Photoredox-catalyzed diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indole derivatives DOI Creative Commons

Xuexue Chang,

Fangqing Zhang,

Shibo Zhu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 30, 2023

Abstract Prenylated and reverse-prenylated indolines are privileged scaffolds in numerous naturally occurring indole alkaloids with a broad spectrum of important biological properties. Development straightforward stereoselective methods to enable the synthesis structurally diverse prenylated indoline derivatives is highly desirable challenging. In this context, most direct approaches achieve goal generally rely on transition-metal-catalyzed dearomative allylic alkylation electron-rich indoles. However, electron-deficient indoles much less explored, probably due their diminished nucleophilicity. Herein, photoredox-catalyzed tandem Giese radical addition/Ireland–Claisen rearrangement disclosed. Diastereoselective prenylation reverse-prenylation proceed smoothly under mild conditions. An array tertiary α-silylamines as precursors readily incorporated 2,3-disubstituted high functional compatibility excellent diastereoselectivity (>20:1 d.r.). The corresponding transformations secondary provide biologically lactam-fused one-pot synthesis. Subsequently, plausible photoredox pathway proposed based control experiments. preliminary bioactivity study reveals potential anticancer property these appealing indolines.

Language: Английский

Catalytic Asymmetric Construction of Axially Chiral Indole‐Based Frameworks: An Emerging Area DOI

Tian‐Zhen Li,

Si‐Jia Liu,

Wei Tan

et al.

Chemistry - A European Journal, Journal Year: 2020, Volume and Issue: 26(68), P. 15779 - 15792

Published: May 4, 2020

Axially chiral indole-based frameworks have been recognized as a class of important five-membered heterobiaryls and developing catalytic asymmetric approaches for constructing these in an enantioselective manner is highly desirable. In recent years, synthetic chemists paid much attention to this research field, rapid developments occurred. At point, range axially scaffolds constructed via various reactions based on different strategies. Thus, the construction has become emerging area. This minireview summarizes advances field gives some insights into future developments, which will help thrive.

Language: Английский

Citations

250
Progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives DOI Open Access

Feng‐Tao Sheng,

Jing‐Yi Wang, Wei Tan

et al.

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 7(23), P. 3967 - 3998

Published: Jan. 1, 2020

This review summarizes the progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives and their applications total synthesis natural products, gives some insights into challenging issues this research field.

Language: Английский

Citations

210
Cascade asymmetric dearomative cyclization reactions via transition-metal-catalysis DOI
Yang‐Zi Liu, Hao Song, Chao Zheng

et al.

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(3), P. 203 - 216

Published: March 14, 2022

Language: Английский

Citations

78
Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis DOI Creative Commons
Wen‐Jun Zhou,

Zhe‐Hao Wang,

Li‐Li Liao

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 29, 2020

Abstract Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic efficient way to construct complex skeletons, which is dominated by transition-metal catalysis via electron transfer. Herein, we report a strategy visible-light photoredox-catalyzed successive single transfer, realizing dearomative arylcarboxylation indoles with CO 2 . This avoids common side reactions in catalysis, including ipso-carboxylation aryl halides β-hydride elimination. photoredox shows high chemoselectivity, low loading photocatalyst, mild reaction conditions (room temperature, 1 atm) good functional group tolerance, providing great potential for the synthesis valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that benzylic radicals anions might be generated as key intermediates, thus direction couplings other electrophiles, D O aldehyde.

Language: Английский

Citations

134
Atroposelective Construction of Axially Chiral Alkene‐Indole Scaffolds via Catalytic Enantioselective Addition Reaction of 3‐Alkynyl‐2‐indolylmethanols† DOI
Jing‐Yi Wang, Meng Sun,

Xian‐Yang Yu

et al.

Chinese Journal of Chemistry, Journal Year: 2021, Volume and Issue: 39(8), P. 2163 - 2171

Published: April 29, 2021

Main observation and conclusion Atroposelective construction of axially chiral alkene‐heteroaryl scaffolds is highly desired but challenging. In this work, we established an atroposelective alkene‐indole via the strategy catalytic enantioselective addition reaction 3‐alkynyl‐2‐indolylmethanols with bulky nucleophiles. strategy, α‐amido sulfones were used as competent nucleophiles phosphoric acid (CPA) acted suitable catalyst for reaction. By a new class acyclic alkene‐indoles was synthesized in overall high yields (up to 86%), excellent ( E / Z )‐selectivity (all > 95 : 5) good enantioselectivities 92 8 er). This represents first frameworks, which will add member family atropoisomeric heterocycles, especially indole compounds.

Language: Английский

Citations

78
Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines DOI
Min Zhu,

Xu‐Lun Huang,

Shuo Sun

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(33), P. 13441 - 13449

Published: Aug. 16, 2021

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, by excitation aromatic rings provide an alternative solution to direct transformations feedstocks under scheme dearomatization. Vinylcyclopropanes (VCPs) well-known reagents in radical clock experiments, working a probe detect transient intermediates. However, applications this regard still remain limited due uncontrollable selectivities. Herein, we report visible-light-induced dearomatization indole- or pyrrole-tethered VCPs, which several competitive reaction pathways, including [5 + 2], [2 interrupted and 4] cycloadditions, can be well regulated engineering substrate structures tuning conditions. The mechanism has been explored combined experimental computational investigations. These convenient method synthesize structurally diverse polycyclic with high efficiency good selectivity.

Language: Английский

Citations

76
Asymmetric Dearomatization of Indoles with Azodicarboxylates via Cascade Electrophilic Amination/Aza-Prins Cyclization/Phenonium-like Rearrangement DOI

Xian-Yun Huang,

Pei‐Pei Xie,

Lei-Ming Zou

et al.

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

Citations

28
Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives DOI
Muzi Li,

Xu‐Lun Huang,

Zuo‐Yu Zhang

et al.

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

Citations

11
Silver-Enabled Dearomative Trifluoromethoxylation of Indoles DOI
Zhijie Deng,

Lingduan Meng,

Bing Xiao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2325 - 2332

Published: Jan. 17, 2024

The only known method for the dearomative trifluoromethoxylation of indoles is preliminary, with one substrate successfully undergoing reaction. In this study, we not developed a broadly applicable indole but also achieved divergent by fine-tuning reaction conditions. Under optimized conditions, silver salt and an easily handled OCF3 reagent, various smoothly underwent dearomatization to afford diverse array ditrifluoromethoxylated indolines in 50–84% isolated yields up 37:1 diastereoselectivity, fluorinated trifluoromethoxylated were obtained exclusive trans selectivity. addition, conditions compatible other heteroaromatic rings as well styrene moieties.

Language: Английский

Citations

10
Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis DOI
Wenjie Shen, Xiaoqin Zou, Muzi Li

et al.

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

Citations

1