Enantioselective Synthesis of Quaternary 3-Aminooxindoles via Organocatalytic Asymmetric Michael Addition of 3-Monosubstituted 3-Aminooxindoles to Nitroolefins
The Journal of Organic ChemistryPublished 12 August 2013
Bao‐Dong Cui, Wen‐Yong Han, Zhijun Wu, Xiaomei Zhang, Wei‐Cheng Yuan
Citations61
SJR quartileQ2
SJR score0.74
SNIP0.86
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The potential synthetic utility of the enantioselective synthesis of quaternary 3-aminooxindoles with 3-monosubstituted 3-AMinoox indoles as nucleophiles is demonstrated by a transformation of the product into a spirocyclic oxindole compound.
Abstract
An enantioselective synthesis of quaternary 3-aminooxindoles with 3-monosubstituted 3-aminooxindoles as nucleophiles is first presented. A Michael addition reaction of 3-monosubstituted 3-aminooxindoles to nitroolefins has been developed with a bifunctional thiourea-tertiary amine as a catalyst to afford a range of 3,3-disubstituted oxindoles bearing adjacent quaternary-tertiary centers in good results (up to 98% yield, >99:1 dr, and 92% ee). We also demonstrate the potential synthetic utility of this methodology by a transformation of the product into a spirocyclic oxindole compound.
Keywords
Chemistry
Angewandte Chemie International EditionPyrrolidinyl‐Spirooxindole Natural Products as Inspirations for the Development of Potential Therapeutic Agents
2,411 Citations2007Chris V. Galliford, Karl A. Scheidt
The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties.
European Journal of Organic ChemistryConstruction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids
1,444 Citations2003Christiane Marti, Erick M. Carreira
Advanced Synthesis & CatalysisCatalytic Asymmetric Synthesis of Oxindoles Bearing a Tetrasubstituted Stereocenter at the C‐3 Position
1,248 Citations2010Feng Zhou, Yun‐Lin Liu +1 more
SynthesisAsymmetric Syntheses of Oxindole and Indole Spirocyclic Alkaloid Natural Products
1,059 Citations2009Barry M. Trost, Megan K. Brennan
This review highlights the advances in the literature up to May2009 in the synthesis of spirocyclic indoline natural products, including bothenantioselective and diastereoselectives methods.
Journal of the American Chemical SocietyEnantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea
1,044 Citations2004Tomotaka Okino, Yasutaka Hoashi +3 more
ChemInformEnantio‐ and Diastereoselective Michael Reaction of 1,3‐Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea.
863 Citations2005Tomotaka Okino, Yasutaka Hoashi +3 more
Journal of the American Chemical SocietyThiourea-Catalyzed Highly Enantio- and Diastereoselective Additions of Oxindoles to Nitroolefins: Application to the Formal Synthesis of (+)-Physostigmine
348 Citations2009Tommy Bui, Salahuddin Syed +1 more
A conceptually novel organocatalytic approach to the syntheses of these materials using thiourea-catalyzed asymmetric 1,4-additions of oxindole derivatives to nitroolefins as a key step is disclosed.
Angewandte Chemie International EditionIdentification of Thiazolidinones Spiro‐Fused to Indolin‐2‐ones as Potent and Selective Inhibitors of the <i>Mycobacterium tuberculosis</i> Protein Tyrosine Phosphatase B
292 Citations2010Viktor V. Vintonyak, Karin Warburg +5 more
Journal of the American Chemical SocietyThiourea-Catalyzed Asymmetric Michael Addition of Activated Methylene Compounds to α,β-Unsaturated Imides: Dual Activation of Imide by Intra- and Intermolecular Hydrogen Bonding
272 Citations2006Tsubasa Inokuma, Yasutaka Hoashi +1 more
The results of spectroscopic experiments clarified that this enhanced reactivity can be attributed to the intramolecular hydrogen-bonding interaction between the N-H of the imide and the methoxy group of the benzamide moiety.
Journal of the American Chemical SocietyCatalytic Asymmetric Synthesis of 3-Aminooxindoles: Enantiofacial Selectivity Switch in Bimetallic vs Monometallic Schiff Base Catalysis
265 Citations2010Shinsuke Mouri, Zhihua Chen +4 more
A highly enantioselective catalytic asymmetric access to 3-aminooxindoles with a tetrasubstituted carbon stereocenter and transformation of the products into an optically active oxindole with a spiro-beta-lactam unit and a known key intermediate for AG-041R synthesis is described.
