Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• compounds is a significant and important reaction for the selective synthesis of homoallylic alcohols in an efficient and sustainable way [2][3]. As carbonyl compounds, alkyl trifluoropyruvates [4][5] are an interesting class of compounds that have been used in addition reactions of different nucleophiles

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• organocatalytic synthesis of 2-cyclohexen-1-ones via a Michael/Michael/retro-Michael cascade reaction [31]. Our research has shown that the Jørgensen–Hayashi catalyst [32][33] is a highly promising organocatalyst, facilitating enantioselective Michael addition reactions with high yields and excellent levels 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

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

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

• enantioenriched form [11][12]. However, such metal/metalloid reagents and the corresponding metal catalyst-bound intermediates often equilibrate between possible regioisomeric forms and can undergo both, SE2 and SE2’ addition reactions, resulting in a mixture of homopropargylic alcohols and α-allenic alcohols [14

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• substitution/addition reactions became the standard for end-capping reactions, although a transition metal–catalyzed cross-coupling reaction has also been used to synthesize CD-based rotaxane. Typically, water-soluble components are prepared, after which the Suzuki coupling reaction in water is used to

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

• blocks [26]. Despite the known instability of trifluoromethylated carbanions [27], their catalytic application has yielded valuable products [28][29][30]. gem-Difluoroalkenes and trifluoroalkenes are excellent acceptors in the Michael addition reactions. There are also known examples of the use of gem

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

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

• thioesters and acyl chlorides (Scheme 1a, path 7) [30]. For β-keto amides, they could be efficiently synthesized from the nucleophilic substitution reactions of amines with β-keto acids (Scheme 1b, path 1) [31][32][33], β-keto esters (Scheme 1b, path 2) [34] and the nucleophilic addition reactions of amines

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

• , systematic studies of addition reactions of heteroatom radicals to isocyanides are still limited. In this perspective paper, we systematically review the addition reactions of heteroatom radicals to isocyanides and discuss prospects. Discussion 1,1-Addition of heteroatom radicals to isocyanides Generation of

• to give the corresponding 1,1-adduct (Et2P–C(=NPh)–GeEt3, 13) in 46% yield [40]. Similarly, Me2N-SnMe3 was known to add to p-tolyl isocyanide to give Me2N–C(=N–C6H4–p-Me)–SnMe3 (14) in good yield [41]. However, the authors did not specify whether the addition reactions proceeded by a radical or ionic

• isocyanides forms boron-substituted imidoyl radical intermediates and rapid β-scission then causes elimination of the substituents on the nitrogen (Scheme 12) [53]. Radical cyclization via formation of imidoyl radical species In the former chapter, we discussed 1,1-addition reactions of typical element

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• [10][11][12][13][14][15][16][17][18][19][20][21]. Among the developed organocatalyzed enantioselective 1,4-addition reactions of pyrazolin-5-ones, the catalytic asymmetric reactions of pyrazolin-5-ones with α,β-unsaturated ketones are comparatively less studied. In 2009, Zhao’s group were the first

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• bromoanisole, the corresponding homo-coupling products 3a, 3c–3e were obtained in good yields. In addition, reactions with substrates having halogen substituents also gave the products (3h and 3i) in moderate yields. It is interesting to note, that the reaction using 3-bromofluorobenzene (5h) gave a small

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

• [1][2][3]. With the development of research investigating the functionalization of fullerenes, several multiple addition reactions of fullerenes have been investigated [4][5][6][7][8]. For example, earlier reports have described that some functionalization reactions of fullerenes afford bis-adducts

• , controlling the regioselectivities of multiple functionalizations of fullerenes for the selective synthesis of specific multi-adducts poses an important challenge. Addition reactions of C60 are well known to occur mainly at the 6,6-bonds (junction between two hexagons) rather than at the 5,6-bonds (junction

• eight possible regioisomers for bis-addition reactions. Hirsch and co-workers reported two-fold additions of C60 using the Bingel–Hirsch and the Bamford–Stevens reactions as well as nitrene addition reactions, indicating the formation of regioisomers as anticipated from the possible addition sites in

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

• yields in CH3CN under 10–20 bar of CO at 140 °C within 15–30 min and with carbon dioxide as the side-product (Scheme 18). Carbon monoxide is a cheap gas but its use requires safe and controlled environments and systems because it is highly toxic to human. In addition, reactions in which carbon monoxide

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations. Keywords: addition reactions; alkenes; alkyl chlorides; hydrochlorination; Markovnikov; Introduction The hydrochlorination of alkenes dates back to its

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

• has become one of the most popular route for the site-selective modification of cysteine residues in bioconjugation technology. We suppose that the maleimide group in porphyrin 11 is a useful target for thiol conjugation via Michael addition reactions [44]. This also concerns biotin-conjugated organic

