2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• Carlos Nieto Alejandro Manchado Angel Garcia-Gonzalez David Diez Narciso M. Garrido Department of Organic Chemistry, Faculty of Chemical Sciences, University of Salamanca, Pl. Caídos, s/n, 37008 Salamanca, Spain 10.3762/bjoc.20.163 Abstract The concept of bioisostere replacement is of paramount

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• -free conditions. Although some new metal or Brønsted acid catalysts have been reported in the last few years, the main innovations can be found in the use of organic catalysts, enzymes, and compartmentations. A few reports on the in situ generation of reactants and on the reaction conducted under flow

• raised up to 83% when the reaction was heated in a MW oven at 150 °C [12]. With the optimized conditions, 22 GBB adducts were assembled with yields ranging from 42–93%. It is worth noting that the catalyst in this case was recovered and reused four times without appreciable loss of activity. 1.2 Organic

• conditions were tried in a GBB reaction, no cooperative effect was observed, but even a slight decrease in catalytic activity. The use of thiamine hydrochloride as organic catalyst was reported by Yamajala et al., who were able to obtain the GBB adduct depicted in Scheme 2 (3, R = t-Bu) in 97% under solvent

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• Ivana Weisheitelova Radek Cibulka Marek Sikorski Tetiana Pavlovska Department of Organic Chemistry, University of Chemistry and Technology, Prague, Czech Republic Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland 10.3762/bjoc.20.161 Abstract Functionalized 5-aryldeazaalloxazines

• 2, as demonstrated in our previous studies with 5-aryldeazaflavins 1 [14][15][16][17][18]. Multicomponent reactions (MCRs) remain a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery. By offering significant advantages over conventional, linear

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• from ligands for catalysts [2], through pharmaceuticals [3], to organic semiconductors [4][5]. Despite their fundamental and applicative importance to many fields, the vast chemical space of PASs has remained largely unexplored. As a result, the relationships between the arrangement and composition of

• molecules have been used in diverse settings, functioning as organic field effect transistors [10][11][12], light-emitting diodes [13][14][15], organic semiconductors [16][17], organic photovoltaics [1][18][19][20][21][22], photocatalysts [23], and biological agents for tracking or inhibition [24][25], and

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• ; post-Ugi transformation; pyrrole derivative; Ugi reaction; Introduction One of the keys to the development of mankind is the constant search for new substances and advanced materials. Today, we have powerful tools at our disposal that allow us to create entire libraries of structurally complex organic

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• described isomers and expand the toolbox of electron-deficient aromatic compounds available to organic materials chemists. Keywords: electron acceptors; organic materials; polycyclic aromatic hydrocarbons; Introduction Aromatic diimides are ubiquitous molecular scaffolds that have served as the basis for

• imides in organic electronic materials [15], the experimental observation of similar electron mobilities across different structural isomers of naphthalene and anthracene diimide [16] confirms the need to experimentally evaluate the unstudied isomers. We became interested in the cata- (i.e. 1,2,3,4

• organic thin-film transistors from heteroacenes. Inspired by these results, we sought to demonstrate the preparation of all-carbon scaffolds, i.e., acenes, that are cata-annulated with cyclic imides. Here, we communicate the successful synthesis of 1,2,3,4-NDIs and -ADIs and the characterization of their

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• synthesis; Introduction Naturally occurring organic compounds with potent biological activities continue to be compelling lead candidates for drug discovery, with advancements in their synthesis and supply techniques progressing rapidly. Of particular note is the progress made in the "chemo-enzymatic

• recombinant SorbC enantioselectively introduced a hydroxy group to generate the reactive intermediate (S)-34 [34]. Cyclohexadienone (S)-34 was relatively stable in aqueous reaction solvents, however, quenching the enzymatic reaction by the addition of organic solvents led to homo-dimerization. Based on these

• experimental results, Gulder and co-workers devised a strategy to control the dimerization modes by adjusting the polarity of the organic co-solvent to establish the divergent synthesis of dimeric scaffolds. Indeed, with 20% DMF in the SorbC-catalyzed enzymatic oxidative dearomatization, the Michael addition

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• Thomas J. Kuczmera Pim Puylaert Boris J. Nachtsheim Institute for Organic and Analytical Chemistry, University of Bremen, Bremen, Germany Institute for Inorganic Chemistry and Crystallography, University of Bremen, Bremen, Germany 10.3762/bjoc.20.149 Abstract We present N-heterocycle-stabilized

• )iodane is proposed as the reactive intermediate. Keywords: alcohol oxidation; hypervalent iodine; N-heterocycles; Introduction The oxidation of alcohols to aldehydes and ketones is an essential transformation in organic chemistry [1][2]. Generating aldehydes is particularly challenging as they are

