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

• Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China 10.3762/bjoc.14.164 Abstract A number of upper rim-functionalized calix[4]thiourea cyclohexanediamine derivatives have been designed, synthesized and used as catalysts for enantioselective Michael addition reactions between

• nitroolefins and acetylacetone. The optimal catalyst 2 with a mono-thiourea group exhibited good performance in the presence of water/toluene (v/v = 1:2). Under the optimal reaction conditions, high yields of up to 99% and moderate to good enantioselectivities up to 94% ee were achieved. Detailed experiments

• clearly showed that the upper rim-functionalized hydrophobic calixarene scaffold played an important role in cooperation with the catalytic center to the good reactivities and enantioselectivities. Keywords: asymmetric Michael addition reaction; calix[4]arene; cyclohexanediamine; thiourea; Introduction

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• reactions [32][33]. As it was elegantly reviewed by Singh and co-workers [33], these organosulfur ligands can be classified into pincer type (symmetrical and unsymmetrical), thioethers, thiourea-based ligands, sulfur-substituted NHCs, thiosemicarbazones and sulfated Schiff bases. Of the pincer ligands

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

• -cyclohepten-1-one and chalcone were also tested as substrates for the Michael addition reaction and the corresponding adducts were obtained in good yield with moderate enantioselectivity (13–23% ee). Calixarene-derived thiourea seemed to be an interesting backbone for design of new organocatalysts for

• asymmetric synthesis. In 2013, we described a novel class of calix[4]arene-based chiral primary amine–thiourea catalysts 47a and 47b derived from p-tert-butylcalix[4]arene (Figure 7) [49]. To evaluate the catalytic efficiency, bifunctional catalysts were applied to promote the Michael addition of aldehydes

• of the achiral calixarene platform, the monomeric analogue carrying both thiourea and primary amine subunits was also prepared and used in the control experiments. Under optimal reaction conditions, the noncyclic analogue afforded the product in lower yields and enantioselectivities (52% yield, 89

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

• first asymmetric organocatalytic synthesis of chiral 3-amino-2-oxindoles based on enantioselective aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines 3 with activated nitroolefins 39 [62]. The best results were achieved by using cinchona alkaloid-derived thiourea catalyst 40 in toluene at −10 °C

• -isatin imines 3 with naphthols performed in the presence of cinchona alkaloid-derived thiourea 40 [66]. As shown in Scheme 15, the reaction of 1-naphthols 42 promoted by 2 mol % of this bifunctional catalyst in toluene at room temperature led to the corresponding chiral 3-substituted 3-amino-2-oxindoles

• Friedel–Crafts reaction of N-Boc-isatin imines 3 with 6-hydroxyquinolines 48 promoted by the cinchona alkaloid-derived thiourea 40 [68]. The process was performed in toluene at room temperature to give the corresponding chiral 3-amino-2-oxindoles 49 bearing a quinoline moiety in moderate to excellent

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• of DNG oligomers were introduced. They enabled chain elongation either in the 5'→3' [52] or 3'→5' [53] direction, respectively. Starting from protected 3',5'-dideoxy-5'-amino-3'-azidothymidine 21, the 5'→3' route was based on the synthesis of the diamino intermediate 22 and thiourea monomer 23, which

• the cleavage conditions used in the solid phase-supported synthesis of native DNA and also allowed the introduction not only of pyrimidine, but also of purine bases into the oligonucleotide analogue [53]. The method was based on the activation of the 5′-monomethoxytrityl (MMTr)-protected 3'-thiourea

• -deprotection cycle afforded thiourea-linked oligonucleotide analogue 41. Subsequent reaction of the thiourea internucleotide linkages with methyl iodide furnished the protected S-methylthiourea-linked oligomer 42 and finally, after cleavage from the solid support and acidic deprotection, the envisioned DNmt

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• synthesis of 7-hydroxy-2,3-benzotropone (241) was successfully realized by Dastan’s group (Scheme 47) [149]. Thiourea reduction of the peroxide linkage of 213 to the diol 282 and then simultaneously dehydration in situ gave the corresponding benzotropolone 241 in nearly quantitative yield. Recently, Arican