Journal of the American Chemical SocietyEnantioselective Base-Free Phase-Transfer Reaction in Water-Rich Solvent
233 Citations2009Rongjun He, Seiji Shirakawa +1 more
It is discovered that even without any base additives, the enantioselective phase-transfer conjugate addition of 3-phenyloxindole to beta-nitrostyrene proceeded smoothly in the presence of a chiral bifunctional ammonium bromide under neutral conditions in water-rich solvent with both high diastereo- and enantiOSElectivity.
Journal of the American Chemical SocietyA Homodinuclear Mn(III)<sub>2</sub>−Schiff Base Complex for Catalytic Asymmetric 1,4-Additions of Oxindoles to Nitroalkenes
214 Citations2009Yuko Kato, Makoto Furutachi +4 more
Catalytic asymmetric 1,4-additions of 3-substituted oxindoles to beta-aryl, beta-heteroaryl, and beta-alkenyl nitroalkenes are described, providing useful chiral building blocks for the synthesis of beta-aminooxindoles with vicinal quaternary/tertiary carbon stereocenters.
Chemistry - A European JournalEnantioselective Synthesis of AG‐041R by using <i>N</i>‐Heteroarenesulfonyl Cinchona Alkaloid Amides as Organocatalysts
206 Citations2012Noriyuki Hara, Shuichi Nakamura +4 more
X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.
Angewandte Chemie International EditionDioxindole in Asymmetric Catalytic Synthesis: Routes to Enantioenriched 3‐Substituted 3‐Hydroxyoxindoles and the Preparation of Maremycin A
204 Citations2011Giulia Bergonzini, Paolo Melchiorre
Chemistry - A European JournalScaffold‐Inspired Enantioselective Synthesis of Biologically Important Spiro[pyrrolidin‐3,2′‐oxindoles] with Structural Diversity through Catalytic Isatin‐Derived 1,3‐Dipolar Cycloadditions
197 Citations2012Feng Shi, Zhong‐Lin Tao +3 more
Preliminary bioassays with spiro[pyrrolidin-3,2'-oxindole] revealed that several compounds showed moderate cytotoxicity to SW116 cells, and this protocol represents the first example of catalytic asymmetric 1,3-dipolar cycloadditions involving azomethine ylides generated in situ from unsymmetrical cyclic ketones.
Organic LettersHighly Enantioselective and Organocatalytic α-Amination of 2-Oxindoles
193 Citations2009Liang Cheng, Li Liu +2 more
An effective method for the asymmetric synthesis of 3-amino-2-oxindoles with azodicarboxylate catalyzed by commercial biscinchona alkaloids in good to excellent yields with high enantioselectivities.
Chemical CommunicationsThe highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids
189 Citations2012Jingchao Feng, Wenjin Yan +4 more
The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported, with excellent enantioselectivities and high yields.
Tetrahedron AsymmetryOrganocatalytic asymmetric synthesis of 3-amino-2-oxindole derivatives bearing a tetra-substituted stereocenter
178 Citations2013Pankaj Chauhan, Swapandeep Singh Chimni
Organic LettersSynthesis of <i>N</i>-Alkoxycarbonyl Ketimines Derived from Isatins and Their Application in Enantioselective Synthesis of 3-Aminooxindoles
174 Citations2012Wenjin Yan, Dong Wang +4 more
The enantioselective addition of 1,3-dicarbonyl compounds to this kind of ketimine affords chiral 3-amino oxindoles in high yield and excellent ee.
Chemical ScienceCinchona alkaloid-based phosphoramide catalyzed highly enantioselective Michael addition of unprotected 3-substituted oxindoles to nitroolefins
170 Citations2011Miao Ding, Feng Zhou +4 more
A newly developed cinchonidine-derived phosphoramide 6b, simple and easily available, was identified as a powerful catalyst for the highly enantioselective addition of both unprotected 3-aryl and 3-alkyloxindoles to β-substituted nitroalkenes.
Organic LettersOrganocatalytic Stereoselective Mannich Reaction of 3-Substituted Oxindoles
169 Citations2008Xu Tian, Kun Jiang +3 more
The asymmetric Mannich reaction of 3-substituted oxindoles and N-Boc imines was investigated for the first time, employing bifunctional thiourea-tertiary amine organocatalysts based on DPEN scaffold and obtained in good to excellent enantioselectivities.
