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

• diastereoselectivity after 24 h of reaction (61% yield and 7:1 dr, Table 1, entry 14). By lowering the reaction temperature to 50 °C using the same catalyst (Table 1, entry 15), the yield of the reaction increased slightly to 73% in 24 hours. Disappointingly, the bifunctional thiourea THIO-1 gave a lower yield and

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• thiourea [112], keeping acetyl or benzoyl protection intact (Scheme 7) [113] which contributed to the selective deprotection of sugars in systematic oligosaccharide synthesis. The chloroacetyl group can also be similarly selectively deprotected with other reagents like N,N-pentamethylene thiourea [114][115

• with significant yield and selectivity (Figure 2). They could also be selectively cleaved with thiourea without affecting other ester-type protecting groups and implemented the antimigratory attribute of the benzoyl group coupled with the neighbouring group participation property making them a

• versatile substitute of the chloroacetyl protection for oligosaccharide synthesis. However, since the thiourea deprotection is often quite slow in nature requiring the application of heat for a prolonged period, there is always a possibility of extensive side reactions producing undesired side products

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• enantioselectivities. Compound 66d was incorporated into a thiourea organocatalyst framework and successfully tested in kinetic resolution with 73% enantioselectivity. The chiral phosphoric acid (CPA) (R)-C22 was used to catalyze the formation of a C–N chiral axis in the axially chiral product 68 from biarylamines 67

• either debenzylated and subsequently transformed into a thiourea organocatalyst or turned into an axially chiral sulfonamide. In 2022, Yang et al. presented their (3 + 2) formal cycloaddition of alkynylindoles 184 with azonaphthalenes 185 catalyzed by the SPINOL-based CPA C26 (Scheme 54) [82]. The

• thiourea organocatalyst was prepared. Hou et al. investigated a way to prepare axially chiral compounds that contain both benzimidazole and quinoline rings 189 (Scheme 55) [83]. One route to access such compounds was possible through the reaction of 2-alkynylbenzimidazoles 187 with o-aminophenylketones 188

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• their structure will be described. In 2012, Wang and co-workers reported a bifunctional thiourea-catalyzed aza-Diels–Alder reaction of cyclic keto/enolate salts 1 and N-tosyl-2-methylene-but-3-enoates 2 (Scheme 1). After a screening of the reaction conditions they found that organocatalyst I, acetic

• organocatalyst acts as a Lewis base forming an enamine which raises the HOMO energy of the dienophile, while the thiourea moiety acts as a Lewis acid, lowering the LUMO level of the diene (Scheme 1). A confined transition state is formed providing a high enantiocontrol of the reaction. In 2016, Shi and co

• -workers reported a cinchona alkaloid-derived thiourea-catalyzed regio- and stereoselective cycloaddition of 3-isothiocyanatooxindoles and imines containing two or three electron-deficient unsaturated bonds [25]. Firstly, the (3 + 2) cycloaddition of 3-isothiocyanatooxindoles 4 and aldimines 5 was explored

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

• securing the enantioselectivity of the reaction by locking the catalyst in the more active and enantioselective Z-configuration (Figure 2). Further, the authors found that H-bond donors featuring urea, thiourea, and guanidine motifs were either inactive or provided racemic mixtures. Among 3,5-dichloro

• [39] developed a direct, highly enantioselective three-component reaction between aromatic acetals, BocNH2, and various 2-monosubstituted or 2,3-disubstituted allyltrimethylsilanes in the presence of 10 mol % of triethylsilyl triflate (TESOTf) and 10 mol % of the chiral bifunctional thiourea catalyst

• . In the optimisation of the catalyst 78 structure, several important observations were made (Scheme 19). Replacing thiourea (91) as the H-bond donor unit with squaramide (93) or urea (92) did not affect the enantioselectivity of the allylation of the benzaldehyde-derived acetal. On the other hand

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With the

• impressive boost of the reaction rate in the ball mill was observed (3 h vs 4 days), the stereochemical outcome suffered giving the desired adduct with 59% ee instead of 94% ee in solution. Owing to the introduction of an additional functional group in the form of a thiourea moiety does not entail a

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

• ][4][9] or even visible light-driven methods [25][26][27][28]. We started our study from the optimization of the reaction conditions using β-ketosulfone 1, benzaldehyde and thiourea as model reaction. According to the literature, the reaction has been shown to work best and most efficiently under

