Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• effective in reactions that depend on hydrogen bonding activation [54], and the substrate effects observed here find some similarities in other Bronsted acid-catalyzed processes. In disulfonimide-catalyzed asymmetric intramolecular hydroamination of alkenyl thioureas, sulfonamides are unreactive compared to

• thioureas and the reaction is favored at lower concentrations, an impact proposed to be due to hydrogen bonding driven self-association of the substrate [55]. In other Bronsted acid-catalyzed processes, thioureas and ureas are both effective substrates, with higher reactivity associated with thioureas

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

• ], amidines [11], isothioureas [12][13], whereas thioureas [14][15], ureas [16], phosphoric acids [17][18], and squaramides [19][20] fall into the second category. The Friedel–Crafts reaction, discovered by Charles Friedel and James Crafts in 1877 allows the aromatic C–H bond functionalization through the

• was shown by synthesizing 110, a key intermediate of (R)-bifonazole (Scheme 25b) [55]. Thioureas and squaramides In 2018, Yang, Deng and co-workers developed an aza-Friedel–Crafts aminoalkylation of 4- and 5-hydroxyindoles 111. As electron-demanding component, N-Boc pyrazolinone ketimines 100 were

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

• -unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• conventional methods; a notable alternative is the cyclodesulfurization, where intramolecular cyclization is combined with desulfurization from thioamide analogs such as thioureas, thiosemicarbazides, and dithiocarbamate salts under mild reaction conditions [10]. These synthesis methods are effective for

• triphenylbismuth dichloride (Ph3BiCl2) to act efficiently in desulfurization reactions (Scheme 1-I and II). In 2018, we reported the preparation of 2-aminobenzoxazoles by the Ph3BiCl2-mediated cyclodesulfurization of thioureas, which were obtained from 2-aminophenols and isothiocyanates [34]. In 2019, Doris et al

• . performed the dehydrosulfurization of thioamides and thioureas that provided nitriles and cyanamides [35]. Using bismuth compounds as desulfurization reagents for synthesizing heteroazoles, this paper presents the syntheses of 2-aryl- and 2-alkylbenzoxazoles through the ring-closure reaction of 2

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

• and Life, Beijing University of Technology, Beijing 100124, China 10.3762/bjoc.18.130 Abstract The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical

• ], dyes [13], etc. These important features of thiazoles have driven intense interests in their facile synthesis [14][15][16][17]. Among various synthetic routes to the thiazole unit, the Hantzsch condensation of α-halo ketones (dielectrophiles) with various thioureas (dinucleophiles) should be the most

• well-known method (Scheme 1a) [18]. Since active methylene ketones are able to be in situ α-halogenated, the modified Hantzsch condensation of active methylene ketones with thioureas has attracted increasing attention in thiazoles’ synthesis, thereby saving costs and time needed to prepare the required

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

• temperature, thioureas 10 were also successfully transformed into 4H-3,1-benzothiazines 11 via intramolecular nucleophilic substitution (Scheme 4). The results were listed in Table 3. Various secondary amines can be used in this one-pot cyclization to prepare 4H-3,1-benzothiazines 11. As indicated in Table 3

New advances in asymmetric organocatalysis

• Radovan Šebesta

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

• early to stimulate greater developments. Things started to change in the late 1990s when short-chain peptides [3], carbohydrate-based ketones [4][5], and thioureas [6] were shown to catalyze enantioselective transformations. The real breakthrough came in the year 2000 when two teams independently

• possibilities in combination of covalent and noncovalent activation, our group designed and synthesized N-sulfinylpyrrolidine-containing ureas and thioureas and applied them in Michael additions of aldehydes to heterocycle containing nitroalkenes [25]. Dubey and Chowdhury showed that 1,4-conjugate additions of

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

• malonates [25]. Herein, we report the results of an asymmetric organocatalytic Michael addition of CPD to alkylidene oxindoles. Results and Discussion Chiral multifunctional thioureas [26][27] and squaramides [28] are extensively used as catalysts in asymmetric Michael additions. We believed that a

• to be more selective catalysts than thioureas. When squaramide C was used as a catalyst, the product was isolated in 80%/87% ee (major/minor diastereoisomer) (Table 1, entry 3). The enantioselectivity was even higher with the cinchonine-derived squaramide D, 85%/92% (major/minor) (Table 1, entry 4

