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

• other isocyanide MCRs is effective and one promising direction to increase the diversity of new peptidomimetics is the use of, for example, α,β-unsaturated aldehydes including those containing a halogen atom in the β-position, in the Ugi-4CR reaction [1][39]. As our previous studies have shown

• bisamides based on the same aldehydes and amines may also demonstrate biological activity. In view of these facts, we decided to develop a new approach for the synthesis of hybrid molecules containing substituted heterocyclic and peptidomimetic moieties. The first stage of this approach was the preparation

• -butylamino)-4-oxobutanoyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate (12e) according to the X-ray diffraction data. Non-hydrogen atoms are presented as thermal ellipsoids with 50% probability. The use of α,β-unsaturated aldehydes in the Ugi reaction. Comparison of isocyanide conversion conditions. Hydrolysis of

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

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• iodanes (NHIs) as suitable reagents for the mild oxidation of activated alcohols. Two different protocols, both involving activation by chloride additives, were used to synthesize benzylic ketones and aldehydes without overoxidation in up to 97% yield. Based on MS experiments an activated hydroxy(chloro

• )iodane is proposed as the reactive intermediate. Keywords: alcohol oxidation; hypervalent iodine; N-heterocycles; Introduction The oxidation of alcohols to aldehydes and ketones is an essential transformation in organic chemistry [1][2]. Generating aldehydes is particularly challenging as they are

• mild oxidation of primary and secondary benzylic alcohols to aldehydes and ketones as an alternative to λ5-iodanes. Results and Discussion Initially, we investigated a variety of pyrazole-, triazole-, and oxazole-substituted hydroxy-NHIs previously developed by our group [25]. However, none of them

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• the corresponding library members were denoted as 4{i,j,k}. Results and Discussion Library synthesis Preliminary experiments on the parallel GBB reaction were performed with heterocyclic amines 1{1–430}, aldehydes 2{1–583}, and isonitriles 3{1–73} available from our stock (based on our previous in

• aromatic aldehydes (e.g., 2{1–3}) did not work in the GBB reaction (Figure 4). This result is in accordance with the previous findings [21]. Notably, steric effects were not significant since o,o′-disubstituted aldehydes (e.g., 2{4–6}) displayed usual efficiency. As might be expected from our previous

• demonstrating poor performance. Using the resulting sets of amino heterocycles 1{22–485}, aldehydes 2{4–867}, and isonitriles 3{4–78}, 892 library members 4{22–485,4–867,4–78} were deliberately selected and subjected to the parallel synthesis using the Sc(OTf)3-based protocol. As a result, 790 library members

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• of anilines through Brønsted acid or transition-metal-promoted conversion of 2-cyclohexanone oximes [15][16][17][18] (Scheme 1, (2)). Moreover, Strauss and co-workers described a green, multicomponent reaction of aromatic aldehydes, 2-cyclohexenone and amines to afford 2-arylmethyl N-substituted

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• synthetic tool for the construction of functionalized molecules. Dating back to the 19th century, this reaction, though initially used for the synthesis of an alcohol and acid functionality from aldehydes, has henceforth proven useful to generate diverse molecular entities using both intermolecular and

• simplified form, focuses on the base-induced disproportionation of two molecules of a non-enolizable aromatic and/or aliphatic aldehyde (without an α-hydrogen atom). These aldehydes undergo in the presence of concentrated alkali or other strong bases, a simultaneous oxidation and reduction sequence of two

• in subsequent reactions. Reddy and coworkers carried out the Cannizzaro reaction of aromatic aldehydes to the corresponding alcohols in high yields by crossed-Cannizzaro reactions employing solid-supported KF-Al2O3 as catalyst [26] under microwave irradiation using solvent-free conditions. The use of

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• photochemical C–O bond cleavage of ethers in organic transformations has attracted considerable interest. In this context, in 2018, Nicewicz and co-workers [57][58] reported a visible-light-photoredox-catalyzed single-step synthesis of polysubstituted aldehydes using easily accessible olefin substrates (Scheme

• bond activation of benzyl alcohols. Deoxygenative arylation of alcohols using NHC to activate alcohols. Deoxygenative conjugate addition of alcohol using NHC as alcohol activator. Synthesis of polysubstituted aldehydes. Funding The author thanks SERB, India (CRG/2021/000402) for financial assistance.

