Stereoselective synthesis and applications of spirocyclic oxindoles

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(5), С. 1026 - 1084

Опубликована: Янв. 1, 2021

This review summaries recent synthetic developments towards spirocyclic oxindoles and applications as valuable medicinal targets.

Язык: Английский

---

An overview of spirooxindole as a promising scaffold for novel drug discovery

Expert Opinion on Drug Discovery, Год журнала: 2020, Номер 15(5), С. 603 - 625

Опубликована: Фев. 28, 2020

Introduction: Spirooxindole, a unique and versatile scaffold, has been widely studied in some fields such as pharmaceutical chemistry synthetic chemistry. Especially the application of medicine, quite few compounds featuring spirooxindole motif have displayed excellent broad pharmacological activities. Many identified candidate molecules used clinical trials, showing promising prospects.Areas covered: This article offers an overview different applications developments spirooxindoles (including related natural products their derivatives) process drug innovation, including anticancer, antimicrobial, anti–inflammatory, analgesic, antioxidant, antimalarial, antiviral Furthermore, crucial structure-activity relationships, molecular mechanisms, pharmacokinetic properties, main methods spirooxindoles-based derivatives are also reviewed.Expert opinion: Recent progress biological activity profiles demonstrated significant position present-day discovery. we believe that multidirectional development novel drugs containing this core scaffold will continue to be research hotspot medicinal future.

Язык: Английский

---

Recent advances in organocatalytic asymmetric multicomponent cascade reactions for enantioselective synthesis of spirooxindoles

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(15), С. 4315 - 4348

Опубликована: Янв. 1, 2021

Catalytic asymmetric MCCRs for enantioselective synthesis of spirooxindoles by using chiral phosphoric acids, amines, bifunctional thiourea/squaramides and metal-based reagents as catalysts.

Язык: Английский

---

Atroposelective Access to Oxindole-Based Axially Chiral Styrenes via the Strategy of Catalytic Kinetic Resolution

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(37), С. 15686 - 15696

Опубликована: Авг. 26, 2020

Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because the importance such molecules. However, catalytic asymmetric styrenes or vinyl arenes is underdeveloped and challenging due to low rotational barrier weak configurational stability Therefore, development powerful strategies for atroposelective great importance. In this work, we have accomplished first access oxindole-based by strategy kinetic resolution, offered two kinds styrene derivatives in good diastereoselectivities (up 94:6 dr) excellent enantioselectivities 98% ee) with high selectivity factors (S up 106). This not only provides easy but also offers a robust method synthesizing bisamide bearing both axial central chirality. More importantly, added new class members atropisomeric family, especially family styrenes.

Язык: Английский

---

Spiroindoles as Intermediates/Products in Transition Metal-Catalyzed Dearomatization of Indoles

ACS Catalysis, Год журнала: 2023, Номер 13(14), С. 9442 - 9475

Опубликована: Июль 3, 2023

Spirocyclic indole derivatives are fascinating tridimensional molecular scaffolds from both a synthetic and biological point of view. Among the many strategies developed to access these structures, transition metal catalysis has recently led impressive advances, especially relying on unique reactivity dearomatized spirocyclic intermediates. These species can indeed evolve toward or nonspirocyclic products through rearomatization-driven processes, which at same time highly challenging control but also source large structural diversity. This review highlights most prominent methods past decade that involve spirocyclization tethered functional group may be activated by metal, leading rearomatized products. The discussion is particularly focused spiroindoleninium intermediate complex mechanistic features regarding its evolution, dependent catalytic systems.

Язык: Английский

---

Switching between the [2π+2σ] and Hetero‐[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(29)

Опубликована: Май 11, 2024

Abstract The exploration of the complex chemical diversity bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over past two decades. Regiodivergent syntheses thiabicyclo[4.1.1]octanes (S‐BCOs) highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid‐catalyzed formal cycloaddition bicyclobutanes (BCBs) 3‐benzylideneindoline‐2‐thione derivatives have been established. first hetero‐(4+3) BCBs, catalyzed by Zn(OTf) 2 , was achieved with broad substrate scope under mild conditions. In contrast, less electrophilic BCB ester undergoes Sc(OTf) 3 ‐catalyzed [2π+2σ] reaction 1,1,2‐trisubstituted alkenes, yielding BCHs spirocyclic quaternary carbon center. Control experiments preliminary theoretical calculations suggest that diastereoselective product formation may involve concerted between zwitterionic intermediate E ‐1,1,2‐trisubstituted alkenes. Additionally, nucleophilic ring‐opening mechanism.

Язык: Английский

---

Organocatalytic Asymmetric [3 + 2] Cycloaddition of N-2,2,2-Trifluoroethylisatin Ketimines with β-Trifluoromethyl Electron-Deficient Alkenes: Access to Vicinally Bis(trifluoromethyl)-Substituted 3,2′-Pyrrolidinyl Spirooxindoles

Organic Letters, Год журнала: 2018, Номер 20(15), С. 4453 - 4457

Опубликована: Июль 25, 2018

N-2,2,2-Trifluoroethylisatin ketimines with β-trifluoromethyl enones, 3-trifluoroethylidene oxindole, and benzofuranone can undergo asymmetric [3 + 2] cycloaddition, catalyzed by chiral bifunctional squaramide-tertiary amine catalysts, affording a wide spectrum of 3,2'-pyrrolidinyl spirooxindoles. The significance this protocol is highlighted its extremely high efficiency in the construction structurally diverse spirocyclic oxindoles, bearing vicinally bis(trifluoromethyl)-substituted pyrrolidine moiety, including four contiguous stereocenters, yields excellent stereocontrol.

Язык: Английский

---

Advances in organocatalytic asymmetric reactions of vinylindoles: powerful access to enantioenriched indole derivatives

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(11), С. 2643 - 2672

Опубликована: Янв. 1, 2021

This review summarizes advances in vinylindole-based organocatalytic asymmetric reactions since 2008 and includes the applications of some methodologies total synthesis natural products, points out remaining challenges this research area.

Язык: Английский

---

Phosphine‐Catalyzed (3+2) Annulation of Isoindigos with Allenes: Enantioselective Formation of Two Vicinal Quaternary Stereogenic Centers

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(19), С. 6260 - 6264

Опубликована: Фев. 12, 2019

Construction of contiguous all-carbon quaternary stereogenic centers is a long-standing challenge in synthetic organic chemistry. In this report, phosphine-catalyzed enantioselective (3+2) annulation reaction between allenes and isoindigos, containing either two identical or different oxindole moieties, introduced as powerful strategy for the construction spirocyclic bisindoline alkaloid core structures. The reported reactions feature high chemical yields, excellent enantioselectivities, very good regioselectivities, are highly useful creating structurally challenging natural products.

Язык: Английский

---

Recent Advances in the Construction of Trifluoromethyl‐Containing Spirooxindoles through Cycloaddition Reactions

Chemistry - An Asian Journal, Год журнала: 2020, Номер 15(8), С. 1225 - 1233

Опубликована: Фев. 27, 2020

The spirooxindole unit is one of the most widely investigated compound skeletons existing in numerous natural and pharmaceutical molecules. Thus, a large number synthetic methodologies have already been reported to construct such core structure. trifluoromethyl group another privileged organic chemistry. introduction CF3 an framework can significantly improve properties molecule. In this context, efficient approach for construction trifluoromethyl-containing spirooxindoles becomes promising research direction among communities industry academia. Minireview, recent advances summarized discussed. addition, representative corresponding reaction mechanisms described as well.

Язык: Английский

---