• 18). Reaction scope We then used optimized reaction conditions from Table 1, entry 16 (method A) and 12 (method B) to further explore the scope of the reaction (Scheme 2). By employing various EWG/EDG-substituted benzaldehydes and urea/thiourea/selenourea we synthesized novel Biginelli products 2a–q

• with up to 95% yield. The use of selenourea has been shown to give low yields of products (up to 33%). In fact, we have thus expanded the range of available selenium-containing DHPMs in addition to the work of other authors [33][34][35]. We also attempted to replace urea/thiourea/selenourea with N

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

• spaces. The confinement of the heterogeneous version of cinchona amine and thiourea catalysts was reported, leading to improved enantioselectivity values in the Michael addition of nitromethane (5) to chalcone (6) through modification of the pore size of mesoporous silica 8 or 9 (Scheme 2) [63]. Thus

• , for cinchona thiourea, enantioselectivity not only increased with reduced pore size but even reached the level of the homogeneous catalyst when the support pore size was reduced to 6.3 nm. This resulted in obtaining the (R)-configured product 7 with 63% yield and 93% ee, as opposed to a 55% yield and

• lead to a decrease in selectivity. Connon and co-workers have attached a cinchona thiourea organocatalyst to magnetic nanoparticles 13 for the Michael addition of dimethyl malonate (10) to trans-β-nitrostyrene (11) (Scheme 3) [31]. To explore the potential impact of nanoparticles on catalyst efficiency

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

• ]. Other groups have also investigated the Michael donor–acceptor reactivity of curcumins [25]. For instance, a quinine-thiourea catalyzed Michael addition of curcumins to nitroalkenes reported by Ye et al. stopped at the single Michael addition stage [35]. In the subsequent year, Yan et al. demonstrated a

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

• transformation (Table 1, entries 2–5). Thiourea, which is regarded as a classic H-bond donor in carbonyl activation, also could not boost the yield (Table 1, entry 6). Fortunately, it was found that the yield of 4aa was gradually increased to 64% upon adding 3a from 2.0 to 10.0 equiv (Table 1, entries 7 and 8

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

• ], Reformatsky reaction [65], azalactone synthesis [66], nitro reduction [67][68], epoxide rearrangement, thiourea guanylation, and others [69][70]. In this article, we describe a simple and direct protocol for the preparation of indanones through a classical Nazarov reaction catalyzed by bismuth(III) triflate

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

• benzothiazolium species would avoid the formation of thiocarbonyl difluoride, which is most likely responsible for the generation of thiourea 7. Pleasingly, under these conditions, amide 5s was formed smoothly with isolation by column chromatography providing the pure product in 71% yield (Scheme 3b). Furthermore

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

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

• strands of TMV, inhibiting their ability to multiply and cause damage to the plant. At the same time, they also display fungicidal activities against more than fourteen types of common fungi, such as Phytophthora alternaria, based on their DNA damaging properties with the thiourea derivative, showing the

• research group explored the activity of cadmium sulfide (CdS) nanotubes as heterogeneous nanocatalysts for the electrophilic condensation between aldehydes and indoles [106]. The nanorods were obtained with a solvothermal technique, where thiourea and cadmium nitrate were mixed in ethylenediamine for 10

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• substituents in the isatin ring showed pronounced negative photochromism upon irradiation with red light (625−650 nm). Supramolecular complexation with Schreiner’s thiourea organocatalyst (STC) allowed to reach better conversion with the isomeric ratio in PSS increased from 46% to 84%. The backward switching

• species. Zwitterionic resonance structures of Z-indigo. Photos of crystalline N,N'-di(Boc)indigo 17a its solutions in 1) DMSO, 2) DMF, 3) N-methyl-2-pyrrolidone. Structural isomers of indigo. Photochromism of indirubin derivatives and supramolecular complexation of the E-isomers with Schreiner’s thiourea

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reacted with N-(arylthio)succinimide 1 or N-(arylthio)phthalimide 14 as the sulfenylating reagents in the presence of cinchona-derived thiourea O as a catalyst to afford the corresponding chiral naphthalenone products 126 under mild reaction conditions. Another work from Anbarasan and Chaitanya on the use

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• multicomponent reactions have been successfully developed to construct multifunctionalized or polycyclic spirooxindoles. For example, Zhang successfully developed a recyclable bifunctional cinchona/thiourea-catalyzed four-component Michael/Mannich cyclization sequence for the asymmetric synthesis of

Retraction: One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2023, 19, 1170–1170, doi:10.3762/bjoc.19.85

• ; thiourea; This article was retracted due to the improper manipulation of NMR spectra with the help of software to obscure peaks corresponding to impurities and solvent.