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• the formation of the corresponding olefin [12]. Another area of application of olefins 1a,b is based on C=C double bond addition reactions. As early as 1968, Atherton and Fields showed that (Z)- and (E)-butenes 1a,b reacted with diazotrifluoroethane to give 3,4,5-tris(trifluoromethyl)pyrazoline [13

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

• type addition reactions (Scheme 4A). In 1991, Okada and co-workers reported the addition of alkyl radicals to α,β-unsaturated ketones, by subjecting NHPI esters to visible-light irradiation in the presence of the photocatalyst [Ru(bpy)3]Cl2 and the reductant 1-benzyl-1,4-dihydronicotinamide (BNAH) [37

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• stereoselective Michael addition reactions. Homogeneous catalysis was carried out in non-polar solvents (i.e., toluene), which allows the high performance of the lipophilic organocatalyst in terms of yield and stereoselectivity. To facilitate the pharmaceutical use of the lipophilic organocatalyst, we

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

• building blocks [91] (Scheme 14). Inspired by previous accounts and this work [92][93], Hu et al. explored 1,2- nucleophilic addition reactions of trifluoromethylated acylhydrazones with organometallic reagents for the synthesis of trifluorinated homoallylic acylhydrazines [94][95][96][97][98

• . [3 + 2] Cycloadditions of difluoromethylated hydrazonoyl halides. Preparation and early applications of trifluoromethylated acylhydrazones. 1,2-Nucleophilic addition reactions of trifluoromethylated acylhydrazones. Cascade oxidation/cyclization reactions of trifluoromethylated homoallylic

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• cycloaddition or addition–elimination reactions with 1,3-dipoles and gem-difluoroalkenes is largely unexplored and the only report of a cycloaddition is with 2-fluoroindolizines (Figure 1A) via a β-fluoride elimination in an SNV (nucleophilic vinylic substitution)-like transformation [9]. Nucleophilic addition

• reactions with azoles and amines (Figure 1B) are also well-precedented [10]. Herein, we address a critical gap in the literature and report the discovery of a cycloaddition of gem-difluoroalkenes and organic azides mediated by a base and with morpholine as a solvent. The cycloaddition adducts, 1,4,5

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• enolate and a new R• that propagates the radical chain (Scheme 1). Initiation occurs upon oxidation of the dialkylzinc reagent by oxygen. The feasibility of such 1,4-addition reactions is fully reliant on the ease of the intermediate enoxyl radical to undergo alkylzinc-group transfer. Secondary α-carbonyl

• -butanesulfinamide (4) and the requisite α-(bromomethyl)acrylates gave satisfactory yields as well. Finally, N-benzyl-N-(tert-butanesulfinyl) α-(aminomethyl)acrylate 10 was prepared by allylation of lithiated N-benzyl tert-butanesulfinamide 9 (Scheme 3). 1,4-Addition reactions Having the requisite α-(aminomethyl

• thus the sense of chiral induction for the 1,4-addition reactions reported in Table 2. Tandem 1,4-addition–aldol condensation reactions We then went on to consider tandem 1,4-addition–aldol condensation reactions (Scheme 6), which offer the interesting prospect of generating an all-carbon quaternary

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• (I) complex at the β-carbon atom of the activated C=C bond thereby catalyzing the reaction. The NHC–Cu(I) complexes have been found to be effective catalysts for conjugate addition reactions because they stabilize the intermediate species involved in the reaction, which can otherwise be highly

• reactive and difficult to isolate. The NHC–Cu complex also helps to control the regioselectivity and stereoselectivity of the reaction, which are of high importance in organic synthesis. Overall, the use of NHC–Cu complexes as catalysts for conjugate addition reactions offers a highly efficient and

• selective method for the synthesis of a wide range of organic compounds [55][56]. Organometallic reagents, such as organolithium, organomagnesium, and organozinc reagents are commonly used in conjugate addition reactions. 2.2.1 Reaction with Grignard reagents: Organomagnesium reagents, such as Grignard

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• report, it augured the potential of RLT to be a general strategy in synthetic method development, with modern examples including new alkene addition reactions and decarboxylative functionalizations (Scheme 2). Recent applications of RLT in catalysis Upon the discovery and initial exploration of the RLT

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• transformations. It was discovered that, in general, arylamines with electron-withdrawing groups deactivated the arylamines and produced the corresponding pyrroles in only modest yields, whereas arylamines with electron-donating groups reacted much faster and produced the pyrroles in excellent yields. In addition

• , reactions of sterically hindered anilines with 2,5-dimethoxytetrahydrofuran give moderate yields, and reactions with less sterically hindered anilines give good yields of products. The Clauson–Kaas method for the synthesis of pyrroles has a wide range of applications, including the synthesis of various

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• obtained by other conjugate addition reactions. Keywords: acylimidazole; asymmetric catalysis; carbocation; conjugate addition; enolate; Introduction Asymmetric metal-catalyzed conjugate additions provide access to numerous chiral scaffolds. This type of C–C bond formation efficiently enables the