New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• from aldehydes, a carboxylic acid, and a isonitrile as the three components [23]. The sequences of Passerini reactions, followed by post-condensation reactions, constitute useful synthetic methods in the preparation of structurally diverse heterocyclic compounds [24][25][26][27][28][29]. The aza-Wittig

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• complex of cobalt and N-heterocyclic ligand supported on carbon nanotubes and pure cobalt nanoparticles was developed [37]. Propargylamine derivatives were synthesized in extremely high yields in green solvents by this catalyst. The catalytic system can be easily recovered and reused 7 times without any

• clearly shown that the complex of Co-N-heterocyclic ligand exhibits a higher activity. Sonogashira cross-coupling reactions were also reported by making use of a heterogeneous, efficient and green cobalt catalyst obtained through complexation of cobalt with methyl salicylate-functionalized chitosan fibres

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• Anna V. Korotina Svetlana G. Tolshchina Rashida I. Ishmetova Natalya P. Evstigneeva Natalya A. Gerasimova Natalya V. Zilberberg Nikolay V. Kungurov Gennady L. Rusinov Oleg N. Chupakhin Valery N. Charushin Laboratory of Heterocyclic Compounds, Postovsky Institute of Organic Synthesis, Russian

• -disubstituted 1,2,4,5-tetrazines bearing amidine fragments. It is shown that the heterocyclic systems obtained can be modified easily at C(3) position in the reactions with aliphatic alcohols and amines. Also, the reactivity of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines towards CH-active compounds has been

• ). Therefore, the development of methods for the synthesis and modification of new triazolo[1,5-b][1,2,4,5]tetrazines can be considered as an attractive task for heterocyclic and medicinal chemistry. Results and Discussion In this work, the synthesis of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines has been

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• an integrated quenching and extraction step. Lastly, the use of an automated in-line chromatography system was exploited to realise a powerful flow platform for the generation of the heterocyclic targets. Keywords: chromatography; flow synthesis; in-line purification; oxadiazole; reaction

• significant development in continuous flow platforms, particularly in industry [16][17][18][19][20]. 1,3,4-Oxadiazoles are biologically relevant 5-membered heterocyclic compounds with various favourable pharmacokinetic properties and have been investigated as potential candidates for antiviral, antifungal and

• ]. Various other methods to access this heterocyclic moiety have been reported in the literature, with many focusing on either cyclodehydration or cyclodesulphurisation (Scheme 1) [27]. However, in recent years, there have been a number of oxidative cyclisation protocols reported to access the same 1,3,4

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• % yield. Bulky 2,2,6,6-tetramethyl-4-piperidone could also be isolated from naphthalene in 94% yield through this approach (Table 3, entry 11). Other heterocyclic amines such as acridine or 1,2-dimethylimidazole could also be isolated with success in 53–65% yields (Table 3, entries 12 and 13). Of

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• ). The disubstituted malonamates underwent facile oxyamination, and the products were obtained in excellent yields and enantioselectivities (4k, 4l). Of note, the reaction was also feasible with heterocyclic malonamate, albeit with moderate yield and enantioselectivity (4m). Aliphatic malonamate was also

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• -phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield. Keywords: anticancer; Fischer indole synthesis; Heck reaction; heterocyclic compounds; indolobenzazepines; latonduines; paullones; Introduction Indolobenzazepines are fused heterocyclic

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• unsubstituted double bond next to the nitrogen atom permits a DHP to react as an enamine, for further transformation to complex heterocyclic scaffolds [26]. The exposed double bond can also undergo modification to produce different kinds of moieties. There are only few reports on the synthesis of C5–C6

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, Kaunas LT-50254, Lithuania Vipergen ApS, Gammel Kongevej 23A, DK-1610 Copenhagen V, Denmark 10.3762/bjoc.18.11 Abstract A convenient and efficient synthesis of novel achiral and chiral heterocyclic amino acid-like building

