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

• detected as a side reaction via mass spectrometry. Vinyl alcohols were also studied, giving carvone (4v) in 74% yield without oxidation of the double bonds. Finally, other heterocyclic benzylic alcohols were investigated, which led to undesired chlorinations in the case of benzimidazoles 3w and 3x and

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

• symmetrical monosubstituted derivatives, or di- or trisubstituted symmetrical or asymmetrical derivatives. The C3 symmetry of 1,3,5-triazine makes it a popular heterocyclic core for the synthesis of star-shaped molecules [43][44][45], which was being used to the construction of triangular molecules, including

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• . These results were used to generate a 271-Mln. readily accessible (REAL) heterocyclic chemical space mostly containing unique chemotypes, which was confirmed by comparative analysis with commercially available compound collections. Meanwhile, this chemical space contained 432 compounds that already

• the corresponding library members were denoted as 4{i,j,k}. Results and Discussion Library synthesis Preliminary experiments on the parallel GBB reaction were performed with heterocyclic amines 1{1–430}, aldehydes 2{1–583}, and isonitriles 3{1–73} available from our stock (based on our previous in

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

• readily converted into a myriad of functional groups including carbonyls, amines, imines, and a variety of heterocyclic scaffolds with well-established procedures [4][5][6][7][8][9]. In particular, tertiary nitriles are common structural motifs in many bioactive compounds and are widely used as

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• ; thiocyanation; thiocyanogen chloride; Introduction Pyrazoles and their derivatives are an important class of five-membered heterocyclic compounds [1][2][3][4][5] that have drawn increasing attention from organic chemists, due to their potential biological and pharmaceutical properties including anti

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

• generated by addition reaction of isocyanides to electron-deficient alkynes, which were sequentially trapped by various electrophiles and nucleophiles to give versatile acyclic and heterocyclic compounds [15][16][17][18][19][20][21][22][23][24][25][26]. In recent years, many multicomponent reactions based

• on alkyl isocyanides, electron-deficient alkynes and other reagents have been successfully developed for the synthesis of various carbocyclic and heterocyclic compounds [27][28][29][30][31][32][33][34][35]. The 5,6-unsubstituted 1,4-dihydropyridine is one of special kinds of 1,4-dihydropyridines. It

• synthetic protocols and in continuation of our aim to develop isocyanide-based multicomponent reactions for construction of diverse nitrogen-containing heterocyclic compounds [47][48][49][50][51][52][53][54][55][56][57][58], herein we wish to report the mutlicomponent reaction of alkyl isocyanides, dialkyl

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• Abstract A new class of heterocyclic N,O-aminal and hemiaminal scaffolds was successfully obtained by means of a three-component reaction (3-CR) of 1,2-diaza-1,3-dienes (DDs), α-aminoacetals and iso(thio)cyanates. These stable imine surrogates are generated from key-substituted (thio)hydantoin

• intermediates through selective FeCl3-catalyzed intramolecular N-annulation. Keywords: α-aminoacetals; fused-ring systems; heterocyclic hemiaminals; heterocyclic N,O-aminals; multicomponent reactions; Introduction N-Fused heterocycles are ubiquitous within crucial molecules, including biologically active

• natural products, pharmaceuticals, and functional materials (Figure 1) [1][2][3]. It has been assessed that almost one-third of the best-selling therapeutics contains fused heterocyclic structures [4]. Among the N-heterocycles, imidazopyrazine structures [5][6], derived from amalgamation of privileged

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• ][2]. We are interested in feasible strategies to synthesize nitrogen-rich heterocyclic scaffolds that can extend the currently available libraries with new drug-like molecules. Our past work on pyrazoles [3][4][5][6] and triazoles [7][8][9][10][11] motivated us to search for suitable and versatile

• pyrazole–triazole hybrids: synthesis of azides 7 or 8 from amines and organohalides and subsequent CuAAC to larger heterocyclic systems 9 or non-substituted amine products 10; Sakai reaction of α-ketoacetal 11 for the synthesis of N-substituted derivative 13 [14][16][17][18][19]. Synthesis of pyrazolyl

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• reaction. AlCl3-mediated Cannizzaro disproportionation of aldehydes. Ru–N-heterocyclic carbene catalyzed dehydrogenative synthesis of carboxylic acids. Intramolecular desymmetrization of tetraethylene glycol. Desymmetrization of oligoethylene glycol dialdehydes. Intramolecular Cannizzaro reaction of calix

