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

• .20.122 Abstract Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using

• nucleophiles were incorporated (Scheme 1b) [29][30][31][32][33][34][35][36][37][38][39][40]. Intermolecular hypervalent iodine catalysis with the regioselective additions of two distinct nucleophilic functionalities across an olefin, however, remains challenging with limited solutions [41][42][43][44][45][46

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• ) [32]. The formation of the products can be explained by Michael reaction (1,4-addition) of 3 to the chromone and ring cleavage to give intermediate G. Subsequent Knoevenagel reaction by attack of the methylene carbon to the aldehyde resulted in the formation of the final products. The regioselective

• to the chromone and ring cleavage to give intermediate I. Subsequent Knoevenagel reaction by attack of the methylene carbon to the carbonyl group adjacent to the ester group resulted in the formation of the final products. The regioselective cyclization can be explained by the higher electrophilicity

• -Ketoamides The reaction of 3-ketoamides 34a–f with 3-halochromones 15a–g afforded 2-(salicyloyl)furans 35a–x in mostly good to excellent yields (Scheme 18) [41]. The reaction proceeds by 1,4-addition of the methylene carbon of 34 to the chromone to give intermediate T, cyclization by regioselective

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• , regioselective aromatic electrophilic substitution is often difficult. Various synthetic strategies have evolved to address such problems and expand the scope of SeO2 beyond the oxidizing capability. Ren et al. adopted potassium-iodide-mediated catalytic selenation of aromatic compounds using SeO2 (Scheme 1) [33

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

• and methanol as a C1 source [86]. A total of 28 desired aminomethylated aromatic products were isolated with moderate to good yields (Scheme 56). Later, Rueping and co-workers developed the regioselective alkylation of indolines with alcohols as the alkylating agent using a manganese-pincer catalyst

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• -arylindoles by reductive carbonylation of unfunctionalized nitroarenes in the presence of arylalkynes and Pd(phen)2(BF4)2 as catalyst has been demonstrated by Cenini's group. The reaction was regioselective, with no detection of 2-arylindole byproducts. No prefunctionalization of the ortho position of the

• controllable and regioselective synthesis of indol-3-α-ketoamides and indol-3-amides via the direct double- and monoaminocarbonylation of indole derivatives by using secondary amines [70]. They used Pd(dppf)Cl2 as catalyst system. The indol-3-α-ketoamides were synthesized by adding dppf as ligand, CuI as co

• -catalyst, and LiCl as additive under 40 bar of CO. To make the process regioselective towards indol-3-amides, dppf as ligand, the base (K2CO3), and I2 were added, and the reaction run under a low pressure of CO (1 bar), in addition to the catalyst. Both processes took place well in THF (Scheme 39). In 2013

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

• investigations demonstrated the ability of diaryliodonium salts for selective mono-arylation of 2-naphthols [34]. In this context, we embark on a strategy to modify the neighbouring position of the diaryliodonium salt with an ester group, presenting a novel copper-catalysed regioselective arylocyclization of

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• Syntheses [83]. The proposed catalytic cycle is shown in Figure 7 and involves the following steps. First, a cobalt hydride complex A is formed in situ from Co(II) complex and the silane. Then, regioselective alkene hydrocobaltation takes place. This step is highly regioselective, placing the cobalt atom on

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• single pentafluorophenyl ring was prepared through the regioselective nucleophilic aromatic substitution reaction of the p-fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin with 9-mercapto-m-carborane. The reaction of this porphyrin with sodium azide led to the selective substitution of

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• , greatly increasing the molecular complexity of the starting substrate. Using radical chemistry would lead to a regioselective addition of azide radicals to the alkene, forming selectively the most stabilized C-centered radical. A prominent method for the generation of azide radicals relies on hypervalent

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• [9][10] are commonly employed for quinazoline modification (Scheme 1). Existing literature underscores the reactivity of the C4 position in aromatic nucleophilic substitutions of quinazolines I while achieving regioselective replacement at the C2 position poses challenges [11]. Modification of the C2

• valuable precursors for the C2-regioselective modification in quinazolines. Furthermore, the developed methodology was valorized by successfully employing it in the synthesis of adrenoblockers terazosin and prazosin. Approaches for quinazoline modifications at the C2 and C4 positions. Attempts toward

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

• reactant ratio produced the desired product 4a in 84% yield as optimal conditions for this protocol (Table 1, entry 13). With the optimized conditions obtained, we examined the generality of our palladium-catalyzed regioselective carboamination of 1,3-dienes with diazo esters and amines (Scheme 2). First

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• using commercially available substrates and allowing the regioselective introduction of functional groups at the desired positions is still needed. By using Pd-catalyzed double C–H bond functionalization of activated arenes, such as (poly)fluoroarenes, or by combining a palladium-catalyzed

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• aromatic ring, forming intermediate 41, which was then oxidized to cation 42, thereby completing the photocatalytic cycle. The reaction proceeded by regioselective nucleophilic addition of H2O, accompanied by the loss of MeOH to deliver spirocycle 43. Notably, the dearomative spirocyclization of biaryl

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• -substituted soluble precursors 3a–f owing to increased modularity (Scheme 5) [62]. To this aim, acenaphthene was selected as key building block and it underwent two successive regioselective halogenations to give bromochloroacenaphthene 8 in 64% overall yield. The latter was next converted into the

