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

• produce simple structured rotaxane species (Scheme 3) [46][47][48]. In this method, dodecanediamine and α-CD are mixed in water to form a pseudo[3]rotaxane (1), and the subsequent one-pot end-capping reaction driven by the amino group on the axle ends and substituted phenyl isocyanate produced [3]rotaxane

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

• unsymmetrical diaryliodonium salts could be improved which were subsequently used to synthesize new oxygen arylated products. Solorio-Alvarado and co-workers introduced a one-pot double arylation of naphthols through the consecutive C–C/O–C bond formation in the presence of hypervalent iodine salts 16 as the

• aryl donor (Scheme 24) [75]. The reaction worked very well at room temperature under base-free conditions. In this one-pot synthesis of double arylation of naphthols 58, a novel radical precursor, [1,1´-oxybis(2,2,6,6-tetramethylpiperidine)] (59), was employed. This precursor undergoes spontaneous

• K2CO3 at 55 °C to yield the corresponding products 62 in good to excellent yield (Scheme 25) [76]. It was observed that both electronic as well as steric effects on the aryl electrophile and phenol nucleophile were well tolerated. Further, this study was used for the one-pot synthesis of diaryl ethers

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

• synthetic platform. Starting from readily available (hetero)aromatic and aliphatic hydrazones, the formation of a C–SCF3 bond was achieved under oxidative and mild reaction conditions in the presence of the readily available AgSCF3 salt via a one-pot sequential process (28 examples, up to 91% yield

• corresponding R1R2NH) [74], we assumed that a one-pot two-step process could be an efficient strategy for the trifluoromethylthiolation of hydrazones. Herein, the synthesis of trifluoromethylthiolated hydrazones from aldehyde hydrazones is depicted. Results and Discussion At the outset of the study, the

• conducted in the presence of 1a in a THF/MeCN mixture (1:1) [75], but no product was detected (Scheme 4D). Based on these experiments and literature data [66], a two-step one-pot process was suggested based on 1) the bromination of the hydrazone 1 followed by 2) the anion metathesis in the presence of

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

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

• -workers reported a one-pot three-component reaction (3-CR) of sulfamate‐derived cyclic imine, isocyanide, and acetylenedicarboxylate. In this reaction too, the pyrrole-fused sulfamate is synthesized through intermediacy of the in situ-formed zwitterion II and [1 + 2 + 2] annulation reaction (Scheme 1b

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N-aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which

• : isocyanide; multicomponent reactions; one-pot reaction; oxidation; spiroindolenine; Ugi reaction; visible light; Introduction Diversity-oriented synthesis (DOS) is a successful approach to biologically active scaffolds directed to create an enormous exploratory space in pharmaceutical hit discovery [1][2

• efficient methods for the synthesis of heterocycles by multicomponent processes and domino reactions [16][17][18][19][20], here we disclosed the oxidative one-pot four-step synthesis of 2-amino-3,3’-spiroindolenines using readily available tertiary amines, electron-rich anilines and isocyanides as starting

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

• somewhat difficult due to strong adsorption or decomposition on silica gel. Since some arylboronates are somewhat unstable, it is desirable to synthesize such compounds and then use them in a one-pot manner for the following reactions without isolation. To gain insight into the reaction pathways, several

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

• , telescoped flow sequences [206][207][208] or one-pot batch synthesis [209] emphasize the use of chemically compatible reagents and solvents in each reaction step to minimize intermediate purification steps. Volk et al. [210] developed AlphaFlow, which utilizes reinforcement learning as an optimization

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• is produced in situ from the imidoyl chloride 9 [21]. The one-pot oxidation and ring-closure reaction [22][23] to iodoloisoxazolium(III) salt 7OTf and the salt metathesis with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF24) were then realized with 85% and 72% yield, respectively

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• report the efficient one-pot synthesis of diarylacetic acids 2 using this protocol (Scheme 1, bottom). Although photochemical synthesis of diarylacetic acids 2 from diarylmethanol species 1 and carbon dioxide has been reported (Scheme 1, top) [20], to the best of our knowledge, this is the first

• in DMSO for electrochemical reduction at the cathode. Conclusion Efficient one-pot synthesis of diarylacetic acids 2 was accomplished by electrochemical direct carboxylation of diarylmethanol species 1 in DMSO. 2,2-Diphenylpropanoic acid (2i) and phenyl(thiophen-2-yl)acetic acid (2l) could also be

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

• purification. The bulky aryl groups in 116 were synthesized in a one-pot procedure, starting from 3,5-dimethylbenzonitrile, by the addition of 3,5-dimethylphenylmagnesium bromide and allylmagnesium chloride (24% combined yield on a 1 g scale). The authors also optimised the protocol for a large-scale synthesis

• crystal XRD of the corresponding hydrochloride salt. Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’-diphenyl-BINOL. Aldehyde and amine scope [26]. aThe reaction was conventionally heated at 50 °C for 24 hours instead of microwave irradiation. b1.0 equiv

