Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• elimination yields the benzofuro[3,2-c]quinolinone product 9 along with a Pd(0) species, which is reoxidized to Pd(II) by BQ (benzoquinone). When the ligand is switched to the sterically bulky and electron-rich dppm, the chemoselectivity is reversed: the palladium center now preferentially coordinates with

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• of the solvent also played a role in the reaction outcome. A decrease both in efficiency and diastereoselectivity was observed when THF was used (Table 1, entry 7). The use of dichloromethane eroded the diastereoselectivity and also the chemoselectivity as shown with the additional formation of 3 as

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• inherent limitations with molecules possessing unsaturated functionalities due to competitive hydrocupration pathways. The approach using 1,1-diborylalkanes 47 circumvents these chemoselectivity issues and enables a selective allylic substitution of substrates containing olefins and alkynes with excellent

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• ; bioorthogonality; chemoselectivity; late-stage functionalization; photochemistry; Introduction Antibodies represent increasingly important tools in several groundbreaking approaches to medical innovation, including basic biomedical research and therapy. One of the most critical requirements for the application of

• below are additional aspects that photochemical transformations could, in our opinion, bring to ADCs that are not easily achieved through traditional, mostly two-electron mechanistic approaches (Figure 9). Chemoselectivity As mentioned in the introduction, there are exceedingly stringent requirements

• chemoselectivity should extend to any molecularly complex linkers and/or payloads being conjugated to the mAbs, allowing highly efficient entry to ADCs. DAR control A noteworthy characteristic of photochemical transformations is the ability to unambiguously start and stop reactions instantaneously using light on

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• , several efforts have been made to improve the chemoselectivity of the oxidation step. Among the most relevant examples, o-iodoxybenzoic acid (IBX) has been used in Ugi and Passerini reactions to oxidize the suitable alcohol to the desired aldehyde [13]. Alternatively, catalytic amounts of a ternary system

• of chemoselectivity becomes important when formaldehyde is used. Moreover, primary amines (alkyl- and arylamines) can also react with two equivalents of both the formaldehyde and the P(O)H compound. In this case, a double Kabachnik–Fields condensation gives bis(phosphorylmethyl)amines 34 as possible

• byproducts (Scheme 26b) [76][78]. Because of the tendency of formaldehyde to generate these byproducts, several efforts have been made to optimize the chemoselectivity of the Kabachnik–Fields reaction. In this context, Zhao et al. proposed a more selective strategy for the synthesis of α-amino phosphorus

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• on both thiols and dioxazolones were well tolerated in late-stage functionalizations, representing excellent chemoselectivity (20e–g). This copper-catalyzed conjugative strategy allows for the modular preparation of biologically relevant N-acyl sulfenamides. Based on several mechanistic experiments

• functionalities were well tolerated in this transformation (26e–g). Moreover, an olefin-containing terminal alkyne was suitable to afford product 26h, demonstrating excellent chemoselectivity. However, the formation of 26i was not observed under the standard reaction conditions. Instead, the decomposition of

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• electron transfer to the metal catalyst without the need for chemical redox agents, thus providing milder and more sustainable reaction conditions (Figure 2) [32]. Electrochemical reactions can be performed at low potentials, thereby suppressing side reactions, and chemoselectivity and reactivity can be

• transformations remains challenging due to the difficulty in controlling the stereo- and chemoselectivity of highly reactive radical intermediates. Future efforts should focus on designing new ligand frameworks to broaden substrate scopes and enhance selectivity control. The use of greener solvents is also

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• further diversification of the triazole products, including chemoselective transition metal-catalysed cross-coupling reactions using bifunctional boryl/germyl species. Keywords: chemoselectivity; click chemistry; copper; germanium; triazole; Introduction Since its inception, click chemistry has been

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

• . The authors studied the stereo-, regio, and chemoselectivity in both cyclic and acyclic substrates. It was observed that the use of acyclic iodane reagents 19 and 20 predominantly led to products with β-stereochemistry, whereas the cyclic iodanes 21 and 22 favour pathways leading to α-stereochemistry

• . The level of this chemoselectivity was dependent on the iodane ligand: OPiv was more selective for aminofluorination than OAc, which was proposed to be due to differences in basicity and nucleophilicity (Scheme 10). Detailed mechanistic studies were carried out using multinuclear NMR spectroscopy

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

• investigated (Scheme 63b) [132]. Vicinal bis-tert-butylperoxides 204 were isolated in low yields among various oxidation products. Xu and Liu with colleagues demonstrated the influence of the solvent and additives on the chemoselectivity of iodine-catalyzed oxidation of styrenes 206 with TBHP (Scheme 64) [133

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

• chemoselectivity of the product is primarily determined by the steric hindrance and electrophilicity of the aryl groups [17]. When the two aryl groups form a cyclic structure with a central iodine atom, they are referred to as cyclic diaryliodonium salts 4 (Figure 1). Cyclic DAISs are predominantly found in simple

