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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Asymmetric Substitution by Alkynyl Copper Driven Dearomatization and Rearomatization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: Oct. 16, 2023

Abstract Catalytic asymmetric transformations by dearomatization have developed into a widely applicable synthetic strategy, but heavily relied on the use of arenes bearing heteroatom. In this case, is facilitated involvement p ‐orbital electron Different from conventional substrate‐dependent model, here we demonstrate that activation d transition‐metal center can serve as driving force for dearomatization, and applied to development novel alkynyl copper remote substitution reaction. A newly modified PyBox chiral ligand enables construction valuable diarylmethyl triarylmethyl skeletons in high enantioselectivities. An unexpected tandem process involving sequential substitution/cyclization/1,5‐H shift leads formation enantioenriched C−N axis. gram‐scale reaction various downstream highlight robustness method potential products. Preliminary mechanistic studies reveal mononuclear Cu‐catalyzed process.

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 16982 - 16989

Published: June 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.

Language: Английский

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Catalytic N-Acylation for Access to N–N Atropisomeric N-Aminoindoles: Choice of Acylation Reagents and Mechanistic Insights

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6926 - 6935

Published: April 18, 2024

The synthesis of N–N axial compounds containing aromatic acyl amides using common acylation reagents remains challenging. We describe a highly atropenantioselective N-aminoindoles axes. A chiral cyclic isothiourea is used as the sole organic catalyst in transformation N-acylation reaction. Aroyl chlorides have been to construct atropisomeric through N-acylation. N-aminoindole products, which bear stereogenic axes, were synthesized with high yields and enantioselectivities. Some enantiopure products exhibited promising antibacterial activities against plant pathogens.

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

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CF₂Br₂ as a Source for Difluoroolefination of 1,3-Enynes via N-Heterocyclic Carbene Catalysis

Organic Letters, Journal Year: 2022, Volume and Issue: 24(38), P. 7047 - 7051

Published: Sept. 19, 2022

Commercially available CF2Br2 has been used as a convenient source for the rapid and reliable incorporation of gem-difluorovinyl motif into an allene framework via N-heterocyclic carbene catalyzed difluoroolefination 1,3-enynes. The reaction proceeds through cascade three-component radical relay/elimination process. This protocol is distinguished by its mild conditions, readily accessible starting materials, wide substrate scope, ease late-stage functionalization, thus unlocking untraditional strategy to construct new class functionalized allenes.

Language: Английский

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Chiral Brønsted Acid-Catalyzed Intramolecular Asymmetric Dearomatization Reaction of Indoles with Cyclobutanones via Cascade Friedel–Crafts/Semipinacol Rearrangement

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(37), P. 25878 - 25887

Published: Sept. 3, 2024

The highly efficient synthesis of chiral indolines fused with an azabicyclo[2.2.1]heptanone moiety is achieved by asymmetric dearomatization reaction indoles cyclobutanones. A new imidodiphosphorimidate (IDPi) catalyst synthesized and exhibits extraordinary activity in promoting a cascade Friedel-Crafts/semipinacol rearrangement. Target molecules are prepared good yields (up to 95%) excellent enantioselectivity 98% ee) operational convenience. Combined experimental computational studies provide detailed mechanistic insights into the energy landscape origin stereochemical induction reaction.

Language: Английский

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The literature of heterocyclic chemistry, part XXII, 2022

Advances in heterocyclic chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Direct Construction of Fused/Bridged 3D Rings via Visible‐Light Induced Dearomative Cycloaddition of Arenes

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 365(1), P. 43 - 52

Published: Nov. 30, 2022

Abstract Three‐dimensional aliphatic fused and bridged rings are key pharmacophores in drugs bioactive natural products. Here, we reported an organocatalytic visible‐light induced dearomative cycloaddition of (hetero)arenes, with organic light‐emitting diode material 4CzIPN or readily accessible thioxanthone as photocatalyst. A series cyclobutane‐fused polycyclic structures bicyclo scaffolds were prepared reasonable yields (27–99% yield) medium to excellent diastereoselectivity (1.4:1 to>20:1 dr ), predictable regioselectivity, good functional group compatibilities broad substrate scopes. The combination experimental computational studies supported the energy transfer pathways. magnified image

Language: Английский

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N-heterocyclic carbene-catalyzed direct enantioselective synthesis of dihydroisoxazolo[5,4-b]pyridin-6-ones

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(4), P. 963 - 969

Published: Jan. 1, 2023

A novel N-heterocyclic carbene (NHC)-catalyzed asymmetric [3 + 3] cycloaddition between α-bromoenals and 5-aminoisoxazoles has been developed.

Language: Английский

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