Chemical CommunicationsAsymmetric construction of quaternary stereocenters by direct organocatalytic amination of 3-substituted oxindoles
161 Citations2009Ziqing Qian, Feng Zhou +5 more
Quinidine derivative (QD)(2)PYR was found to catalyze the asymmetric direct amination of unprotected prochiral 3-oxindole with DIAD to construct quaternary stereocenters at the C3 position with excellent enantioselectivity.
Organic LettersHighly Efficient and Stereocontrolled Construction of 3,3′-Pyrrolidonyl Spirooxindoles via Organocatalytic Domino Michael/Cyclization Reaction
161 Citations2013Xiong‐Li Liu, Wen‐Yong Han +2 more
A wide range of structurally diverse 3,3'-thiopyrrolidonyl spirooxindoles bearing three contiguous stereogenic centers can be smoothly obtained via a domino Michael/cyclization reaction between 3-isothiocyanato oxindoles and 3-methyl-4-nitro-5-alkenyl-isoxazoles with commercially available quinine as the catalyst under mild conditions.
Advanced Synthesis & CatalysisAn Easy Entry to Optically Active Spiroindolinones: Chiral Brønsted Acid‐Catalysed Pictet–Spengler Reactions of Isatins
159 Citations2011Sara Duce, Fabio Pesciaioli +6 more
Angewandte Chemie International EditionFacile and Efficient Enantioselective Hydroxyamination Reaction: Synthesis of 3‐Hydroxyamino‐2‐Oxindoles Using Nitrosoarenes
155 Citations2011Ke Shen, Xiaohua Liu +3 more
Chemical CommunicationsOrganocatalytic asymmetric cyanation of isatin derived N-Boc ketoimines
150 Citations2012Yun‐Lin Liu, Jian Zhou
The first catalytic asymmetric cyanation of N-Boc ketoimines is reported, which enables highly enantioselective synthesis of oxindole based α-amino nitriles and an unprecedented tandem aza-Wittig/Strecker reaction is developed.
Chemistry - A European JournalCatalytic Asymmetric Michael Addition/Cyclization of Isothiocyanato Oxindoles: Highly Efficient and Versatile Approach for the Synthesis of 3,2′‐Pyrrolidinyl Mono‐ and Bi‐spirooxindole Frameworks
140 Citations2012Yiming Cao, Fangfang Shen +2 more
The development of a new synthetic method for the catalytic asymmetric construction of the 3,2’-pyrrolidinyl spirooxindole framework with high efficiency is reported, and as oxindole-based bi-spiro motifs have been found to be present in many bioactive compounds, the validity of this method is identified.
Angewandte Chemie International EditionRobust Generation of Lead Compounds for Protein–Protein Interactions by Computational and MCR Chemistry: p53/Hdm2 Antagonists
134 Citations2010Anna Czarna, Barbara Beck +7 more
Organic & Biomolecular ChemistryA facile method for the synthesis of oxindole based quaternary α-aminonitriles via the Strecker reaction
122 Citations2010Yun‐Lin Liu, Feng Zhou +4 more
A new bifunctional cinchona alkaloid-based phosphinamide catalyst 7 could promote the Strecker reaction of isatins derived ketimine with TMSCN in up to 74% ee.
Chemistry - A European JournalBrønsted Acid/Rhodium(II) Cooperative Catalytic Asymmetric Three‐Component Aldol‐Type Reaction for the Synthesis of 3‐Amino Oxindoles
120 Citations2013Lei Ren, Xiao‐Lei Lian +1 more
Chiral Brønsted acid/rhodium(II) cooperative catalysis enabled an enantioselective three-component aldol-type reaction of 3-diazo oxindoles and anilines with glyoxylates to give highly functionalized and structurally diverse 3-amino oxindole in high stereoselectivity.
Organic LettersNew Type of Trimeric and Pentameric Indole Alkaloids from <i>Psychotria </i><i>r</i><i>ostrata</i>
120 Citations2004Hiromitsu Takayama, Ikue Mori +3 more
Two new tryptamine-related alkaloids, psychotrimine and psychopentamine, were isolated from the leaves of Psychotria rostrata, and their novel structures were elucidated on the basis of spectroscopic analyses.
