Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• , our methodology involves a biphasic reaction medium where the starting material, viz. arylidenemalonate, remains in the organic layer and prevents itself from undergoing saponification because it requires either aqueous or alcoholic (MeOH or EtOH) medium. Furthermore, deprotonation of curcumin

• methodology (Table 2). At first, various arylidenemalonates 2 were tested with a phenyl analog of curcumin 1. The reaction of 1a with arylidene malonates 2a–c, bearing weakly electron-withdrawing para-substituents, produced the corresponding double Michael adducts 3a–c, respectively, in good to high yields

• [26][29]. In order to demonstrate the synthetic utility of our methodology, we performed a scale-up reaction with representative starting materials, viz. 1a and 2b on a 1.0 mmol scale (Scheme 3). The reaction required slightly more time and resulted in the corresponding double and triple Michael

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• substituents on the aromatic moiety regardless of their electronic properties. However, 4,5-disubstituted 1,2,3-thiadiazoles could not be accessed with this methodology. Mechanistically, control experiments with radical trapping agent such as TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) or 1,1

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• to their populations [25]. The calculated specific rotations −11.4 and +16.1 were obtained for R-configured 2 and 3 from the DFT computations (see DFT methodology section), respectively, which were in good agreement with the experimentally obtained values, −6.1 for 2 and +15 for 3. Thus, R

• monitored by TLC. The solution was diluted with water and extracted with EtOAc three times. The organic layer was washed with brine and evaporated to dryness to afford bismethylated derivative of 1 (1a, 1.9 mg, 88% yield). DFT methodology Prior to the calculations of the molecular properties of compounds 2

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• Supporting Information File 1). We decided to explore the potential of this methodology for the formation of α-heteroarylacetates. In particular, we were curious to see whether this methodology translates well for five-membered heteroarene substrates (e.g., thiazoles, pyrazoles, imidazoles) which are usually

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• efficient synthesis of isoquinolinone derivatives using a PISA-mediated methodology that chemoselectively yielded 3- or 4-substituted isoquinolinone derivatives by simply adjusting the solvent. When acetonitrile was used, the 4-substituted isoquinolinone derivatives were the reaction products, whereas

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

• synthesis (DOS) where a single methodology should generate diverse scaffolds. This comprehensive review focuses on all these aspects, and has been divided into five chapters, describing, respectively: a) efforts to develop new and milder reaction conditions; b) the use of new building blocks; c) the

• -aminoimidazole moiety can be found in different alkaloids isolated from sponges and exhibits useful bioactive properties. The methodology employed by the authors to assemble C4/C5-functionalized 2-aminoimidazoles 49 exploited a Mannich condensation followed by an iodoxybenzoic acid (IBX) and N-iodophthalimide

• found to be compatible to the reaction conditions and a gram-scale synthesis was carried out to demonstrate the versatility of this methodology. 3.3 Post functionalization of GBB adducts The structural complexity of the original scaffolds of the GBB adducts can be increased by decorating the structure

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

• Discussion Regarding the synthesis of 5-aryldeazaalloxazines 2 (5-arylpyrimido[4,5-b]quinoline-2,4(1H,3H)-diones), the data in the literature are quite limited, and the known methodology describes the dehydrogenation of initially formed 5,10-dihydro analogues (5-aryl-5,10-dihydropyrimido[4,5-b]quinoline-2,4

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• properties against S. epidermidis and P. aeruginosa resistant strains and failed to exhibit the same effects against E. coli and C. difficile. As a result, we present the discovery of two new lantibiotics that have demonstrated efficacy in combating both Gram-positive and Gram-negative pathogens. Methodology

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• methodology has several drawbacks, as the need to synthesise the 2-azidobenzoic acid from anthranilic acid and sodium azide, the requirement of anhydrous conditions to perform the Staudinger/aza-Wittig sequence or the generation of large quantities of triphenylphosphine oxide which needs to be removed by

