Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• -diaminopyrimidin-4-one to the nitroolefin 2-[(2E)-3-nitroprop-2-en-1-yl]-1H-isoindole-1,3(2H)-dione [23]. Finally, Carell reported a cycloaddition route relying on α-brominated 3-phthalimidopropanal and diaminopyrimidin-4-one [24][25]. We further optimized this path for the synthesis of 15N-labeled prequeuosine

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• , indicating the importance of water as solvent in this protocol along with its high efficiency as absorber for microwave irradiation providing environmentally benign reaction conditions. The authors further extended the acid-catalyzed protocol for the synthesis of pentacyclic isoindole-fused furo[1,4

• intermediate B generated by the addition of aldehyde to enaminone A on intramolecular cyclization furnishes the final product 24 via C. Cyclic isoindole-fused furo[1,4]diazepines 26 were obtained by dehydration of the carbonyl group on the aromatic ring on treatment with an amino group. The authors attributed

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• convincingly assigned due to overlapping signals with the starting compound. Diels–Alder reaction of dihydropyran 12b with N-phenylmaleimide (13) 3-(But-2-yn-1-yl)-5-methyl-8-phenyl-3,4,6,6a,9a,9b-hexahydropyrano[3,4-e]isoindole-7,9(1H,8H)-dione (14) Dihydropyran 12b (100 mg, 0.567 mmol) and N-phenylmaleimide

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• , gave isomeric aldehyde 2a (48%) and the dimer-like racemic product 3a (11%). Both transformations were rationalized by the intermediacy of the isoindole 4a (Scheme 1). The formation of aldehyde 2a can be explained by a protonation of the ring tautomer 1a, followed by an acid-catalyzed water elimination

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole

• [8], and isoindole [3][9][10] to dimerize and polymerize was observed long ago. A repeatedly mentioned example was the formation of type 5 dimers under various conditions. They were first isolated during the synthesis of 1-arylisoindoles 6 by hydrogenation of o-cyanobenzophenones 7 in the presence of

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• activity [15][16] and great diversity as building block [17][18]. Among the tetracyclic scaffolds, isoindolo[2,1-a]indoles have attracted a particular interest from the synthetic point of view, either as the target or the motif for designing novel annulation methodologies [19][20][21]. Indeed, isoindole

• ratio (99.9:0.1) was in good agreement. For the cycloaddition of the pyrrolo[2,1-a]isoindole 18a with 7c, there was an additional conjugated system involved capable of perturbing the electronic density of the diene. If one assumes that the nitrogen lone-pair was partially delocalized to the benzene ring

• isoindolyl diene 18a and 7c can be also accounted for by a perceptible Cmethylene–H···π interaction (2.429 Å to the benzene ring centroid) (Table 7 and Figure 4f) between a proton of the C-5 methylene group of the pyrrolo[2,1-a]isoindole ring of 18a and the N-phenyl ring of 7c (Figure 5f). Additional

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• '-Hydroxy-5'-oxo-1',2',5',9b'-tetrahydrospiro[cyclohexane-1,3'-pyrrolo[2,1-a]isoindole]-1'-carbonitrile (7): 2 mg (2%), oily crystals; 1H NMR (CD3OD, 600 MHz) δ 7.81 (dd, J = 1.0, 7.6 Hz, 1H), 7.70 (dt, J = 1.3, 7.6 Hz, 1H), 7.65 (dt, J = 1.3, 7.6 Hz, 1H), 7.48 (dd, J = 1.0, 7.6 Hz, 1H), 4.55 (br s, 3H

• –25 min (MeOH), 25–30 min (0−35% H2O/MeOH, 0.1% TFA). 9b'-Methyl-5'-oxo-1',2',5',9b'-tetrahydrospiro[adamantane-2,3'-pyrrolo[2,1-a]isoindole]-1'-carbonitrile (11): 2 mg (2%), oily crystals; 1H NMR (CD3OD, 300 MHz) δ 7.70–7.65 (m, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.53 (dt, J = 0.6, 7.4 Hz, 1H), 4.03 (d

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• study, we developed a new addition reaction of chlorosulfonyl isocyanate (CSI), starting from 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione. The addition reaction of CSI with 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione resulted in the formation of ylidenesulfamoyl chloride, whose

• Schwarz [15]. In our continuing studies on the synthesis of isoindole derivatives, we have included the addition of CSI to unsaturated systems and obtained unexpected results. When the reactions were performed by heating without any solvent, the condensation product imine was the sole product. In this

• material was 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (9), which we have synthesized in previous studies [16][17]. Imide 9 was synthesized via the cycloaddition of 3-sulfone to maleic anhydride. The reaction of ethylamine with anhydride 8 in the presence of a toluene/triethylamine mixture (3

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• -aminobutyric acid by high-performance liquid chromatography with molecular fluorescence detection [5]. In addition to the above manipulations, OPA and its derivatives are also valuable reagents [6] in organic chemistry, used to generate phthalimidine [7], imines [8], isoindole [9], 3-hydroxyindanone [10

