Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• -condensation method performed under low surfactant concentration conditions [46][47][48][49][50], changing the concentration, molecular size, and hydrophilicity/hydrophobicity of the organoalkoxysilane precursors [51]. Various morphologies of mesoporous silica, including fibre, platelet, rod, and film, can be

• conditions (Scheme 4). Thiel and co-workers examined N-benzylthiazolium salts 17 anchored covalently to mesoporous materials in a benzoin condensation reaction (Scheme 5) [65]. Initially good yields were observed, even after a short reaction time, but a drop in yield was seen after reusing the catalysts for

• ability to predesign both primary and high-order structures serves as a great advantage in these catalytic systems, making them easily fine tuneable. Catalytically active sites can be formed by direct condensation or post-synthetic modifications. In the case of catalyst immobilisation post-synthetic

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• in favor of the second mechanism. To identify the structure obtained on the surface of the droplets during the formation of the Pickering emulsion, we used fluorescent labels. Aminofluorescein was introduced into the CMC composition with a ratio of 3 mg per 1 g of cellulose using condensation in the

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

• syntheses known in the literature are based on the condensation of 1,3-dielectrophiles and their synthesis equivalents as C3-building blocks, along with hydrazines as N2-building blocks [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Conceptually, the en route generation of these C3-building

• oxalate (9) and alkylphenones 10 through a sterically hindered Claisen condensation, producing a six-membered lithium enolate salt. Subsequent cyclocondensation with hydrazines concludes the formation of pyrazoles. However, this process could not be performed as a one-pot synthesis, as the solvent had to

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

• ; Introduction Hydrazones represent an important class of organic compounds. They can be readily prepared through the condensation of hydrazine derivatives with aldehydes or ketones. They have found widespread applications in materials sciences and supramolecular chemistry [1][2][3][4][5]. Importantly, they are

• prepared prior to the electrolysis through the condensation of 2-hydrazinopyridine 13 and various aromatic, aliphatic and α,β-unsaturated aldehydes 14. The electrooxidative transformation was performed under constant current at 7 mA in a mixture of acetonitrile and water under heating. From a mechanistic

• -derived NH-acylhydrazones to build 1,3,4-oxadiazole derivatives in good yields. The electrolysis was conducted under galvanostatic conditions in methanol using a carbon graphite anode and a platinum cathode. From a mechanistic point of view, in situ condensation of acylhydrazines 28 with α-keto acids 27

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• (porphyrins) including heme, chlorophyll, and vitamin B12 [1][2] (Figure S54 in Supporting Information File 1). Porphobilinogen, the fundamental biological precursor of tetrapyrroles, is biosynthesized via asymmetric condensation of two δ-aminolevulinic acid molecules [2][3]. From another aspect

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

• -amino acids as primary diversity elements [10]. The pursuit of achieving the efficient synthesis of α-amino acids has been an ongoing challenge since 1850, marked by the initial report of the Strecker condensation [11]. The Strecker synthesis and the related Bucherer−Bergs hydantoin formation remains

• carbonyl group to an oxime through condensation with hydroxylamine (Scheme 5, bottom) [62][63][64]. In order to develop a synthetic approach applicable to several different substrates, we decided to screen the three methods on one example from each type of heteroaryl halides. According to our experimental

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

• -free conditions at room temperature for 2 h [16]. Although thiamine had already been reported to be effective in other chemical transformations and its role in carbonyl activation in vivo through its thiazole ring is well known, no mechanism of action in the GBB condensation was proposed by the authors

• -aminoimidazole moiety can be found in different alkaloids isolated from sponges and exhibits useful bioactive properties. The methodology employed by the authors to assemble C4/C5-functionalized 2-aminoimidazoles 49 exploited a Mannich condensation followed by an iodoxybenzoic acid (IBX) and N-iodophthalimide

• -bromoethyl)benzaldehyde 79 was utilized to form the highly reactive cyclic iminium intermediates 81 through the condensation with amidines 80. The subsequent formal [4 + 1] cycloaddition with the isocyanide and the 1,3-H-shift occurred to afford pentacycles 82. Performing the one-pot reaction under the

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

• (1H,3H)-dione) by refluxing with thionyl chloride [20][23]. However, the preparation of partially hydrogenated 5,10-dihydropyrimido[4,5-b]quinolinediones has been repeatedly reported by one-pot condensation of substituted anilines, aldehydes and barbituric acids, usually in protic solvents (alcohols

