Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• is plausible to assume as the key step for ring formation an aza-Diels–Alder reaction between the alkyne and the imine generated by dehydration between the aldehyde and aniline. The catalyst promotes the formation of the imine XI, while the high regioselectivity is ascribable to the favored

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• -naphthols, new atroposelective reactions of quinones and iminoquinones were developed [63]. The reaction of quinones with an ester group 109 and indoles with alkyl substituents 110 catalyzed by CPA C29 provided products 112 with regioselectivity on the pyrrole ring of indole (Scheme 35). On the contrary

• , adding a hydroxy group to the benzene ring of indoles 111 and reacting them with tosyl-protected iminoquinone 109 with the help of CPA C30 led to the shift in regioselectivity providing different axially chiral products 113. All products were obtained with high degree of enantiomeric purity as well as

• in the regioselectivity change. Song et al. broadened the scope of usable substrates for the asymmetric arylation of naphthoquinones 115 with indolizines 114 catalyzed by CPA (R)-C23 forming atropoisomers 116 (Scheme 36) [64]. A broad range of indolizine substrates was tested with substituents in

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• the regioselectivity of the reaction when 3-pyridylboronic acid is used as substrate as there are two different positions (C2 and C4) on the pyridine ring available for the C–H arylation step. Interestingly, azafluoranthene 15h was obtained as the only product in this reaction, albeit in a lower yield

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

• HVI reagent has also shown to dictate the regioselectivity of the reaction. Future research efforts should focus on further developing access to new heterocycles, as well as designing better systems to incorporate high levels of diastereoselectivity and enantioselectivity into chiral halogenated

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

• propargyltrichlorosilane without N,N-diisopropylethylamine and (b) with N,N-diisopropylethylamine. It includes Gibbs free energies (kcal/mol) and Mulliken charges (in parentheses). Metallotropic rearrangement and regioselectivity issues. Asymmetric catalytic allenylation of aldehydes. Selective preparation of

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

• regioselectivity of attachment to a double bond with a neighboring electron-withdrawing group was found (Scheme 37). The in situ-generated radical species A and B abstract a hydrogen atom from the cycloalkane 105 to generate a cycloalkyl radical species C. The allylic CH2 of the indene 104 is oxidized to C=O in

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

• reductive elimination in exceptional yields (Scheme 20) [71]. Although screening studies indicated the possibility of achieving the N-arylation at both, the N1- and N2-positions of the triazoles, N2-arylation was predominantly observed. It was incredible to achieve splendid regioselectivity without the

• usage of directing groups and any metal catalyst. Also, the electronic nature of a substituent at the C4 position of the starting triazole did not negatively impact the regioselectivity. Further, C4 and C5 disubstituted triazoles also produced the N2-arylated product. Remarkably, this is the only

• diaryliodonium salts 73. Remarkably, the method exhibited high regioselectivity, with the substitution at the meta position being observed with up to 99% selectivity in comparison to the ortho position. Specifically, only electron-withdrawing groups like OMe or CF3 when substituted at the m-position relative to

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

• from p-fluoroaniline which can be explained by the π-donating effect of fluorine which facilitates the cyclization via the ortho-position in case of m-, but not of p-fluoroaniline. It is worth to be noted that the formation of 23d proceeded with excellent regioselectivity via carbon C-6 rather than C-2

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

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

• nucleophiles (Scheme 1b). However, to achieve a highly selective yne-allylic substitution, a range of challenges must be addressed. First, how to achieve the regioselectivity under the coexistence of alkenyl and alkynyl units; second, how to realize the enantioselectivity control that is remote from the

• substitutions, the realm of yne-allylic substitution remains relatively unexplored. This scarcity of reports stems primarily from the inherent challenges posed by the presence of two unsaturated bonds in the substrates, which often complicates the control of regioselectivity. Additionally, the competition among

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

• initial study, it can be concluded that the mechanism for our system proceeds according to mechanism two. The following simulations were performed on this conclusion. Regioselectivity PO exhibits two distinct electrophilic sites, which can be subject to nucleophilic attack (Figure 2B). Thus, the

• regioselectivity of the CO2 insertion into PO must be addressed as part of the full mechanistic investigation. The compound 3-boryl-2-propen-1-amine is now considered as the catalyst (Figure 2B). As observed in Figure 2A, the bond length and electron density at the bond critical point (BCP) difference are minimal

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• reported over the years (Figure 2) [2]. Conventionally, benzophenones are synthesized by Friedel–Crafts acylation of benzoyl halides and aromatic compounds. However, the regioselectivity of Friedel–Crafts benzoylation at the desired position is difficult to control [9]. On the other hand, 2

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

• oxidation strategy to obtain α-chlorosulfoxides from sulfides using hydrochloric acid as a bifunctional reagent [22]. This strategy accommodates a broad range of substrates and offers high diastereoselectivity and regioselectivity. Several LSF modifications of amino acids and pharmaceutical derivatives

