Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• conversion of the reagents was not achieved until after 12 h of boiling, and the yield of the product varied in the range of 25–35% (entries 1 and 2, Table 1). In the cases of DMF and MeCN, the formation of complex, inseparable mixtures of numerous intermediates and products of their subsequent

• polyfunctional precursors 1, 2, and 3, two pathways are theoretically possible (Scheme 2 and Scheme 3). The first one involves the N-nucleophilic Michael addition to the activated multiple bond of the imide, leading to the formation of linear intermediates 6 or 8 (pathways A1 and B1) at the expense of the endo

• -nitrogen atom. The second route involves the participation of an amino group which allows the formation of adducts 7 and 9 (routes A2 and B2). The intermediates formed then undergo subsequent tandem recyclization of succinimide/citraconimide fragments at the expense of one of the carbonyl groups and the

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• through the formation of novel reactive intermediates [15][16][17][18]. Fluorine-containing functional groups are essential structural motifs in the development of new bioactive compounds and functional materials. Compared to their non-fluorinated analogs, the presence of fluorine atoms in molecular

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

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

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

• materials (Scheme 1d). The synthetic procedure is achieved using blue light irradiation and bromotrichloromethane (BrCCl3), as a one-pot procedure, minimizing chemical wastes, avoiding purification of intermediates, and simplifying practical aspects. Results and Discussion We have recently published the one

• argon atmosphere to prevent the interaction of oxygen or reactive oxygen intermediates, which are not always compatible with the substrates, as well as the key intermediates. Moreover, BrCCl3 and its reduced form (chloroform) can be easily removed from the reaction mixture thanks to their low boiling

• and the intermediates involved, the relationship between the product conversions and the reaction time was investigated in the reaction between N-Ph-THIQ, 3,5-dimethoxyaniline and t-BuNC in the presence of BrCCl3 under light irradiation (Figure 2). This time profile shows that, as soon as the N-Ph

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• imidazolium ring formation. The resulting carbene was metalated at the C2 position with Au(I), Cu(I), and Ir(I), obtaining an L-shaped NHC ligand scaffold. Līpiņš et al. introduced a new method for synthesizing 4-azido-6,7-dimethoxy-2-alkyl/arylsulfonylquinazolines, which are key intermediates in the

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

• product (Scheme 15). The synthesis of aziridines can be achieved via the formation of nitrenes in either a metal-catalyzed or metal-free fashion. In this context, Wickens and colleagues presented a remarkable dication pool strategy for accessing N-alkylaziridines via metastable dicationic intermediates

• cross-coupling between these two intermediates, followed by intramolecular cyclization and subsequent deprotonation results in the desired product (Scheme 20). Furthermore, Budny and coworkers demonstrated that (±)-triticonazole and related compounds could be cyclized and alkoxylated to the

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• limitation, we analyzed the mechanism underlying the formation of resorcin[n]arenes. The first step of the cyclization reaction is a hydroxyalkylation involving various cationic intermediates [69]. Hence, we hypothesized that any factor enhancing the rate of the first step by stabilizing carbocations will

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

• -centered radicals, such as aminyl, amidyl, or iminyl radicals, N-heterocyclic amidyl radicals were largely underinvestigated despite their importance as intermediates or relevant N-heterocyclic products in medicinal chemistry [7][8][9][10]. Recently, photoredox catalysis has emerged as a novel area of

• thiophenolate. Conclusion To conclude, we have employed a photoredox methodology to access clavam and pyrrolyloxazole intermediates, showing the possibility of using the nucleophilic nitrogen atom of β-lactams under photoredox conditions. The acridinium catalyst IV was able to oxidize the C=C double bond

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

• Gauntlett for assistance with synthesis of some intermediates. Funding This study was supported by an EPSRC Doctoral Training Partnership (grant number EP/T51813X/1) held at the University of Huddersfield (K.K.), a University of Huddersfield funded Ph.D. studentship (S.B.), and by the Université de Pau et

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• approach from levoglucosan 1 (Figure 1a) [23]. Allopyranose inter-halides 4 incorporating the 2,3-cis, 3,4-cis relationship for the halogens were prepared via intermediates 2 and 3 from levoglucosan (1). Compounds 4 were the starting point to complex 2,3,4-trihalohexanetriols and 2,3,4,5

• 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose (5) readily accessible form levoglucosan (1, Scheme 1) [24]. Activation of the C4 hydroxy group as triflate and direct treatment with a nucleophilic halogen furnished intermediates 8–11. The latter compounds proved to be difficult to purify

