Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• nitro functionality (Scheme 5). Similarly, Kesavan and co-workers reacted 3-O-Boc-oxindoles 23 with MBH carbonates 22 to generate a range of spirocyclic scaffolds containing α-exo-methylene-γ-butyrolactone 24 – again using β-ICPD (Scheme 6) [30]. Nazarov cyclization An asymmetric Nazarov cyclization has

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. Keywords: 7-azaisatins; β-isocupreidine; bifunctional catalysis; maleimide; MBH

• addition, 7-azaisatins were also applied in asymmetric synthesis [18][19]. Therefore, with our continuing interest in the catalytic application of bifunctional β-ICD [20][21][22][23], herein we report the enantioselective MBH reaction of 7-azaisatins with maleimides. A series of 3-hydroxy-7-aza-2-oxindoles

• -ICD (Table 2). At first, a variety of N-substituted maleimides 2 were explored in the reaction with 7-azaisatin 1a in toluene. Maleimides bearing an electron-rich N-aryl ring generally afforded the corresponding 3-hydroxy-7-aza-2-oxindoles in high yields and with excellent enantioselectivity (Table 2

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• alkanes resulting in alkyl-substituted oxindoles (Scheme 1a) [43]. However, cyclization of N-allylbenzamides initiated by the functionalization of sp3 C–H bonds of simple alkanes remains unexplored. Very recently, our group developed a metal-free hydroxyalkylation-initiated radical six-membered

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. Keywords: ene-sulfonamide; imine

• '-formamidoethyl)-2-oxindoles. These transformations add new dimensions to the growing radical chemistry of ene-sulfonamides. (a) Radical reactions of ene-sulfonamides give diverse isolated products; (b) these products are often derived from transient imine intermediates. Isolation of stable imines strengthens the

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• method for the synthesis of oxindoles and 3-oxotetrahydroisoquinolines 47 via intramolecular cyclization under C–C-bond formation was reported by Atobe, Fuchigami et al. (Scheme 18) [63]. The protocol is based on the anodic oxidation of α-(phenylthio)acetamides 46 in the presence of Et3N∙3HF. The latter

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• activated isatin-based alkenes (Scheme 39) [76]. The reactions, performed in chloroform in the presence of molecular sieves at room temperature, provided biologically important 3-spirocyclopentene-2-oxindoles with two contiguous quaternary centers in very high yields and with good enantioselectivities; they

• ] cycloadducts, 3-spirocyclohexene-2-oxindoles, in high yields with excellent ee and dr. These asymmetric [4 + 2] annulations of allenoates with activated alkenes significantly offset the limitations of Diels–Alder reactions when synthesizing enantioenriched multisubstituted cyclohexenes. At about the same time

• development of chiral phosphine–assisted asymmetric Michael reactions has lagged behind other phosphine-catalyzed reactions. Recently, using bifunctional chiral amino acid–derived phosphines, Lu and co-workers developed asymmetric Michael additions of oxindoles to α,β-unsaturated carbonyl compounds (Scheme 55

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• additions or spiroannulation [2][3]. Oxindoles represent a common structural element in various natural products and biologically active compounds. Diverse oxindole derivatives act as non-peptide scaffolds [4] in peptidomimetic chemistry, either as enzyme inhibitors or as ligands of G-protein-coupled

• receptors [5]. In particular, 3,3-disubstituted 3-amino-2-oxindoles are present in several drug candidates. They exhibit various types of bioactivity, such as the potent gastrin/CCK-B receptor antagonist I [6], the vasopressin VIb receptor antagonist II [7][8], the CRTH2 (DP2) receptor antagonist

• spirohydantoin III [9], and the new antimalarial lead IV [10][11] (Figure 1). Giving the importance of this structural motif, the development of rapid synthetic methods for oxindoles bearing a nitrogen atom at the C3-stereogenic center is highly required [12][13][14][15]. In the course of our studies on new

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

• G. Gangadhararao,
• Ramesh Kotikalapudi,
• M. Nagarjuna Reddy and
• K. C. Kumara Swamy

Beilstein J. Org. Chem. 2014, 10, 996–1005, doi:10.3762/bjoc.10.99

• series include phosphonobenzofurans/indenones [21][22], -pyrazoles [23], -chromenes/thiochromenes [24][25], -pyrroles [26], multiply substituted furans [27], indolopyran-1-ones [28], N-hydroxyindolinones [29], and oxindoles [30]. In the reaction shown in Scheme 1a, for the formation of the

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• -component version of the reaction by a domino Knoevenagel–Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner. Keywords: 3,3'-disubstituted oxindoles; Michael reaction; organocatalysis; primary-tertiary

• attention as novel substrates for the enantioselective synthesis of 3,3'-disubstituted oxindoles [18][19][20][21][22]. The organocatalytic Michael addition of ketones to isatylidenemalononitriles via enamine-catalysis has emerged as a useful tool for the synthesis of 3,3'-disubstituted oxindoles, which

• ][45]. We describe herein that a similar catalyst system could also efficiently catalyze the asymmetric Michael addition reaction between ketones 2 and isatylidenemalononitrile derivatives 3 to procure highly functionalized 3,3'-disubstituted oxindoles 4 which could easily be transformed into

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

• prepare a series of novel spiropyrrolidine-oxindoles – 4′-acetyl-3′,5′-diarylspiro[indoline-3,2′-pyrrolidin]-2-ones and 3′-acetyl-4′,5′-diarylspiro[indoline-3,2′-pyrrolidine]-2-ones in good yields of up to 94% and with good regioselectivities. Regioselectivities are reversible by the addition of water or

