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

---

Recent advances in the dearomative functionalisation of heteroarenes

Chemical Science, Год журнала: 2022, Номер 13(48), С. 14213 - 14225

Опубликована: Янв. 1, 2022

This Perspective outlines the myriad of products that can be obtained by dearomatisation and functionalization heteroarene substrates. Complex 3D molecules often prepared in one step from simple arene starting materials.

Язык: Английский

---

Recent Advances in the Dearomative Skeletal Editing of Mono-azaarenes

Synthesis, Год журнала: 2023, Номер 56(01), С. 55 - 70

Опубликована: Янв. 17, 2023

Abstract Despite its challenges, the skeletal editing of mono-azaarenes (pyridines, quinolines, and isoquinolines) has shown unparalleled synthetic utility in construction complex molecules that are difficult to access by conventional methods. In this short review, we summarize three most recently developed strategies for deconstruction azaarene cores, with a focus on their generality, limitations, mechanistic aspects. Also, application strategy total synthesis some important natural products is discussed. 1 Introduction 2 Skeletal Editing Mono-Azaarenes through Zincke-like Reactions 3 Mono-azaarenes Aza-Buchner 4 via Photoinduced Radical or Energy-Transfer Processes 5 Conclusion

Язык: Английский

---

Dearomative Construction of 2D/3D Frameworks from Quinolines via Nucleophilic Addition/Borate‐Mediated Photocycloaddition

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(41)

Опубликована: Май 28, 2024

Dearomative construction of multiply-fused 2D/3D frameworks, composed aromatic two-dimensional (2D) rings and saturated three-dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions in the presence photocatalysts usually afford 5,6,7,8-tetrahydroquinoline (THQ)-based polycycles, access 1,2,3,4-THQ-based structures remains limited. Herein, we present a chemo-, regio-, diastereo-, enantioselective transformation into 6-6-4-membered without any catalyst, through combination nucleophilic addition borate-mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that photoexcited borate complex, generated quinoline, organolithium, HB(pin), accelerates cycloaddition suppresses rearomatization occurs conventional Based on our analysis, also developed further photoinduced affording other types frameworks isoquinoline phenanthrene.

Язык: Английский

---

Synthesis of Pyrazolo[1,5-a]pyridinyl, Pyrazolo[1,5-a]quinolinyl, and Pyrazolo[5,1-a]isoquinolinyl Sulfonyl Fluorides via a [3 + 2] Annulation

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(5), С. 3266 - 3276

Опубликована: Фев. 16, 2023

A [3 + 2] cycloaddition reaction of N-aminopyridines, N-aminoquinolines, and N-aminoisoquinolines with 1-bromoethene-1-sulfonyl fluoride (BESF) was performed to obtain optimum yields various useful pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]quinolinyl, pyrazolo[5,1-a]isoquinolinyl sulfonyl fluorides (43–90% yield). The transformation process showed broad substrate specificity, mild conditions, operational simplicity. Therefore, the has great applicable value in field medicinal chemistry other disciplines.

Язык: Английский

---

Synthesis of 1,3,5-trisubstituted pyrazolesvia1,3-dipolar cycloaddition of nitrile imines with ninhydrin-derived Morita–Baylis–Hillman carbonates

Organic & Biomolecular Chemistry, Год журнала: 2022, Номер 20(34), С. 6923 - 6930

Опубликована: Янв. 1, 2022

An effective method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction from ninhydrin-derived Morita–Baylis–Hillman carbonates and nitrilimines has been developed.

Язык: Английский

---

A Three‐Component Domino Reaction Enabled by Phase‐Transfer Catalysis for the Assembly of 3‐Thioquinoline‐2,5‐Diones

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(6), С. 1388 - 1396

Опубликована: Янв. 23, 2024

Abstract A three‐component phase‐transfer catalytic domino reaction involving cyclohexane‐1,3‐dione‐derived enaminones, 5‐alkenyl rhodanines, and haloalkanes has been developed. This protocol produces a wide range of 3‐thioquinoline‐2,5‐diones in yields 52–81%. The construction C−S bond at the C‐3 position quinoline‐2,5‐dione framework expands its structural diversity. Studies into mechanism revealed that undergoes conjugate addition, ammonolysis, elimination, nucleophilic substitution sequence. synthetic potential was demonstrated by gram‐scale syntheses representative products. Chloroalkyl chains were installed on sulfur atoms most products obtained this reaction. Diversified product derivatives exploiting favorable leaving nature chloride moiety.

Язык: Английский

---

Facile Construction of Benzo[d][1,3]oxazocine: Reductive Radical Dearomatization of N-Alkyl Quinoline Quaternary Ammonium Salts

Organic Letters, Год журнала: 2024, Номер 26(10), С. 1996 - 2001

Опубликована: Март 4, 2024

Reductive radical dearomatization N-alkyl quinoline quaternary ammonium salts to synthesize structurally complex and challenging polysubstituted benzo[d][1,3]oxazocines was first reported. The mechanism showed various allyl alcohols can be converted into alkyl radicals under reduction conditions of iron/silane. These then nucleophilically attack the C4 site salts, intramolecular cyclization resulting intermediate generates target product. This method not only produced a series novel but also prepared polycyclic benzo[d][1,3]oxazocines. Finally, this strategy made up for lack reductive reports on N-alkylquinolinium had advantages mild reaction conditions, wide substrate range, product structure.

Язык: Английский

---

Construction of Fused Tetrahydroquinolines by Catalytic Hydride-Transfer-Initiated Tandem Functionalization of Quinolines

Organic Letters, Год журнала: 2022, Номер 24(16), С. 3048 - 3052

Опубликована: Апрель 15, 2022

Herein, we present a new annulation reaction of quinolinium salts with indoles and paraformaldehyde, which enables syn-diastereoselective construction vast range fused tetrahydroquinolines via ruthenium-catalyzed hydride-transfer-initiated tandem functionalization the quinoline skeleton. The developed transformation proceeds mild conditions, good substrate functional group compatibility, readily available feedstocks, operational simplicity.

Язык: Английский

---

An interrupted Corey–Chaykovsky reaction of designed azaarenium salts: synthesis of complex polycyclic spiro- and fused cyclopropanoids

Chemical Science, Год журнала: 2023, Номер 14(25), С. 6963 - 6969

Опубликована: Янв. 1, 2023

Simultaneous dearomatizing spirannulation of pyridinium salts is still in its infancy. Here, we present an organized skeletal remodeling designed by utilizing interrupted Corey-Chaykovsky reaction to access unprecedented and structurally intriguing molecular architectures such as the vicinal bis-spirocyclic indanones spirannulated benzocycloheptanones. This hybrid strategy rationally merges nucleophilic features sulfur ylides with electrophilic achieve regio- stereoselective synthesis new classes cyclopropanoids. The plausible mechanistic pathways were derived from experimental results control experiments.

Язык: Английский

---