Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• to explain the stereochemistry of the product of the IEDADA reaction, the Si face of the azadiene should be attacked by the enecarbamate with endo selectivity, thus leading to the (4S,5R,6R)-cycloadduct 46. In 2019, as a follow-up work of their previous work, Masson and co-workers published a

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• Jon Atiba Buldt Wang-Yeuk Kong Yannick Kraemer Masiel M. Belsuzarri Ansh Hiten Patel James C. Fettinger Dean J. Tantillo Cody Ross Pitts Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, U.S.A. 10.3762/bjoc.20.259 Abstract Selectivity in radical chain

• a single oligomer across a panoply of different transformations typically range from <1% to ≈30% when n > 1 is desired [35]. To the best of our knowledge, the assembly of functionalized [n]staffanes from 1 in high yield/selectivity and in one step via controlled radical oligomerization remains a

• chloropentafluorosulfanylated [2]staffane (SF5-BCP-BCP-Cl, 2), based on alternating radical polarity matching in the chain-propagation steps (Figure 1, bottom) [45][46][47]. Density functional theory (DFT) calculations provide insight into our observed selectivity, and our hypothesis is bolstered by computation of relative

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , we have collected and described the HVI-mediated halocyclisation reactions reported in the literature for each halide. We have organised the examples firstly by the halide nucleophile, and then secondly by the internal heteroatom nucleophile involved in the cyclisation. The selectivity (chemo-, regio

• cyclisation of alkenyl N-tosylamides using BF3-activated aryl iodane(III) carboxylates to create 3-fluoropiperidines [35]. The challenges faced relate to selectivity due to competing carboxyaminations (18, 18’), rather than fluoroamination (17, 17’), and difficulties in controlling the diastereoselectivity

• (Scheme 10). The selectivity of the reaction was also found to be influenced by the presence of electrolytes like TBABF4, and the ligand attached to I(III). Carboxyfluorination was observed, in which a ligand from the iodane, e.g., OAc, OPiv or o-I-OBz, adds and was found to compete with fluoroamination

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• solutions [18]. Similarly, Burns and co-workers reported di- and tetra-urea picket porphyrins highlighting, the impact of buried solvent molecules, such as DMSO, on the selectivity, affinity, and stoichiometry of anion binding [19]. Iron complexes of tetra-urea picket porphyrins further demonstrate how

• second-sphere interactions with a multipoint hydrogen-bonding pattern enhance CO2 reduction in organic solvents, improving stability, facilitating proton transfer, reducing energy barriers, and increasing selectivity [20]. Apart from advances in synthetic methodologies [2][21][22][23], the exploration of

• 100 °C for 6 hours in dichloroethane (DCE). All catalysts demonstrated regioselectivities of 95:5 (70b:71b) with 100% selectivity and good conversions (60% for 18a, 84% for 18b, 100% for 18c, 8% for 18d, 27% for 18e, and 8% for 18f), irrespective of the nature of anion. Additionally, they performed

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• with greater efficacy and selectivity against targets related to BC. Thus, the 1,5-disubstituted tetrazole-indole hybrids, presented different effects on cell proliferation inhibition in MCF-7 cells (Figure 1) that could be attributable to the molecular background of cells [46][47][48][49]. The

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99

• stable allenyltrichlorosilane that affords undesired homopropargylic alcohols [35][36] (Scheme 2b). Furthermore, Iseki [35] and Nakajima [36] evaluated only one chiral catalyst in their independent studies (i.e., no catalyst structure–reactivity and selectivity relationship study). In this context, we

• selectivity. Although both protocols reported the same result with respect to the selectivity, we decided to test whether the combination of propargyl bromide and CuF2 could afford isomerically pure propargyltrichlorosilane on a preparative scale. To our delight, we were able to generate

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• biased towards (or against) certain amino acids; while these trends are statistically valid, whether there is an underlying chemical principle that governs the observed selectivity remains unclear [52]. For example, tailoring enzymes for β-hydroxylation most often act on aspartate and asparagine. In

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• qualitative comparison of the guest binding tendency was accomplished by 1H NMR competition experiments to find out about the selectivity of the new receptor and to circumvent the drawback that no binding constants for longer dicarboxylates could be determined. Therefore, the behavior of [L2Zn2] with

