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

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• catalyzed by cinchona-based thiourea catalysts [27]. As guest editor of this thematic issue, I am grateful to all authors for their excellent contributions. I thank the referees for providing their expertise and time, and the whole team at the Beilstein Journal of Organic Chemistry for their great level of

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• 226031, India Academy of Scientific and Innovative Research, Ghaziabad, 201002, India 10.3762/bjoc.18.25 Abstract A practical enantioselective N-selective nitroso aldol reaction of α-methylmalonamates with a nitrosoarene is reported. The reaction employs the Takemoto thiourea catalyst for the induction

• also found useful in catalyzing the nitroso aldol reaction [44][45][46][47][48]. Surprisingly, the utility of thiourea catalysts in nitroso aldol reactions remains far less developed. The scattered reports where bifunctional thiourea catalysis was found useful for this type of reaction, describe the

• reported a squaramide-catalyzed asymmetric nitroso aldol reaction of cyclic β-ketoesters and malonamate [61]. Inspired by this, we decided to investigate the use of malonamate in the asymmetric nitroso aldol reaction using thiourea catalysis. Herein, we report a novel nitroso aldol reaction of malonamates

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• bifunctional hydrogen-bonding catalyst would activate both CPD via a tertiary amino group of a quinuclidine moiety acting as a base via anion-binding, and an oxindole through the squaramide or thiourea moieties of the catalyst as hydrogen bond donors (Figure 1) [29][30][31][32]. Therefore, squaramide and

• thiourea catalysts were screened in a model reaction between CPD 1 and Boc-protected benzylidene oxindole 2a at room temperature in the presence of 10 mol % of catalyst (Figure 2). First, the quinidine-derived squaramide A was used and the desired product was obtained as a mixture of chromatographically

• inseparable diastereoisomers in 53% yield but in low enantiomeric excess for both diastereomers (Table 1, entry 1). With the quinine-derived thiourea B, the reaction was slow and the yield was very low, 12% (Table 1, entry 2). For that reason, we focused on the screening of squaramides. Squaramides were found

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• Jiang-Song Zhai Da-Ming Du School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No.5 Zhongguancun South Street, Beijing 100081, People’s Republic of China 10.3762/bjoc.18.3 Abstract Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2

• conveniently and comprehensively. However, as we know, the construction of these compounds is mostly carried out through transition-metal-catalyzed cyclization reactions [11][12][13][14], whereas strategies using bifunctional chiral thiourea catalysts are rarely reported. In 2018, Du's group reported a novel

• bifunctional thiourea catalyst, a series of target products in excellent yields with excellent stereoselectivities can be obtained under mild conditions in this reaction. Notably, this protocol provides direct access to indanone-derived spirobarbiturates, which are difficult to access with other methods

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• , as a single isomer (Scheme 3). Then, the chloroacetyl group was selectively removed using thiourea and 2,4,6-collidine [47] to afford the 3’-OH acceptor 5 in 87% yield. Finally, NIS/TMSOTf-promoted coupling of donor 3 with disaccharide acceptor 5 provided the desired β-linked trisaccharide 2 in 89

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• heterocalixarenes, which all comprised benzimidazol-2-one and 1,3-phenylene units in an alternate cyclic arrangement. In 2008, Kwit et al. [35] synthesized urea and thiourea derivatives of chiral triangular polyimine macrocycles. The macrocycles above mainly consisted of imidazole analogs and aromatic fragments

• . Šindelář and Lizal [36] also presented the synthesis of hybrid macrocycles containing glycoluril and aromatic units. In 2014, Keinan et al. [37] reported a series of macrocycles, consisting of alternating urea or thiourea and phenol units, namely, multifarenes. Hitherto, multifarenes and their derivatives

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The N-sulfinylurea catalyst was more efficient than the corresponding thiourea. For some substrates, enantioselectivities reached 98% ee. The stereogenic center on the sulfur did not have a considerable