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• Versailles (ILV), UMR CNRS 8180, 45 avenue des Etats-Unis, 78 035 Versailles Cedex, France Université de Versailles Saint-Quentin-en-Yvelines, Département de chimie, 45 avenue des Etats-Unis, 78 035 Versailles Cedex, France 10.3762/bjoc.14.271 Abstract New chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5

• widely distributed in nature and possess several biological activities. In 1967, Geigy described the preparation of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones I which are recognized as anti-inflammatory and analgesic agents [1]. Other compounds, such as 1H-imidazo[2,1-a]isoindole-2,5-diones II

• ]isoindole-2,5(3H,9bH)-diones [6] and 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones [13] has been described by Katritzky et al. using α-aminoamides and diamines, respectively. Also, the imidazo[2,1-a]isoindole-2,5-dione derivatives of primaquin have been synthesized from α-amino acids [14]. Focusing

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• anhydrides as reactive intermediates blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are formed by consecutive pseudo three-component syntheses in a one-pot fashion. The Stokes shifts correlate excellently with the Hammett–Taft σR parameter indicating an extended degree of resonance stabilization

• activation of benzyl alcohols in the synthesis of N-benzylphenothiazine derivatives [48], we reasoned that T3P® might be equally well suited for furnishing 4-phenylnaphtho[2,3-c]furan-1,3-diones, and thereby opening a straightforward entry to 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones in a diversity-oriented

• -arylnaphtho[2,3-c]furan-1,3-diones and 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones Starting from phenylpropiolic acids 1 we first set out to optimize the reaction conditions for the domino synthesis of the 4-arylnaphtho[2,3-c]furan-1,3-diones 2a and 2b with T3P® as an activating agent, varying temperature and

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• ), 28.8 (C-10), 23.2 (C-15), 22.2 (C-14); MS (EI+) m/z: 234 [M+.] (3), 178 [M − C4H8]+ (10), 150 (18), 107 [C8H11]+ (10), 106 (47), 105 (37), 93 (59), 91 (100), 79 [C6H7]+ (28), 77 (58), 69 [C5H9]+ (81), 55 [C4H7]+ (25). 6-Methyl-4-(3-methylbut-3-en-1-yl)-2-phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H

• ), 93 (65), 91 (89), 77 (67), 69 (30), 56 (28), 55 (28). 2,6-Dimethyl-4-(3-methylbut-3-en-1-yl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (6c) Following the general procedure, the reaction of 2-TT with N-methylmaleimide (111 mg, 1.0 mmol, 1.0 equiv) gave 6c as a colorless oil (225 mg, 0.91 mmol

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy 10.3762/bjoc.12.278 Abstract A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N

• complete regioselectivity and a high stereoselectivity in favour of the [1(RS),4’(RS)]2,2’-dibenzyl-4’-substituted spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones 6a–f. The structure of adducts 6 and 7 has been elucidated by 1H NMR and 13C NMR spectroscopies and MS spectrometry. In particular, the 1H NMR

• could be related to the greater stability of the complex ligand/MDM2 (Figure 13) and to the better biological activity. Conclusion Spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones 6a–f, synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones, have shown interesting

New depsidones and isoindolinones from the mangrove endophytic fungus Meyerozyma guilliermondii (HZ-Y₂) isolated from the South China Sea

• Senhua Chen,
• Zhaoming Liu,
• Yayue Liu,
• Yongjun Lu,
• Lei He and
• Zhigang She

Beilstein J. Org. Chem. 2015, 11, 1187–1193, doi:10.3762/bjoc.11.133

• structure of 9 was thus established as 6-hydroxy-4-methoxyisoindoline-1,3-dione. In addition, the structures of the known compounds were identified as botryorhodine A (4) [6], botryorhodine B (5) [6], botryorhodine D (6) [6], 4,6-dihydroxy-2,3-dihydro-1H-isoindol-1-one (8) [18], 4,6-dihydroxy-1H-isoindole

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• addition of the same pyrimidinone to the nitroolefin 2-[(2E)-3-nitroprop-2-en-1-yl]-1H-isoindole-1,3(2H)-dione [13], however, this route seemed inconvenient for our purposes because access to the nitroolefin requires several additional steps. Results and Discussion Our aim was to develop a robust synthetic

• , DMSO-d6) δ 4.41 (s, 1H, CH), 5.82 (s, 2H, NH2), 6.70 (d, J = 89.03 Hz, 2H, 15NH2), 7.91 (d, J = 89.51 Hz, 1H, 15NH) ppm. [15N1,15N3,H215N(C2)]-2-[(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-1,3-dihydro-2H-isoindole-1,3-dione (8). Compound 6 (46 mg, 0.37 mmol) and α-bromoaldehyde