• = 4.39 with a high selectivity over the other mono- and dicarboxylate guests of this study which was shown qualitatively by competition experiments. For the future, we aim at developing a universal charge-neutral zinc(II) container capable of binding oxalate as well as longer dicarboxylates in a clean

• fashion with an included lever to control the selectivity by an external stimulus. Additionally, the clear take home messages from recent conferences paired with the latest insights from working with such charge-neutral hosts in the laboratory show that one major task is to find a solution for the so far

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• photoredox catalysis [26][27][28]. These methods allow selectivity to be controlled despite the presence of the complex cocktail of radical species generated by hydroperoxides under redox or homolysis conditions. The main challenge in selective radical peroxidation is the wide range of possible pathways

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• ]. They offer several advantages over traditional reagents, including low toxicity, high reactivity, and excellent selectivity [43] under simple reaction conditions. The distinctive reactivity of DIAS enables the smooth arylation of various carbon and heteroatom nucleophiles under gentle conditions, with

• -donating groups. The reaction exhibited high selectivity, with substitution at the C3 position not impeding the reaction. Different substituted diaryliodonium tetrafluoroborates were also investigated, yielding good product yields. The above protocol for the arylation of pyridine N-oxides 28, resulted in

• the reaction efficiency and selectivity was explored. A high selectivity was found for electron-withdrawing moieties, resulting in high yields of the N2-substituted products. Also, tetrazole 50 was arylated using the same hypervalent iodonium salts as a follow-up, but less than 14% of the targeted

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• mixture. When the reaction was conducted in the presence of NBS in acetonitrile for 10 min, followed by the addition of AgSCF3, the desired product was isolated in 91% yield. A total selectivity for the formation of the Z isomer was observed as ascertained by 2D NMR (for more details, see Supporting

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• achieve this goal [7][33]. Among them, isocyanide-based multicomponent reactions (I-MCRs) are one of the well-known strategies in this field due to their operational simplicity, one-pot, convergent properties and atom economy, high efficiency, and high levels of chemical selectivity [34][35][36]. In

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• indirubin-N-glycosides Thioindirubin-N-glycososides In our group, we studied the reaction of isatin-N-glycoside 16a with thiaindan-3-one which afforded red colored thioindirubin-N-rhamnoside β-32a in very good yield and with excellent Z-selectivity (Scheme 20) [26]. Deprotection of β-32a afforded β-33a in

• excellent Z-selectivity (Scheme 23) [38]. Deprotection of β-37a gave β-38a in very good yield. Likewise, rhamnosides β-38b–d, mannosides β-33e–g, and glucoside β-38h were prepared. The reaction of 36f with isatins 39a–h afforded novel non-glycosylated selenoindirubins 40a–h (Scheme 24) [38]. In

• coumaranone carbonyl group resulting in a downfield shift in case of the Z-isomers. The different E/Z-selectivity in case of oxoindirubins as compared to other indirubin derivatives can be explained, on the one hand, by the absence of the favorable intramolecular hydrogen bond which is present in case of

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• detecting aqueous H2S are in development [8][9][10][11][12][13][14], lack of sensitivity, selectivity, and cost effectiveness remain major challenges. For a number of years we have explored the properties of lanthanide-based chemosensors (Ln = Eu3+ or Tb3+) due to their significant advantages over

• removal of Na2S followed by the precipitation and re-addition of Cu2+ ions (Figure 5). Comprehensive selectivity studies were conducted with various anions/sulfur compounds (SO42−, SO32−, S2O52−, S2O42−, S2O32−, ClO−, OAc−, NO3−, I−, HCO3−, CO32−, Cl−, lipoic acid, and glutathione, as depicted in Figure 6

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• footprint of organic reactions [12][13]. Beyond environmental benefits and enhanced human safety, mechanochemical reactions often feature shorter reaction times, eliminate the need for external heating, and offer alternative product selectivity [3][14]. In general, such reactions are characterized by the

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• catalytic center; finally, the selectivity affording E-enyne and Z-enyne product is also an issue to be addressed, and possible side reactions need to be suppressed (Scheme 2). In this review, we summarize the recent development of copper-catalyzed yne-allylic substitutions. It is worth noting that when we