• aldehydes and hydrogen-bond activation of nitroalkenes. Keywords: asymmetric organocatalysis; hydrogen bond; Michael addition; pyrrolidine; thiourea; urea; Introduction Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. Bifunctional catalysis

• syntheses, including total syntheses of natural compounds [15]. The pyrrolidine moiety has been successfully combined with thiourea [16][17][18] and the squaramide unit [19][20]. Thioureas and squaramides often feature the electron-withdrawing group attached to one of the nitrogen atoms to increase the

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• derivatives, phase-transfer catalysts and bifunctional thiourea derivatives. 1.1 Reactions catalyzed by chiral cinchona alkaloid derivatives Cai et al. prepared and used a number of organocatalysts from Cinchona alkaloids for the aza-MR of aniline (1) with chalcone (2) to obtain the adducts 4 in poor to very

• bifunctional thioureas Thioureas constitute one of the most important class of organocatalysts [49]. Wang et al. reported a cascade aza-Michael/Michael reaction of anilines 60 to nitroolefin enoates 61 using chiral bifunctional thiourea as catalyst (cat. 62). It provided a mild and efficient approach to the

• enantioselectivity (85% ee) was obtained with quinine-derived thiourea in dichloroethane as the solvent. The scope of the reaction was also investigated vis-a-vis the effect of the substitution on the isoxazolinone ring and p-quinone methide (p-QM) partner. (Table 15) [51]. Takemoto and co-workers investigated three

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• (Table 2). Apart from model catalyst II, equipped with five (−)-menthol units, also the sterically less demanding amide-type catalyst III and the thiourea derivative IV were tested (Table 2). First, the diamide-type catalyst III was examined (Table 2, entry 4). Although complete conversion of 1a and 2a

• was achieved after a significantly prolonged time (7 days), the aminal 3a was isolated in a good yield of 60%. Unfortunately, the reaction proceeded nearly in a racemic fashion. An inefficient catalyst showed up to be the PCCP catalyst derivatized with thiourea functional units (IV); a formation of 3a

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• The concept of anion-binding catalysis was first penned by Schreiner et al. in 2006, who realized the acetalization of benzaldehyde (1) with a thiourea catalyst (3, Scheme 1) [30][31]. They proposed the reaction to proceed via thiourea-catalyzed orthoester hydrolysis, leading to the formation of a

• -workers reported in 2004 an asymmetric Pictet–Spengler reaction of tryptamine-derived imines 4 in the presence of acetyl chloride and 2,6-lutidine, where the chiral thiourea catalyst 6 was employed to enable good yields and enantioselectivities (Scheme 2a) [32]. The initial motivation of their first

• , right). However, based on the freshly coined concept of anion-binding activation [30][31] and as the exact interaction mode of the catalyst remained elusive, Jacobsen’s group focused their attention towards mechanistic studies of thiourea-catalyzed reactions. In 2007, they reported a Pictet–Spengler

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• (denoted as CuO@GO, 0.38 mol %) catalyzed S-arylation (C–S coupling) of 2-iodoindole (92) to synthesize diindol-2-ylsulfide (84) in 75% yield (Scheme 12) [79]. Here 1.5 equivalents of thiourea acted as the sulfur source. Bis(indol-3-yl)sulfides are also present as structural motifs in important organic

• with 5-iodoindole (182) in the presence of thiourea and a recyclable CuO nanoparticle catalyst (Scheme 26) [116]. This heterogeneous catalysis strategy bypasses the use of unpleasant aryl thiols, which are generally coupled with other aryl halides in the presence of transition-metal catalysts for

• )silanes reported by Han. Base-mediated syntheses of bis and tris(indol-2-yl)phosphines. Synthesis of bis(indol-2-yl)sulfides using SL2-type reagents. Synthesis of 2,3’- and 2,2’-bis(indolyl)sulfides using disulfides as substrates. Synthesis of diindol-2-ylsulfide (84) from 2-iodoindole (92) and thiourea