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

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

• addition of dimethyl malonate. An initial catalyst screening was performed in dichloromethane, based on our previous experiences with this type of Michael additions [18]. We have employed a range of squaramide and thiourea organocatalysts C1–C7 [18][27][28][29][30][31][32][33][34], as well as two newly

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• containing the two substrates with LiCl was pumped through the zinc column followed by a scavenger cartridge containing QuadraPure polymer-supported sulfonic acid and polymer-supported thiourea. This allowed diastereopure product 36 (98% de) to be obtained in 70% yield. Intramolecular Reformatsky reactions

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• lactim ethers [50]. For the preparation of 2-thioxopyrimidinones 7, 8a and 8b, the most common method is the reaction of the appropriate amino esters with phenyl isothiocyanate, followed by cyclization of the resulting thiourea with hydrogen chloride under reflux [45][49]. The starting materials were

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• development of chiral bifunctional urea 1 [35], thiourea 2 and 3 [36][37], sulfonamide 4 [38][39][40] and squaramide 5 [38][39][40] catalysts derived from chloramphenicol base (Figure 1), which showed excellent reactivity and enantioselectivity for this asymmetric transformation. A typical example of the

• chloramphenicol-derived bifunctional amide organocatalysts and their application for enantioselective alcoholysis of meso-cyclic anhydrides. In the precedented urea- or thiourea-based organocatalytic methanolysis of anhydrides, one big problem is the homo-aggregation of the catalysts via hydrogen bonding, which

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• directly by fusion of thiourea/urea with 5-aminopyrazole 126 in an oil bath at 120 °C. N-Thiocarbamoyl pyrazole derivatives 180 and 183 underwent cyclization with hydrazine hydrate to give 5-(N-triazolyl)aminopyrazole derivative 182 and hydrazinopyrazolo[3,4-d]pyrimidines 185, respectively (Scheme 51). El

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• thiourea derivative giving the Eosin Y radical anion and a thiyl radical. Aerobic oxidation closes the catalytic cycle and after hydrogen atom abstraction of the carbon-centred radical intermediate the final product is formed. Formation of 1,3,4-thiadiazoles In a second article the same concept led to the

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• obtained (Table 1, entries 2 and 3). These results are not surprising as the substrate 1a is a weaker dinucleophile than aminopyridine and thiourea used previously [20][21][22]. However, 56% yield of 3a was obtained with KOH (Table 1, entry 4). The use of KOH as a base in the α-bromination of 1,3

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• from the group of Ma described the development of a chiral thiourea-catalyzed enantioselective decarboxylative Mannich reaction of malonic acid monoesters with 4-trifluoromethylquinazolin-2(1H)-ones as heterocyclic trifluoromethylketimine substrates for the preparation of enantioenriched 3,4

• , entries 5 and 6). Unfortunately, quinine and the chiral quinine-derived thiourea organocatalyst QT in toluene led to a mixture of racemic products along with 19% and 38% of unreacted starting material, respectively (Table 1, entries 7 and 8). As seen from the screening results, the reaction

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• trichloroacetimidate donors using a synergistic catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives at room temperature is demonstrated. The acidity of the adduct formed by the 1,2-addition of alcohol to the electron-deficient pyridinium salt is increased in the presence of an aryl

• thiourea derivative as an hydrogen-bonding cocatalyst. This transformation occurs under mild reaction conditions with a wide range of O-glycosyl trichloroacetimidate donors and glycosyl acceptors to afford the corresponding O-glycosides in moderate to good yields with predictable selectivity. In addition

• , the optimized method is also utilized for the regioselective O-glycosylation by using a partially protected acceptor. Keywords: cooperative catalysis; electron-deficient pyridinium salts; O-glycoside; regioselectivity; thiourea; Introduction The glycosidic linkage is the principal bond present in a

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• corresponding E-1 [10] (Scheme 2). Alternatively, the same transformation can be performed with 3 and thiourea derivative 4 in a two-step reaction through intermediate 5 [11] (Scheme 2). The latter, upon treatment with Et3N, generates a carbene [:C(CN)CO2Et], which dimerizes to give E-1a albeit in low yield