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• and provide the desired products with good yield. Cyclopentanol-derived oxalates, some heterocyclic oxalates, and natural-product-derived oxalates were also compatible with this method. In 2018, Chu and co-workers [47] devised an elegant protocol for achieving syn-alkylarylation of terminal alkynes

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• heterocyclic or aliphatic bromides scarcely proceeded. A Rh(III)–bis(aryl) complex, which might be formed from RhCl(PPh3)3 and the aryl Grignard reagents, plays an important role in giving the homo-coupling products in this reaction. Furthermore, we applied the reaction to the synthesis of a novel inhibitor

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• elaborated. The suggested approach can be applied to various aromatic and heterocyclic hydrazines. At the same time for unsubstituted hydrazine the Boulton–Katritzky recyclization is not implemented. In this case the opening of the pyranone ring was observed leading to pyrazolylisoxazole derivatives. Both

• types of aforementioned structures were proved by X-ray analysis. Keywords: allomaltol; Boulton–Katritzky rearrangement; hydrazones; pyrano[2,3-d]isoxazolones; recyclization; 1,2,3-triazoles; Introduction The Boulton–Katritzky rearrangement (BKR) also known as mononuclear heterocyclic rearrangement is

• ionic liquids [8][9]. Also, thermal and photochemical variants of studied recyclization are known in the literature [10][11]. Besides that, an unusual procedure for Boulton–Katritzky reaction including the use of surfactants is suggested by Fontana and co-workers [12]. Other heterocyclic systems capable

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• reactions. In this study, we revisit the design of the phenotellurazine redox catalysts. In particular, we investigate the level of cooperativity between the Te- and N-centers, the effect of secondary versus tertiary N-centers, the effect of heterocyclic versus non-heterocyclic structures, and the effect of

• of secondary versus tertiary N-centers, the effect of heterocyclic versus non-heterocyclic structures, and the effect of various substitution patterns. Results and Discussion With this aim in mind, we thus started investigating Te(II) redox catalyst candidates that do not necessarily carry a N-atom

• investigate and optimize their redox contribution within the Te(II) catalysts. Multiple synthetic efforts were therefore deployed in order to access several key Te(II) targets, both with and without N-functional groups, in heterocyclic as well as in non-heterocyclic fashion. These were then investigated in

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• heterocyclic compounds [20][21][22]. Particularly dialkyl bromoketones have been utilized in natural product synthesis [23][24][25], also as a precursor to reactive oxyallyl cation intermediates [26][27][28], and for their photochemical reactions [29]. However, the direct halogenation of unsymmetrical ketones

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• , we studied also cyclization reactions of chromones with heterocyclic enamines [30][31]. The present review aims to provide a personalized account of our work related to domino reactions of various types of chromones with carbonyl compounds, such as 3 and 4, and with 1,3-bis(silyloxy)-1,3-butadienes

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• -acetamide carboxamide oxindole hybrids 5 was obtained in moderate yields (26–63%), at room temperature, in short time (2 hours), proving the efficiency and the generality of this methodology. Aliphatic (2a, 2c and 2m), aromatic (2d, 2f, 2g, 2k and 2l), heterocyclic (2e, 2h, 2i, 2n and 2o), alkyne 2b and

• alkene 2j carboxylic acids were used successfully in this MCR, demonstrating a great reaction scope (Scheme 2 and Figure 2). Remarkably, the best yields were obtained when heterocyclic carboxylic acid components like 1H-pyrrole-3-carboxylic acid (2n), 2-furoic acid (2o) and 5-nitrofuran-2-carboxylic acid

• the 3-protected oxindole counterparts 5 and 7, in moderate to good yields (Scheme 4). The best yield was obtained when 3-protected oxindole derivatives 5 possess an aromatic or heterocyclic unit substituted in the 5-amide position of the oxindole ring. Compounds 8c, 8d, 8e and 8m were obtained in 83

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• heterocyclic alcohols were tested and showed good functional group tolerances. However, ester and nitrile-substituted ketones were not alkylated with this protocol. The proposed mechanism showed that the Mn(CO)5Br reacted with ligand L3 to generate the active complex Mn-L3-I in the presence of a base. The

• mechanism suggested that dearomatization–aromatization pathways operated for the dehydrogenation of the alcohol and C–C bond formations. After the successful attempt of bidentate N-heterocyclic carbene-manganese complex-catalyzed N-alkylation of amines with alcohols at room temperature [41], Liu and Ke's