• conditions, the arylation of tyrosine methyl ester was also performed. The resulting compound was arylated at both O- and N-positions. The investigations were continued with the unsymmetric anisyl salts, and the results showed high chemoselectivity for N-arylation. Iodonium salts containing the anisyl

• product were obtained. However, the yield of products 52 could be improved up to 66% by using iodonium salt 51 having the TMP group substituted with anisyl (Scheme 21) [72]. Switching the base in the arylation process can influence the chemoselectivity of the reaction as was reported by Onomura and group

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

• ), S1 is the substituent on the LB, and S2 is the substituent on the LA. Capture of CO2 and PO by an FLP Chemoselectivity Our investigations began by examining the uncatalysed coupling reaction between CO2 and PO (Scheme 1), which exhibits a calculated activation barrier (ΔG‡) greater than 55 kcal·mol−1

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

• )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group

• complex, C(sp3)–H bonds underwent azidation with high chemoselectivity, even in the absence of a directing group. The proposed mechanism involves the formation of the active catalyst Mn(III)(N3) via ligand exchange, followed by anodic oxidation to a Mn(IV)(N3)2 complex. This high–valent Mn(IV) species

• results in this respect [68]. This C–H photoelectrochemical functionalization reaction proved to be a mild method, as shown in the alkylation of drug derivatives such as voriconazole and quinine, along with excellent regio- and chemoselectivity. The reaction pathway begins with the photoexcitation of Mes

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• was the five-membered prolinol 7a rather than the initially assigned isomeric seven-membered tetrahydrooxazepine 6 [16]. Subsequently, we set out to understand the O- versus N-chemoselectivity by DFT modelling, and to develop an effective synthetic protocol for the preparation of prolinols 7 in high

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

• the C-nucleophile on 81 is very slow, which determines the chemoselectivity of the reaction. Complex 83 of the iminium ion and the catalyst then reacts with allylsilane 84 through an open, type 2 [33] transition state from the exposed enantiotopic face, as in int-79, to afford product 85 and to

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

• (IEDDA), and recently, azomethine imine (AMIs)–isonitrile ligation [37][55][56][57][58][59][60]. The kinetics, chemoselectivity, stability, and steric demand of the bioorthogonal tag attached on the probe are decisive factors during the selection procedure [61][62]. The most commonly used strategy is

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

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

• –intramolecular cyclization cascade with excellent chemoselectivity in aqueous CH3CN [25]. Herein, as part of our continuing studies of heterocyclic scaffold synthesis mediated by hypervalent iodine reagents, we present the solvent-dependent chemoselective synthesis of a series of isoquinolinones mediated by PISA

• -methylisoquinolinone 3a, an isomer of 2a, was formed in 51% yield. Apparently, the change of solvent resulted in a different chemoselectivity of the reaction. With this in mind, we investigated the reaction conditions (see Supporting Information File 1 for details) and obtained the optimal conditions for the synthesis

• - or 4-substituted isoquinolinone derivatives with excellent chemoselectivity. These interesting findings led us to investigate the reaction mechanism. To gain insight into the mechanism and chemoselectivity of the reactions above, we performed a control experiment. With acetonitrile as the solvent, a

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

• design diaryliodonium(III) salts including a commercially available and inexpensive auxiliary group to achieve efficient preparation of the salts and a high degree of chemoselectivity for transferring the required aryl group. Electron-rich aryl ligands derived from anisole, mesitylene, and particularly

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• 6-substituted product. This behavior has also been observed in previous studies [63]. It was expected that there would be a low chemoselectivity, due to the availability of two halogenated positions in the starting material. However, the 5-substituted product was not observed. At higher temperatures

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

• , expanding the benzocoumarin family (Scheme 1b) [14]. Recently, ortho-functionalized diaryliodonium salts, due to their coordinating and electrophilic effects, have exhibited unique reactivity and chemoselectivity [15]. As such, a wide range of functional groups including the trimethylsilyl group, boronic

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• , requiring four steps, coupled with the expense of the palladium catalyst. Interestingly, when the hydroxy group in L3 was protected, the chemoselectivity of the reaction was poor, resulting in a 1:2 mixture of the desired chloride and the corresponding terminal alkene. Liu and colleagues put forth the

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• the current issues, such as insufficient regioselectivity, intermolecular oligomerization, and the overuse of protective groups. The biosynthetic studies demonstrated that thioesterase (TE) domains exhibit a high level of chemoselectivity and regioselectivity in late-stage macrocyclizations. This

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• chemoselectivity (1,2-/1,4-addition = 4:1). Diazo esters suitable for this transformation were examined next. The MCRs with diazo substrates equipped with different substitution patterns were accommodated under the mild photocatalytic conditions to generate the desired 1,4-addition products in moderate to good

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• green catalyst with greater chemical and thermal stability in comparison to other heteropolyacids [43]. HPW has been shown to catalyze MCRs in the synthesis of heterocyclic compounds with high efficiency and chemoselectivity (Figure 2), including functionalized benzo[c]chromeno[2,3-a]phenazine [44