• addition of 4-nitrobenzoic acid, which led to the formation of spirooxindoles with novel substitution patterns (Scheme 1). Accordingly, a series of novel functionalized 3-spiropyrrolidine-oxindoles bearing an acetyl group were prepared via this 1,3-dipolar cycloaddition with up to 94% yield. To the best of

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

• spiro cycloadducts can be obtained in methanol dihydropyrrolizinyl oxindoles are formed in aqueous ethanol media at higher temperatures. Therefore, reactions involving aroylacrylic acids as substrates can afford the product in a regiocontrolled manner. Experimental Reagents and analytics: The 1H NMR

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• -spirocyclic oxindole γ-lactams by the cycloaddition of imines and succinic anhydrides [5]. Tandem radical cyclization can also provide a powerful tool for the construction of heterocycles [6][7][8][9][10][11][12]. One of us previously reported on the construction of spirocyclic pyrrolidinyl oxindoles by the

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

• ]. The unique structures and the highly pronounced pharmacological activity displayed by the spirooxindoles have made them attractive synthetic targets [6][7][8][9]. In various heterocyclic and carbocyclic spirooxindoles, the spiro-oxirane-oxindoles are a particular class of compounds with both spiro

• and enantioselective synthesis of versatile spiro-oxirane-oxindoles [14][15][16][17][18][19]. With the aim of expanding our previous studies on the synthesis of various spirooxindoles [20][21][22][23][24][25], we decided to systematically investigate the Darzens reactions of a series of isatins with

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

• hydride-AIBN initiated radical cyclization [33][34]. In 2005, Player and co-workers reported a tandem Heck/Suzuki–Miyaura coupling process for the synthesis of (E)-3,3-(diaryl)oxindoles [35][36][37]. Recently, alkenylation of indolin-2-ones has been developed by palladium-catalyzed aromatic C–H activation

• 3-alkenyl-2-oxindoles being based on expensive catalysts, non-commercially available precursors, and multistep time-consuming synthetic protocols, the development of an efficient, economical and short synthesis was inevitable and desirable. In this regard, we have now developed an efficient new

• protocol for the direct alkenylation of 2-oxindole by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles 3 to deliver 3-alkenyl-2-oxindoles 8 in moderate yield. This procedure is quite efficient, noncatalytic, economical and easy in workup. Moreover, it opens a new avenue for the synthesis of 3-alkenyl-2

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

• [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

• ][13][14]. Considering the above reports, and as part of our program aimed at developing new multicomponent reactions for the construction of complex heterocyclic compounds, we wish in this work to report the efficient synthesis of unprecedented cyclopentyl-fused spiro[dihydropyridine-oxindoles] by the

• condensation of isatins with cyclic 1,3-dicarbonyl compounds [30][31][32][33], the condensation reaction of isatin with cyclopentane-1,3-dione seemed still not to have been investigated and the 3,3-bis(2-hydroxy-5-oxo-cyclopent-1-enyl)oxindoles 3a–3d have not been prepared until now. Thus, the direct

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

• Michael addition of unprotected 3-prochiral oxindoles 1 to 1,4-naphthoquinone. Quinidine derivative (DHQD)2PYR was found to be able to catalyze this reaction in up to 83% ee, with moderate to excellent yields. This method could be used for the synthesis of enantioenriched 3,3-diaryloxindoles, and the

• catalytic synthesis of which was unprecedented. Keywords: 3,3-disubstituted oxindoles; Michael addition; organocatalysis; quaternary stereogenic center; unprotected 3-substituted oxindoles; Introduction The catalytic asymmetric synthesis of 3,3-disubstituted oxindoles has recently received great attention

• biological activities [4]. Accordingly, the development of efficient synthetic methods to enable the synthesis of 3,3-disubstituted oxindoles in great structural diversity is of current interest, and much progress had been made in the catalytic enantioselective synthesis of 3-hydroxyoxindoles [5][6][7][8][9

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• investigation of a Lewis base catalyzed asymmetric allylic amination of Morita–Baylis–Hillman carbonates derived from isatins afforded an electrophilic pathway to access multifunctional oxindoles bearing a C3-quaternary stereocenter, provided with good to excellent enantioselectivity (up to 94% ee) and in high

• yields (up to 97%). Keywords: allylic amination; asymmetric organocatalysis; Morita–Baylis–Hillman carbonates; 2-oxindoles; quaternary chiral center; Introduction Chiral 3-amino-2-oxindoles are versatile and useful units for the preparation of natural products and drug candidates, such as the

• oxindoles as nucleophiles in the reactions with azodicarboxylates or nitrosobenzene provides a very simple and direct approach for the synthesis of optically active 3-amino-2-oxindole derivatives [7], either by the catalysis of chiral metal complexes [8][9][10] or organic catalysts [11][12][13][14][15]. On

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• oxindoles into chiral non-racemic spirooxindoles containing an alkylidene cyclobutene moiety. The enantiomeric excesses were determined by chiral lanthanide shift NMR analysis and the transfer of chiral information from the allene to the spirooxindole was found to be greater than 95%. Keywords: alkylidene

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• 60% yield. The physical data of synthetic coerulescine and horsfiline were comparable in all respects with the literature data. Conclusion In summary, we have described a new and efficient synthesis of (±)-coerulescine and (±)-horsfiline. Spiro[pyrrolidin-3,3'-oxindoles]. Reagents and conditions: a

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• fluorination of a wide range of substrates, including β-keto esters, β-keto phosphonates, oxindoles [38][40][43][51][53][56][57]. They have also recently reported the enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with their extended catalytic system, NiCl2-BINAP/R3SiOTf-lutidine with high