• –Alder reaction of naphthodiyne precursor 55 with isobenzofuran 61 to give monoepoxide 62 as a mixture of regioisomers. Further treatment of the latter with one equivalent of cesium fluoride allowed the regioselective Diels–Alder with the previous diene 61, to afford 63 as another mixture of position

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• Cristina Castanyer Anna Pla-Quintana Anna Roglans Albert Artigas Miquel Sola Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Universitat de Girona (UdG), Girona 17003 Catalunya, Spain 10.3762/bjoc.20.28 Abstract The regioselective functionalization of fullerenes

• regioselective [2 + 2 + 2] cycloaddition reactions as a means to tailor the properties of fullerenes for specific applications. Types of [6,6]-bonds together with the [5,6]-bond of C60 with their C–C distances in pristine C60 and C70. 1H NMR (CS2/CDCl3, 400 MHz) spectrum of compound 2a as a mixture of two

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• strategy was reported by Laha et al., aiming to access dibenzodiazepinone structures via a double N-arylation of 2-aminobenzamides with 1,2-dihaloarenes using a palladium-based catalytic system [15]. Mechanistic investigations supported the fact that the regioselective N-arylation of the 2-aminobenzamide

• and led to the desired structures in moderate to good yields (Scheme 3). The reactions were generally regioselective, except in the case of 4-methyl-o-phenylenediamine (1b) and o-bromophenylboronic acid (7) which gave a mixture of products 3b and 3c in 60% yield (the ratio could not be determined

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• glycosylation reactions. The 3’-sulfate was finally introduced through tin activation in benzene/DMF followed by treatment with a sulfur trioxide–trimethylamine complex in a 66% yield. Keywords: regioselective sulfation; thioglycoside donors; Thomsen–Friedenreich antigen; Introduction In a collaboration

• sulfated 2 (Figure 2). This showed that regioselective 3’-O-sulfation had been achieved, with HRMS also indicating that only one sulfate group was present. Conclusion An efficient synthesis of the important TF and 3’-Su-TF antigens equipped with a TEG-N3 linker to allow formation of various conjugates has

• regioselective 3’-O-sulfation. Supporting Information Supporting Information File 44: NMR spectra of compounds 1–5, 7 and 8. Acknowledgements We thank Dr Yannick Ortin and Dr Jimmy Muldoon for NMR and MS support. Funding The authors kindly acknowledge Science Foundation Ireland awards 13/IA/1959 and 20/FFP-P

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• selective C5-bromination of 8-aminoquinoline amides using carbon tetrabromide and dibromomethane under photo- and electrocatalysis conditions [27][28]. In 2017, Xia and co-workers reported a novel, mild, metal-free, and regioselective bromination of amides, wherein the organic dye eosin Y acted as the

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• acid, the conditions reported in entry 9 of Table 1 were chosen as reference for the study of the reactivity of different alkynes. For the internal alkyl(aryl)alkynes a regioselective hydration occurred, with the only generation of the corresponding aryl ketones, formed after the attack of water to the

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• sequentially underwent a [4 + 3] cycloaddition reaction (reaction 1 in Scheme 1) [54]. Recently, Chen and co-workers reported a chiral tertiary amine-catalyzed asymmetric γ-regioselective [4 + 3] annulation reaction of isatin-derived MBH carbonates and cyclic 2-benzylidenebenzo[b]thiophen-3-ylidene

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• also highly regioselective, proceeding via attack on the 2-N atom to give products 6m–o. In the instance of unsubstituted benzotriazole, a minor regioisomer 6m' was identified with a calculated yield of 6% using NMR data. Benzotriazoles featuring electron-withdrawing substituents showed incomplete

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• functionalized coumarin derivatives and related nitrogen-containing heterocycles, opening up exciting possibilities for their diverse applications in other fields. Similarly, the regioselective photodecarboxylative C–H alkylation of 2H-indazoles and azauracils using NaI/PPh3 as mediators and redox esters 3 was

• construction of these scaffolds [28][29][30][31], and one of the most efficient approaches is the cascade cyclization strategy [29][30][31]. Xu, Li, Wei and their co-workers successfully devised a series of highly regioselective iodide/phosphine synergistically catalyzed photocatalytic cascade annulations for

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• regioselective [3 + 2] cycloadditions [59][60][61][62][63] (Scheme 10a). Similarly, trifluoroacetonitrile imine reacted with mercaptoacetaldehyde and mercaptocarboxylic acids to generate fluorinated 1,3,4-thiadiazines with good yields via a [3 + 3] annulation [64] (Scheme 10b). Meanwhile, mercaptoacetaldehyde as

• reported practical methods, which extended the structural scope of such dipoles. This has allowed the synthesis of trifluoromethylpyrazoles by a range of regioselective [3 + 2] cycloadditions of trifluoroacetonitrile imines with electron-poor olefins [73][74][75][76] (Scheme 11b). Moreover, the

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the starting material. This compound was prepared according to the described regioselective method [42] based on the reaction of malononitrile with triethyl orthoformate followed by subsequent treatment of the obtained dinitrile 2 with benzaldehyde methyl hydrazone in benzene, conc. aqueous HCl in