Catalytic Atroposelective Electrophilic Amination of Indoles

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 25, 2022

Abstract Reported here is the first catalytic atroposelective electrophilic amination of indoles, which delivers functionalized atropochiral N ‐sulfonyl‐3‐arylaminoindoles with excellent optical purity. This reaction was furnished by 1,6‐nucleophilic addition to p ‐quinone diimines. Control experiments suggest an ionic mechanism that differs from radical pathway commonly proposed for 1,6‐addition quinones. The origin selectivity investigated through computational studies. Preliminary studies show obtained 3‐aminoindoles atropisomers exhibit anticancer activities. method valuable respect enlarging toolbox amine derivatives.

Language: Английский

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Organocatalytic cycloaddition–elimination cascade for atroposelective construction of heterobiaryls

Chemical Science, Journal Year: 2021, Volume and Issue: 12(44), P. 14920 - 14926

Published: Jan. 1, 2021

The first chiral phosphoric acid (CPA) catalyzed cycloaddition-elimination cascade reaction of 2-naphthol- and phenol-derived enecarbamates with azonaphthalenes has been established, providing a highly atroposelective route to an array axially aryl-C3-benzoindoles in excellent yields enantioselectivities. success this strategy derives from the stepwise process involving CPA-catalyzed asymmetric formal [3 + 2] cycloaddition subsequent central-to-axial chirality conversion by elimination carbamate. In addition, practicality had verified varieties transformations towards functionalized atropisomers.

Language: Английский

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Enamides and dienamides in phosphoric acid-catalysed enantioselective cycloadditions for the synthesis of chiral amines

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(34), P. 4089 - 4105

Published: Jan. 1, 2021

This feature article describes how enamides and dienamides can participate in chiral phosphoric acid catalyzed enantioselective cycloadditions to prepare a wide range of cyclic amines.

Language: Английский

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Enantioselective and Diastereodivergent Synthesis of Spiroindolenines via Chiral Phosphoric Acid-Catalyzed Cycloaddition

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(30), P. 11611 - 11619

Published: July 23, 2021

A diastereodivergent and enantioselective synthesis of chiral spirocyclohexyl-indolenines with four contiguous stereogenic centers is achieved by a phosphoric acid-catalyzed cycloaddition 2-susbtituted 3-indolylmethanols 1,3-dienecarbamates. Modular access to two different diastereoisomers high enantioselectivities was obtained careful choice reaction conditions. Their functional group manipulation provides an efficient enantioenriched spirocyclohexyl-indolines -oxindoles. The origins this stereocontrol have been identified using DFT calculations, which reveal unexpected mechanism compared our previous work dealing enecarbamates.

Language: Английский

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Strategies toward the Difunctionalizations of Enamide Derivatives for Synthesizing α,β-Substituted Amines

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(22), P. 3265 - 3283

Published: Nov. 1, 2022

ConspectusEnamide and enecarbamate derivatives containing a nucleophilic center at the β-position from their nitrogen atom as well latent electrophilic site α-position are interesting motifs in organic chemistry. This dual reactivity─analogous that of enamines─enables difunctionalization increased structural complexity. Furthermore, an electron-withdrawing group on drastically increases stability. In respect, enamides enecarbamates excellent partners for multicomponent transformations, our research primarily focuses these compounds particular.Difunctionalization generally occurs through addition electrophile to form iminium, which can subsequently react with species. Although potent, such approach is highly challenging due low stability intermediate leading undesired hydrolysis or oligomerization. Epimerization, competitivity, compatibility issues between reaction additional hindrances developing methodologies. To overcome limitations, we described many complementary strategies.To control enantioselectivity chiral phosphoric acids were found be particularly well-suited activate multiple reactants formation hydrogen bonds network, allowing organized transition state pocket. Interestingly, when deprotonated phosphates, they also play role ligands Lewis acidic metals.To avoid iminium oligomerization, successfully used stabilized α-arylated enamides. However, this was restricted simple β-position. achieve difunctionalizations α-unsubstituted derivatives, explored reversibly linked nucleophile address problem. Alternatively, devised sequential methodology resolving issue N-acyl based its trapping using temporary (alcohol thiol). agent could further displaced by desired final α-substituent under photocatalytic activation. led us design new bifunctional acid catalysts bearing chromophores merge asymmetric organocatalysis photochemistry.These photocatalysis studies incited focus radical processes manage original functionalizations would not feasible otherwise. β-Alkylation β-trifluoromethylation via visible-light-promoted transfer additions performed. As β-allylations remained unattainable precedent methods, eventually turned attention cerium(IV)-mediated oxidative single electron transfers. It allowed singly occupied molecular orbital activation substrates elicit umpolung reactivity.Thus, functionalization appears valid synthetic strategy obtaining important building blocks agrochemical, pharmaceutical, cosmetic industries, including diamines, haloamines, aminotryptamines, less accessible trifluoromethylated allylic compounds.

