Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• bioactive compounds and natural products such as PB1-5 [74], lixivaptan, and (+)-anthramycin (Figure 5) [73]. Stepwise synthesis of pyrrolo[2,1-a]isoquinolines A stepwise synthesis involving [3 + 2] cycloaddition, N-allylation and Heck reactions has been developed for the synthesis of pyrrolo[2,1-a

• ]isoquinolines. The reaction of 2-bromobenzaldehydes, 2-aminoisobutyric acid, and maleimides in MeCN under the catalysis of AcOH at 110 °C for 6 h afforded the cycloaddition products 26. The purified intermediates were used for the one-pot N-allylation with allyl bromide to afford intermediate 25 followed by a

• pyrrolo[2,1-a]isoquinolines and hexahydropyrrolo[2,1-a]isoquinolines. Bioactive tetrahydropyrrolothiazoles. Aminoester- and amino acid-based AMYs for single and double [3+2] cycloadditions. Formation of semi-stabilized AMYs B1 from pyrrolidines. Cyclic amine-based AMYs A3 and B1 for [3 + 2] cycloadditions

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• , pyrazines, pyridines, quinolines, isoquinolines, benzothiazoles, benzoquinones, etc. Under the reaction conditions, various ethers such as 1,4-dioxane, tetrahydropyran, tetrahydrofuran, diethyl ether, etc. are suitable substrates. Immediately thereafter, various photocatalytic catalysts were developed for

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• Xiu-Yu Chen Hui Zheng Ying Han Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Jiangsu, Yangzhou 225002, China 10.3762/bjoc.19.73 Abstract The three-component reaction of isoquinolines, dialkyl acetylenedicarboxylates, and 5,6-unsubstituted 1,4

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• the use of pyridines for the formation of quinolines and isoquinolines, an oxidant-dependent rhodium-catalyzed C–H annulation of pyridines with alkynes was reported by Li and co-workers [105] in 2011 for the direct synthesis of quinolines 180 and isoquinolines 181 involving a two-fold C–H activation

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• catalyst [36][37][38][39][40]. However, pre-functionalization of isoquinolines to the corresponding halogenated isoquinolines is the main limitation associated with these protocols as they require noxious halogenated acids for their starting materials preparation. Alternative strategies include, amination

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• ) [35]. During this early period, the group of Jacobsen also reported an asymmetric thiourea-catalyzed Reissert reaction of isoquinolines 21 (Scheme 5a) [36]. The mechanism proceeds by initial activation of the isoquinoline via N-acylation and subsequent dearomatization by a nucleophilic attack in the

• , that Reissert dearomatizations of N-heteroarenes, especially of isoquinolines [36], and nucleophilic addition to 1-chloroisochromanes [38] have become benchmark reactions in the context of anion-binding catalysis. Besides reports of thiourea-catalyzed reactions with different nucleophiles [39][40], the

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• could be performed only with AlCl3 under harsh conditions and, therefore, cannot be used for the preparation of compounds with acid-sensitive substituents. In addition, the debenzylation of 1-benzyl-3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinolines A was found to accompany by isomerization to 2-aryl

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• tetrahydrotrimethyldithioxo and [3-oxo-1-thioxo or 1-oxo-3-thioxo]isoquinolines 306 and 307 with olefins 215a,b, and 186c or indene (198), the regioselective [2 + 2] cycloaddition occurred to give oxo- or thiooxospiro[isoquinoline-1,2'(or 3,2')-thietane] derivatives 208–310. In some cases, the products were accompanied with

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• involving an isonitrile group is the reaction of β,γ-unsaturated oximes 119 with vinyl isocyanides 120 to form substituted isoquinolines 121 (Scheme 39) [129]. Both α,α-disubstituted aromatic oximes (products 121a,b,e–h) and unsubstituted (R2 = R3 = H, products 121c,d) undergo the reaction successfully. The

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• ]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions. Keywords: [3 + 2] cycloaddition; Heck reaction; hexahydropyrrolo[2,1-a]isoquinoline; one-pot reactions

• ]isoquinolines and related ring systems [11][12][13][14][15], while medicinal chemists have also been interested in making related compounds for biological screening and drug development [16][17]. Multicomponent reactions (MCRs) have been developed as highly efficient tools for assembling heterocyclic scaffolds