• analysis, 1H, 13C, and 15N NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data. Keywords: β-enamino ketoesters; heterocyclic amino acids; 15N-labeled 1,2-oxazole; NMR (1H; 13C; 15N); 1,2-oxazole (isoxazole); X-ray structure analysis; Introduction 1,2-Oxazoles (isoxazoles) constitute an

• important class of heterocyclic compounds that plays a fundamental role in drug discovery [1][2][3][4][5][6][7]. Many amino-functionalized 1,2-oxazole derivatives are biologically active substances that include naturally occurring and synthetic neuroactive compounds. Specifically, natural products such as

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• enhancement behavior with a blueshift in the emission maximum upon enclathration of various types of organic solvents. It is important to note that other authors carried out the reaction of 18 with N,N-diethylaniline without the presence of Ni(II) [104][105]. In the search for fluorophores of heterocyclic

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• of other metals such as Au, Pt, Pd, Rh, Ag, and Fe and found that they were less efficient compared to Ru. The benzylic alcohols showed higher reactivity than aliphatic alcohols towards this methodology. Moreover, this protocol worked well for differently substituted heterocyclic alcohols and

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• field of synthetic organic chemistry and pharmaceutical chemistry all over the world. In the previous few decades, a large number of strategies emerged to construct heterocyclic compounds with this skeleton or similar ones [6][7][8][9][10], aiming to explore biological activity and medicinal value

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• -anilinoquinazoline; anticancer agents; N-arylation; 4-chloroquinazoline; microwave irradiation; Introduction N-Heterocyclic compounds are commonly present in pharmaceuticals, bioactive natural products, agrochemicals, and synthetic drugs [1][2]. Quinazoline, a benzo-fused N-heterocyclic framework (benzo-1,3-diazine

• -anilinoquinazolines can be prepared from N-methylanilines under basic [14] or acidic [15][16] (Scheme 1c) conditions. Due to our interest in the functionalization of aromatic and heterocyclic compounds of medicinal relevance [21][22][23][24][25][26], we recently reported the preparation of an iodo-substituted analog

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• , affording the heterocycle D, a pathway which should not be base-catalyzed, and thus may be reasonably predominant under appropriate conditions. From heterocycle D, a C–C cleavage would produce the N-formyl product 8 and a re-aromatized C8 heterocyclic byproduct E. Rearrangement to hydroxyindole (F) would

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• cyclization with the aryl ring constructs the 6-membered heterocyclic framework. In 2015, the Li group investigated the radical addition/cyclization of olefinic malonate and β-diketone compounds 96 with aldehydes 97 (Scheme 19) [97]. The reaction was feasible with ketones; however, lower product yields were

• Cheng investigated the cascade cyclization of dienes 119 with alkyl carbazates 117 for the synthesis of fused nitrogen heterocyclic compounds 120 (Scheme 25) [117]. Diene substrates possessing EDGs reacted smoothly under the optimized conditions while their electron-deficient counterparts delivered the

• different coupling partners, both bi- [142] and tricyclic [143] fused heterocyclic frameworks have been synthesized through iminyl radical cascade cyclization and annulation reactions. Carbooxygenation In 2017, the Bao group reported the first decarboxylative alkyl etherification of alkenes 108 with

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• ultraviolet range, the observed transitions can be attributed to the π → π* transitions and refer to the heterocyclic ring. Transitions above 350 nm can be attributed to the n → π* transition referring to the imine moiety, causing an intramolecular charge-transfer type (ICT) transition [27]. Complementary

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

• . Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale. Keywords: 1-aminoisoquinolines; CWJ-a-5; intramolecular cyclisation; 2-(2-oxo-2-phenylethyl)benzonitriles; nucleophilic addition; Introduction Heterocyclic compounds

• the development of several approaches for the efficient construction of these heterocyclic frameworks (Scheme 1). Traditional preparations for 1-aminoisoquinolines include nucleophilic substitution of 1-haloisoquinolines with amines either employing a base [31][32][33][34][35] or a transition metal