Language: Английский

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Diversity‐Oriented Catalytic Asymmetric Dearomatization of Indoles with o‐Quinone Diimides

Advanced Science, Journal Year: 2023, Volume and Issue: 10(35)

Published: Oct. 23, 2023

Abstract Herein, the first diversity‐oriented catalytic asymmetric dearomatization of indoles with o ‐quinone diimides ( ‐QDIs) is reported. The (CADA) one research focuses in terms structural and biological importance dearomatized indole derivatives. Although great achievements have been made target‐oriented CADA reactions, reactions are regarded as more challenging remain elusive due to lack synthons featuring multiple reaction sites difficulty precise control chemo‐, regio‐, enantio‐selectivity. In this work, ‐QDIs employed a versatile building block, enabling chemo‐divergent dearomative arylation [4 + 2] cycloaddition indoles. Under catalysis chiral phosphoric acid mild conditions, various indolenines, furoindolines/pyrroloindolines, six‐membered‐ring fused indolines collectively prepared good yields excellent enantioselectivities. This synthesis protocol enriches chemistry offers new opportunities for reactions.

Language: Английский

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Practical Access to meta‐Substituted Anilines by Amination of Quinone Imine Ketals Derived from Anisidines: Efficient Synthesis of Anti‐Psychotic Drugs

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 21, 2023

Reversing the conventional site-selectivity of C-H activation provides efficient retrosynthetic disconnections to otherwise unreactive bonds. Described herein is Brønsted acid-catalyzed reaction that selectively performs meta-amination anisidines with aliphatic-, heterocyclic- and aromatic amines in a one-pot procedure. In addition dramatically simplifying synthesis meta-substituted anilines, our approach has advantage scalability remarkable functional group tolerance, including late-stage functionalization pharmaceutical compounds natural products. The control experiments detailed computational analysis provide insight into mechanism origin meta-selectivity. protocol extended challenging tri-aminated arenes successfully applied for 5-HT6 receptor antagonists, anti-psychotic drugs viz.. SB-214111, SB-258510, specifically, anti-schizophrenic drug SB-271046.

Language: Английский

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Stereoselective intermolecular radical cascade reactions of tryptophans or ɤ-alkenyl-α-amino acids with acrylamides via photoredox catalysis

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 1, 2022

Abstract The radical cascade reaction is considered as one of the most powerful methods to build molecular complexity. However, highly stereoselective intermolecular reactions that can produce complex cyclic compounds bearing multiple stereocenters via visible-light-induced photocatalysis have been challenging yet desirable. Herein we report a facile and efficient synthesis multi-substituted trans -fused hexahydrocarbazoles readily available tryptophans acrylamides enabled by photoredox catalysis. with up five including two quaternary ones be accessed in 82% yield, >20/1 diastereoselectivity, 96% ee. Interestingly, tetrahydrocarbazoles are favorably formed when performed under air. Moreover, simply switching starting material from ɤ-alkenyl substituted α-amino acids, this protocol further applied syntheses 1,3,5-trisubstituted cyclohexanes which otherwise access. Preliminary mechanistic studies suggest goes through addition radical-polar crossover processes.

Language: Английский

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Enantioselective [3 + 2] annulation of 3-hydroxymaleimides with quinone monoimines

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(10), P. 2268 - 2273

Published: Jan. 1, 2021

Enantioselective [3 + 2] annulation of 3-hydroxymaleimides with quinone monoimines provided a large variety succinimide fused indolines in moderate to good yields enantioselectivities.

Language: Английский

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Recent advances in catalytic oxidative reactions of phenols and naphthalenols

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(19), P. 5395 - 5413

Published: Jan. 1, 2022

This critical review aims to provide an overview of oxidative phenol and naphthalenol transformations in nature synthetic chemistry.

Language: Английский

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