Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• reactions between pyrrole and chloromethylcarbene, and 2,3-dimethylindole and dichloromethylcarbene [20][21]. It was suggested that the quinoline ring system is formed by ring expension of a labile indoline cyclopropane intermediate. In analogy to the postulated literature pathway, we propose that the

• reactions in our study start by cyclopropanation of the rhodium carbenoid to produce an indoline halocyclopropyl ester. The labile indoline intermediate then undergoes ring opening of the cyclopropane and elimination of H–X to form the quinoline structure (Scheme 3). We attempted to find support for the

• proposed reaction pathway by using N-Boc-indole as a substrate (Scheme 4). Reactions between N-Boc-indole and carbenoids typically give N-Boc-indoline cyclopropanation products that can be purified and isolated [5][6][7][8]. We exposed Br-EDA to Rh2(esp)2 in the presence of N-Boc-indole in order to obtain

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

• /fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3

• substrates were chosen to provide imines with spirocyclic indoline and indolone substituents. We discovered that these imines are rather reactive, being either reduced or undergoing an unusual hydration and retro-Claisen-type reaction of an amide. Here we report the results of these experiments, which add to

• hydride-mediated cyclizations at C3 of N-sulfonylindoles to make spiro rings occur with ejection of the sulfonyl radical. When the indole C2 substituent is hydrogen, this imine is reduced in situ to a spiro-indoline, most likely by a radical hydrostannation. When the C2 substituent is an ester, the imine

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• indoline-2-ones 11 from isatins and methyl ketones has previously been realized [32][33]. In particular, preparation of 2-methyl-8H-thieno[2,3-b]indole from unsubstituted isatin and acetone in 15% yield has been reported [32] (Scheme 2). Although it seems to be a very harmonious strategy, it has hardly a

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• amines were also good substrates for this reaction, affording the desired products (3q, 3r, 3s) in good to high yields (77–98% yields) with DCE as the solvent under reflux conditions. The reaction with indoline, tetrahydroquinoline, and tetrahydroisoquinoline could also be realized to give products 3t

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• cyanoacetate) with triethylamine as base catalyst afforded functionalized 1-benzamidospiro[indoline-3,4'-pyridines] in good yields. 1H NMR spectra indicated that an equilibrium of cis/trans-conformations exist in the obtained products. Keywords: acetylenedicarboxylate; benzohydrazide; 1,4-dihydropyridine

• ; multicomponent reaction; one-pot reaction; spiro[indoline-3,4'-pyridine]; Introduction The spirooxindole system is the core structure of many natural products and pharmaceutically important structures with notable structural complexity and biological activities of great interest [1][2][3][4]. Accordingly, many

• reactions [19][20][21]. Recently, we and Perumal have demonstrated that the four-component reaction of arylamine, acetylenedicarboxylate, isatin and malononitrile can afford the spiro[indoline-3,4’-pyridine] derivatives in satisfactory yields [22][23][24]. We envisioned that functionalized spiro[indoline

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

• F1, but-3-yn-2-one reacted with a series of N-protected isatins in ethyl ether at −20 °C to afford enantioenriched spiro[furan-2,3´-indoline]-2´,4(5H)-diones with good to excellent ee's, albeit moderate yields. 2.7 [4 + 2] Annulations of allenes with activated imines Compared with phosphine-catalyzed

• enantioselectivity. In a relatively successful example, the chiral aminophosphine G9 catalyzed the asymmetric double-Michael reaction between o-tosylamidophenyl malonate and 3-butyn-2-one to give the indoline derivative in 69% yield and up to 10% ee (Scheme 53). 2.15 Annulation through tandem Michael addition/Wittig

Novel indolin-2-one-substituted methanofullerenes bearing long n-alkyl chains: synthesis and application in bulk-heterojunction solar cells

• Irina P. Romanova,
• Andrei V. Bogdanov,
• Inessa A. Izdelieva,
• Vasily A. Trukhanov,
• Gulnara R. Shaikhutdinova,
• Dmitry G. Yakhvarov,
• Shamil K. Latypov,
• Vladimir F. Mironov,
• Vladimir A. Dyakov,
• Ilya V. Golovnin,
• Dmitry Yu. Paraschuk and
• Oleg G. Sinyashin

Beilstein J. Org. Chem. 2014, 10, 1121–1128, doi:10.3762/bjoc.10.111

• on P3HT/AIM blends were fabricated and characterized. Results and Discussion Synthesis of AIMs 1–9 The reaction for the synthesis of IM allows us to obtain a wide range of various IM [7][9]. The variation of IM is easy carried out by the variation of pristine indoline-2,3-diones (isatins). Thus the