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• using 5-amino-1-benzyl-3,3-dimethoxyindolin-2-one (1) [12] and benzyl isocyanide (4), as amine and isocyanide components, respectively. Different carboxylic acids 2 and aldehydes/ketones 3 were evaluated using ZnF2 as catalyst (10 mol %) and MeOH as the solvent (Scheme 2 and Figure 2). A library of α

• substitution occurs due to the presence of acetic acid (2a) as reaction component. Aliphatic aldehydes with small chains (3b and 3c) were used successfully in the reaction approach, as expected. Also, aromatic 2-chlorobenzaldehyde (3d) was used and the desired compound 5ad was obtained in 36% yield (Scheme 2

• ]. Carboxylic acids 2 and aldehydes/ketones 3 used in the Ugi4CR. GI50 range plot against human solid tumor cell lines of investigated α-acetamide carboxamide isatin hybrids. Green most potent, yellow intermediate, red less potent. (A) Library of isatin-based α-acetamide carboxamide oxindole derivatives

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

• aldehydes or ketones, undergo base-assisted condensation reactions with amines providing the corresponding imines. In the last step, the active manganese hydride complexes reduce the imine compounds and afford the desired alkylated amine products (Scheme 2B). Several well-defined manganese complexes have

• aldehydes, leading to the corresponding imine intermediate, which again undergoes hydrogenation by Mn9-c and yield the N-alkylated product and the regeneration of complex Mn9-a (Scheme 20). Very recently, Bühl and Kumar reported a novel and efficient methodology for the synthesis of branched

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent

• Passerini-tetrazole product. Then, the Swern oxidation [22][23][24], which is widely exploited and has a wide tolerance of functional groups, was used to convert the tetrazole containing alcohols to aldehydes, in particular for derivatives bearing convertible isocyanides. Most building blocks were well

• tolerated in Swern oxidation providing moderate to excellent yields of the target aldehydes, except cyclohexyl isocyanide, which decreased the reaction yield and only gave trace amount of product. Importantly, the synthetized carboxaldehyde-tetrazole building blocks are bench stable and can be easily and

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• by Lewis acid-catalysed cyclisation of bicyclobutanes with aldehydes [84] and polysubstituted 2-oxa-BCHs bearing more complex substitution patterns were synthesised by triplet energy transfer catalysis from benzoylformate esters and bicyclobutanes [85]. Reports of polysubstituted scaffolds larger

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• open chain aldehydes present in solution (≈5%) with a doublet at δ 9.6 ppm, with the configuration of the hemiacetal centre confirmed in the solid state by X-ray crystallography on 12a and 12d. The 1H and 13C NMR spectra for 13b,d,e were similar to the starting materials, except that the resonances

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• ) acetate complexes of ligands I–IV were screened as enantioselective catalysts for asymmetric Henry reactions. The series of nine different aldehydes (aliphatic, aromatic bearing an electron-withdrawing or an electron-donating group, heteroaromatic) was chosen for these studies. The reaction conditions

• explained by the sterical demand of the aldehyde (R = t-Bu), leading to suppressing its coordination with the complex. The ee values achieved with the complex of ligand Ia were variable (29–83%), whereas better enantioselectivity was found for less reactive aldehydes (aliphatic and bearing electron-donating

• ligand IIIa possesses lower catalytic activity than the pyridine derivative (for TON and TOF parameters see Supporting Information File 1, part S5). The conversions were poor in the case of less reactive aldehydes, e.g., thiophene-2-carbaldehyde, and 3-phenylpropionaldehyde. To achieve satisfactory

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

• activities. The most direct way of obtaining this nucleus is the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being

• 99%), with a low catalyst loading (2 mol %) in only 30 minutes, and allows the successful use of aliphatic aldehydes, substrates not so frequently explored with most usual catalysts for this reaction. Furthermore, the aforementioned advantages make this methodology very attractive and superior to the

• conditions and the employment of relatively complex starting materials [19]. A more efficient way of obtaining this nucleus is through the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between amidines (aminoazoles), aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis [20

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• synthesis of spiro-annulated pyrrolidine-2,5-diones by catalyzed spirocyclizations involving aldehydes [11], tetrahydrofuran [12][13], and in the O–H insertion/Claisen rearrangement/intramolecular oxa-Michael addition cascade [14] (Scheme 1). Herein, we report our findings obtained, while investigating the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• reaction between aldehydes with indoles, while focusing on the more environmentally friendly methods developed over the years. Keywords: aldehyde; BIMs; Friedel–Crafts reaction; green chemistry; indole; Review Medicinal properties In recent years, diindolylmethane (DIM, 1) and its derivatives known as

• pharmaceutical and biological activities. Among indole derivatives, bis(indolyl)methanes (BIMs) are profoundly interesting, due to their wide range of pharmaceutical properties. The most common approach involves the electrophilic substitution of various aldehydes and ketones by indoles, utilizing either protic

• :0.05, under solvent-free conditions at 50 °C for 50 min, the product was obtained in 90% yield. To emphasize the role of DBDMH, when the reaction was performed without DBDMH, no product was observed. The generality of this protocol was also tested by employing various aromatic aldehydes, which formed