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• catalyst efficiency and selectivity in sustainable chemistry applications. Keywords: asymmetric catalysis; carbon dioxide; CO2; epoxide; frustrated Lewis pairs (FLPs); volcano plot; Introduction The field of frustrated Lewis pairs (FLPs) has flourished since their seminal discovery in 2006 by Stephan and

• was engineered to produce a single enantiomer preferentially from both enantiomers of the epoxide substrate. An enantiomeric excess of 95%ee was initially achieved, with the predominant (R) enantiomer. Enhanced selectivity was subsequently observed through additional transition states, resulting in a

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• (at 10–30 nM) of the CLK1, CLK2 and CLK4 kinases, and a remarkable selectivity since it does not show any action (at 100 μM) against the closely related DYRKs kinases [2][3]. Very recently, this skeleton proved to be also very useful in the research of antimicrobial agents [4], and the closely related

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• air under mild conditions. Therefore, many triarylbismuthines could be used to form a variety of useful arylboronates in moderate to good yields with excellent product selectivity. We hope that this new approach to the generation of aryl radicals from triarylbismuthines will lead to an increased use

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• C–H hydroxylation process by combining continuous flow chemistry and electrochemistry (Scheme 8) [16]. The surface modification of electrodes can lead to improved reactivity and selectivity. In this regard, Li and coworkers developed electron-deficient W2C nanocrystal-based electrodes to enhance the

• celestolide showed high yields and good selectivity (Scheme 9). The Lei group also disclosed another C(sp3)–H functionalization involving C–O-bond formation [18]. The reported method allows the straightforward preparation of α-acyloxy sulfides from ubiquitous carboxylic acids and sulfides, providing an

• oxidation then yields the intermediate. Subsequent desilylation and substrate/product exchange complete the catalytic cycle (Scheme 40). This approach underlines the potential of asymmetric electrosynthesis in achieving high selectivity and efficiency in complex molecule synthesis, further broadening the

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• production as a result of the expensive cost of Ni-DVBP and Ag/AgCl electrode, low surface-to-volume ratio, ineffective mixing, and sluggish heat exchange. The longer inter-electrode distances, may also lead to longer reaction times and poorer reaction selectivity and decreased yields [21]. Jeremy Robertson

• reaction selectivity [25]. Continuous flow technology has emerged as an attractive solution for many of these challenges, gaining popularity for its ability to efficiently address these issues. Additionally, this platform offers the advantage of integrating multiple steps, i.e., performing multistep

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• and local models to guide the design of synthetic processes. Global models exploit the information from comprehensive databases to suggest general reaction conditions for new reactions, while local models fine-tune the specific parameters for a given reaction family to improve yield and selectivity

• volumes of data and accelerate the prediction of optimal reaction condition combinations. It has been widely demonstrated that ML algorithms can be used for various chemistry-related tasks, such as yield prediction [14][15], site-selectivity prediction [16][17], reaction conditions recommendation [18

• ][116][117], regioselectivity, and site-selectivity [16][17][118][119][120]. However, this approach is also computationally demanding and requires a good initial guess of the TS structure. Moreover, it may face difficulties in simulating some classes of reactions and large-size molecules [121], and the

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• ]. The reaction time and temperature were reduced from >2 h and 80 °C in industrial operation to 10 min and 65 °C in the microreactor with high conversion and selectivity. Since O-methylisouronium sulfate can be dissolved in high concentrations of sulfuric acid, it is expected to construct a homogeneous

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

• simultaneous construction of homoallylamine scaffolds, exemplified by compounds 16–20 with up to 3 contiguous stereocentres, including a quaternary centre in moderate to high yields (60–94%) with 90–99% ee and dr in the range from 97:3 to >99:1 (Scheme 4). The selectivity of the reaction arises from the

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• give the desired product 99 after 72 h returning hemiaminal (Scheme 21). Alkyl acetals, such as cyclohexyl carboxaldehyde acetal reacted sluggishly with low yield and selectivity (<10% yield, 43–50% ee), possibly due to their inability to participate in π–π interactions. In general, the π-stacking