Organic LettersHighly Enantioselective Organocatalytic α-Amination Reactions of Aryl Oxindoles: Developing Designer Multifunctional Alkaloid Catalysts
118 Citations2010Tommy Bui, Gloria Hernández‐Torres +2 more
This study provides the first examples of a general organocatalytic method for the creation of nitrogen-containing, tetrasubstituted chiral centers at C(3) of various aryl oxindoles.
Bioorganic & Medicinal Chemistry LettersDesign and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif" overflow="scroll"><mml:mrow><mml:msubsup><mml:mrow><mml:mi mathvariant="normal">P</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow><mml:mrow><mml:mo>′</mml:mo></mml:mrow></mml:msubsup></mml:mrow></mml:math>-ligands
106 Citations2006Arun K. Ghosh, Gary E. Schiltz +7 more
A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon the X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV- 1 protease and exhibited low nanomolar inhibitory potencies against HIV protease.
Chemistry - A European JournalHighly Enantioselective Synthesis of 3‐Amino‐2‐oxindole Derivatives: Catalytic Asymmetric α‐Amination of 3‐Substituted 2‐Oxindoles with a Chiral Scandium Complex
106 Citations2010Zhigang Yang, Zhen Wang +6 more
A highly enantioselective alpha-amination of 3-substituted oxindoles with azodicarboxylates catalyzed by a chiral Sc(OTf)(3)/N,N'-dioxide complex (Tf: triflate) has been developed and affords the corresponding 3-amino-2-oxindole derivatives in high yields with excellent enantiOSElectivities.
Chemistry - A European Journal3‐Isothiocyanato Oxindoles Serving as Powerful and Versatile Precursors to Structurally Diverse Dispirocyclic Thiopyrrolidineoxindoles through a Cascade Michael/Cyclization Process with Amino‐Thiocarbamate Catalysts
104 Citations2013Wen‐Yong Han, Shi‐Wu Li +3 more
3-Isothiocyanato oxindoles act as powerful and versatile precursors for a range of structurally diverse dispirocyclic thiopyrrolidineoxindoles containing two spiro-quaternary and three contiguous stereogenic centers in quantitative yields with excellent disatereo- and enantioselectivities by only using 1 mol % amino-thiocarbamate catalyst.
The Journal of Organic ChemistryEfficient Asymmetric Synthesis of Novel Gastrin Receptor Antagonist AG-041R via Highly Stereoselective Alkylation of Oxindole Enolates
99 Citations2006Takashi Emura, Toru Esaki +2 more
An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed and core oxindole stereochemistry was established by asymmetric alkylation of oxindoles enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary.
The Journal of Organic ChemistryEnantioselective and Solvent-Controlled Diastereoselective Mannich Reaction of Isatin Imines with Hydroxyacetone: Synthesis of 3-Substituted 3-Aminooxindoles
92 Citations2012Qi‐Xiang Guo, Yu‐wan Liu +3 more
The diastereoselectively switchable enantioselective Mannich reaction of isatin imines with hydroxyacetone with chiral primary amino acid catalyzed to afford both anti- and syn-Mannich adducts in high yields, good diastreoselectivities, and enantiOSElectivities is reported.
Chemical CommunicationsOrganocatalytic asymmetric synthesis of 3,3-disubstituted oxindoles featuring two heteroatoms at the C3 position
86 Citations2013Feng Zhou, Xing‐Ping Zeng +3 more
This work reports the first organocatalytic asymmetric synthesis of 3,3-disubstituted oxindoles featuring two heteroatoms at the C3 position and demonstrates 3-thiooxindoles and 3-alkoxyoxindole to be reactive nucleophiles for the development of catalytic asymmetrical reactions for the first time.
Organic LettersOrganocatalytic Asymmetric Synthesis of 3-Chlorooxindoles Bearing Adjacent Quaternary–Tertiary Centers
85 Citations2012Artur Noole, Ivar Järving +4 more
This is the first example where 3-chloroxoindoles 1 have been used as nucleophiles in a highly stereoselective organocatalytic reaction.
Advanced Synthesis & CatalysisOrganocatalytic Asymmetric α‐Amination of Unprotected 3‐Aryl and 3‐Aliphatic Substituted Oxindoles using Di‐<i>tert</i>‐butyl Azodicarboxylate
73 Citations2011Feng Zhou, Miao Ding +5 more
The bifunctional quinine-derived thiourea catalyst 14 was found to catalyze the direct amination of unprotected 3-aryl and aliphatic substituted oxindoles with di-tert-butyl azodicarboxylate to construct a tetrasubstituted stereogenic carbon center at the C-3 position of oxindole in good to excellent yield and enantioselectivity.