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

• intermediates at the anode. The produced acetate ion D and a magnesium ion form the salt E, which upon acid treatment during workup gives a diphenylacetic acid 2. The effects of DMSO as solvent are not clear at present, and one reasonable and acceptable aspect might be the solubility of the salt of intermediate

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

• process and the rich toolkit of advanced organic synthesis [5]. Homoallylic amines occupy a significant niche in alkaloid synthesis as they frequently appear as key intermediates in syntheses of the various nitrogen-containing natural products [6][7][8][9][10][11][12][13][14]. Additionally, they can be

• , that the 2-aminophenol functionality in the substrates is a prerequisite for attaining high enantioselectivity in the allylation. Interestingly, the aldimines synthesised from 2-hydroxy-4-methylaniline produced inferior yields. While the N-aryl homoallylic amines 66 can be useful intermediates in total

• release catalyst 78 completing the catalytic cycle (Scheme 17). In a mechanistic probe, the proposed reaction intermediates were used as starting electrophiles under the standard reaction conditions (Scheme 18). In all three cases, identical outcomes were achieved, supporting the proposed catalytic cycle

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• challenging iminoiodinanes). In situ preparation of the iminoiodinane intermediates is possible, and for those reagents that undergo facile decomposition, aziridination is more efficient using these conditions (yields for in situ-generated iminoiodinanes are in parentheses in Scheme 3, with N-o-methyl (6g

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

• structural characters and multiple good reactivities [1][2][3][4]. Both β-keto thioesters [5][6][7][8][9][10][11][12] and β-keto amides [13][14][15][16][17][18][19][20][21][22] have served as useful synthetic intermediates for the synthesis of a range of potent natural products. Therefore, much effort has

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• intermediates [34] (e.g., G) or side products [35] (e.g., H) during their total synthesis, are neither systematically covered in this review. A number of wrongly assigned structures have been proposed over the decades (Figure 3). These are mentioned here in summary, where further details will be given in the

• fecal microbiota [107]. Alternariol methyl ethers: Methyl ethers of alternariol have been obtained during chemical structure elucidation and as intermediates in total syntheses of natural products, but some of these have been furthermore isolated as natural products (Figure 5). First to mention is 9-O

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

• -Addition of molecular bromine to phenyl isocyanide was reported by E. Kühle et al. to afford the corresponding 1,1-adduct (PhN=CBr2) [23]. Since dichloro compounds (RN=CCl2) [24] are the imino derivatives of highly toxic phosgene (O=CCl2), reactions using them as key intermediates are not safe synthetic

• (R = EWG-C6H4, E = PhS and PhTe) in moderate to high yields [30]. Very few examples of intermolecular cascade reactions with imidoyl radicals as key intermediates have been reported. The intermolecular cascade reaction of diselenide, electron-deficient acetylene, and isocyanide under photoirradiation

• 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

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

• pyrazoles. The review will primarily focus on two major categories: two-carbon and three-carbon building blocks as key intermediates, while other special cases will be summarized separately. Review (3 + 2)-Cyclocondensation – C3-building blocks as key intermediates The majority of the numerous pyrazole

• of the carbonyl groups and their derivatives. 1,3-Dicarbonyl compounds as key intermediates The most common and classic synthesis of ring-forming pyrazoles is the cyclocondensation of 1,3-dicarbonyl compounds with hydrazines (Knorr synthesis) [42][43]. Therefore, the in situ generation of 1,3

• , 3,4,5-substituted pyrazoles 5 are formed (Scheme 2) [45]. The Lewis acid catalyst accelerates the reaction via participation in the formation of β-diketonate complexes. Other carbonyl compounds suitable for pyrazole synthesis are 2,4-diketoesters 13. These intermediates can be prepared from diethyl

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• access to diazo compounds as either synthetic intermediates or products. A special attention is paid to the reaction mechanism with the aim to encourage further development in this field. Keywords: C–H functionalization; diazo compound; electrosynthesis; hydrazone; nitrogen-containing heterocycle

• have been harnessed as valuable intermediates in Wolff–Kishner reduction reactions [12][13][14] or for the synthesis of various olefins via diazo or vinyllithium intermediates in the Bamford–Stevens reaction [15] and Shapiro reaction [16], respectively [17]. SAMP/RAMP ((S)/(R)-1-amino-2

• -methoxymethylpyrrolidine)hydrazones could be also key intermediates for the asymmetric synthesis of α-substituted aldehydes and ketones [18][19]. Interestingly, depending on the substitution pattern, the C=N bond can feature different electronic properties [20]. For instance, various hydrazones have been employed for the