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• produce compound 98 [213] (Figure 28A). A second example corresponds to the nucleophilic addition of N-heterocyclic phosphine 99 to a nitroalkene (phospho-Michael reaction) as shown in Figure 28B. The thiourea unit in 99 plays a crucial role by assuming intramolecular interaction with the nitro function

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• ][54][55][56][57]. Modified macrocycles with the amide fragments at the lower rim can form complexes with the anions by hydrogen bonds of the amide group with the guest. It was shown that (thia)calix[4]arene derivatives with urea and thiourea fragments at the lower rim can bind anions through hydrogen

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• substituted thiourea-based organocatalysts were screened for the reaction to achieve stereoselective adducts through hydrogen bonding. Only with 2.5 mol % of thiourea-based catalyst B, α-nitrocyclohexanone and nitroalkene derivatives could undergo a Michael addition to yield up to 95% of the desired product

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• intermediate for the preparation of 6I-S-monodeoxy-6I-monothio-β-CD [26]. Having selected the 6I-O-monotosyl-β-CD (Ts-β-CD) as the benchmark, the nucleophilic displacement of the tosylate group in the presence of azido or thiourea (TU) nucleophiles was chosen for the study under different milling conditions

• was investigated using a reaction scale of dominantly 1 mmol of substrate, in the presence of 3 equivalents of NaN3 or thiourea (TU) as nucleophiles (Scheme 1). Being the removal of the starting Ts-β-CD from the 6-monoazido-β-CD complicated due to the solubility similarities, the time to reach

• contact between balls. Unlike the reactivity in solution, under mechanochemical conditions the sulfur nucleophile (thiourea, TU) was less effective than the azide ion in the substitution reaction. A similar reversal of reactivity has been already observed for halogens [12][13][28]. The experimental

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• -withdrawing aryl isothiocyanates with anilines used for the synthesis of N,N'-disubstituted thioureas, thorough mixing in an agate mortar typically leads to the formation of the products in a couple of minutes. As an extension of the mechanochemical click-coupling of amines with isothiocyanates, the thiourea

• paper, the ball milling approach was then applied for a quantitative click-mechanosynthesis of thiourea-based organocatalysts and anion sensors (Scheme 5) [34]. The demonstrated efficiency of mechanochemical milling synthesis of thioureas was exploited for a quantitative transformation of

• organocatalyst design was first introduced by reacting 3,5-di(trifluoromethyl)phenyl isothiocyanate with 3,5-di(trifluoromethyl)aniline and 4-chloroaniline in a 1:1 ratio under LAG conditions using methanol as the grinding liquid. This led to quantitative formation of the Schreiner's catalyst 5 and thiourea 17

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• , Zu Chong Zhi Road, Shanghai 201203, China University of Chinese Academy of Sciences, NO.19A Yuquan Road, Beijing 100049, China 10.3762/bjoc.13.131 Abstract The thiourea-catalyzed asymmetric synthesis of highly enantioenriched spirocyclopentaneoxindoles containing chiral amide functional groups using

• derivatives with good enantiomeric excess (ee) values, respectively. However, the utility of the reaction is limited to α,β-unsaturated aldehydes with aromatic/alkane substitutions and nitroolefins with aromatic substitutions. Additionally, Shao’s group (Scheme 1, reaction 1C) developed a one-pot thiourea

• asymmetric catalytic synthesis of saturated spirocyclopentaneoxindoles containing four consecutive stereocenters with 3-substituted oxindoles and nitrovinylacetamide using a bifunctional thiourea catalyst in good yields (up to 95%) with excellent diastereoselectivity (up to 3:97) and enantioselectivity (up

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• , however, they proposed that first the thiol acetate reacts with DMC to form a thiouronium ester which could be attacked by the deprotonated anomeric alcohol of the saccharide to provide the glycosyl acetate and the isolable thiourea byproduct (Scheme 27). One key advantage of this strategy is the absence

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• well as the silicon AFM tip, were first functionalized by a polysiloxane monolayer bearing isothiocyanate groups, which smoothly react with amines forming stable thiourea links [48]. Monolayers of β-CD or β-CD-polymer were obtained by attachment of monoamino β-CD or amino-modified CD polymer 12