• [29], through post-condensation reactions. Following the methodology previously described in our group [30], the reduction of the nitro group on indole and pyrrole derivatives 9f,g,l–o (Scheme 9, Table 5) employing tin(II) chloride under acidic conditions in boiling n-butanol (120 °C) afforded the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• phosphine-based ligand (L). This methodology was applied to the alkynol moiety of ethinylestradiol (8) (86% yield), and alkynols derived from ethisterone, levonorgestrel, lynestrenol, and epiandrosterone (epi-ADT), obtaining excellent yields (85–93%) and high diastereoselectivity (dr > 20:1) in all cases. α

• /mL. Since the cytotoxicity of the parent 16-arylidene steroids was LC50 > 100 µg/mL, it was concluded that the presence of the pyrrolidine moiety was essential for the activity [28]. Additional derivatives have been reported on different steroidal positions [29] or with variations in the methodology

• yields in all cases (Scheme 25). The same methodology was applied to prepare spiro 1,3-thiazolidin-4-one 89, at the C-3 steroidal position from cholest-5-en-3-one (87), yielding an overall yield of 55%. The stereochemical information regarding the new chiral carbons was not provided in any instance. The

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

• combination with an ML model to predict a variety of properties. These properties encompass the site of metabolism [31][33], the strengths of hydrogen bond donors and acceptors [34][35][36], and the regioselectivity of electrophilic aromatic substitution reactions [14]. Building on the methodology from

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

• subsequently attack electrophilic Selectfluor to afford the benzyl fluoride (Figure 2) [34]. The methodology was demonstrated on eight para-substituted benzylic substrates. The authors noted that resubjecting the monofluorinated compound 1 to the same reaction conditions afforded the difluorinated compound 2

• in good yield. The requirement of adjacent to nitro or nitrile groups limits the scope of this approach. Furthermore, the use of strong bases, particularly n-BuLi, prevents the application of this methodology on any substrate bearing sensitive functional groups. An analogous method for

• ; however, the methodology was only shown on secondary benzylic positions. The stereoselective benzylic monofluorination of α-amino acids was also reported by Yu and co-workers, employing a similar directing group strategy (Figure 7) [41]. The use of the monodentate directing group 2,3,5,6-tetrafluoro-4

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

• plausible mechanistic understanding at hand, we next investigated the application scope and limitations of this methodology. As outlined in Scheme 3, a series of differently substituted α-azido-β-ketoesters 2 as well as analogous α-azido-β-ketoketones 5 and the α-azido-β-ketoamide 6 could be accessed

• straightforwardly. Furthermore, this procedure was also successfully extended to γ-butyrolactone-based products 7. Unfortunately, this methodology came to its limits when using tetralone-based β-ketoesters like compound 8, which resulted in a complex product mixture, or the acylic β-ketoester 9, which did not show

• any conversion under these conditions. The later limitation shows a clear difference between our methodology and Uyanik’s and Ishihara’s protocol [31], underscoring the higher reactivity of their designer catalyst (Scheme 1B). Having established the TBAI/DBPO-mediated α-azidation using NaN3, we also

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

• the o,o’-bis-substituted derivative failed. For the β-S-galactosyl azobenzene derivatives which are accessible by our previously reported Pd-catalyzed cross-coupling methodology between glycosyl thiols and iodoaryl partners [30][38], the required p-, m- or o-iodo-p’-hydroxyazobenzenes 12, 17, and 21

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

• full conversion of 2a under the standard reactions, 1.0 equiv of each substrate was added synchronously. After running 5 times, 65% yield was obtained within a total reaction time of 60 h. Finally, we explored the synthetic versatility of the products in this methodology. Debenzylation of product 4aa

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

• selectfluor and a carbocation is formed by bonding with fluorine. Subsequently, fluoroalkoxy compound 4 is formed by Wagner–Meerwein rearrangement followed by alcohol addition and deprotonation. Conclusion New bicyclic fluoroalkoxy compounds were synthesized by a molecular fluorine and metal-free methodology

• distinct advantageous such as (i) the methodology does not require the presence of any metal moities, (ii) enables the synthesis of corresponding oxyfluorinated analogues with high yields and selectivity, (iii) allows derivatization of natural chiral molecules, (iv) uses a safe solvent in mild reaction