• group planned the α-alkylation of ketones using alcohols as an alkylating agent [64]. A number of substituted aromatic and heterocyclic ketones with different alcohols were tested and gave good to excellent yields (38–96%) using 4 mol % of Mn6 and 50 mol % of NaOH in toluene at 110 °C for 2 h (Scheme 33

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• Figure 1. A number of isoxazolo[4,5-b]pyridines has been described in patents, however, there are only a few methods for their synthesis reported in the literature. First representatives of this heterocyclic system were described by Gewald et al. in 1980 [14]. The known methods are usually based on

• -oriented heterocyclic systems. Some examples of biologically active isoxazolo[4,5-b]pyridines with antibacterial [8], anticancer [12] and cytotoxic [10][13] acitivities. Biologically active analogs of compounds 13. X-ray crystal structures of compounds 12c (top left; the second crystallographically unique

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• the beginning of the pandemic, a variety of heterocyclic small molecules – either of natural or synthetic origin – was reported as promising inhibitors of the SARS-CoV-2 RdRp [13][14][15]. However, compounds with a sufficient combination of high potency and suitable pharmacokinetic properties are

• . We focused on the modification of the central heterocyclic core and on the simplification and truncation of the relatively large molecule 1 (Figure 1). In this work, replacing the sulfur atom with a (bio)isosteric oxygen atom yielded two novel structural analogues, whilst our effort towards more

• , led to two crucial mesoionic compounds, 22 and 27. The recrystallized intermediates then underwent a formal cycloaddition with ethyl acrylate, followed by the elimination of H2S, forming the desired heterocyclic core structures (intermediates 23 and 28, respectively). A subsequent saponification step

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• practical, direct approach for the synthesis of aryl(TMP)iodonium(III) carboxylates, utilizing readily accessible iodosoarenes or (diacetoxyiodo)arenes as starting materials in a fluoroalcohol solvent (Scheme 2C). This protocol allows for the synthesis of electron-rich, electron-poor, heterocyclic, and

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• the synthesis of high-value compounds. Given the great importance of heterocyclic compounds, the carbonylative approach has become increasingly important for their synthesis. In this mini-review, as a class of benzo-fused nitrogen-containing heterocyclic compounds, we summarized and discussed the

• recent achievements on the synthesis and functionalization of indole derivatives via carbonylative approaches. Keywords: carbonylation; functionalization; indole; metal catalyst; organometallic chemistry; Introduction Indole is a heterocyclic compound consisting of a benzene ring fused with a pyrrole

• complexes are important for the synthesis of heterocyclic and non-heterocyclic compounds. In 2009, Arthuis and co-workers developed a new process for the synthesis of 2-aroylindoles and 2-heteroaroylindoles by a one-pot palladium-catalyzed domino reaction that involves an initial C,N-coupling followed by

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• moderate to good yields, mainly lower yields were obtained with β-cyanoethyl isocyanide (e.g., 3g). In addition, good substrate tolerance was also achieved for the acid component with both aliphatic, aromatic, and heterocyclic acids. The excellent overall performance of these tetrazole-aldehyde building

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• Chemistry and Center for Green Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA 10.3762/bjoc.20.81 Abstract A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide

• -tetrazoles (1,5-DS-1H-Ts) B. The performance of post-condensation reactions of UA-4CR adducts has resulted in various 1,5-DS-1H-Ts containing heterocyclic compounds [28][29][30][31][32], such as bis-heterocyclic lactam-tetrazoles [33][34], 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines [35

• ], ketopiperazinetetrazoles [36], imidazotetrazolodiazepinones [37], tetracyclic tetrazolylpyridoimidazoquinolines [38], bis-heterocyclic 1,5-disubstituted tetrazoleindolizines [39] and (E)-12-tetrazolyl-5H-quinazolino[3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• was also employed for the synthesis of 1,2,4-BCHs [35]. Heterocycle-substituted BCHs were accessed by [2π + 2σ] photocycloaddition by Glorius and co-workers [79] and Houk, Glorius and co-workers [80]. This reactivity was enabled by triplet energy transfer catalysis activating the heterocyclic

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• have been employed in benzocyclization and arylocyclization reactions, enabling intramolecular cyclization by forming aromatic or heterocyclic rings as a part of cyclic structures [8]. In these reactions, the dual activation of a C–I bond and vicinal C–H bonds/functional groups features a distinct