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• 21 in 52% yield. The fused indoline motif was formed via an intramolecular Heck reaction under Fu’s conditions [41] to provide a mixture of two olefinic regioisomers 22, which were converted to saturated fused indoline 23 under standard catalytic hydrogenation conditions in a combined yield of 40

• allylic amine. Substrate scope. Synthesis of a fused indoline. Proposed catalytic cycle. Catalyst screening. Supporting Information Supporting Information File 216: Experimental procedures, compound characterization, and NMR spectra. Acknowledgements This publication was supported by the University of

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ; cyclization; Diels–Alder; inverse electron demand; N-acyliminium ion; tert-enamide; Introduction Fused indoline, isoindoline, quinoline and isoquinoline substructures are found in many natural products and bioactive synthetic compounds (Figure 1). For example, nuevamine is a naturally-occurring isoindolo[1,2

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

• ′-diarylspiro(indoline-3,2′-pyrrolidin)-2-one was formed when using chalcone or dienone as dipolarophiles [20][31]. Presumably, this might be attributed to the electronic and steric effects of the acetyl group. Therefore, reaction conditions including various solvents and additives (Table 1, entries 2–9) were

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• substituted anilines that constitutes the C–C bond forming event of indoline synthesis via homolytic substitution with computational methods. The results are of general interest for the understanding of radical addition to electron rich arenes and should be helpful in the design of novel radical reactions

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• . Finally, we demonstrate the synthetic application of this reaction in the construction of the 3a-(phenylselenyl)bispyrrolidino[2,3-b]indoline core structure (Scheme 2). Under the optimized reaction conditions, the enantioselective substitution reaction gave 4a in 78% yield and 86% ee. However, when the

• chiral precursor of the (+)-alline. Catalysts and seleno reagents evaluated in this study. Generality for substitution at the indoline moiety. The reaction was performed in 0.1 mmol scale in DCE (1 mL) with 5 Å MS (100 mg) in 0 °C and the ratio of 2/1 is 3:1. The reaction was performed for 1–3 days. The

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

• azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields. Keywords: 4,4-spirocyclic indol γ-lactams; carbon monoxide; free radical

• reaction of 1a with Bu3SnH (2.0 equiv) and AIBN (2,2’- azobisisobutyronitrile, 0.3 equiv) was carried out under CO pressure (80 atm) in THF (0.02 M) at 80 °C for 12 h, which gave the desired 4,4-spirocyclic indoline γ-lactam 2a in 48% yield (Scheme 4). We found that the modest improvement in the yield of

• indoline γ-lactam 2f and a (TMS)3Si radical, thus creating a radical chain. On the other hand, the unusual formation of THF-incorporating lactam 3 from 1g may be rationalized by the consecutive 6-endo cyclization of E and β-elimination of an azidyl radical from the resulting F, to give 2-methylene lactam G

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

• Qin Fu Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.105 Abstract A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N

• phenacyl bromides and report the facile synthesis of versatile spiro[indoline-3,2'-oxiran]-2-ones. Results and Discussion In recent years we have found that pyridinium salts react with versatile reactive methylene compounds to give different kinds of products, including functionalized cyclopropanes, 2,3

• . 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

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

• malononitrile afforded the functionalized spiro[indoline-3,4’-pyridine] derivatives in good yields. Similar reactions with ethyl cyanoacetate successfully afforded the functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] as the main products according to the structures of the

• [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

• reactions of arylamines, methyl propiolate, aromatic aldehydes and malononitrile (ethyl cyanoacetate) and successfully developed a facile synthetic procedure for functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones]. Results and Discussion The efficient formation of

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

• of the weak noncovalent interactions operating in the supramolecular architectures of alkenylated indoline-2-ones and to explain the relative stability of one of the tautomers with respect to the others. Keywords: alkenylation; dibenzo[d,f][1,3]diazepin-6(7H)-one; indolin-2-one; ketene dithioacetal

• Perkin-Elmer AX-1 spectrophotometer in KBr disc and are reported in wave number (cm−1). ESIMS spectrometers were used for mass spectra analysis. Synthesis of 1-phenyl-3-(methylthio)-5H-dibenzo[d,f][1,3]diazepin-6(7H)-one (5) A mixture of indoline-2-one (4, 1.1 mmol) and 2-pyranone (3, 1.0 mmol) and t

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• outcome of the cyclization differs. While allylic ethers are relatively poor substrates that undergo a side elimination and need an intracyclic double bond to proceed, allylic amines react well and afford indoline and indole derivatives. Finally, the synthesis of the trinuclear ACE core of a morphine-like