• amine was used. c8 mol % BINOL catalyst was used. d4 mol % BINOL catalyst was used. Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’-diphenyl-BINOL. Crotylation studies [26]. aNot determined, but estimated to be high; racemate did not produce 4 clear

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• (MCRs) are one-pot reactions that utilize three or more readily available starting materials [1][2][3][4]. Typically, MCRs use reactive functional groups such as ketones or aldehydes, carboxylic acids, amines, and isocyanides where these simple building blocks can be utilized to form large libraries of

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• Federation Research Institute of Chemistry, Рeoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya Street, 6, Moscow, 117198, Russian Federation 10.3762/bjoc.20.188 Abstract A one-pot three-component synthesis of substituted meta-hetarylanilines from heterocycle-substituted 1,3

• -thumb, 1,3-diketones bearing substituents with σm or σp > 0.300 afford meta-anilines from alkylamines in good synthetic yields, and higher σm or σp are required for three-component condensation with less nucleophilic arylamines. The developed one-pot three-component reaction is efficient (yields up to

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

• Kateryna V. Dil Vitalii A. Palchykov Research Institute of Chemistry and Geology, Oles Honchar Dnipro National University, Nauky Av. 72, Dnipro, 49045, Ukraine Enamine Ltd. (www.enamine.net), Winston Churchill Str. 78, Kyiv, 02094, Ukraine 10.3762/bjoc.20.184 Abstract A one-pot three-component

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

• which a wide-range of 2-phosphoryl-substituted quinoxalines 26 were prepared in one pot via reaction of ortho-diisocyanoarenes with diarylphosphine oxides in the presence of AgNO3 (Scheme 18b) [65]. Chalcogen compounds such as PhSH and (PhSe)2 can be used as chalcogeno radical sources for the

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• strategy to improve or modulate their physicochemical and biological properties [41][42][43][44][45], only few publications have reported a [3,3]-rearrangement with fluorinated molecules (Scheme 1c). In 2020, Wang and co-workers have developed a one-pot [3,3]-sigmatropic rearrangement/Haller–Bauer reaction

• Yang Li Guillaume Dagousset Emmanuel Magnier Bruce Pegot Université Paris-Saclay, UVSQ, CNRS, UMR 8180, Institut Lavoisier de Versailles, 78035 Versailles Cedex, France 10.3762/bjoc.20.181 Abstract Access to original ortho thioether derivatives was achieved through a [3,3]-rearrangement in a one

• -pot two-step protocol. Several aryl-SCF3 compounds are reported by variation of the nitrile or of the trifluoroalkyl sulfoxide starting material. The variation of the perfluoroalkyl chain was also possible. Keywords: ortho functionalization; rearrangement; sulfoxide; Introduction Since decades

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

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• ; one-pot reactions; pyrazole; Introduction Pyrazoles and 1,2-diazoles [1] have received considerable interest in the past years. Although they are rarely found in nature [2], their spectrum of biological activity is remarkably broad, leading to numerous applications in pharmaceutical chemistry [3][4

• concatenation of organic elementary steps in a one-pot fashion. Many reviews on general syntheses of pyrazoles have been published [25][26][27][28][29][30][31][32][33][34][35][36][37][38], as well as a few dedicated reviews on MCR synthesis of pyrazole derivatives [39][40][41]. In sensu stricto, multicomponent

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• , curcumin showcases its Michael donor–acceptor ability in different ways, such as simple Michael addition, [4 + 2] annulation, Michael addition followed by cyclization or one-pot multicomponent reactions (MCR), etc. (Scheme 1) [25]. In 2011, our group reported the reactivity of curcumin as a Michael donor

• cascade triple-Michael (Michael/Michael/oxa-Michael) reaction between curcumins and isatylidene malononitriles, giving spiro-oxindoles in excellent yields and diastereoselectivities [36]. Sahu et al. introduced a one-pot multicomponent reaction of curcumin, arylaldehyde and 2-aminobenzothiazole to

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• , obtaining an enzyme-metal biohybrid catalyst [22]. The authors tested it in a one-pot GBB reaction–Suzuki coupling, employing 5-bromo-2-aminopyridine (20), benzaldehyde (2), tert-butyl isocyanide (5) and phenylboronic acid (21). Compound 22 was obtained in 87% yield by performing the GBB reaction at room

• their reduced nucleophilicity. Also the synthesis of a bis-imidazo[1,2-a]pyridine scaffold was achieved in 43% yield from the pseudo-para-substituted bis-aldehyde, using the same conditions, but longer reactions times (6 days). Following the same approach, the authors also developed a one-pot protocol

• (IPT)-mediated intramolecular oxidative annulation and a hydroxylamine-induced ring cleavage of intermediate 48. With this one-pot sequential procedure they synthesized 49 in yields up to 95% (Scheme 19). The subsequent GBB-3CR led to the unique 1H-imidazo[1,2-a]imidazole core 50 with 4 distinct

