Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ]. Mechanochemical methods of the Mannich reaction, Paal–Knorr synthesis, Bigineli reaction, Hantzsch reaction, and syntheses of substituted pyran, thiophene, isoquinoline derivatives, etc. are also reported [104][107][112][113]. Isocyanide-based multi-component reactions are also well known [114][115]. Recently, in

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• ]. Original Pd/C lead to sluggish reactions compared to the modified form. The catalyst could also be recycled at least thrice (Scheme 24). This facile synthesis demonstrated seamless production of dihydroisoquinolines. They were the predominant products with nearly 3–5% formation of the aromatic isoquinoline

• isoquinoline 82 from diverse 1,2,3,4-tetrahydroquinolines 81 in moderate to good yield (Scheme 29). Ferrous chloride (FeCl2) acted as a single electron transfer agent in the presence of DMSO to facilitate the reaction. Metal-catalyzed oxidant induced dehydrogenation Our next discussion involved the oxidative

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• starting from an isoquinoline bearing an ester group at C-8. In a photoredox-catalyzed direct C–H arylation a 4-methoxyphenyl residue from a methoxyphenyldiazonium salt was introduced at C-1, and after ester hydrolysis intramolecular Friedel–Crafts acylation afforded menisporphine (2). In continuation of

• were inspired by Knochel’s reports on the direct metalation of isoquinoline [22] and 6,7-dimethoxyisoquinoline [23] as well as by our own results for the metalation of various alkoxyisoquinolines [13] at C-1 with the Knochel–Hauser base TMPMgCl·LiCl. Transmetalation of the intermediate organomagnesium

• ) at C-8 of the isoquinoline ring, which should be followed by an intramolecular trapping of the amide group to give the oxoisoaporphine bianfugecine (6, Scheme 5). However, only starting material 12 was recovered from this reaction. A D2O quenching experiment after the metalation period (4 equiv LDA

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• have recently demonstrated that bifunctional organocatalysts can also be applied to the asymmetric synthesis of axially chiral compounds (biaryls bearing isoquinoline N-oxides or quinolines and phenolic moieties) by translating a specific conformation, recognized by bifunctional organocatalysts, into

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• [10]. The use of cyclic imines (or surrogates thereof such as isoquinoline [11]) in the CCR is quite scarce in the literature [12][13][14]. As an example, 1-pyrroline (in the form of its trimer 3) has been reported by Smith and co-workers [15][16][17] to condense efficiently with HPA analogs to

• deliver hexahydropyrrolo[1,2-b]isoquinolones 4. The hexahydropyrrolo[1,2-b]isoquinoline core in general is ubiquitous to many natural products exemplified by tylophorine (5) [18], lycorine (6) [19] and its entire family of alkaloids, including zephyranthine (7) [20] and galantine (8) [21]. Considering the

• reaction with homophthalic anhydride (HPA). The compounds obtained contain a benzene-fused, privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline core and are distinctly encumbered from steric perspective. The novel compounds have been characterized by NMR spectroscopy, high-resolution mass

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• synthesis of the biologically intriguing imidazo[1,2-a]pyridine-fused isoquinoline systems from readily available starting materials was achieved through the Groebke–Blackburn–Bienaymé reaction followed by a gold-catalyzed cyclization strategy. The synthetic approach is characterized by mild reaction

• (Figure 1) [6]. Furthermore, the isoquinoline motif represents a privileged medicinal skeleton widely found in a number of natural alkaloids and pharmaceutically active compounds [7]. Some of them exhibit diversified biological properties, including anti-inflammatory [8], antibacterial [9], antiviral [10

• synthesis of biologically interesting heterocycles [43][44][45][46][47], we were interested in a practical synthetic strategy towards imidazo[1,2-a]pyridine-fused isoquinoline systems. We believe that this type of polycyclic systems may have interesting biological profiles [48]. Herein, we report our recent

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• sp. 085242 afforded eight isocoumarin derivatives 1–8 and one isoquinoline 9. Asperisocoumarins A and B (1 and 2) were new furoisocoumarins, and asperisocoumarins E and F (5 and 6) were new isocoumarins. Their structures were established by analysis of their spectroscopic data and the absolute

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• and 1,5-benzodiazepine 95, respectively (Scheme 21). 2.2.7 Isoquinolone-1-phosphonates: From Lewis acid catalyzed 6-endo-dig cyclizations of acetylenic Kabachnik–Fields adducts: A modified Kabachnik–Fields reaction for the synthesis of isoquinoline-1-phosphonate derivatives is the three-component

