Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• of 3,3-difluoro-2-oxindoles to give the corresponding 3,3-difluoroindoines when electron-withdrawing groups were present as substituents in the benzene nucleus. The 3,3-difluoro-2-oxindoles were prepared by the reaction of appropriately substituted isatin derivatives with DAST [18]. Anodic

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• activities and their applications for pharmaceutical lead discovery. These compounds are the central skeleton of numerous alkaloids [1][2][3][4][5][6][7][8] and have found wide biological applications, e.g., as potent p53–MDM2 inhibitors [9][10][11][12][13][14][15]. Usually, isatin and its derivatives were

• employed as starting materials to conduct 1,3-dipolar cycloadditions to yield spirooxindole core structures [16][17][18][19][20]. Owing to the ease of preparation, the azomethine ylides generated from isatin with α-amino acids or amines were frequently chosen as important 1,3-dipolar intermediates to react

• , chalcone derivatives are the most widely used dipolarophiles. Sarrafi and co-workers reported a 1,3-dipolar cycloaddition reaction of isatin, benzylamine and chalcone derivatives [31], and only one single regioisomer was obtained in high yield, in which the benzoyl group was connected to C-3 of the newly

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• ’(6’-CH) and 2’-CCH3. Also, multiplets for 7a’-CH and 2’-(6’-CH) and singlet for 2’-CCH3 show correlation signals to the neighboring methylene groups. Additionally, the absence of the NOE cross peak of 4-CH of the isatin nucleus and 2’(6’-CH) or 2’-CCH3 of the pyrrolizidine moiety was indicative for

• signals of 2’-CH and doublet at 7.30 ppm (J =1.8 Hz) for 2-CH of the aroyl acrylic acid moiety. In addition, the absence of NOE cross peaks between 4-CH of the isatin core and 2’-CH of the pyrrolizidine fragment supports the assignment. The NH-proton of the oxindole moiety and the 1’-COOH proton of the

• 22.9° and the shortest distance between carbon atoms (C6…C15) is 3.04 Å). The mechanism of the azomethine ylide formation by a decarboxylative route has been repeatedly described by a number of authors and is depicted in Scheme 1 [35][36]. The reaction between isatin and the α-amino acid affords the

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• nitrilium intermediate, in agreement with a Sorensen report (Scheme 4, route iii) [21]. Finally, the imino-nitrilium cation can be trapped by an aromatic ring when using isatin imines, leading to bis(imino)tetrahydroquinoline 8, (Scheme 4, route iv). In a reaction using a large isocyanide excess, a triple

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• less efficient because it needs heating and/or long reaction time to complete the fluorination [48][49]. Nevertheless by the use of a flow microreactor device, isatin underwent gem-difluorination to give the corresponding difluoride in 73% yield (residence time in the reactor: within 1 h). Reactions

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• -alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles. Keywords: Darzens reaction; isatin

• . Isatins, phenacyl bromide and other reagents are commercial reagents and were used as received. Solvents were purified by standard techniques. All reactions were monitored by TLC. Typical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 3a–h: A mixture of isatin (1.0 mmol), phenacyl

• C16H11NNaO3, 288.0631; found, 288.0628. Typical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 4a–e: A mixture of isatin (1.0 mmol), phenacyl bromide (2.2 mmol) and potassium carbonate (2.6 mmol) in 20.0 mL of chloroform was stirred at 50 °C for 10–24 h (TLC analysis). After cooling, the

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• Li-Juan Zhang Qun Wu Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.97 Abstract In the presence of triethylamine as catalyst, the one-pot four-component reactions of arylamines, methyl propiolate, isatin and

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

• [12][13][14][15][16][17][18][19][20][21][22][23]. Recently, Perumal and we have both developed an efficient synthetic procedure for functionalized spiro[indoline-3,4’-pyridines] by domino reactions of in situ generated β-enamino esters, isatin and malononitrile with triethylamine as the base catalyst

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• only recently been reported. There are plenty of literature reports available on the construction of 3-alkenylindolin-2-ones [21]. The widely used highly facile protocol for the alkenylation of indolin-2-ones is through aldol condensation [22] of isatin with compounds containing an active methylene

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• -component reactions of arylamine, isatin and cyclopentane-1,3-dione in acetic acid at room temperature. On the other hand the condensation of isatin with two equivalents of cyclopentane-1,3-dione gave 3,3-bis(2-hydroxy-5-oxo-cyclopent-1-enyl)oxindole in high yields. The reaction mechanism and substrate

