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

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• and C-5 (δ 145.0), C-3a (δ 130.2) and C-3 (δ 139.5). Besides, long-range interactions were also observed between H-2 (δ 6.96) and carbon at δ 139.5 (C-3), 159.7 (C-1) and 123.1 (C-1a), which suggested the isoquinoline core. Further correlations were noted from H-11 (δ 8.18) to C-11a (δ 141.9), C-10 (δ

• 163.2) and C-9 (δ 114.8). Finally, the interaction between H-8 and C-7a in conjunction with the carbonyl signal revealed in the 13C NMR spectrum at δ 180.1, suggested a benzocyclohexenone scaffold. Combining the isoquinoline and the benzocyclohexenone skeletons led to the 7H-dibenzo[de,g]quinolone-7-one

• = 9.5 Hz) and 8.15 (H-3, J = 9.5 Hz) representing the methine groups of the isoquinoline part. The difference was found in the benzocyclohexenone part where an additional AB-pattern was observed at δ 7.52 (H-10, J = 8.6 Hz) and 7.07 (H-11, J = 8.6 Hz). The HMBC data (Figure 2) revealed interactions

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

• synthesis of enantiomerically pure isoquinoline rings [34][37], but just a few examples of the enantioselective variant have been reported so far. Thus, as shown on Scheme 18, the cyclization of the aryllithium generated from 49a does not occur on the unsubstituted alkene, whereas the introduction of an

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• two terminal units of porphyrin–Zn noncovalently associated to a host molecule of bis-isoquinoline 13 (Figure 14). The exposure of azo derivative 13 to light of λ = 350 ± 10 nm leads to a mixture of isomers trans/cis 22:78. Irradiation of this mixture of isomers at λ > 420 nm returns the system to an

• that distances the porphyrin units, causing a mechanical spin rotation in the bis-isoquinoline molecule similar to a pedal. This device is effective if the porphyrin–Zn and bis-isoquinoline units remain associated during the photoisomerization, i.e., the dynamics of dissociation between these units is

• slower than the photoinduced movement itself. In this case, the dissociation constant is six orders of magnitude slower than the trans–cis photoisomerization, which ensures that the bis-isoquinoline unit is coordinated to azocompound 13 during the isomerization process of the azobenzene unit. Nanovehicle

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

• -Methoxypyridine (7c) provided the desired product 3g in 78% isolated yield in only 6 h at room temperature (Table 2, entry 7). Isoquinoline (7d) and 4-acetylpyridine (7e) also underwent the reaction to provide the desired products in moderate yields (Table 2, entries 8–9), but required an elevated temperature (60

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• - and N-substituents [22][23][24][25] (for related isoquinoline oxidations, see [26][27]). Related oxidative processes involve, for instance, a cascade Povarov–hydrogen transfer reaction using Tf2NH as a catalyst and the imine as an oxidant, as recently described [28]. In addition, Povarov adducts

• , chemical manganese dioxide (CMD) has been widely used in this type of transformations, and already in 1982 the oxidation of tetrahydroisoquinoline (11, Scheme 2) was reported to yield the corresponding isoquinoline 12, the intermediate dihydroisoquinoline 13 being obtained as a by-product [26]. Later

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• -polycyclic aromatic compounds has been developed utilizing charge migration [42][45]. For example, alcohol 155 reacts in superacid to give 5-methylbenzo[f]isoquinoline (158, Scheme 31) in good yield. This conversion involves formation of the 1,4-dication 156, which then undergoes charge migration to the 1,5

• -dication 157. Intramolecular cyclization and benzene elimination gives the benzo[f]isoquinoline system 158. Olah and coworkers have described a series of reactions involving glycols and related substrates in superacids [46]. These substrates are found to give protonated aldehydes and hydride shifts are

Preparation of pyridine-3,4-diols, their crystal packing and their use as precursors for palladium-catalyzed cross-coupling reactions

• Tilman Lechel,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 42, doi:10.3762/bjoc.6.42

• route to isoquinoline derivatives. Experimental Deprotection of 3-alkoxypyridin-4-ols 1, typical procedures Cleavage of the benzyloxy group by hydrogenolysis A mixture of 1a (970 mg, 3.43 mmol) and palladium (365 mg, 10% on charcoal, 0.34 mmol) in methanol (6 mL) was stirred for one day under an

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• , especially when oxygen is excluded prior to and during the hydrogenation. Experimental 5-Benzoyl-5,6,7,8-tetrahydro-4aH-isoquinoline-2-carboxylic acid methyl ester (8) Methyl chloroformate (0.056 ml, 0.722 mmol) was added to a solution of 9 (45 mg, 0.144 mmol) and triethylamine (0.02 ml, 0.144 mmol) in