• pathway affording indoline 3c is slightly increased, and a (2c + 2c’)/3c ratio of 62/38 is observed (Table 1, entry 4). In conclusion to the first part of this study, the formation and cyclization of arylnickel intermediates 1-Ni is observed in all cases. Afterward, the stability of the exo-methylene

• , with a lesser amount of indoline 3 being obtained above when this protecting group was employed. The carbonickelation protocol was applied to the cyclization of crotyl derivatives 5 (Scheme 3). When applied to ether 5a, as expected, the substitution of the allyl moiety at the terminal position by a

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• –cyclisation leading to indoline 97 with an intramolecular Friedel–Crafts reaction to afford a tricyclic derivative 98 substituted by a trifluoromethyl group [44]. The second exploits the presence of both a protected primary amine and an easily substitutable chlorine on the pyrimidine ring in 99a,b to afford

• and cyclisation of the latter into indoline 109 [47]. Diverse otherwise inaccessible chloroketones become readily available. Haloketones in general are ideal precursors for the synthesis of numerous heteroaromatic derivatives. For example, Hantzsch condensation of indoline 109 with thionicotinamide

• . Synthesis of bicyclic cyclobutane motifs. Construction of the CD rings of steroids. Rapid assembly of polyquinanes. Formation of a polycyclic structure via an allene intermediate. A polycyclic structure via the alkylative Birch reduction. Synthesis of polycyclic pyrimidines and indoline structures

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• L8, leading to the indoline of opposite configuration. Unfortunately, this diamine is not commercially available, and its synthesis requires resolution. More recently, O’Brien [48] has reported that (+)-sparteine surrogate L2 gave a similar degree of enantioselectivity and indoline (S)-38a of 85:15

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

• three-component reaction of arylamine, isatin and cyclopentane-1,3-dione. Results and Discussion Recently we found that the four-component reactions of arylamine, acetylenedicarboxylate, isatin and dimedone in acetic acid resulted in the novel functionalized tetrahydrospiro[indoline-3,2’-quinoline

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• as the substrate, and the N-alkyl-indoline product 10 was obtained in good yields (70–82%) mainly by the method of the Pan group (Scheme 7). In this case, another molecule of indoline acts as the hydride donor and is converted to indole. Both Tunge and Pan suggested redox isomerization in the

• azomethine ylide intermediates in the Tunge pyrrole formation and in the formation of N-alkylindoles from indoline [19]. These reactions are considered C–H activation reactions, as during the azomethine ylide formation, the C–H bond that is cleaved is not activated by electron-withdrawing (such as ester

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• , when PtCl2 (under an atmosphere of CO) is used, the major products are 2,3-indoline-fused cyclopentenes 44, which arise from a formal (3 + 2) cycloaddition (lower arrow) [86]. Thus, the appropriate choice of a Pt or Au catalyst determines whether the allenyl intermediate 42 participates as a 2C- or as

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• the p-quinone are called mitosanes or mitosenes depending whether they are at the oxidation state of an indoline (Y1 or Y2 = H) or an indole (Y1 = Y2 = C=C). Compounds bearing an aziridine at C1 and C2 are described specifically as aziridinomitosanes and aziridinomitosenes respectively. Compounds

• reagent, N-phenylselenophthalimide (N-PSP) [83][84]. The attack of this reagent upon the double bond led to indoline 81 which underwent a second alkylation to generate the complete pyrroloindole system 82. It is noteworthy that the cyclization reaction was completely stereospecific. Indeed, one could

• argue that the addition of N-PSP to the olefin 80 to form a selenonium ion is reversible and that the attack of the nitrogen is favored when the two large groups emerge trans relative to the indoline ring. Treatment with m-CPBA then created the double bond which was later fashioned into aziridine 84

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• : cyclization; electron transfer; indole; indoline; radical; Introduction Arenediazonium salts have long proved useful as sources of aryl radicals in many reactions featuring carbon-carbon (e.g., Meerwein [1], Pschorr [2][3], Gomberg [3] reactions) and carbon-heteroatom bond (e.g., Sandmeyer [4]) formation

• vinblastine (58a) and vincristine (58b) contain such a system. Aryl C-C bond formation As a final extension of this methodology, we probed the feasibility of this methodology in aryl-aryl C-C bond formation reactions. Accordingly, the diazonium salt 62 was prepared from indoline (59), and treated with one

• translocation) by the aryl radical 67 from the carbon atom in the α-position to the nitrogen atom of the indoline nucleus within the same molecule. The indolinyl radical 71 might follow pathway A and undergo radical fragmentation to the intermediate 75 which would eventually tautomerise to indole (63). The