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• have been successfully synthesised through a one-pot, three-component reaction involving N,N-dimethylbarbituric acid, an aromatic aldehyde and aniline. By utilizing readily available reagents, this approach opens up the opportunity for the efficient formation of a variety of 5-aryldeazaalloxazines

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

• continuation of our work on the synthesis of powerful photoredox flavins [14][15][16][17][18][19], we developed an efficient, general, one-pot domino method for the synthesis of a series of novel 5-aryldeazaalloxazines 2 from readily available substrates via a three-component fashion (Figure 1C). Results and

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• (I) precursor 18 in 73% isolated yield in a one-pot procedure using 5.5 equivalents of Selectfluor (see Supporting Information File 1). Unfortunately, we were never able to replicate Amey and Martin’s fluorination of phenylmagnesium bromide using bis(trifluoromethyl)trifluoroiodane 22 (Scheme 6). The

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• University, Svobody sq., 4, 61022, Kharkiv, Ukraine 10.3762/bjoc.20.156 Abstract By one-pot four- and three-component Ugi reactions involving convertible isocyanides and unexplored pyrrole-containing β-chlorovinylaldehyde, a small library of 20 bisamides with unusual behavior in post-Ugi transformations was

• of the bisamides 6–8. Moreover, traces of the ketobisamides 12 were also observed when the synthesis was carried out in 96% EtOH. The one-pot synthesis allows to combine two consecutive steps, the Ugi-4CR and the post-Ugi reaction, by keeping the mixture of starting materials 1, 2c, 3 and 4d at 25 °C

• Ugi bisamide 5d in the presence of HCl. Conditions: (A) 5 equiv HCl, MeOH, 80 °C, 3 h; (B) 5 equiv HCl, EtOH, MW 120 °C, 15 min; (C) 5 equiv HCl, MeCN, MW 100 °C, 20 min. The Ugi-4CR with the participation of p-anisidine and benzyl isocyanide. Successful attempt at tandem one-pot coupling of the Ugi

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• considering the diastereoselectivity observed when enantiopure (S)-α-methylbenzylamine was used as chiral component in the two-step syntheses from amine surrogates [22], we assayed our new strategy to achieve a one-pot diastereoselective synthesis of benzodiazepinones 6 (Scheme 2, Table 2). Interestingly, the

• dipyrrolopiperazinone 12 quantitatively. In view of the interest of these structures and the poor global yield obtained because of the purification in the first step, we tried the synthesis of these polycyclic systems in a one-pot sequence. In this way, after performing the Ugi reaction for 24 h, the reaction mixture

• (right). The thermal ellipsoid plot (Olex2) is at the 40% probability level. X-ray diffraction structure of dipyrrolopiperazinone 12c. The thermal ellipsoid plot (Olex2) is at the 40 % probability level. Synthesis of benzodiazepinones 5 from anthranilic acid derivatives. Diastereoselective one-pot

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• preparing spiro α-methylene-β-lactones from different steroidal propargylic alcohols [13]. The procedure involves a one-pot Pd-catalyzed cyclocarbonylation of alkynols using 5 mol % of Pd(CH3CN)2Cl2 as a catalyst precursor and 30 mol % of 2-(dibutyl)phosphine-1-(2,6-diisopropylphenyl)-1H-imidazole as

• as a 1:1 mixture of diastereomers (Scheme 4). The same procedure was also applied to estrone to insert the spiro moiety at C-17 in 70% yield [14]. Spiro-β-lactam steroids A novel one-pot procedure to build spiro-β-lactams from enamides was described by Liu et al. The research group had previously

• -2H-furan-3-one framework at position C-17 [22]. The one-pot procedure involved the condensation of diethyl oxalate with the α-hydroxy ketone moiety of derivatives 28, immediately followed by a cyclization between the 17α-hydroxy group and the carbonyl group of the α-ketoester in 29. Spiro compounds

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• and subsequent oxidation yielded aldehyde 18, a precursor for the intramolecular ring closure of the eight-membered ring. Upon treatment of 18 with BF3·Et2O, diastereoselective Prins cyclization of 18 proceeded to generate secondary alcohol 19. Subsequent one-pot treatment with (n-Bu)4NF·HF resulted

• to the biosynthetic conversion of 9 into 11 (Scheme 2B), an α-hydroxylated ketone 25 with suitable protections of the C3 and C8 hydroxy groups was synthesized from 23 in one pot. Conversion of the secondary alcohol in 25 into triflate 26 enabled the alkenyl shift from C1 to C12 followed by

• JuvEV, homologous enzymes to TylGIV and TylGV (Scheme 8) [68]. Reconstruction of the JuvEIV–JuvEV-catalyzed cascade enzymatic conversions successfully furnished 4 in one pot from chemically synthesized thioester 77 mimicking biosynthetic intermediate 64. For the chemical synthesis of mimic 77, the left

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• promising starting point for pursuing this ring-opening attempt [41]. We hypothesized that this approach would allow the synthesis of 3-amino-1,2-diols, a motif commonly found in pharmaceuticals such as, e.g., β-blockers [42]. Our envisioned one-pot protocol features protonation of the azetidine from