by various methods, including single-crystal X-ray diffraction (XRD) analysis. The quantum theory of atoms in molecules' analysis based on the XRD data indicated that hydride···σ-hole short contacts observed crystal structures each compound a purely noncovalent nature. telluronium provide significantly higher rate model reaction imine hydrogenation compared with sodium tetrabutylammonium cyanoborohydrides. Based NMR high-resolution electrospray ionization mass spectrometry indicating progress is accompanied cation reduction, mechanism involving intermediate formation elusive onium hydrides has proposed as an alternative to conventional electrophilic activation moiety its ligation cation's σ-hole.

Язык: Английский

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A Dual Cobalt‐Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides via C−H Activation

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

Опубликована: Июнь 19, 2024

Abstract In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C−H bonds amides and subsequent migratory insertion π‐bonds present in indole as reactive partner, achieve syn ‐selective tetrahydro‐5 H ‐indolo[2,3‐ c ]isoquinolin‐5‐one derivatives with excellent yields enantiomeric excesses up to >99 %. The developed operates without metal oxidant, relying solely on oxygen oxidant employing an organic dye photocatalyst irradiation. Control experiments stoichiometric studies elucidate reversible nature enantiodetermining activation step, albeit not being rate‐determining. This study only expands horizon cobalt‐catalyzed bond functionalization, but also showcases potential synergy between cobalt photoredox catalysis enabling synthesis complex molecules.

Язык: Английский

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Visible-Light-Induced Enantioselective Dearomative [2+2]-Cycloaddition/Ring-Expansion Sequence of Indoles with Simple Alkenes

Synlett, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Abstract Catalytic asymmetric dearomatization reactions represent a versatile platform for constructing complex optically active three-dimensional molecules. We present visible-light-induced dearomative [2+2] cycloaddition/ring-expansion reaction of indole derivatives with simple alkenes in the presence chiral N,N′-dioxide/terbium complex. This strategy provides access to range valuable cyclopenta[b]indoles, and its synthetic potential is further showcased through gram-scale synthesis, bioactivity against human breast cancer, transformation into yuehchukene analogue. A series control spectral experiments, as well DFT calculations, provide compelling evidence elucidate mechanism.

Язык: Английский

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Enantioselective synthesis of 3a-azido-pyrroloindolines by copper-catalyzed asymmetric dearomative azidation of tryptamines

Chemical Communications, Год журнала: 2023, Номер 59(50), С. 7831 - 7834

Опубликована: Янв. 1, 2023

Copper-catalyzed asymmetric dearomative azidation of tryptamines using azidobenziodoxolone as an azidating reagent was developed, which affords a variety 3a-azido-pyrroloindolines in good to high enantioselectivities under mild reaction conditions. The azides could be readily transformed into the corresponding 3a-amino-pyrroloindolines via reduction and 1,2,3-triazole derivatives click reaction.

Язык: Английский

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