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

• ][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

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• present in the substrates to access the corresponding radical cation. The reaction shows high regioselectivity and good to moderate diastereoselectivity with satisfactory yield. The limitation, which will be further addressed by a more powerful catalyst, is related to the unreactivity of unsubstituted

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• the position of the double bond in the molecule. Notably, a longer reaction time was required for less reactive or more hindered substrates. The reaction was stereoselective as only the anti products were obtained. A good regioselectivity was generally observed, as at least 80% of the main regioisomer

• were usually obtained when the substituents at the double bond differed significantly. When the substituent hindrance was less pronounced, the ratio was less significant (2f, 2j). Interestingly, a reverse regioselectivity was observed depending on the starting alkenes. For the terminal alkenes, the

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

• between catalyst, substrate and the DABCOnium moiety. Subsequently, a random forest model was used to predict exo/endo- and regioselectivity of the reaction. Using random forest as an interpretable machine learning model allowed to extract the important features of the model, which indicated that the

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions – synthesis

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• efficiency of these reactions. In particular, traditional multistep syntheses of pyrazoles have considerably been extended by MCR. Progress has been made in the cyclocondensation of 1,3-dielectrophiles that are generated in situ. Limitations in the regioselectivity of cyclocondensation with 1,3-dicarbonyls

• -acetoacetylcoumarin 41, 3-bromoacylpyran 42, and semicarbazide 40 (Scheme 12) [65]. Alternatively, the corresponding chromenes can replace the 3-bromoacylpyrans. A notable advantage of this process is its catalyst-free nature and the achievement of good regioselectivity. Due to the high heterocycle density, this

• regioselectivity, with 3,4-fused pyrazoles being accessible when cyclic β-oxodithioesters are employed as substrates. However, aromatic amines cannot be successfully employed in the sequence. Alkenoyl derivatives as key intermediates The Michael addition and cyclocondensation of hydrazines and α,β-unsaturated

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

• LUMO (Figure 1) [11]. Reactions with nucleophiles (Nu) proceed with perfect regioselectivity at the distal β-position relative to the meso-position [12][13][14][15]. On the other hand, reactions with electrophiles (El) also occur preferentially at the β-positions, but the regioselectivity depends on

• governed the regioselectivity. Reactivities of norcorroles with various reagents. Top and side views of the X-ray structures of a) 2a and b) 1 [2]. Mesityl groups and hydrogen atoms were omitted for clarity. Thermal ellipsoids are drawn at 50% probability. UV–vis–NIR absorption spectra of 1 and 2a in

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• compounds 6, 18, and 21 via natural bond orbital (NBO) analyses which further support the suggested reaction pathways. Keywords: DFT; indazole; indazole substitution; mechanism; N1-substituted indazole; N2-substituted indazole; regioselectivity; Introduction Indazoles constitute an important class of

• pharmacophore in medicinal chemistry and the challenges in obtaining either N1- or N2-alkylated indazoles as the dominant regioisomer [30][34][35][36][37][38][39], we were interested in exploring the regioselectivity with methyl 5-bromo-1H-indazole-3-carboxylate (6, Figure 1) as a multifunctional model compound

• potassium carbonate, isopropyl bromide and cesium carbonate, and bromocyclohexane with potassium carbonate, and only afforded yields not higher than 52% in various solvents [41][42][43]. Recently, Alam and Keeting [37] explored the regioselectivity in the alkylation of variously substituted indazoles

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

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity. Keywords: amide coupling; hypervalent iodine catalysis

• α-phenylstyrene produced the respective oxazoline products with high regioselectivity and reasonable yields using iodoanisole as the catalyst precursor (Figure 3, products 24 and 25). The proposed catalytic cycle (Figure 4) begins with iodotoluene A which is oxidized by Selectfluor salt into the

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

• using tertiary alkyl oxalates and aryl bromides (Scheme 10). This is achieved through the synergistic combination of photoredox and nickel catalysis. This approach facilitates the formation of diverse trisubstituted olefins with outstanding regioselectivity and syn-stereoselectivity. The proposed

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free

• versatile building blocks in organic syntheses. To achieve this transformation with high efficiency and predictable regioselectivity, numerous efforts have been made to develop transition-metal-catalyzed reactions based on a C–H activation strategy [1][2][3][4] or the reductive coupling of aryl halides with

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• carbonyl compounds, such as dimethyl acetone-1,3-dicarboxylate and 1,3-diphenylacetone, and with 1,3-bis(silyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, allow for a convenient synthesis of a great variety of products. The regioselectivity and course of the reaction depends

• of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed. Keywords: cyclizations; 1,3-dicarbonyl compounds; domino reactions; heterocycles; regioselectivity; silyl enol ethers; Introduction Domino reactions (also called cascade or tandem reactions

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10