• utilized in this reaction. For example, the one-pot reaction of isoquinoline (246) with KCN and chlorophosphates or chlorothiophosphates 247 has been described by Spatz and Popp. The corresponding N-phosphorylated isoquinolines 248 were obtained in 21–85% yields in CH2Cl2 at room temperature (Scheme 51

• the nature of the acyl chlorides and substituents X (Scheme 52) [89][90]. The three-component reaction of dimethyl phosphite, acetyl chloride and isoquinoline under refluxing in CH2Cl2 in the presence or absence of triethylamine led to the desired 1,2-dihydroisoquinoline-1-phosphonates in 66% and 45

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

• substituent on the C–C double bond was found to play a key role for the progress of the reaction to give the expected products with good chemical yields. Additionally, N-methacryloylbenzamides were also suitable substrates for the current reaction and provided the alkyl-substituted isoquinoline-1,3(2H,4H

• substituent on the C–C double bond was found to play a key role for the formation of the desired products. Also, N-methacryloylbenzamides worked well in the current reaction, which provides an easy way for the preparation of alkyl-subsituted isoquinoline-1,3(2H,4H)-diones. Experimental General procedure for

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• observed lower ee’s with Pybox and Box ligands, and only 49% ee with Quinap. However, investigation of novel Pinap ligands led to notably higher ee’s (Scheme 7) [29]. These reaction conditions enable alkynylation of quinoline (20), isoquinoline (21), and pyridine (22) substrates, albeit in lower yields

• substituents are tolerated on the isoquinoline, including halides, which provides a handle for further manipulation. Furthermore, the Cbz group can be easily removed via hydrogenation, as demonstrated in Liu’s efficient synthesis of homoprotoberberine. Very recently, Aponick’s group reported the use of a new P

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• leads to the formation of polycyclic isoquinoline derivatives [29] and the reaction of 3,5-di(tert-butyl)-1,2-benzoquinone with 1,2,3-trimethyl-benzimidazolium salts gives rise a spirocyclic derivative of sterically hindered pyrocatechol [30]. The structures of the prepared 2-hetaryl-1,3-tropolones have

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• with methylaminoacetaldehyde dimethylacetal and cyclized to form an isoquinoline ring. The nitro group in that intermediate was reduced following a one-pot oxidation and cyclization to afford the target molecule (Scheme 3) [61]. Method B: Neoamphimedine was prepared by Li et al. [62] in eight and nine

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

• generation of Huisgen’s 1,4-dipoles are aromatic heterocycles such as N-alkylimidazole, pyridine, quinoline, isoquinoline and primary aromatic amines. In recent years, other nitrogen-containing nucleophiles such as hydrazine and arylhydrazines are also used to generate Huisgen’s 1,4-dipoles in domino

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• and isoquinoline-derived heterocycles are prevalent structural motifs in natural products and pharmaceuticals that exhibit remarkable biological activities [1][2]. Therefore, great attention has been directed toward the development of efficient methods for the selective functionalization of the

• isoquinoline cores. Among these, pyrazolo[5,1-a]isoquinoline is an important class of isoquinoline derivatives. Recently, much effort has been spent on the synthesis of these compounds due to their promising biological activities [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. For instance, in 2010

• , Wu and co-workers found some pyrazolo[5,1-a]isoquinoline derivatives showing activities for the inhibition of CDC25B, TC-PTP, and PTP1B [4]. It has been proved that the physical, chemical, and biological activity of organic molecules can be dramatically improved by substitution of hydrogen with

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• Carlos Vila Jonathan Lau Magnus Rueping Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.10.122 Abstract Pyrrolo[2,1-a]isoquinoline alkaloids have been prepared via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition

• presence of Rose Bengal (5 mol %) in acetonitrile under irradiation with visible light, the reaction was not selective affording the dihydropyrrolo[2,1-a]isoquinoline 3aa in 35% yield and the hexahydropyrrolo[2,1-a]isoquinoline 4aa in 26% yield, after column chromatography (Scheme 1). In order to improve

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

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• for the syntheses of various isoquinoline alkaloids [5][6][7]. Spontaneous dehydrocyanation afforded the 1-benzylated 3,4-dihydroisoquinoline which was subsequently reduced in situ to tetrahydroisoquinoline 3 in a one-pot procedure with sodium borohydride in 63% yield. N-Acylation was effected