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

• , Yotphan and colleagues realized a direct thiocyanation of N-substituted pyrazolones under metal-free conditions [49]. Besides, Choudhury and co-workers developed an additive and metal-free methodology for the C–H thiocyanation of aminopyrazoles, using H2O2 as a benign oxidizing agent (Scheme 1b) [41]. Pan

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

• the triazole unit via a copper-catalyzed azide–alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty new multi-substituted pyrazole–triazole hybrids. We also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In

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

• oxidation of the aryl methyl ketones 5 to the corresponding aryl glyoxal with concomitant rearrangement of the aryl glyoxal to the target α-hydroxycarboxylic acid derivatives 6, catalyzed by Yb(OTf)3. The simple process reflects the generality of the methodology with yields ranging from 78–99% as

• ]. The methodology afforded smooth transformation of aromatic aldehydes 16 to the corresponding alcohols 17 and carboxylic acids 18 in good yields (>80%). They also extended the methodology to dialdehydes such as phenylglyoxal (7a) and phthalaldehyde (16m), achieving an intramolecular version of the

• (R1 and R2) were obtained in good to excellent yields witnessing the feasibility of the methodology (Scheme 25). The mechanism depicting the proposed strategy for the Cannizzaro-aldol transformation involves an initial Cannizzaro reaction between paraformaldehyde and the isatin substrate, followed by

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

• relevance. In 2022, Yu et al. [29] showcased a very mild procedure for the effective synthesis of α,α′-diarylated ketones (Scheme 2). Compared to previous procedures, this methodology was a significant improvement as it did not require an excessive amount of additives or high temperature. The methodology

• , Wang and co-workers [30] demonstrated the photomediated synthesis of γ,γ-difluoroallylic ketones by reacting trifluoromethyl alkenes and acids in the presence of PPh3 additive and iridium photocatalyst in basic medium (Scheme 3). This methodology was suitable for a wide range of carboxylic acids in the

• hydroacylation of azobenzenes employing acids as hydroacylating reagents (Scheme 4). The reaction progressed smoothly, involving the cleavage of the C–O bond using a photogenerated phosphoranyl radical. The methodology demonstrated an excellent compatibility with a wide range of azobenzenes and carboxylic acids

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

• and Discussion Methodology development In our work towards Rh-catalyzed homo-coupling reactions of benzyl halides, we observed that a similar rhodium–bis(benzyl) complex can also be formed from benzyl halide by using a Grignard reagent instead R2Zn in the presence of RhCl(PPh3)3 to subsequently give

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• 2.5 mol % or switching to more simple Pd(PPh3)4 still achieved quantitative yields. Less catalyst led to a reduced yield (Table 1). Consequently, we chose 2.5 mol % Pd(PPh3)4 for all further reactions. As a next step, we analysed the scope of our methodology (Scheme 2). The optimized conditions allow

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

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• Figure 1 [5]. Diederich and co-workers developed a general methodology using tether-directed remote functionalization for the regioselective formation of multiple adducts of fullerenes [6]. In our earlier reports, the reactions of C60 and C70, with silylene Dip2Si (1, Dip = 2,6-diisopropylphenyl), a

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

• reactions via hydrogen auto-transfer, emphasizing the importance of this methodology and manganese catalysts in sustainable synthesis strategies. Keywords: alcohols; alkylation; amines; borrowing hydrogen; hydrogen auto-transfer; manganese; Introduction The construction of C–C and C–N bonds is of utmost

• team introduced a manganese(III) porphyrin system as a catalyst for the BH methodology to achieve C–N coupling reactions [43]. Various tertiary amines were isolated by coupling secondary amines and benzylic alcohols using Mn7 (3 mol %) in the presence of K2CO3 (20 mol %) under reflux conditions in

• aldehydes, leading to the corresponding imine intermediate, which again undergoes hydrogenation by Mn9-c and yield the N-alkylated product and the regeneration of complex Mn9-a (Scheme 20). Very recently, Bühl and Kumar reported a novel and efficient methodology for the synthesis of branched