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

• coupling of NHPI esters with aldehydes enabled by NHC catalysis [106]. The reaction proceeds with the catalyst NHC-1 at 60 °C and gives rise to ketones (Scheme 30A). The proposed mechanism begins with the reaction of benzaldehyde (143) and the NHC-catalyst 144 to form the neutral Breslow intermediate 145

• mechanism discussed in Scheme 7B. Lastly, radical–radical coupling between 64 and 147, accompanied by elimination of the NHC catalyst, yields ketone product 149. In subsequent studies, this NHC-catalyzed radical relay activation mode has been extended to the alkylation of aliphatic aldehydes [107] and to

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• mention that allylic hydroperoxides are conveniently produced by the photooxygenation of alkene substrates [14][15][16]. Taking all these informations together, since alkenes can be easier intermediates than aldehydes to handle, we envisaged to use a prenyl (= 3-methyl-2-buten-1-yl) group as an aldehyde

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• alkylphosphine, an aldehyde and an alkyne [32]. Another example resulting from phosphine addition to α,β-unsaturated aldehydes was published shortly afterwards [33]. Phosphonium carboxylate zwitterions have been obtained by the reaction of phosphines with acrylic acid [8] and ortho-carboxylated arylphosphines

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• selective synthesis of expanded porphyrins and their chemistry with regard to their aromaticity and coordination properties. They used meso-aryl-substituted dipyrromethanes and aldehydes in the synthesis of A3B3-type hexaphyrins [13] and 5,10-diaryl-substituted tripyrranes in A4B2-hexaphyrin synthesis [6

• ][17][18][19][20]. Similarly, the syntheses of AmBn-type hexaphyrins, octaphyrins, or higher expanded porphyrins were handled by improved methods in recent years with the use of tripyrranes or bilanes and aldehydes [7][14][21][22][23][24][25]. In our previous studies, we used N-tosylimines throughout

• the syntheses of several porphyrinic compounds which emphasized the usability of N-tosylimines with dipyrromethanes, tripyrranes, or bilanes instead of aldehydes in the synthesis of porphyrins and contracted/expanded porphyrins [26][27][28]. It was shown that the reaction of meso-pentafluorophenyl

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

• nitroarenes 48 (Scheme 22). The protocol demonstrated excellent tolerance towards a wide range of reducible functional groups, including halogens (such as chlorine, bromine, and even iodine), aldehydes, ketones, carboxyl groups, and cyano groups. Iodination Alkyl iodide is considered to be the most reactive

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

• [44] (Scheme 6). El Kaim and Jia reported a Mannich-type reaction of trifluoroacetaldehyde hydrazones with formaldehyde and aromatic aldehydes to obtain valuable starting materials for the generation of other trifluoromethyl-substituted heterocycles. The study demonstrated that the electron

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• aldehydes and α-amino esters (via dehydration) or α-amino acids (via decarboxylation) could be classified based on the substitution groups on the N atom to: 1) N-substituted (N–R type), 2) hydrogen containing (N–H type), and 3) metal complexes (N–M type) (Figure 1) [16][17]. These AMYs could also be

• : A1-type AMYs can be generated from the condensation of aldehydes with α- and N-dialkylglycine esters, A2-type AMYs are derived from α-alkylglycine esters, A3-type AMYs are derived from N-alkylglycine esters, and A4-type AMYs are derived from glycine esters. Stabilized zwitterions A1–A4 have the

• group on the α-carbon atom are semi-stabilized (Scheme 1) [16]. The B1-type AMYs can be generated from the decarboxylative condensation of aldehydes with α- and N-dialkylglycines or from cyclic amino acids (such as proline) [31][32][33], while AMYs of type B2 are accessible through the decarboxylative

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• [12][13][16][19][26]. 1H derivatives can be obtained in a number of ways, including direct condensation of N,N'-dimethylphenylene-1,2-diamine derivatives with the appropriate aldehydes, YCHO [24][27], or borohydride reduction of 1+ salts [24]. The cations conversely can be obtained from 1H derivatives

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• Knoevenagel condensation of rhodanine with different aldehydes [3]. The reactions were performed in ChCl/urea (1:2) at 90 °C, without needing a catalyst and the products were obtained in low to good yields (10–78%). On another hand, ʟ-proline is well known as an organocatalyst and its use in aldol and

• reaction of benzofuranone and aldehydes in good to excellent yields in a few minutes under ultrasound irradiation. Results and Discussion As a part of our ongoing research in DES chemistry, we were mainly interested in the conditions reported by Detsi [20], and attempted to apply them for rhodanine

• aldehydes to study the scope of this reaction (Scheme 1). It must be noted that in most of the cases, the reaction mixture changed its appearance from colorless to yellow or orange and that some solid precipitate formed during the reaction. The addition of water at the end of the reaction clearly led to the