Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• dialkyl acetylenedicarboxylate or sodium diethyl oxalacetate [28][29][30][31][32][33][34]. The resulting products have the 4-position locked by the alkoxycarbonyl (–COOR) group and these 2-pyrrolidinone derivatives can be functionalized with amines as nucleophiles via the 3-position [10][35][36][37][38

• antibacterial and antifungal activities [39][40][41]. The presence of an acyl group at the 4-position enables these heterocycles to be functionalized via nucleophilic addition reactions between the carbonyl group and nucleophiles like hydroxylamine and semicarbazide [42]. Herein, we report the synthesis of 4

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• has also been applied to organic synthesis [17][18][19][20]. However, when electrochemical oxidation of amides/carbamates in the presence of nucleophiles, such as electron-rich arenes or silyl enol ethers, is carried out for Friedel–Crafts-type amidomethylation, electrochemical oxidation of electron

• substrate 1 but DMA successfully proceeded at the anode. In other words, N-acyliminium ions of DMA would expectedly be formed. We speculated that the reason for the lower product yields of 2 and 3 was a side reaction of the produced N-acyliminium ions with other nucleophiles in the reaction medium. The most

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• secondary carbon atom at 40 °C (Scheme 2). Furthermore, increasing the temperature to 70 °C was not found to generate the product and instead resulted in slight decomposition of the starting materials. Attempting to trap the sulfinate nucleophiles with primary benzyl bromide (4) with catalytic sodium iodide

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• phenol (2a, 1 equiv Cs2CO3, DMF, 50–55 °C, 3 h) to afford the corresponding product 4a in 29% isolated yield (Scheme 4). We tested aniline and 2-naphthylamine as nucleophiles (DMF, 50–55 °C) in the reaction of bromopropargylic alcohol 1a (Scheme 5). But such a protocol turned out to be ineffective

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• mol % bismuth(III) triflate catalyst and compound 73 was obtained in 75% yield (Scheme 23). Carbonyl condensation Another possible derivatization involves transformations at the carbonyl groups in menadione that can be achieved through the addition of nucleophiles to the carbonyl group at position C-4

• isomers and trans-conformers. Menadione as a nucleophile Electron-rich 1,4-naphthoquinones, such as 2-hydroxy-, 2-amino-, and 2-alkylnaphtho-1,4-quinones may react as nucleophiles. Hence, menadione (10) can act as a nucleophile in, for example, bromination reactions [127] and aldol-type reactions with

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• capsule led to the formation of the intermediate carbocationic species that was stabilized within the cavity of the hexamer and converted to limonene as major product. We also tried to intercept the carbocationic intermediate using good nucleophiles in equimolar amounts such as N-methylindole or 2

• -mercaptoethanol but in all cases the reactions conducted in the presence of such nucleophiles proceeded forming only the isomerization products. It is worth to notice that the conversion observed with the capsule was comparable to that what was frequently observed with typical heterogeneous Lewis or Brønsted

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

• –Spengler-like cyclization processes [12]. Some 4-substituted 3,4-dihydroquinazolines were prepared by copper-catalyzed oxidative cross coupling of hydroxy intermediates with various nucleophiles [13]. Other 3,4-dihydroquinazolines were also obtained efficiently by intramolecular aza-Wittig reactions [14

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

• ][1,2,4,5]tetrazines 3a,j, as well as triazolo[4,3-b][1,2,4,5]tetrazines [33][34][35], react with N- and O-nucleophiles to give the corresponding nucleophilic substitution products 4a–c, 5a–c, derived from the displacement of the azolyl group in the tetrazine ring (Scheme 3). These reactions can be used to

• reactions with nucleophiles known for annulated tetrazine systems. It has been revealed that the synthesized compounds exhibit a pronounced activity against dermatophyte fungal strains Trichophyton, Epidermophyton, Microsporum: Seven compounds with a high fungistatic activity (0.38 ≤ MIC ≤ 1.5 μg/mL) have

