Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• Jan Wallbaum Daniel B. Werz Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany 10.3762/bjoc.13.254 Abstract A variety of novel imidazolidinone-based organocatalysts with bulky substituents were synthesized under mild reaction conditions

• ][3][4][5][6][7]. Initially, proline and proline-derived catalysts have been widely used in asymmetric iminium and enamine organocatalysis [8][9][10][11][12]. Since the beginning of the 21th century imidazolidinone-based organocatalysts developed by MacMillan and co-workers, which are easily

• enamine complex. Scheme 1b shows our regio-, diastereo- and enantioselective 1,3-chlorosulfenation of meso-cyclopropyl carbaldehydes employing a newly designed organocatalyst 7a·DCA for chiral induction [25]. In the course of these studies we prepared a variety of imidazolidinone organocatalysts with

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

• transformations [14][15][16][17]. One of the major applications of organocatalysis lies in the field of enantioselective synthesis, where organocatalysts are considered as fundamental tools in the catalysis toolbox [18][19][20][21][22]. Moreover, the reactivity and selectivity of organocatalysts can be further

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

• depolymerization of cellulose [18] and the synthesis of dihydropyrimidine derivatives [19]. The monosodium salt of phosphonic acids were also employed as organocatalysts for Michael addition [20]. The capacity of phosphonic acids to increase the solubility of organic compounds in water was employed to develop

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

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• application as organocatalysts and sensors. On the other hand, the specific and unique nature of each of these functionalities render (thio)ureas and guanidines as the key constituents of pharmaceuticals and other biologically active compounds. Keywords: guanidines; mechanochemistry; solid state synthesis

• years, molecules with incorporated (thio)urea and guanidine subunits, due to their ability to coordinate other molecules and ions via N–H hydrogen bonding, have also been considered as organocatalysts and anion sensors [7][8][9][10][11][12]. In Scheme 2, several examples of (thio)urea- and guanidine

• -based organocatalysts are shown. Green Chemistry, which aims at turning chemical reactions into more effective and sustainable processes with high conversions of the starting materials and no byproduct formation, has emerged as a mainstream paradigm in chemical research in the past 25 years. Anastas and

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• use of chiral metal complexes, or chiral organocatalysts have been reported, and the use of chiral PTCs became a powerful strategy herein too [44][56][57][73][74][75][76][77][78][79]. The seminal report on asymmetric phase-transfer-catalysed electrophilic α-fluorinations of prochiral carbonyl

• alkaloid-based organocatalysts to carry out the α-trifluoromethylthiolation of β-ketoesters 1 by using the hypervalent iodine-based CF3S-transfer reagent 36 in an asymmetric fashion. Very interestingly, they realized that for indanone-based ketoesters 1 (with n = 1) simple cinchona alkaloids themselves

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• . Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• Ryota Miyaji Yuuki Wada Akira Matsumoto Keisuke Asano Seijiro Matsubara Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan 10.3762/bjoc.13.151 Abstract Bifunctional organocatalysts bearing amino and urea

• functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds

• . Moderate to good enantioselectivities were afforded with a range of benzamide substrates. Mechanistic investigations were also carried out. Keywords: axial chirality; benzamide; bifunctional organocatalyst; molecular conformation; multipoint recognition; Introduction Bifunctional organocatalysts have

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

• strategies with chiral transition metals [27][28][29][30][31][32][33], organocatalysts such as secondary amines [34][35][36], nucleophilic phosphines [26][37][38][39][40][41][42][43][44], tertiary amines [45], N-heterocyclic carbenes (NHCs) [46][47][48], and cinchona alkaloid derivatives [25][28][49][50

• variety of organocatalysts (a–f) were investigated in CH2Cl2 at −20 °C for 12 h to evaluate their ability to promote the transformation (Table 1, entries 1–6). When cinchona alkaloid-derived catalyst a and quinine-derived amine catalyst b were tested, however, poor yields or ee values were obtained

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• modified with trimethylsilazane [13]. The L- or DL-lactide were polymerized in the presence of organocatalysts like 4-dimethylaminopyridine [12] using β-CD and modified CD (β-CD-(OBn)19(OH)2) as initiators. Normand et al. [14] applied a similar approach as Zinck and co-workers [12] in order to prepare CD

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• applications in medicinal chemistry, sulfamide groups have been incorporated in self-assembling molecules [22][23][24][25][26][27], peptides [28], polymers [29], ligands [30], chiral auxiliaries [31][32][33] and in organocatalysts [34][35][36][37]. In light of the importance of the sulfamide functionality, our

