Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• used as substrate, selective C–O bond cleavage, followed by fixation of carbon dioxide, occurred at the benzylic C(sp3)–O bond rather than the C(sp2)–O bond on the phenyl ring to give the corresponding diphenylacetic acid 2h in 45% yield. Not only a secondary alcohol but also a tertiary alcohol was

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• directly to the unprotected chiral (S,Z)-homoallylic amines 38 in high yields and with an excellent retention of the enantiopurity (Scheme 8B). The method remains the only direct Z-selective crotylation to attain enantioenriched unprotected homoallylic amines, and the only example of an effective kinetic

• boroxine with dramatically increased reactivity towards C=N electrophiles. Because of the small steric size of the (BO2) group, the reaction is highly selective towards (E)-α-trifluoromethyl homoallylic amine 44, which otherwise is difficult to obtain in a regiospecific manner. It has to be noted though

• . Optimisation of the catalysts structure revealed that the 3-phenanthrylpyrrolidine derivative provided superior yields and selectivities. Notably, the isomeric 9-phenanthrylpyrrolidines remained selective but gave noticeably lower yields. The methyl group, geminal to the phenanthryl, plays an important part in

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• , the linkers were proposed and designed to mainly facilitate the enrichment of the probe–protein or probe–peptide conjugates and their selective release after enrichment. In this review we would like to highlight the fragmentation properties of the different linkers and resulting ions as the valuable

• synthesis. The higher-energy collisional dissociation (HCD) releases the characteristic reporter ion at m/z 126.1277. In case the electron-transfer dissociation (ETD) is used the DMP-tag yields the reporter ion at m/z 114.1275. Of note, although ETD is more selective towards fragmentation of the peptide

• -down of the probe-modified proteins [94]. The biotin-containing linker is introduced into the probe–protein conjugate via a selective bioorthogonal reaction. The main advantage of the biotin-based linkers is the possibility to apply stringent wash steps, due to the almost irreversible non-covalent

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• . However, careful consideration has to be paid towards combining different reactions, as mechanistic transferability has to be ensured. Furthermore, the usage of ML to identify general catalysts demonstrate that the application of modern ML tools is not limited to predicting selective catalysts. 4 ML for

• substituent and the substrate is key for stereoinduction, they designed new catalyst structures maximising the predicted selectivity. The predictions were experimentally validated confirming that their model can be used to guide the design of highly selective catalysts (Figure 15B). 4.2 High-throughput

• screening approaches [107][144][145][146][147]. Thereby, experimental efforts can be focused on the most promising candidates predicted by the model. Denmark and co-workers utilised such an approach to design highly selective catalysts for a peptide-catalysed annulation reaction [68]. Using conformer

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• selective deuteration of often metabolically soft benzylic C–H sites. Lastly and most importantly, preliminary surrogate metabolic stability studies on site selective [D1]-DHPs suggest these novel deuterated analogs may afford increased exposure in an in vivo setting. The methodology is likely to have wide

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• Haifeng Yu Wanting Zhang Xuejing Cui Zida Liu Xifu Zhang Xiaobo Zhao College of Chemistry, Baicheng Normal University, Baicheng, Jilin 137000, China 10.3762/bjoc.20.190 Abstract An eco-friendly selective hydrolysis of chain α-oxo ketene N,S-acetals in water for the switchable synthesis of β-keto

• dithioacetals and nitroethane/amines [72][73]. As part of our continuous research in this context, more recently we investigated the selective hydrolysis of α-oxo ketene N,S-acetals in water to gain an environmentally compliant synthetic method for β-keto thioesters and β-keto amides (Scheme 1c). Herein, we

• report our findings. Results and Discussion At the outset of our studies, to optimize the reaction conditions for the selective synthesis of β-keto thioesters and β-keto amides, we explored the hydrolysis reaction of (E)-3-(ethylthio)-1-phenyl-3-(phenylamino)prop-2-en-1-one (1a, 0.25 mmol, 70.8 mg) in

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• aggregation, attracting interest for the treatment of Alzheimer’s disease [240], was a selective agonist of the farnesoid X receptor FXR (EC50: 3.2 µM) [241], and displayed remarkable neuroprotective effects against oxidative injuries by acting as potent activator of nuclear factor erythroid-derived 2-like 2