• of photocatalysts by tuning their redox and photophysical properties. Thus, we successfully developed a one-pot, three-component synthetic method with those substituents in 5-aryldeazaflavins 1 on the deazaisoalloxazine core or on the phenyl ring by condensation of N-substituted anilines, aromatic

• highly important for the outcome of this reaction. Thus, we decided to significantly improve our approach by optimizing the reaction conditions of a three-component condensation of commercially available 3,4-dimethylaniline (3a, 1.0 mmol), benzaldehyde (4a, 1.0 mmol) and N,N-dimethylbarbituric acid (5

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

• acid, indole-2-carboxylic acid, pyrrole-2-carboxylic acid or N-phenylglycine has allowed the use of these compounds in the Ugi reaction without triggering competitive reactions. The additional functional group present in the resulting Ugi adduct can be leveraged in different post-condensation

• reactions have become a useful tool for the synthesis of complex structures which overcome many of these problems, with the Ugi reaction leading these strategies. The scope of the Ugi reaction further increases when coupled with post-condensation reactions, which usually require the use of starting reagents

• more complex systems, we explored post-condensation reactions on the 2-nitrobenzylamine and 3-bromopropylamine derivatives. Thus, we carried out the reduction of the nitro group on derivatives 5b and 5h employing tin(II) chloride and chlorhydric acid in boiling n-butanol (120 °C), conditions previously

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

• obtained in a 43% overall yield after acid hydrolysis (Scheme 8). Unsaturated spiro-2H-furan-3-ones have been synthesized using various procedures. In 2000, Lee et al. employed an intramolecular condensation reaction involving an α-ketoester derived from prednisolone precursors to produce the target spiro

• -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

• with similar yields. In 2006, Akita et al. used an intramolecular Knoevenagel–Claisen type condensation between a β-ketoester and an acetate residue to synthesize spiro-2H-furan-3-ones [24]. For instance, the intermediate orthoester 35 was obtained in 86% yield after a cyclization–carbonylation

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

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

• -terminus of SorbB catalyzes conversion of thioester 31 using NADPH to liberate aldehyde 32, and subsequent Knoevenagel condensation-type cyclization leads to sorbicillin (33). The FAD-dependent monooxygenase SorbC, utilized in the chemo-enzymatic total synthesis of 2, catalyzes the oxidative

• isolated [47][49]. As shown in Scheme 5A, the proposed biosynthetic pathway of chalcomoracin (3) commence with the addition of three C2 units from the acetate pathway to 4-coumaroyl-CoA supplied from the shikimate pathway, leading to compound 42 [47]. Subsequent Claisen condensation, dehydration and

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• the specialised metabolism of bacteria and fungi. Each NRPS module is minimally composed of a condensation (C) domain, an adenylation (A) domain, and a peptidyl carrier protein (PCP or thiolation/T domain), and one module typically incorporates one amino acid into the final natural product. In

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

• reaction is a three-component condensation of an α-amino heterocycle (e.g., 2-aminopyridine) 1, an aldehyde 2, and an isonitrile 3 providing the corresponding fused imidazoles (e.g., imidazo[1,2-a]pyridines) of general formula 4 (Scheme 1) [18][19][20][21]. Imidazo[1,2-a]pyridines and related heterocycles

• (sEH) inhibitors [50], HIV-1 non-nucleoside reverse transcriptase inhibitors [51], or potential agents against visceral leishmaniasis [52] were found (Figure 8). Conclusion The Groebke–Blackburn–Bienaymé (GBB) reaction, a three-component condensation of amino heterocycles, aldehydes, and isonitriles

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

• presence of one equivalent Brønsted acid additive A5, the catalyst II generates the monoprotonated diamine II-A5. The condensation of the primary amine moiety in II-A5 with the carbonyl group of the α,β-unsaturated ketone 1b in presence of the Brønsted acid leads to the formation of the iminium ion

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• ) [3][4]. The building blocks for PKS biosynthesis often include malonyl-CoA or methylmalonyl-CoA, which are loaded onto the ACP by the AT domain. Subsequently, the KS domain catalyzes the decarboxylative Claisen condensation between the ACP-tethered extender unit and the KS-tethered growing chain. The

• ) Sequence alignment of KR domains whose stereoselectivity cannot be predicted based on the reported motifs. The labels show the product name and the order of the module where KR is located in the PKS assembly line (starting from the module with condensation function). KR types predicted based on the

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

• additive-free synthesis of 2-benzyl N-substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary amines has been reported. The reaction proceeds smoothly through a sequential imine condensation–isoaromatization pathway, affording a series of synthetically useful aniline derivatives in

• acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation. Keywords: aniline; (E)-2-arylidene-3-cyclohexenone; imine condensation; isoaromatization

• speculate that the solvation effect might be beneficial for stabilizing the condensation intermediate I and avoiding further unwanted conversions, e.g., nucleophilic attack of excessive benzylamine to the intermediate I. The following examination on solvents demonstrated that using ether solvents as the

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

• this protocol. Under basic conditions, the mechanism involves the condensation of a benzoxazolium salt 80, creating NHC–alcohol adduct 81. The [Ir(III)] photocatalyst is excited when exposed to blue light, leading to the formation of a long-lived triplet-excited-state *[Ir(III)] complex. This excited

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• can be used as starting materials in the studied condensation. We tested this hypothesis using the interaction of ketone 1b and phenylhydrazine hydrochloride (2a). It was shown that reflux of the starting compounds in ethanol for 1 h leads to the target hydrazone 3b in 64% yield (Scheme 3). It should

• , t-BuNHNH2). Unfortunately, in this case interaction of ketones 1 with aforementioned hydrazines led only to a complex mixture of unidentified products. At the same time the use of benzhydrazide or semicarbazide in the similar condensation resulted in recovery of starting compounds 1. Further, in

• order to test the Boulton–Katritzky reaction for unsubstituted hydrazones we investigated the condensation of ketone 1d with hydrazine. The process was carried out with 3-fold excess of hydrazine hydrate in EtOH at reflux for 4 h. Unexpectedly, in this case instead of desired hydrazone 3n we have

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• laboratory according to a previously published procedure [107]. The starting aminofuranes were easily prepared by reduction of Schiff bases (formed by condensation of the corresponding mono- or bis-amines with furfural) with sodium borohydride in methanol [83][108][109][110][111]. In order to determine the

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• scalability [38][39][40][41][42]. The substituted imidazoles 1–9 were synthesized using a condensation reaction between the corresponding aniline and diacetyl monoxime (Scheme 1), since the condensation using diacetyl was not successful for electron-poor aniline derivatives. This reaction leads to the

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• Knoevenagel condensation via the carbonyl group. In contrast, in case of 3-formylchromones the cyclization proceeds via the formyl group, due to its higher electrophilicity. The same regioselectivity was observed for 3-(methoxalyl)- and 3-benzoylchromones. In contrast, a cyclization via the carbonyl group of

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• synthesis has been reported for several transformations, such as epoxide opening [56], ketal formation and deprotection [57][58], Mannich reaction [59], intramolecular Sakurai cyclization [60], alcohol oxidation [61], aromatic hydrocarbon nitration [62], imine allylation [63], Knoevenagel condensation [64

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

• condenses with hydrazine followed by reduction and condensation with another aldehyde to afford the N-substituted hydrazones (Scheme 8). Balaraman and co-workers established a phosphine-free manganese catalyst generated in situ from a manganese precursor and a ligand for the N-alkylation of anilines with

• then undergo condensation with formaldehyde providing an N-phenylmethanimine intermediate which was confirmed by 1H NMR spectroscopy. In the final step, the imine undergoes hydrogenation with Mn3-b to yield the N-methylated product (Scheme 16). In 2020, Maji et al. synthesized manganese(I) complexes

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• equiv of 1,2-aceanthrylenedione, the reaction provided pure 3a product in moderate yield (41%). Subsequent recrystallization with boiling DMSO provided pristine red-brown crystals of 3a. The synthesis of DCPQ 4a was simple and proceeded with the condensation of a 1:1 mixture of acenaphthenequinone and

• modified procedure from the literature was implemented [28]. To synthesize 6a, the condensation was performed with 9,10-phenanthrenequinone, building block 12 in the presence of glacial CH3COOH, trifluoracetic acid, and 1,4-dioxane at reflux. Then, recrystallization from DMF and sublimation under ambient

• in Table S2 (Supporting Information File 1). First, the starting material 7e was obtained using 1,10-phenanthroline under harsh conditions as shown in Scheme 3 [29]. The same condensation reaction that worked for structurally similar 6a, produced a poorly separable mixture in the case of 7a. In the

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• benzothiazolimine species 6 which results from Boc-deprotection and subsequent condensation of the amide product onto the benzothiazolium core. Although the other identified by-product, thiourea 7, is not derived from the limiting carboxylic acid substrate, it was found to coelute with the amide product