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -hydroxyindoles allowing the 4-indolyl-substituted stereocenter formation. In both cases, few more products were added by altering N1 and C3 substituents of 100 (Scheme 26) [56]. In the same year, a quinine-derived chiral thiourea-mediated aza-Friedel–Crafts reaction between hydroxyquinolines 115 and isatin

• N-substituted Boc group of 49 were H-bonded with NH groups of the thiourea framework whereas the hydroxy functionality of 116 engaged itself in H-bonding with the quaternary nitrogen of the catalyst (see transition state 117). These noncovalent interactions were responsible for the stereochemical

• (Scheme 28) [58]. In 2021, Wang, Jin and co-workers deployed chiral thiourea T2 as the catalytic agent for executing a highly enantioselective aza-Friedel–Crafts process between β-naphthols 119 and isatin-derived ketimines 49 in the course of accessing enantioenriched 3-amino-2-oxindoles 122 (Scheme 29

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• end, we first tested the achiral thiourea derivative 10, which exhibited very low activity at 23 °C when used in catalytic and stoichiometric amounts (Table 1, entries 9 and 10) [59][60]. The yield of the aza-Nazarov product 7b increased to 40% when 20 mol % of thiourea 10 were used at 80 °C in CH3CN

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• and stereocontrol of the reaction depends on the conformational rigidity of the macrocyclic framework and a synergy between the thiourea and tertiary amine sites. Recently, many efforts were focused on the synthesis and applications of mechanically interlocked molecules (MIMs), such as catenanes and

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ketones and thiourea via an oxidative cyclization initiated by a radical process and a following condensation reaction (Scheme 1c) [29]. Although these methods are practical, most of these strategies require stoichiometric or excess amounts of halogenating reagents or oxidants, which are toxic, hazardous

• demonstrate the feasibility of our idea, ethyl acetoacetate (1a) and thiourea (2a) were chosen as model substrates for the optimization of reaction conditions. Based on our previous studies on the halide-mediated α-C–H functionalization of carbonyl compounds [32][33][34][35], graphite was chosen as the

• reacted smoothly with thiourea 2a under the optimized conditions, giving the corresponding products in 30–80% yields (3a–d). In addition, allyl and benzyl acetoacetate were also suitable substrates to give the desired 2-aminothiazoles 3e and 3f in 78% and 52% yields, respectively. β-ketoesters containing

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• . Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and

• Mannich reactions; supramolecular catalysis; thiourea; Introduction In the past decades, the development of supramolecular chemistry has enabled abundant host scaffolds and assembly tools for boosting catalytic processes, and stimulated the emergence of supramolecular catalysis [1][2][3][4][5][6][7][8][9

• situation. In this way the catalytic functionalities are permanently installed within the macrocyclic skeleton by forming a persistent catalytic cavity. Following this idea, we have recently constructed a series of bisthiourea macrocycles [28][29][30]. Thiourea groups were introduced due to their superior

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• (entry 10, Table 1) [41]. The scope of this method was further extended by employing this protocol to the synthesis of a thio derivative of 5-unsubstituted DHPM. Since thiourea does not form a clear melt with tartaric acid, the tartaric acid–choline chloride melt was employed for the reaction involving

• thiourea as one of the reactants. Hence, (E)-ethyl 4-(4-bromophenyl)-2-oxobut-3-enoate (19) on treatment with tartaric acid–choline chloride melt by employing thiourea as one of the reactants furnished the corresponding thio derivative of 5-unsubstituted DHPM derivative (entry 8, Table 1). The melt medium

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• obtained (compounds 8s, NR4R5 = NPh2). The aza-Wittig reaction of iminophosphoranes 5 with an excess of CS2 took place smoothly at 40 °C to produce isothiocyanates 9, which were allowed to react with secondary amines to generate thiourea intermediates 10. In the presence of K2CO3 in CH3CN at refluxing