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• ]. An advantage of dendrimer-supported organocatalysts are their enzyme-like properties [111][112]. Selective binding and cooperative catalysis can give the catalyst high selectivity and activity. Interactions between the support and other components The interaction between the solid support and the

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• ] because isocyanide is susceptible to multiple imidoylation [9][10][11], whereas carbon monoxide is less susceptible to multiple carbonylation. Therefore, precise control of the reaction is required for selective formation of the monoimidoylation product. Regarding the radical reaction of isocyanides, the

• imine 6’ (96%), which underwent [2 + 2] cycloaddition with methoxyketene to afford β-lactam derivative 7 (79%) (Scheme 4). Selective replacement of the PhSe group of 7 with a 3-butanonyl group (34%) and the subsequent intramolecular Horner–Emmons reaction successfully led to carbacephem skeleton 8 (96

• hope that this Perspective will help in the development of such new reactions. Resonance structures and reactivity of carbon monoxide. Resonance structures and reactivity of isocyanides. Possible three pathways of the E• formation for imidoylation. Radical addition of thiols to isocyanides. Selective

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

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

• treatment of Alzheimer's disease [3][4]. Likewise, RL91 and BHMPC are active for selective cell growth inhibition of the resistant lines (Figure 1) [5][6]. Their synthesis mainly involves a cascade Michael–aldol reaction between enones and suitable Michael donors such as β-ketosulfones, β-diketones, or

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

• , copolymerized β-alkylpyrroles are among the most investigated organic materials for their enhanced physical and electrochemical properties [4][5]. Accordingly, chemists have focused on developing selective synthetic strategies for the construction of β-alkylpyrroles [1]. While the pyrrole nucleus is featured in

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• through denitrogenation of AIBN, is closer to the HOMO level of Ni(II) norcorrole 1 (−4.68 eV) rather than its LUMO (−3.16 eV). This result explains the selective addition of the electrophilic isobutyronitrile radical to the distal α-position of the pyrrole unit. The calculated molecular orbital

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• . Furthermore, the reaction with 4-(acetylamino)benzenethiol led to the selective formation of the disubstituted compound 3c in 53% yield. Phenols are less nucleophilic than thiols and, depending on the substitution pattern, a stronger base is often required to generate the corresponding alkoxide, which is the

• the protons of the N–CH2C6F5 and N–CH2C6F4XR groups, respectively. All 19F NMR spectra confirmed the selective substitution of the 4-fluorine atoms (in one or in two rings) by the disappearance of the signal corresponding to the resonance of those atoms. Mass spectra of compounds 3a–f, 4a, 4d and 4f

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• diphenylamines yielding N,N-diarylbenzidines and N,N-diaryldihydrophenazines were reported in [21]. By varying the reaction conditions and additional substituents in the phenyl rings, a possibility for the selective oxidation of ortho-(2-pyridyl)diphenylamine to the corresponding nitroxide, as well as the

• the post-electrolysis mixture. Instead, a complex mixture of products was obtained. It looks as if the oxidation is non-selective; not a single reaction path dominates. This is typical for diarylamines containing electron-withdrawing substituents in both rings; commonly, electrochemical oxidation

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

• De Esch et al. [55] and by Kazuta el al. [56]. The primary aim was the design of a new class of highly H3-selective agonists lacking H4 affinity by restricting the flexibility of the aminoethyl chain. Previous structure–activity exercises demonstrated an impact on selectivity upon introducing a

• studies. Thiazoles: 2-Thiazolylethylamine was characterized as a more selective and potent histamine H1 agonist [70]. Based on this, Govoni et al. [71] analyzed the pharmacological profile of several histamine H1 antagonists, with a section covering thiazole-based compounds. 2-(Thiazol-4-yl)ethylamine (99

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

• compatibility of the GBB reaction with typical KTGS conditions, such as aqueous solvent at near-physiological pH and high dilution, and the achievement of selective ligand amplification. First, molecular modeling studies were carried out to verify that building blocks and intermediates could bind the target

