Construction of bridged polycycles through dearomatization strategies

Organic & Biomolecular Chemistry, Journal Year: 2021, Volume and Issue: 19(18), P. 3960 - 3982

Published: Jan. 1, 2021

Bridged polycycles are privileged molecular skeletons with wide occurrence in bioactive natural products and pharmaceuticals. Therefore, they have been the pursing target molecules of numerous chemists. The rapid convenient generation sp3-rich complex three-dimensional from simple easily available aromatics has made dearomatization a highly valuable synthetic tool for construction rigid challenging bridged rings. This review summarizes the-state-of-the-art advances strategies application ring formation, discusses their advantages limitations in-depth mechanism, highlights value total synthesis products. We wish this will provide an important reference medicinal chemists inspire further development intriguing research area.

Language: Английский

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Hypoiodite-Catalyzed Oxidative Umpolung of Indoles for Enantioselective Dearomatization

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 5756 - 5761

Published: March 23, 2022

Here we report the oxidative umpolung of 2,3-disubstituted indoles toward enantioselective dearomative aza-spirocyclization to give corresponding spiroindolenines using chiral quaternary ammonium hypoiodite catalysis. Mechanistic studies revealed reactivity C3 by iodination indole nitrogen atom. Moreover, introduction pyrazole as an electron-withdrawing auxiliary group at C2 suppressed a competitive dissociative racemic pathway, and spirocyclization proceeded not only spiropyrrolidines but also four-membered spiroazetidines that are otherwise difficult access.

Language: Английский

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Asymmetric Dearomatization of Indoles with Azodicarboxylates via Cascade Electrophilic Amination/Aza-Prins Cyclization/Phenonium-like Rearrangement

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(21), P. 11745 - 11753

Published: May 19, 2023

Herein, we report a highly efficient synthesis of enantioenriched aza-[3.3.1]-bicyclic enamines and ketones, class structural cores in many natural products, via asymmetric dearomatization indoles with azodicarboxylates. The reaction is initiated by electrophilic amination followed aza-Prins cyclization/phenonium-like rearrangement. A newly developed fluorine-containing chiral phosphoric acid displays excellent activity promoting this cascade reaction. absence or presence water as the additive directs pathway toward either enamine ketone products high yields (up to 93%) enantiopurity 98% ee). Comprehensive density functional theory (DFT) calculations reveal energy profile origins enantioselectivity water-induced chemoselectivity.

Language: Английский

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Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides

Organic Letters, Journal Year: 2021, Volume and Issue: 23(21), P. 8600 - 8605

Published: Oct. 21, 2021

An enantioselective dearomative 1,3-dipolar cycloaddition of 2-nitrobenzothiophenes and isatin-derived azomethine ylides with a bifunctional hydrogen-bonding thiourea catalyst was established, giving polyheterocyclic compounds in excellent results (up to 99% yield, >20:1 dr for all cases up ee). The enantioselectivity could be reversed by the squaramide containing same chiral source as catalyst. DFT calculations revealed origin observed stereochemistry reversal enantioselectivity.

Language: Английский

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Ag-Catalyzed Asymmetric Interrupted Barton–Zard Reaction Enabling the Enantioselective Dearomatization of 2- and 3-Nitroindoles

Organic Letters, Journal Year: 2022, Volume and Issue: 24(3), P. 826 - 831

Published: Jan. 14, 2022

We disclose a Ag-catalyzed asymmetric interrupted Barton–Zard reaction of α-aryl-substituted isocyanoacetates with 2- and 3-nitroindoles, which enables the dearomatization nitroindoles hence offers rapid access to an array optically active tetrahydropyrrolo[3,4-b]indole derivatives bearing three contiguous stereogenic centers, including two tetrasubstituted chiral carbon atoms pretty outcomes (up 99% yield, 91:9 dr, 96% ee). The synthetic potential protocol was showcased by gram-scale versatile transformations product.

Language: Английский

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Enantioselective Dearomatization of Indoles via SmI₂-Mediated Intermolecular Reductive Coupling with Ketones

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10314 - 10321

Published: April 26, 2023

Samarium diiodide (SmI2) mediated reductive coupling reactions are powerful methods for the construction of carbon-carbon bond in organic synthesis. Despite extensive development recent decades, successful examples corresponding asymmetric remained scarce, probably due to involvement highly reactive radical intermediates. In this Article, we report an enantioselective dearomatization indoles via SmI2-mediated intermolecular with ketones. The utilization samarium reductant supported by chiral tridentate aminodiol ligands allows facile synthesis indoline molecules bearing two contiguous stereogenic centers high yields (up 99%) and stereoselectivity 99:1 er >20:1 dr). Combined experimental computational investigations suggested that parallel single-electron transfer each substrate from radical-radical recombination manner, which is a unique mechanistic scenario reactions.

Language: Английский

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Dearomative [4 + 2] cycloaddition of 3‐nitroindoles with ortho‐amino Morita−Baylis−Hillman carbonates to forge indole‐fused quinolines

Journal of Heterocyclic Chemistry, Journal Year: 2024, Volume and Issue: 61(3), P. 528 - 537

Published: Jan. 16, 2024

Abstract A dearomative [4 + 2] cycloaddition of 3‐nitroindoles ortho ‐amino Morita−Baylis−Hillman carbonates was established under mild conditions. This method provides an efficient and practical approach for delivering tetrahydro‐5 H ‐indolo[2,3‐ b ]quinolines containing three contiguous stereocenters, two tertiary one quaternary, in high yield (up to 95%) with excellent diastereoselectivity (all cases >25:1 dr ). The potential synthetic applications this strategy were also highlighted by the scale‐up experiment further transformation. Moreover, structure relative configuration cycloadduct unequivocally confirmed single‐crystal X‐ray diffraction.

Language: Английский

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Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3310 - 3315

Published: April 8, 2024

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable triggering dearomatization 3-nitroindoles for diastereo- enantioselective [3+2] cycloaddition, leading formation series highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up 99% yield, 88:12 dr, 96% ee).

Language: Английский

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Dearomative (3 + 2) Cycloadditions of 3-Nitroheteroarenes with Allenyl Sulfones Mediated by Ion Pair Organocatalysis

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

We report the first example of dearomative (3 + 2) cycloadditions 3-nitro(aza)-indole, -benzofuran, and -benzothiophene derivatives in presence allenyl sulfones, using sulfinate ammonium ion pairs as organocatalytic promoters. The methodology provides a new, facile, efficient protocol for synthesis functionalized 2,3-fused cyclopentannulated indolines dihydrobenzofurans.

Language: Английский

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Dearomatization of 3-Nitroindoles Enabled Using Palladium-Catalyzed Decarboxylative [4 + 2] Cycloaddition of 2-Alkylidenetrimethylene Carbonates

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(9), P. 6025 - 6037

Published: April 18, 2022

A dearomatization process of 3-nitroindoles enabled using palladium-catalyzed decarboxylative [4 + 2] cycloaddition either 2-alkylidenetrimethylene carbonates or 2-(hydroxymethyl)-3-arylallyl has been developed, affording a wide range indoline-fused tetrahydropyrans in good yields with excellent diastereoselectivities. This reaction features substrate scope and mild conditions represents the first example application π-allyl palladium 1,4-[O,C]-dipole species for dearomative electron-deficient heteroarenes.

Language: Английский

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