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• Abstract A flow photochemical reaction system for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence was developed, which utilizes in situ-generated 2-benzopyrylium intermediates as the photoredox catalyst and electrophilic substrates. The key 2-benzopyrylium intermediates were

• generated in the flow reaction system through the intramolecular cyclization of ortho-carbonyl alkynylbenzene derivatives by the π-Lewis acidic metal catalyst AgNTf2 and the subsequent proto-demetalation with trifluoroacetic acid. The 2-benzopyrylium intermediates underwent further photoreactions with

• catalytic cycles). In catalytic cycle I, the key cationic components, 2-benzopyrylium intermediates A, are generated in situ by the activation of the alkyne moiety of ortho-carbonyl alkynylbenzene derivatives 1 in the presence of the π-Lewis acidic metal catalyst [M]X [AgNTf2 or Cu(NTf2)2] and subsequent

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

• state (TS) structures that would produce both the N1- and N2-products from CH3OTs as a model system. When the Boltzmann average of the cesium-coordinated intermediates is calculated, a 3:1 ratio of 6(N-H)NOCs-Z:6(N-H)NNCs-E is found. This average is 10.6 kcal/mol more stable than 6(N-H), and was

• favorable under conditions A. Postulating that O or N-dative interactions with phosphorus were responsible for the high N2-selectivity in an analogous fashion to conditions A, we searched for intermediates and TSs that included this possibility. No O–P or N2–P-coordinated intermediates were found. The

• indazole and the deprotonated indazole was only −0.2 kcal/mol (Figure 11). Again, no preorganized intermediates were found. The NCIs were consistent with the parent system. The hydrogen bond between the H on the electrophilic methyl group and an ester oxygen was found in the transition state leading to the

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• that α-heteroaryl acetates accessed through Negishi coupling can be used as key intermediates towards NCAs (Scheme 1c). Indeed, oximation of these motifs followed by reduction gave access to the desired NCAs. Results and Discussion Negishi cross-coupling step The Negishi reaction provides convenient

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

• radical clock experiment was carried out with 1d under the optimal reaction conditions, resulting in the formation of 2d in 54% yield, and no cyclopropyl ring opening products were observed. This result suggested that no radical intermediates were generated during the reaction (Scheme 5). According to the

• the substrate, and thus preventing the possible interaction between the amide moiety and PISA, as opposed to CH3CN. The olefin moiety of the complex then interacts with the exposed central iodine(III) atom in PISA [25], forming the intermediate D. Similar cyclic iodonium intermediates were also

• HFIP (3.0 mL) at room temperature. Isolated yield is stated. aThe yield of 2k was 56%. bThe yield of 2m was 24%. cThe yield of 2n was 11%. Control experiment to test for radical intermediates. Proposed mechanism for the reaction between 1a and PISA in anhydrous acetonitrile. Two other resonance

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• cations that offer unique reactivities as intermediates in various bond-formation processes. Such intermediates can potentially take part in both radical and ionic bond formation; however, the mechanisms involved are complicated and not fully understood. Herein, we report electrochemical radical cation

• organic chemistry [11][12][13][14][15]. Single-electron oxidation of bench-stable substrates can generate radical cations that offer unique reactivities as intermediates for various bond-formation processes (also true for reduction). Because the reactivities of radicals and ions are fundamentally

• different, their creative use may pave the way for complementary bond formation. This merging is unique and such intermediates could potentially take part in both radical and ionic bond formation. However, the mechanisms involved can be complicated and are not fully understood. Alkenes and styrenes are

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

• , was not observed. In 2016, Sashidhara et al. reported the catalytic effect of Ag(OTf) on GBB reactions, postulating its role in activating the attack of the isocyanides onto the imine intermediates [7]; some years later Liu et al. reported a similar role of AgOAc [8]. Although the reaction was tested

• compatibility of the GBB reaction with typical KTGS conditions, such as aqueous solvent at near-physiological pH and high dilution, and the achievement of selective ligand amplification. First, molecular modeling studies were carried out to verify that building blocks and intermediates could bind the target

• yield of 83–95%. The second strategy, based on the deacetylation of 29 followed by the GBB-3CR, led to a lower overall yield of 21–23%. The reaction with different 2-aminopyridines and alkyl/aryl isocyanides afforded the intermediates 30 in 86 to 96% yield, and the subsequent deacetylation with

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

• that bear two functional groups. In order to avoid competitive reactions, these groups need to be compatible with the components of the Ugi reaction or the intermediates generated during the reaction. Thus, an amine can rarely be directly incorporated as an additional functional group, because of