• cyclophanyl-imidazole-based library of ligands. The synthesis of ligands based on the [2.2]paracyclophane (PCP) moiety, thanks to its structural features and inherent planar chirality upon selective substitution, has been recently reviewed by the same author [46]. Starting from 4-formylcyclophane 37, a GBB

• multistep procedure, however, by employing 3,6-diamino-1,2,4-triazin-5-one 44 as amidine derivative, 46 could be simply obtained through a GBB-3CR. The amino group in position 3 was opportunely protected to drive the GBB reaction to the selective formation of 45. Microwave heating appeared to be beneficial

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

• . Lanthipeptide biosynthetic genes have undergone complex evolutionary processes that have produced chemically diverse active peptides [11][12]. These genes are predominantly found in bacteria and have evolved through selective pressures driven by competition for resources and defense against predators [13]. The

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• to be overoxidized and provided only traces of multiple products. Some overoxidation of 4d was observed as 12-methoxychrysene-5,6-dione (10), but the alternative product chrysene-6,12-dione was not formed. In contrast to the ortho-selective oxidations of PAPs with SIBX [18], the electrochemical

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

• the future design of more potent and selective drugs. Keywords: biological activity; drug development; heterocycle; spiro steroid; synthetic transformations; Introduction Small-ring heterocycles constitute valuable scaffolds in medicinal chemistry for generating biologically active derivatives

• cyclopamine. Comparing the biological results of the compound with the activity of desmethylveramiline (a des-E analogue of cyclopamine) has suggested that the rigidity of the oxetane ring is crucial for the potency of compound 7 [12]. Spiro-β-lactone steroids Beller et al. reported a selective method for

• 9763), displaying selective antifungal activity akin to nystatin, alongside with low cytotoxicity on cancer cell lines (HeLa, MDA-MB-453, and MDA-MB-361). Additionally, they exhibited robust activity against leukemia K562 cells [51]. Spiro-1,2,4-triazolidin-3-one steroids Sharma et al. developed a

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

• toward developing a chemo-enzymatic synthetic process. Presumably, the reactive iron(IV)-oxo species in dioxygenase BscD abstracts an allylic hydrogen at C1 and generates intermediate A. Subsequent α-face-selective hydroxylation of the resulting allylic radical at the C3 position would yield brassicicene

• skeletal rearrangement, providing the distinct skeleton of 11 via carbocation C. This rearrangement involves the preferential migration of an alkenyl group in C to the carbocation, followed by deprotonation at C18 to form an exo-olefin. β-face-selective hydroxylation at C12 in 11 by the P450 enzyme BscG

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

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

• established in several oxidative transformations including the synthesis of complex molecules and drugs [12][13]. The most prominent examples are the pentavalent derivatives 2-iodoxybenzoic acid (IBX) and Dess–Martin periodinane (DMP) [14][15]. Although mild and selective oxidants, these highly oxidized λ5

• the corresponding carboxylic acids [16]. Additives such as bromide salts or Al2O3 can eliminate this problem and allow selective oxidation to some extent [17][18][19][20]. During the past years, N-heterocycle-stabilized iodanes (NHIs) were demonstrated as suitable tools for various applications among

• iodanes (NHIs) as effective λ3-iodane oxidants for the selective synthesis of ketones and aldehydes, avoiding overoxidation to carboxylic acids. The developed protocols proved particularly effective for benzylic alcohols, yielding good to excellent results. The beneficial role of chloride salt additives

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

• bond to create new connections has attracted increasing interest [1]. While past methods allowed for C–H transformations in simple molecules, recent synthetic protocols [2] enable selective C–H activation and diversification in larger molecules. This has, for example, attracted the pharmaceutical

• pharmaceutical intermediates that undergo selective borylation to compare our QM workflow and ML model with experimentally determined reaction sites. The quantum chemistry-based workflow Following work by Ree et al. [12][13][14][15], we present a fully automated QM-based workflow for computing C–H pKa values. A

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• straightforward conditions (Scheme 1). The synthesis of aryl halides is of great academic and industrial importance. Recently, our research group has developed a new procedure for the ortho-selective chlorination of phenols under mild conditions in a short reaction time [26]. The chlorinating species was