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

• , Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 10.3762/bjoc.17.176 Abstract The synthesis of bifunctional N-sulfinylureas and thioureas with an appended pyrrolidine unit is presented. These organocatalysts were evaluated in

• 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

• -Butanesulfinamide is highly useful in stereoselective synthesis as a stereoinducing group [21]. Thus, N-sulfinylureas and thioureas are a new class of organocatalysts, with the sulfinyl group acting both as an acidifying and a chiral controlling moiety. A variety of N-sulfinylureas catalyzed aza-Henry reaction

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

• asymmetric aza-MR. Thus, the review includes the examples wherein cinchona alkaloids, squaramides, chiral amines, phase-transfer catalysts and chiral bifunctional thioureas have been used, which activate the substrates through hydrogen bond formation. Most of these reactions are accompanied by high yields

• aza-MRs. However, the last three review articles are almost 10 years old and they do not cover the application of many important organocatalysts, such as thioureas and nitrogen heterocyclic carbenes (NHCs) used for the asymmetric aza-MRs. Furthermore, in the last review article [24], the application

• 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

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

• , nonproductive dimeric aggregates form under standard reaction conditions. These dimers exist in different combinations of the thiourea rotamers and lead to competing catalytic pathways (Scheme 16a). Moreover, anion abstraction was calculated to proceed either through a 4H abstraction mechanism of two thioureas

• The combination of anion-binding catalysis and supramolecular chemistry is a fairly new arisen field, with a set number of notable examples [79][80][81][82][83]. Next to thioureas, investigations in this area of anion binding were also conducted for other catalytic systems. In 2014, the García group

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• stereogenic centers. Review A plethora of highly effective small‐molecule organocatalysts have enriched the field of organic synthesis [27], including chiral proline derivatives, N‐heterocyclic carbenes, chiral thioureas and Brønsted acids as well as phase‐transfer catalysts (PTC), such as the quaternary

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• being susceptible to nucleophilic attack. The resulting substituted thioureas underwent a cyclization reaction providing the desired triazinethiones (Scheme 1a and 1b). However, this method required the preparation of the starting isothiocyanates, which limited its synthetic applications. In another

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• were synthetized and the liquid crystal properties studied. Thioureas were obtained using a condensation reaction of benzoyl chlorides, arylamines and ammonium thiocyanate. The amides, on the other hand, were the byproduct of a quantitative reaction which used potassium cyanate as the starting material

• . Thiourea and amide derivatives were predominantly SmA mesophase inductors. A nematic mesophase was observed only for thioureas and amides containing an isoxazole ring. Additionaly, the liquid crystal behavior was also dependent on the relative position of nitrogen and oxygen atoms on the 5-membered

• heterocycle. Keywords: amides; isoxazole; isoxazoline; liquid crystal; thiourea; Introduction Thioureas are a structurally diversified group of organic compounds, with technological applications in different areas. The structural diversity of the thiourea moiety is linked to possibly one or both nitrogen

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• [7], insecticides (cartap) [8], and herbicides [9]. They are also used as key intermediates in the generation of carbonyl sulfide/hydrogen sulfide [10], the synthesis of isothiocyanates [11], asymmetric thioureas [12], and thiazolidine/thiaoxazine [13]. Therefore, as a result, numerous synthetic

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• rearrangements of O-allyl β-ketoesters [35][36][37]. Hiersemann and Strassner studied the Claisen rearrangement with H-bond-donating organocatalysts by computational methods and concluded that thioureas are not efficient in transition-state stabilization [38]. Regarding the usefulness of the Ireland–Claisen

• organocatalysts, including chiral squaramides, thioureas, alkaloids and their derivatives, taddols, binol, chiral phosphoric acid, (S)-proline and its derivatives, amide of tryptophan (Figure 1). These catalysts feature varying steric properties from sterically encumbered, such as C1, C5, C8, or C10, to less

• Chiral hydrogen-bond-donating organocatalysts such as thioureas, squaramides, or alcohols failed to catalyze the Ireland–Claisen rearrangement of silyl ketene acetals. Comparison experiments showed that increasing catalyst loading gradually slowed-down the reaction. DFT calculations using long-range