• synthesis of hexahydropyrrolo[2,1-a]isoquinolines by employing stable 1,3-dilpolar compounds generated from amino esters [15][40] or isoquinolines [41][42][43][44][45][46][47][48][49]. We like to report in this paper our effort on the synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• borylations [41][42], heteroarylations [43], and thioesterifications [44]. Additionally, several methods using photoredox chemistry were also published. For instance, the alkylation of isoquinolines under iridium catalysis and alkynylation with eosin Y as the catalyst [45][46]. In this contribution, we

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• Knochel’s [19][20] and our group [21][22][23] on direct metalation of substituted isoquinolines at C-1 and in continuation of our recent work on the synthesis of aromatic oxoaporphine, oxoisoaporphine and pyridoacridine alkaloids [17][18][21][22] using direct ring metalations of heterocycles with the

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• reaction [14]. Recently, several hydroxyalkylation reactions followed by alkylation of arenes have been reported involving heterocycle-based superelectrophiles: pyridines, thiazoles, quinolines, isoquinolines, pyrazines, pyrazoles, imidazole and furans, bearing a formyl (carbonyl) group [15][16][17][18][19

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• ]triazolo[4,3-a]pyridines was accessed through a 5-exo-dig-type cyclization of chloroethynylphosphonates and commercially available N-unsubstituted 2-hydrazinylpyridines. In addition, 3-methylphosphonylated [1,2,4]triazolo[4,3-a]quinolines and 1-methylphosphonylated [1,2,4]triazolo[3,4-a]isoquinolines were

• ]triazolo[4,3-a]quinolines 13 and [1,2,4]triazolo[3,4-a]isoquinolines 14, respectively (Scheme 5). In the 31P NMR spectra the chemical shifts of the phosphorus nuclei in 13 and 14 are observed in the 18.40–22.75 ppm region. The 1H NMR spectra contain characteristic doublet signals of the methylene group in

• ). Conclusion In conclusion, a series of new 3-methylphosphonylated [1,2,4]triazolo[4,3-a]pyridines, [1,2,4]triazolo[3,4-a]isoquinolines and 1-methylphosphonylated [1,2,4]triazolo[4,3-a]quinolines were synthesized through a catalyst-free 5-exo-dig-type cyclization of chloroethynylphosphonates and commercially

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• isoquinolines (Scheme 1) involved the following steps: alkylation of isoquinolines to afford isoquinolinium salts 1, its reduction with formic acid giving rise to tetrahydroisoquinolines 2 in a nearly quantitative yield, which upon alkylation gave quaternary salts 3, finally these salts underwent the Hofmann

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• confirm the present interest in the chemistry of terminal alkynes, e.g., in the synthesis of sulfinamides and isothiazoles [4], 1,3-enynes [5], α-monosubstituted propargylamines [6], 2-substituted pyrazolo[5,1-a]isoquinolines [7], etc. Terminal alkynes can be prepared by dehydrohalogenation of vicinal

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• Benedikt C. Melzer Jan G. Felber Franz Bracher Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians University of Munich, Butenandtstr. 5–13, D-81377 Munich, Germany 10.3762/bjoc.14.8 Abstract Highly-substituted isoquinolines are important scaffolds in syntheses of natural

• products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of

• methods have been published over the decades for the construction of highly substituted isoquinolines [4]. Alternatively, subsequent functionalization of isoquinolines is feasible, e.g., via Pd-catalyzed C–H functionalization [5] or regioselective direct ring metalation (at C1) [6][7][8]. General aspects

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• for related activities (Figure 1). Isoquinolines can be obtained from benzaldehyde and 2,2-diethoxyethylamine under Pomeranz–Fritsch (PF) reaction conditions (Scheme 1), as first reported in 1893 [6][7]. A modification of the classic reaction reported by Bobbitt allows access to THIQ analogues (Scheme

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

• -substituted isoquinolines at C-1, followed by reaction with iodine. Subsequent Suzuki cross-coupling of the resulting 1-iodoisoquinolines to methyl 2-(isoquinolin-1-yl)benzoates and intramolecular acylation of the corresponding carboxylic acids with Eaton’s reagent afforded five alkaloids of the

• cytotoxicity against the HL-60 tumor cell line. Keywords: directed ortho/remote metalation; Eaton’s reagent; isoquinolines; Suzuki cross-coupling; Introduction Benzylisoquinoline alkaloids represent a very large group of plant secondary metabolites, which includes about 2,500 known structures. Besides simple

• ) [17], which start with the synthesis of 1-(2-bromoaryl)isoquinolines using Bischler–Napieralski chemistry, followed by tedious replacement of the bromine substituent by cyanide (for modern variants, see ref. [18][19]), and subsequent conversion to a carboxylate and Friedel–Crafts-type cyclization