• ]triazolo[1,5-b][1,2,4,5]tetrazine (b), 7H-purine (c). Synthesis of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines 3a–k. Reactions of triazolo[1,5-b][1,2,4,5]tetrazines 3a,j with N- and O-nucleophiles. Reactions of triazolo[1,5-b][1,2,4,5]tetrazines 3a,j with C-nucleophiles. Reactions of 6-(3,5-dimethyl-1H

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• asymmetric organocatalytic methods to assemble biologically relevant compounds is highlighted by a review article devoted to the syntheses of coumarin derivatives [16]. Conjugated additions of stabilized nucleophiles are the cornerstone of organocatalytic methodology. Recent advances in this area are covered

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• spectroscopy (Scheme 3h). Formation of 4a could have occurred from the direct reaction of the N–H nitrogen of 3a with NFSI, which would agree with the propensity for NFSI to react with some hard oxygen and nitrogen nucleophiles at the sulfur atom instead of at the fluorine atom [39][40]. Similarly, NFSI has

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• ] arenesulfonyl chlorides. Böhme and Schurhoff [8] similarly found that the solvolyses, in several homogeneous mixtures of an ether and water, were relatively slow. They found that the overall reaction rate could be considerably increased by the addition of reasonably powerful anionic nucleophiles. Indeed, Swain

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• , heterocycles, such as carbazole, can also be used as nucleophiles in this reaction. Keywords: indole; N-acylation; nucleophilic substitution; thioesters; Introduction Molecules containing N-acylindoles have attracted wide attention in the synthetic polymers and pharmaceutical industry because of their unique

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

• possible to identify three alternatives for the functionalization of β-NQS with amines: a) substitution of sulfonate by secondary amines; b) substitution of sulfonate by primary amines, followed by isomerization; and c) double addition of primary amines. In addition, other nucleophiles can also be used

• with other nitrogenous nucleophiles, such as azide ions. The reaction of 18 in the presence of sodium azide and water produces 4-azido-1,2-naphthoquinone (39) in a 52% yield. Although 39 can produce many other derivatives, few reactions have been studied. The reaction of 39 with concentrated sulfuric

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

• , alkynes, and halides were compatible with this strategy. A photoredox-catalyzed oxidative coupling of 4-alkyl-3,4-dihydroquinoxalin-2(1H)-ones with nucleophiles was reported by Hong and co-workers [42]. The reaction was performed using 20 mol % of Ru(bpy)3Cl2.6H2O in methanol under CFL light irradiation

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

• ]. These limitations can be overcome by using microwave irradiation [12][13][18][19][20], which promotes fast and efficient anilination reactions when a wide range of anilines bearing both electron-donating and electron-withdrawing groups are employed as nucleophiles (Scheme 1b) [12][13]. Moreover, 4

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• + as the nucleophiles in the two-phase system (Scheme 6). To a three-necked flask were added 2a (2.0 mmol), DMSO (2 mL), H2O (4 mL), CHCl3 (10 mL), and n-Bu4N+OH− (1.2 equiv in aqueous solution), and stirred vigorously for 10 min at 25 °C. Then, a solution of PhS−Na+ (1.2 mmol) in H2O (4 mL) was slowly

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

• catalyst wasn’t necessary to promote the reaction, but the yield of the cascade was significantly increased upon loading. The scope of the π-systems was limited to alkenes conjugated to electron-rich aryl species. Various nitrogen nucleophiles including primary/secondary amines and sulfonamides were

• various nucleophiles 108 (Scheme 22) [105]. This protocol offers an expedient approach to 1-amino-2-silylalkanes, a classically difficult framework to synthesize, typically requiring harsh reaction conditions, multistep synthetic routes, or the use of expensive silicon reagents [106]. Moreover, the

• methodology was extended to the carbosilylation of olefins with carbon nucleophiles 108 including indoles, pyrroles, and 1,3-dicarbonyls. The scope of the reaction was broad and could tolerate a variety of functional groups; however, electron-deficient alkenes afforded the products in slightly diminished