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• pyrrole-2-one fragment involving the reaction of [e]-fused 1H-pyrrole-2,3-diones with thioureas was developed. The obtained spiro pseudothiohydantoin derivatives were found to undergo a pseudothiohydantoin–thiohydantoin rearrangement. The reactions were shown to proceed under catalyst-free conditions in

• identifiable products due to the occurrence of multiple side reactions involving the ethoxycarbonyl group. Next, we examined the influence of substituents in the thiourea motif on its reaction with FPDs 1. It was found that monosubstituted thioureas (N-methylthiourea, N-phenylthiourea, N-(4-chlorophenyl

• developed a divergent approach to pharmaceutically interesting regiomeric thiohydantoins and pseudothiohydantoins spiro-fused to a pyrrole-2-one fragment via the reaction of [e]-fused 1H-pyrrole-2,3-diones with thioureas. The obtained pseudothiohydantoins were found to be prone to undergo a

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• yield [70]. In certain cases, sulfur can be trapped by in situ generated carbenes to afford O-thiocarbamates [71][72]. Thioureas and S-thiocarbamates are also accessible through multicomponent reactions starting from isocyanides and sulfur [73][74][75]. The cumbersome synthesis of isothiocyanates from

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , etc. The urea component has the main structural restrictions, since monosubstituted alkyl ureas work well but thioureas have provided much lower yields. Wang et al. produced a library of steroidal [17,16-d]pyrimidine derivatives such as 40 employing a particular extension of the Biginelli reaction

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• ]. In 2016, Hernández-Rodríguez and co-workers reported the preparation of bifunctional thioureas that contained either a methyl or trifluoromethyl group [14]. They discovered that the employment of chiral moieties with an α-trifluoromethyl group in thioureas show a positive effect on the selectivity

• compound 6. Subsequently, different chiral cyclohexanediamine derivatives were reacted with calix[4]arene-based compound 6 to form the corresponding substituted thioureas. By this route the monosubstituted primary amine 1, monosubstituted tertiary amine 2 and disubstituted tertiary amine 3, respectively

• the new chiral amino-substituted thioureas [33][39]. For this, the Michael addition reaction of acetylacetone (8) to β-nitrostyrene (7a) was chosen as the model reaction to evaluate the efficiency of compounds 1–4 as chiral organocatalysts (Table 1, entries 1–4). From Table 1, it can be seen that the

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• % ee), which displayed the importance of the calix[4]arene skeleton. We also employed calixarene-based chiral primary amine thioureas 47a and 47b in the enantioselective Michael addition of α,α-disubstituted aldehydes 51 to maleimides 52 (Scheme 14) [50]. The reactions proceeded under mild conditions

• times with slightly decrease in its yields and diastereoselectivities. Genc et al. reported that the calixarene-based chiral tertiary amine–thioureas 55 and 56 (Scheme 15) could be used as catalyst in the asymmetric aldol reactions between 94 and 72 [53]. The aldol adducts were obtained in 79–90% yield

• addition of 48 with 49 catalyzed by 47a and 47b. Enantioselective Michael addition of 51 to 52 catalyzed by calix[4]arene thioureas. Synthesis of calix[4]arene-based tertiary amine–thioureas 54–56. Asymmetric Michael addition of 34 and 57 to nitroalkenes 49 catalyzed by 54b. Synthesis of p-tert-butylcalix

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• organocatalyzed by cinchona-alkaloids, and unprecedented Friedel–Crafts reactions of isatin imines with naphthols and hydroxyquinolines promoted by cinchona-alkaloid-derived thioureas and cinchona-alkaloid-derived squaramides. Slightly lower enantioselectivity levels of up to 94% ee were described in aza-Henry

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• and pregabalin [9][10]. Later, hydrogen-bonding activation proved to be more general for obtaining Michael adducts via the addition of 1,3-dicarbonyl compounds to nitroalkenes. Chiral thioureas and squaramides, particularly those with the bifunctional mode of action, served as excellent catalysts in

• numerous Michael additions, as well as other reactions [11][12][13][14]. In this way, chiral thioureas, and squaramides were used to synthesize various GABA derivatives [15][16][17][18][19]. Interestingly, hydrogen-bonding activation of this kind of Michael additions worked well also in aqueous media [20