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• organocatalysts with a bulky substituent at C2 were synthesized from chiral imines derived from (R)-glyceraldehyde acetonide by diastereoselective allylation followed by a sequential hydrozirconation/iodination reaction. The new compounds were found to be effective organocatalysts for the Michael addition of

• privileged motif [5] with a powerful capacity in aminocatalysis [6][7][8][9][10]. In this context diarylprolinol silyl ethers have proven to be extremely efficient organocatalysts for a wide variety of chemical transformations [11]. In the course of our research we have been involved in the synthesis of new

• evaluated as chiral organocatalysts in the enantioselective α-chlorination of β-ketoesters, with excellent results obtained after optimisation of the organocatalyst structure [12]. In an effort to identify new, easily accessible and tuneable organocatalysts with the privileged pyrrolidine motif from the

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• evidence for two hydrogen bonds formed between the halide or bromide anion and C–H2/C–Hc bonds of another cation L13. Mixed N–H/C–H hydrogen bond donors as organocatalysts The involvement of the ortho C–H bond in the binding event with Lewis-basic sites was proposed by Etter in the late 1980s and later

• demonstrated by Schreiner in a detailed study of hydrogen-bonding thiourea organocatalysts containing a 3,5-bis(trifluoromethyl)phenyl group as the privileged motif [56][57][58]. A recent example of utilizing such interactions in catalysis was demonstrated by Bibal and co-workers [58]. In this study, Bibal and

• co-workers explored the use of α-halogenated acetanilides L14 and L15 as hydrogen-bonding organocatalysts that activate the carbonyl functionality of lactide and thus enhance their reactivity toward ROP (Scheme 11). In addition to their ability to form more conventional N–H hydrogen bonds, L14 and

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• ], versatile organocatalysts [8][9][10], and starting materials for heterocycle syntheses [11][12][13]. Consequently books [14][15][16] and reviews cover the range from NHC structures in the light of their early history [17], syntheses [6][18], coordination chemistry [19][20], and catalysis [21][22], to

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• Maurizio Selva Alvise Perosa Sandro Guidi Lisa Cattelan Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari Venezia, Via Torino, 155 – Venezia Mestre, Italy 10.3762/bjoc.12.181 Abstract The use of ionic liquids (ILs) as organocatalysts is reviewed for transesterification

• /nucleophilic) activation of reactants. Keywords: ionic liquids; transesterification; organocatalysts; organic carbonates; Review Introduction Transesterification catalysts The transesterification is one of the classical organic reactions that has found numerous applications in laboratory practice as well as

• ., glycerol) to produce the expected transesterification products with total conversion and selectivity. Ionic liquid-based organocatalysts Conventional acid or base liquid catalysts for transesterification processes often entail several synthetic and environmental concerns including equipment corrosion

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• organocatalysts [262][263]. There are also Green chemistry approaches for Baeyer−Villiger oxidations based on enzyme-mediated processes, which are used for the preparation of chiral lactones. This type of biocatalysis is useful in synthetic chemistry and either isolated enzymes or living whole cells are applied

• % and 9% yields, respectively (Scheme 30) [273]. However, in order to perform the asymmetric oxidation of 3-substituted cyclobutanones 96a–f to the corresponding lactones 97a–f (Table 7) [274], it is necessary to employ chiral Brønsted acids [274][275][276][277], organocatalysts [278][279] or enzymes

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• of organocatalysts [38][39][40][41][42][43][44][45], we have reported the catalytic asymmetric decarboxylative aldol addition reaction of isatins with benzoylacetic acids catalyzed by chiral binaphthyl-based squaramide [46]. Here we wish to report the enantioselective addition reaction of diphenyl

• phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified bifunctional organocatalysts (Figure 1). Results and Discussion To determine suitable reaction conditions for the organocatalytic enantioselective addition reaction of diphenyl phosphonate to ketimines derived from isatins, we

• initially investigated a reaction system with ketimine 1a derived from N-allylisatin and diphenyl phosphonate (2) with organocatalyst in the presence of 4 Å molecular sieves. We first surveyed the effect of the structure of bifunctional organocatalysts I–VI (Figure 1) on enantioselectivity in ethyl acetate

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• have been reported; for example, Co [13], Cu [14][15][16][17][18][19][20][21][22][23], Ag [24][25][26][27][28][29][30][31][32], Zn [33][34], Ni [35][36], and Ca [37][38][39] catalyst systems, and organocatalysts [40][41][42][43][44][45] have been successfully employed. In most cases, however

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. Keywords: asymmetric catalysis; conjugate addition; enantioselective protonation; enolate; Introduction Due to their ubiquity in natural products and drugs, many

• –enantioselective protonation reactions that have been reported in the literature. These reports have been grouped by class of Michael acceptor and further subdivided by the type of catalyst system used (Lewis acids, organocatalysts and transition metals). While numerous efficient methods have been developed for