Chemical CommunicationsZn-mediated asymmetric allylation of N-tert-butanesulfinyl ketimines: an efficient and practical access to chiral quaternary 3-aminooxindoles
66 Citations2012Chen Diao, Ming‐Hua Xu
Room temperature zinc-mediated diastereoselective allylation or propargylation of isatin-derived N-tert-butanesulfinyl ketimines for synthesis of highly enantiomerically enriched tetrasubstituted 3-aminooxindoles is described.
Chemistry - A European JournalOrganocatalytic Asymmetric Conjugate Addition of 3‐Monosubstituted Oxindoles to (<i>E</i>)‐1,4‐Diaryl‐2‐buten‐1,4‐diones: A Strategy for the Indirect Enantioselective Furanylation and Pyrrolylation of 3‐Alkyloxindoles
60 Citations2012Yu‐Hua Liao, Xiong‐Li Liu +4 more
The studies presented here sufficiently confirm that this two-step strategy of sequential conjugate addition/Paal-Knorr cyclization is not only an attractive method for the indirect enantioselective heteroarylation of 3-alkyloxindoles, but also opens up new avenues toward asymmetric synthesis of structurally diverse 3,3'-disubstituted oxindole derivatives.
Organic & Biomolecular ChemistryAsymmetric hydroxyamination of oxindoles catalyzed by chiral bifunctional tertiary aminethiourea: construction of 3-amino-2-oxindoles with quaternary stereocenters
52 Citations2011Lina Jia, Jun Huang +9 more
Chiral bifunctional tertiary amine thiourea was applied to catalyze the asymmetric hydroxyamination of 3-subsituted oxindoles with nitrosobenzene to construct 3-amino-2-oxindole with quaternary stereocenters in good yields and enantioselectivities.
Chemistry - A European JournalOrganocatalytic Enantioselective Stereoablative Hydroxylation of 3‐Halooxindoles: An Effective Method for the Construction of Enantioenriched 3‐Substituted 3‐Hydroxy‐2‐Oxindoles
51 Citations2012Yu‐Hua Liao, Zhijun Wu +3 more
An unprecedented method for the construction of hydroxylated 3-substituted oxindoles in high yields and excellent enantioselectivities through stereoablativehydroxylation of 3-halooxindoles with an organocatalyst has been developed.
Organic & Biomolecular ChemistryAddition of TMSCN to chiral ketimines derived from isatin. Synthesis of an oxindole-based peptidomimetic and a bioactive spirohydantoin
51 Citations2011Alessandro Sacchetti, Alessandra Silvani +4 more
The Strecker-type reaction of isatin derived chiral ketimines with TMSCN in the presence of a Lewis acid has been investigated and the desired α-amino nitriles have been obtained in good yields with moderate diastereoselectivity.
Tetrahedron AsymmetryAsymmetric organocatalytic N-nitroso-aldol reaction of oxindoles
51 Citations2010Tao Zhang, Liang Cheng +3 more
An organocatalytic enantioselective N-nitroso-aldol reaction of 2-oxindoles promoted by a cinchona alkaloid catalyst has been developed and shows exclusively N-selectivity.
Chemical Communications3-Bromooxindoles as nucleophiles in asymmetric organocatalytic Mannich reactions with N-Ts-imines
49 Citations2012Jianhao Li, Taiping Du +2 more
A direct asymmetric Mannich reaction of N-unprotected 3-bromooxindoles with N-Ts-imines catalyzed by bifunctional thiourea derived from 2-substituted cinchona alkaloid was developed, achieving excellent diastereo- and enantioselectivity.
Organic LettersSynthesis of Enantiomerically Enriched 3-Amino-2-oxindoles through a Palladium-Mediated Asymmetric Intramolecular Arylation of α-Ketimino Amides
49 Citations2012Päivi Tolstoy, S.X.Y. Lee +2 more
This report constitutes the first enantioselective palladium-catalyzed arylation of ketimines, using (R)-DiFluorPhos as the coordinating ligand.
Beilstein Journal of Organic ChemistryOrganocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins
31 Citations2012Hang Zhang, Shanjun Zhang +3 more