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• nucleophiles to β-silyl α,β-unsaturated carbonyl compounds were documented as one of the straightforward and atom-economic approaches for the facile synthesis of chiral organosilanes (Scheme 1c–f) [30][31][32][33]. Recently, the aforementioned reaction under organocatalytic conditions has gained attention [34

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

• as an important synthetic strategy for the preparation of a large variety of β-amino carbonyl and similar motifs which are present in many bioactive natural products [8][9], antibiotics [10][11][12] and chiral auxiliaries [13][14][15]. However, the reaction of many nitrogen-nucleophiles, such as

• the non-covalent and covalent organocatalysis. It is intended to overview the literature of the last 10 years, i.e., from 2011 through 2020 only. Nevertheless, wherever necessary, earlier references may also be cited to maintain coherence. Furthermore, nitrogen nucleophiles comprise a large variety of

• the nitrogen nucleophiles, such as aromatic amines and amides which are otherwise averse to reacting. The organocatalysts have emerged as catalysts of choice due to various reasons, such as their compatibility with the ‘Green Chemistry’ and possibility of tailoring them according to the requirements

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

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• the copper-catalyzed oxidative coupling of alkynes, nucleophiles (e.g., phenols 25 and 28; amines 24, 27, 29, and 32; 2-hydrazinylpyridine 26; alkyne 33; and alcohol 30), and oxidants (benzoquinone or O2). Based on the literature and mechanistic experiments [72][73], the reaction is initiated by the

• nucleophile and the alkyl or aryl radicals. From 2013 to 2019, the authors disclosed a series of nitrogen, sulfur, oxygen, and carbon nucleophiles for photoinduced, copper-catalyzed cross-couplings with organic halides. The copper–nucleophile complexes that were generated in situ as photoredox catalysts

• undergoes radical addition with the N-substituted maleimide (Scheme 25). In 2017, Wu and co-workers [94] reported the α-amino C−H functionalization of aromatic amines 51 with nucleophiles, including arynes or aromatic olefins 52, indoles, acyclic β-ketoester 53, and β-diketone 54 (Scheme 26). Mechanistic

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

• . However, these reactions were mainly suitable to strong nucleophiles such as malonates, amines, or alcohols etc. [20][21][22][23]. The allylic substitution reactions using some weak nucleophiles, such as alkyl aza-arenes, were very limited [24][25][26][27][28][29]. In 2014, Rios and coworkers developed a

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• periodic table [32]. Hg(II) salts have already manifested some unique reactivity and therefore attracted increasing interest from chemists [33]. Many examples involving Hg(II) salts with unsaturated bonds in presence of various nucleophiles giving rise to various types of products are abound in the

• literature. Utilization of Hg(II) salts in the intramolecular cationic cyclization of olefinic, acetylenic, and allenic substrates having aromatic rings, nucleophiles, and heteroatoms in the neighborhood were well documented. Hg(II) reagents were also often employed in the important cyclization step during

• ). Cyclization involving catalytic Hg(II) salts Cyclization involving alkenes (>C=C<) Apart from the stoichiometric amount used in cyclization, there is abundant literature where a catalytic amount of Hg(II) salt was employed for cyclization reactions between nucleophiles and unsaturated bonds. The synthesis of

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• recently as precursors in Friedel–Crafts reactions of arenes [30][31] and cross-coupling reactions of arylboronic reagents [32]. However, the direct SN1 reaction of such isatin-derived 3-phosphate-substituted oxindoles by halide ions as nucleophiles has not been developed yet and remains an unsolved

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

• obtain the dihydroisoquinolines 22 in good yields and enantioselectivities up to 92% ee. The Takemoto group with their system also achieved yields up to 78% and enantioselectivities up to 97% ee, using phenyl chloroformate as the acylating reagent and vinylboronic acids as the nucleophiles 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

• anion-binding catalysis has been successfully demonstrated for other halogens, and different types of substrates such as the benzhydryl cation [48][49][50][51]. Halides as counter-anions vs nucleophiles The latest advances in anion-binding catalysis not only allowed for excellent translation of