• ) reacted in low yield and poor enantioselectivity. Sterically bulky 2-substituents (ortho-substituted phenyl, tert-butyl) showed attenuated reactivity but retained high enantioselectivity. Organocatalysts In a pioneering work from 1977 on conjugate addition–enantioselective protonation, Pracejus and co

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• excellent ee values (up to 97% ee) from DMTr (Di(p-methoxyphenyl)phenylmethyl)-N-protected isatins in one-pot under modified conditions. Organocatalyzed synthesis of 3-substituted 3-hydroxyoxindoles Organocatalysis has witnessed significant progress in the last decades, a large number of new organocatalysts

• progress in this field, the asymmetric catalytic synthesis of 3-hydroxyoxindoles are summarized based on the organocatalysts used. Amino acid-derived organocatalysts Amino acids (AAs) have been widely used to develop novel AAs-based organocatalysts for asymmetric synthesis [30]. Representative examples are

• certain influence on the reactivity. Interestingly, the final compounds bear the 3-hydroxyoxindole and butenolide moieties and could be used for biological screening or serve as intermediates for further transformations. After screening different chicona alkanoid-derived organocatalysts, Chimni et al

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• devoted to the development of new efficient chiral catalysts, both metal catalysts and organocatalysts, together with the search for appropriate (pro)nucleophiles and/or electrophiles. In this context, the enantioselective construction of tetrasubstituted stereocenters is another challenge [5][6][7][8][9

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• [22] with 1,4-dithiane-2,5-diol. Based on all above considerations and prompted by our interest in asymmetric synthesis of functionalized tetrahydrothiophenes [14], we wondered whether we could use bifunctional organocatalysts to develop a diastereo- and enantioselective cascade sulfa-Michael

• -dithiane-2,5-diol as precursor of mercaptoacetaldehyde, using 10 mol % loading of different bifunctional organocatalysts (Scheme 1, Table 1). In the case of trans-β-nitrostyrene (1), a mixture of diastereoisomers 5 and 6 were rapidly formed, irrespective of the catalyst used, with a poor level of diastereo

• the bifunctional organocatalyst structure and reaction conditions will be required for further improvements of the challenging cascade process. Organocatalysts screened in the cascade reaction. Synthesis of catalyst VIII. Asymmetric sulfa-Michael/nitroaldol reaction of nitroalkenes 1–3 with 1,4

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well. Keywords: bifunctional organocatalysts; organocatalysis; stereoselective

• [12]. Cinchona-derived thioureas have been also prepared by co-polymerization of polyfunctionalized thiols with olefins [23]. Our interest in the search for novel bifunctional thioureas as organocatalysts [24][25][26][27] lead us to consider the preparation of different polymeric materials decorated

• organocatalysts in the stereoselective aza-Henry reaction [31]. Now we describe the results obtained in different stereoselective nitro-Michael additions promoted by these materials. Results and Discussion The ability of the supported catalysts (II–V) to promote the stereoselective nitro-Michael reaction was

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• The 1,2-aminoindanol scaffold has been found to be very efficient, enhancing the enantioselectivity when present in organocatalysts. This may be explained by its ability to induce a bifunctional activation of the substrates involved in the reaction. Thus, it is easy to find hydrogen-bonding

• organocatalysts ((thio)ureas, squaramides, quinolinium thioamide, etc.) in the literature containing this favored structural core. They have been successfully employed in reactions such as Friedel–Crafts alkylation, Michael addition, Diels–Alder and aza-Henry reactions. However, the 1,2-aminoindanol core

• incorporated into proline derivatives has been scarcely explored. Herein, the most representative and illustrative examples are compiled and this review will be mainly focused on the cases where the aminoindanol moiety confers bifunctionality to the organocatalysts. Keywords: aminocatalysis; 1,2-aminoindanol

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• will be summarized. Initially, the use of primary amine-thioureas as organocatalysts for the above transformation is being discussed, followed by the examples employing secondary amine-thioureas. Finally, the use of tertiary amine-thioureas and miscellaneous examples are presented. Keywords: multiple

• of intermediates have been proposed to be the reactive intermediates in many reactions such as aldol, Michael, Mannich, and α-functionalization (α-chlorination, α-amination, α-fluorination) reactions. Proline-type organocatalysts are considered priviliged, because their corresponding enamines exist

• depicted in the left, in Scheme 2, seems to be operative, when the R group of the organocatalyst possesses a moiety, that is able to form hydrogen bonds, being the hydrogen bond donor. Employing this logic, many organocatalysts have been developed, possessing various groups, that are able to form hydrogen