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• strain; Introduction Identifying efficient methods for the preparation of densely functionalized molecules is one of the central goals of modern organic chemistry. In this context, application of strained molecules has garnered increasing attention due to their intrinsic reactivity [1][2]. However

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• reclassified as Saccharophagus degradans 2-40 [118]. Two additional GH18 chitinases, MtCh509 [50] and rChi1602 [79] were characterized from Microbulbifer thermotolerans DAU221 and Microbulbifer sp. BN3, respectively. MtCh509 was expressed in E. coli. Some organic solvents (benzene, DMSO, hexane, isoamyl

• macroalgae-derived Microbulbifer sp. YNDZ01 and expressed in E coli [88]. The recombinant enzyme Lip4346 showed high stability at high temperatures and in alkaline conditions, and tolerance to organic solvents. α-Amylases are glycoside hydrolases that catalyze the hydrolysis of internal α-1,4-O-glycosidic

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• structural properties of the membranes restrain their stability and durability, their humidity and temperature application conditions, and their efficiency and consequently, the performance of fuel cells or eletrolysers [18][19]. Many organic polymers with acidic functional groups have been developed as

• -triazine isomers [30]. There have been reported several and diverse applications to a large number of compounds with a triazine moiety, ranging from biological applications [31][32][33][34], such as fungicide, herbicide, antiviral, antimicrobial, antitumor, to their use in organic synthesis, including

• molecular cages [46][47] and at porous materials, as linkers in metal-organic frameworks (MOFs) [48], used in the evaluation of the cycloaddition of CO2 to epoxides [49] and CO2 uptake [50]. Taking in consideration the strategy of the incorporation of dopants to promote the proton conduction in Nafion

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• Rasmus M. Borup Nicolai Ree Jan H. Jensen Department of Chemistry, University of Copenhagen, Copenhagen, DK-2100, Denmark 10.3762/bjoc.20.144 Abstract Determining the pKa values of various C–H sites in organic molecules offers valuable insights for synthetic chemists in predicting reaction sites

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• moiety. The excellent photoswitchability in organic medium and the photoresponsiveness in aqueous medium, driven by visible light, were investigated by UV–vis absorption spectroscopy. The assembled supramolecular nanostructures were confirmed by electron microscopy, while the supramolecular packing was

• -responsiveness, and molecular functional tunability of synthetic supramolecular systems can be precisely controlled through the delicate design and synthesis of organic molecules [9][10][11][12][13][14]. Synthetic supramolecular systems can respond to various external stimuli, e.g., light, pH, organic solvents

• , ions, and heat [15][16][17][18][19][20][21][22]. Light enables noninvasive stimulation with high spatial and temporal precision to control structural transformations of supramolecular assemblies in organic and aqueous media [19][23][24][25]. Various photochromic and photoresponsive moieties, such as

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• pervade biochemistry in peptides and proteins. The chemical and biological properties of substituted pyrrolidine derivatives, along with many other compounds, hinge on the relative stereochemistry. It is well established that the presence of fluorine in an organic molecule can significantly influence the

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ; quinoline; Introduction Nitrogen-containing molecules are important bioactive compounds and intermediates in chemical synthesis. Therefore, the chemical transformations of nitrogen-containing compounds have been widely studied in the field of organic synthesis [1][2][3][4]. For instance, the reduction of

• for a supporting electrolyte, which is necessary for conventional organic electrolysis, reduces the environmental impact, and facilitates product purification. In addition, using nanoparticles in the catalyst layer, which serve as the electrode, results in a large specific surface area and efficient

• of 6a using an aqueous proton source instead of hydrogen. The use of DSE® as an anode and H2SO4 aq as an anolyte was effective, and 7a was obtained in 80% yield (Scheme 5b). Reduction of pyridines to piperidines As mentioned previously, reduction of pyridines to piperidines is important for organic

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• pervasive in organic synthesis and can also be used to efficiently fluorinate benzylic C(sp3)–H bonds. The general blueprint for this transformation follows a metal insertion into the C(sp3)–H bond followed by C–F reductive elimination [11][22][38]. In 2006, Sanford and co-workers published a seminal and

• disclosed the use of catalytic amounts of the organic dye Acr+-Mes under visible-light irradiation in combination with stoichiometric amounts of Selectfluor to achieve benzylic fluorination (Figure 29) [74]. It was proposed that a SET between Selectfluor and the photoexcited catalyst liberated fluoride and

• under the cell potentials required to initiate the first single-electron transfer, resulting in benzylic cation IV [89][90]. This species can then be captured by fluoride to give benzylic fluoride product V. HF·amine ionic liquids are a popular choice of fluoride source in organic electrochemistry as

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• Pooja Goyal Akhil K. Dubey Raghunath Chowdhury Amey Wadawale Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• Christopher Mairhofer David Naderer Mario Waser Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz, Austria 10.3762/bjoc.20.135 Abstract We herein report the oxidative α-azidation of carbonyl compounds by using NaN3 in the presence of dibenzoyl