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

• reactions are known to exhibit this type of regioselectivity, and it can be explained based on charge control [40] (Scheme 2). The polarization of the iminium cation places the positive charge on the benzylic C of the isoindole ring and subsequently the N-aryl ring develops a negative charge at the ortho

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• -oxo-5-phenyl-3H-isoindole-4-carboxylate (40). Keywords: aminopyranes; arylbenzoic acid; DABCO; L-proline; multicomponent; tetrahydronaphthalene; three-component reaction; Introduction The reaction of arylidenemalononitriles with active methyl and methylene compounds was extensively utilized for the

• acid derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3-oxo-5-phenyl-3H-isoindole-4-carboxylate 40. X-ray crystal structure of 9. X-ray crystal structure of 13a. X-ray

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• -oxo-2-phenylethyl)cyclohexa-1,4-diene-1,2-dicarboxylate (3l). Following the general procedures described above, 20 mg (48% yield) of 3l were obtained as a dark brown oil starting from 20 mg of 1d. 5-(1,1-Difluoro-2-oxo-2-phenylethyl)-2-phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (3m

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• Klaus Speck Thomas Magauer Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, 81377 München, Germany 10.3762/bjoc.9.243 Abstract This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton

• have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well. Keywords: isoindole; isoindoline

• ; isoindolinone; isoindolone; natural products; Introduction Isoindole (2H-isoindole, 1), known since more than a century, consists of a fused benzopyrrole ring system and constitutes the regioisomer of the abundant 1H-indole heterocycle. The fully reduced member of the isoindole family is termed isoindoline

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• ]isoindole (11, 12.5% yield) and trans-3-(4-methylphenyl)-3a,8-dihydro-3H-pyrazolo[5,1-a]isoindole (12, 5% yield). Thermal reactions afforded 3-(4-methylphenyl)-3,3a,8,8a-tetrahydroindeno[2,1-c]pyrazole (14, 50% yield) and 11-(4-methylphenyl)-9,10-diazatricyclo[7.2.1.02,7]dodeca-2,4,6,10-tetraene (15, 22

• (Scheme 4) in which, as expected for the predicted structures, the aromatization reaction took place forming the pyrazolo-isoindole 13. Compound 13 arose also on silica gel during the purification of either 11 or 12. The irradiation of 3a or 3b until full conversion, as previously mentioned, produced a

Synthesis of mesogenic phthalocyanine-C₆₀ donor–acceptor dyads designed for molecular heterojunction photovoltaic devices

• Yves Henri Geerts,
• Olivier Debever,
• Claire Amato and
• Sergey Sergeyev

Beilstein J. Org. Chem. 2009, 5, No. 49, doi:10.3762/bjoc.5.49

• phthalonitriles 6a–d (80–86% yield) starting from the corresponding commercially available ω-bromoalcohols. Several strategies for the synthesis of low-symmetry A3B phthalocyanines (where A and B refer to the chemically different isoindole units comprising the phthalocyanine core) were reported earlier, including

Preparation and Diels–Alder/cross coupling reactions of a 2-diethanolaminoboron- substituted 1,3-diene

• Liqiong Wang,
• Cynthia S. Day,
• Marcus W. Wright and
• Mark E. Welker

Beilstein J. Org. Chem. 2009, 5, No. 45, doi:10.3762/bjoc.5.45

• . Preparation of 6-(4-methoxyphenyl)-3a-methyl-2-phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (14): Following the general procedure, 4-iodoanisole (0.234 g, 1 mmol) and 5 (0.178 g, 0.5 mmol) were added along with Pd2(dba)3 (10 mg) and K2CO3 (0.207 g, 1.5 mmol) to a flask under N2 (30 mL acetonitrile

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

• Wolfgang Maison,
• Marina Büchert and
• Nina Deppermann

Beilstein J. Org. Chem. 2007, 3, No. 48, doi:10.1186/1860-5397-3-48

• isoindole derivative 11 in good yield, verifying our previous assumptions. As a general trend, it turned out that benzannelated azabicycloalkene derivatives like 8 and 10 give relatively unstable products. In consequence, products can only be isolated as pyridones 9, derived from spontaneous aromatization

• and 12. A sequence of ring opening and cross metathesis is extremely efficient for desymmetrization of 7 and 12 as depicted in Scheme 4 for the synthesis of isoindole 19 and the disubstituted pyrrolidine 20. In these cases, catalyst loadings can be low and yields are excellent. Unfortunately the ROCM

• . Ruthenium based precatalysts used in this study. RORCM of 2-azabicycloalkenes 5 to bicyclic scaffolds 6. RORCM of 7-azabicycloalkenes 8 and 10 to pyridone 9 and isoindole scaffold 11. RORCM of 7-azabicycloalkenes 13 and 16 to bicyclic scaffolds 14, 15, 17 and 18. Conditions A: 10 mol % 1, C2H4, 3 equiv