• heterocyclic frameworks. On the other hand, organonitrile, the polar unsaturated carbon−nitrogen multiple bond, recognized as one of the most versatile chemotypes in both the laboratory and industry because of their vital role displayed in various transformations [1][2][3][4]. They capture a major area in the

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• -(−)-enantiomer 2, exhibits potential antiviral activity against HIV-1 (EC50 = 0.009 µM) in CEM cells. However, the corresponding ᴅ-(+)-enantiomer is less active against HIV-1 (EC50 = 0.84 µM) [15]. The fusion of an appropriate sugar element, carbacycle, or heterocyclic equivalent with an activated base results

• reverse transcriptase [25]. Nucleosides with sulfur atom-containing heterocyclic sugar rings at the 3’-position are important pharmaceutical substances. Two well-known important molecules in this category are lamivudine (1) and emtricitabine (2), as shown in Figure 1. It was found that there is a

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• take part in electrophilic [1][2] and nucleophilic [3][4][5][6] addition reactions onto the acetylene bond leading to various substituted nitriles. Reactions onto both acetylene and nitrile groups are widely used for the construction of various heterocyclic systems [7][8][9][10][11][12][13][14][15

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• ) was reacted with 4-fluoro-β-nitrostyrene (7c). In the presence of catalyst (S,R)-C2 only traces of product 8f (THF/H2O, NMM as the base, and additive PhCO2H) were obtained (Scheme 3). Michael acceptors containing heterocyclic groups have been studied only sparingly, but the corresponding chiral

• compounds with heterocyclic substituents are of high biological and medicinal relevance [34][35]. Therefore, we have decided to evaluate sulfinylurea and thiourea catalysts C1 and C2 also with (E)-2-(2-nitrovinyl)furan (9) and (E)-3-(2-nitrovinyl)pyridine (11) as Michael acceptors. As Michael donor, we

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• and metabolic stability of the molecule [16]. Steroid molecules with nitrogen-containing heterocyclic rings are promising candidates for the treatment of many types of cancer or hormonal disorders [17]. There are several examples of steroidal tetrazoles showing anticancer potential (Figure 1) [18][19

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• and enantiomeric excesses. On the other hand, N-heterocyclic carbenes and chiral pyrrolidine derivatives acting through covalent bond formation such as the iminium ions with the substrates have also been included. Wherever possible, a comparison has been made between the efficacies of various

• aza-MRs. However, the last three review articles are almost 10 years old and they do not cover the application of many important organocatalysts, such as thioureas and nitrogen heterocyclic carbenes (NHCs) used for the asymmetric aza-MRs. Furthermore, in the last review article [24], the application

• . Review In the present review, the known stereoselective syntheses of pharmacology-oriented nitrogen containing heterocyclic scaffolds via non-covalent bonding and covalent bonding organocatalytic aza-MRs has been systematized. This classification is especially useful for researchers to understand both

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• enaminones as both nucleophiles and electrophiles have frequently been exploited in the synthesis of heterocyclic products, including pyrroles and related systems [22][23][24][25][26][27][28]. Nonetheless, encouraged by the ease of access to pyrrole-containing products of type 12 and their potential

• , entries 21–24). Reaction of the electron-rich furyl- and thiophenyl-bearing precursors 15u and 15v was slower than with the phenyl parent 15a, once again reflecting the rate-retarding effect of the electron-donating rings. However, cyclization of both the benzo-fused heterocyclic systems 15w and 15x was

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• stereogenic carbon center with good enantioselectivity (ee up to 80%) and excellent yields (up to 97%). Keywords: aminalization; Brønsted acid; organocatalysis; PCCP; pentacarboxycyclopentadiene; Introduction Nitrogen-containing heterocyclic compounds are commonly occurring in nature and constitute the core