• . Keywords: azidation; nitration; organocatalysis; oxidation; quaternary ammonium iodides; Introduction Organic compounds containing an azide functionality are highly valuable synthesis targets that offer considerable potential for various applications and further manipulations [1][2][3][4][5][6][7][8][9

• consequence, the synthesis of organic azides is an important task and it comes as no surprise that a variety of conceptually complementary strategies to install azide groups in organic molecules have been reported [1][2][3][4][5][6][7][8]. α-Azido carbonyl derivatives are especially interesting targets which

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• Behzad Nasiri Ghaffar Pasdar Paul Zebrowski Katharina Roser David Naderer Mario Waser Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz, Austria Department of Chemistry, Faculty of Science, University of Kurdistan, 66177-15175 Sanandaj, Kurdistan

• ; quaternary ammonium salt catalysis; Introduction The development of asymmetric synthesis routes to access non-natural amino acids has for decades been one of the most heavily investigated tasks in organic synthesis and catalysis-oriented research [1][2][3][4][5][6][7][8][9][10][11][12][13]. As a consequence

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• synthesis; electrophotocatalysis; radical decarboxylation; Introduction Alkylnitriles and their derivatives are widely found in pharmaceuticals and biologically active compounds [1][2][3]. In addition, within the field of synthetic organic chemistry, nitriles are synthetically useful handles that can be

• intermediates in organic synthesis for the construction of all-carbon-substituted quaternary centers (Figure 1A). However, conventional methods for the synthesis of tertiary alkylnitriles such as direct functionalization of alkylnitriles [10] and hydrocyanation of alkenes [11][12][13][14] are typically hindered

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• , neutralized with HCl (1 M), and extracted with EtOAc (3 times). The organic phase was washed with brine, dried over anhydrous Na2SO4, evaporated under reduced pressure in vacuo, and purified by CombiFlash Rf+ (CH2Cl2/MeOH 15:1). General procedure II for the Boc deprotection: To a solution of the Boc-protected

• iodinated azobenzene (1 equiv). After Ar flushing, dry THF (0.25 M) was added and the mixture stirred for 5 min before NEt3 (1.1 equiv) was added. The reaction mixture was stirred at rt under Ar for 6–8 h, diluted with EtOAc, filtered over celite, and washed with EtOAc. The collected organic layers were

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• substrates [7][8]. Pre-functionalized arenes are essential precusors in all of these general approaches. 2-Cyclohexenones are fundamental and versatile organic synthetic materials [9][10]. They have been applied as an ideal arylation platform to construct functionalized anilines via an amination

• ). However, carrying out the reaction under neat conditions rendered to dramatically dropped yield (Table 1, entry 9). It indicates that the involvement of conventional organic solvents into the reaction system seems to be critical for target transformation. Though the exact reason is not apparent now, we

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• . Keywords: alkoxyfluorine compounds; bicyclic alkene; oxyfluorination; selectfluor; Wagner–Meerwein rearrangement; Introduction Organofluorines are of great importance in the pharmaceutical and agrochemical industries, as the presence of fluorine has a serious effect on the biological activities of organic

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• Yingbo Shao Zhiyuan Ren Zhihui Han Li Chen Yao Li Xiao-Song Xue State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P. R. China Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry

• become staples in organic chemistry, the exploration of their isoelectronic counterparts, namely hypervalent bromine(III) and chlorine(III) reagents, has been relatively limited, partly due to challenges in synthesizing and stabilizing these compounds. In this study, we conduct a thorough examination of

• ; machine learning; Introduction Hypervalent iodine reagents are increasingly gaining attention in the fields of organic synthesis and catalysis due to their environmental benefits, accessibility, and cost-efficiency [1][2][3][4][5][6][7][8][9][10][11]. Over the last three decades, a series of cyclic

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

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

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• reaction with 5,6-unsubstituted 1,4-dihydropyridine. Keywords: [3 + 2] cycloaddition; cyclopenta-1,3-diene; cyclopenta[4,5]pyrrolo[2,3-b]pyridine; 1,4-dihydropyridine; electron-deficient alkyne; isocyanide; Introduction Isocyanide is a unique and attractive functional group in organic chemistry. The

• been known as indispensable building blocks in modern organic chemistry. Many isocyanide-based carbon–carbon and carbon–heteroatom bond forming reactions have been developed in fascinating ways over the past decades [4][5][6]. The famous multicomponent reactions such as Passerini reaction, Ugi reaction

• , Orru reaction and Van Leusen reaction, in which isocyanides were employed as key substrates have become the most powerful tools for rapid construction of various nitrogen-containing organic compounds [7][8][9][10][11][12][13][14]. On the other hand, the reactive Huisgen’ 1,4-dipoles can be in situ