• scope of this novel reaction is briefly discussed. Keywords: arylamine; cyclopentanedione; isatin; multicomponent reaction; spiro compound; Introduction The spirooxindole is among the most important class of naturally occurring substances, characterized by highly pronounced biological properties, and

• [3][4][5][6]. Isatin and its derivatives may be the most useful starting materials or precursors in the synthesis of a wide number of spirocyclic oxindoles [7][8]. Due to its simple process, easy operation, efficiency and high atomic economy, the multicomponent reaction based on isatin and its

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• with the aldehyde carbonyl in the transition state (TS 3). Under ball-milling conditions, thiodipeptide VI catalyses the enantioselective aldol reaction of acetone (1d) with isatin derivatives 4 to provide 3-substituted-3-hydroxyoxindole derivatives 5 in moderate yield (54–68%) and moderate to good

• of (A) ketones with aldehydes and (B) acetone with isatin derivatives. Enantioselective Michael reaction of aldehydes with nitroalkenes catalysed by pyrrolidine-derived organocatalysts. Chiral squaramide catalysed asymmetric Michael reaction assisted by ball-milling. Asymmetric organocatalytic

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• enantioenriched 3-hydroxyoxindoles [22][23][24]. For the synthesis of chiral 3-aminooxindoles, we developed the first example of catalytic asymmetric addition of nucleophiles to isatin-derived ketoimines using TMSCN [25] and the amination of unprotected 3-prochiral oxindoles using di-tert-butyl azodicarboxylate

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

• Chunhui Dai,
• Bo Liang and
• Corey R. J. Stephenson

Beilstein J. Org. Chem. 2012, 8, 986–993, doi:10.3762/bjoc.8.111

• ], we previously reported a Lewis acid catalyzed, three-component synthesis of spirooxindole pyranochromenedione derivatives using isatin and two 1,3-dicarbonyl compounds (Scheme 1) [14]. Mechanistically, we believed this reaction to proceed through an intermediate isatylidene 1 [15][16][17]. As a means

• with isatin and 1,3-cyclohexanedione (5a) as coupling partners, we isolated a relatively poor yield of product 6a (Table 1, entry 1). We speculated that the free indole nitrogen was inhibiting the reaction, thus we switched to N-substituted isatins and found that the reaction improved to provide

• moderate to high yields (Table 1, entries 2–10). Subtle substitution effects were observed when the C(5)–H of isatin was replaced with various functionalities. Specifically, an electron-donating group at the 5-position, such as a methyl group, decreased the reactivity and only gave 57% yield (Table 1

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• Intramolecular inverse electron demand cycloadditions of isatin-derived 1,2,4-triazines with acetylenic dienophiles tethered by amidations or transesterifications proceed in excellent yields to produce lactam- or lactone-fused α-carbolines. Beginning with various isatins and alkynyl dienophiles, a pilot-scale

• library of eighty-eight α-carbolines was prepared by using this robust methodology for biological evaluation. Keywords: α-carboline; chemical diversity; inverse electron demand Diels–Alder; isatin; pyrido[2,3-b]indole; 1,2,4-triazine; Introduction In comparison with the well-known β-carbolines, α

• library of annulated α-carboline structures 6 could be prepared by the intramolecular inverse electron demand Diels–Alder reaction (IEDDA) of isatin-derived 1,2,4-triazines 7 with tethered electron-rich dienophiles (Scheme 1) [69]. Inverse electron demand Diels–Alder cycloadditions employing electron

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• 7701, South Africa 10.3762/bjoc.6.78 Abstract A simple and straightforward synthetic approach to potential anti-infective thiolactone-isatin hybrids led to the discovery of novel tetracyclic compounds which bear a macrocylic motif containing an unusual bridged amide bond. Keywords: bridged amides

• ; hybrids; isatin; tetracycles; thiolactomycin; thiolactone; Introduction Hybrid structures have been found in nature and their synthesis has become a useful drug discovery strategy for new anti-infective agents [1]. Improved pharmacokinetics, therapeutic and toxicity profiles have been reported for

• natural and natural product-like hybrid constructs such as the artemisinin-quinine [2], nostocarboline-ciprofloxacin [3] and isatin-lamuvidine [4] (Figure 1). Interest in exploring this approach also derives from the pharmacophore-rich compound library it offers. This precludes the need for large

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• 5 could be obtained by way of a thermal [3,3]-sigmatropic rearrangement of the propargylic acetate 6 to give compound 5 where R2 = OAc (Figure 2) [27]. Preparation of propargylic acetate 9a was accomplished by the addition of the lithium acetylide of 8 to N-methyl isatin (7) followed by acetylation