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• derivatives were unreactive. Interestingly, two stereocenters are generated during the reactions. However, the observed diastereoselectivities were poor, ranging from 50:50 to 76:24. MCRs yielding isoquinoline cores are well documented in the literature and several examples involving alkynylbenzaldehydes and

• different reaction mechanism and allows for the synthesis of tricyclic H-pyrazolo[5,1-a]isoquinoline 48 (Scheme 25). With these results in hand, a MCR involving 2-alkynylbenzaldehydes 25, tosylhydrazide (41), methanol and α,β-unsaturated aldehydes or ketones 49 was set up to synthesize a library of 24 H

• (enamines and carbanions) or be involved in cycloaddition reactions affording tricyclic compounds by cascade processes. An unprecedented, co-catalyzed reaction involving enamines 51 as nucleophilic partners, also yields the H-pyrazolo[5,1-a]isoquinoline nucleus 48, in the presence of silver triflate and

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• -ethanone under aerial oxidation conditions [24]. Later this methodology was successfully employed in the synthesis of isoquinoline alkaloids [27]. The synthesis of eudistomin Y (6) was initiated with the conversion of the respective 2,2-dibromo-1-phenylethanone to the corresponding Schiff base 14 by

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

• Adrián Gómez-Suárez,
• David J. Nelson,
• David G. Thompson,
• David B. Cordes,
• Duncan Graham,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2013, 9, 2216–2223, doi:10.3762/bjoc.9.260

• ) with each (hetero)aromatic amine in THF at room temperature for 20 h. A range of aromatic amines were employed, including aniline, diphenylamine, pyridines, a pyrimidine and one isoquinoline. The corresponding complexes were obtained in analytically pure form and in good yields as yellow or white

• fluorescence behavior of these materials, with more electron-rich 2-pyridine derivatives showing strong emission, and isoquinoline-derived complexes showing the strongest fluorescence. While the present study has been conducted using commercial reagent-grade amines, there is significant scope to prepare a much

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

• yielding synthesis, ample quantities could be obtained for a preliminary evaluation of the biological activity of 79. In a first screen against A2058 melanoma and DU145 prostate cancer cell lines, 79 showed to be inactive [73]. Isoindolinones derived from isoquinoline alkaloids: The aporhoeadane alkaloids

• , a term designated by Shamma [75], are abundantly found in South American members of the botanical family of Berberis (Berberidaceae). Along with the ever present isoquinoline berberine (92), the isoindole-containing benzazepines chilenine (93) [76], lennoxamine (94) [77] and chilenamine (95) [78

• ], the isoquinoline nuevamine (96) [77] and the benzazocine magallanesine (97) [79] were isolated from different Berberidaceae species (Figure 6). Chilenine (93) was the first isoindolobenzazepine alkaloid isolated from Berberis empetrifolia in 1982. The biogenesis proceeds most likely via a Pictet

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• nucleophile 28 in situ, which is then added to photogenically formed iminium ion 27 to yield the Mannich product 23. The Mannich reaction was sluggish without the Lewis base, and a side reaction, formation of the oxidized isoquinoline, became significant. The choice of Lewis base was found to be also crucial

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• various α,β-unsaturated carbonyl compounds under mild conditions are described, which provides a facile and efficient pathway for the synthesis of 1-alkylated isoquinoline derivatives. The method tolerates a wide range of substrates and allows for the preparation of the products of interest in moderate to

• processes. Isoquinoline derivatives, an important class of nitrogen-containing polycyclic heteroarenes, have attracted considerable attention because of their pharmacological activities, including antitumor, antifungal, antimalarial, antihypertensive and antihistaminic activity, and their photo- and

• electrochemical properties [7][8][9][10][11][12][13][14][15]. Over the past decade, there has been growing interest in the development of new methods for the construction of isoquinoline. For instance, Yamamoto [16][17][18][19], Larock [20][21][22][23][24][25][26][27], and Wu [28][29][30][31][32][33][34][35] have

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• stabilisation of spiro-cyclised radical 12a, these rate parameters seem to be very reasonable estimates (Table 3). Curiously, analysis of the products from a photolysis of 2a carried out at higher temperature (rt) in benzotrifluoride solvent, showed benzofuro[3,2-c]isoquinoline derivative 14a to be the main