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

• 96% ee and 73% yield. Conclusion In conclusion, we developed a unique bifunctional chiral organocatalyst via introducing a simple amide functionality at C-1 of the easily available chloramphenicol scaffold, which shows good catalytic reactivity and enantioselectivity in the alcoholytic

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• transformation. After many experiments, we found that the use of ethyl 2-formylbenzoate (10) [36] instead of nitrile 2 resulted in the formation of 1a with 27% ee upon exposure to organocatalyst 9b (0.1 equiv) and tetramethylammonium fluoride (0.5 equiv, Scheme 5). Conclusion In summary, we have demonstrated a

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• good yields (Scheme 49). The oxidation–reduction potentials were determined by cyclic voltammetry and a catalytic cycle was proposed in which the CF3 radical was generated from CF3SO2Na via the organocatalyst AQN-2-CO2H and visible light (Scheme 49) [72]. Rueping’s group described three examples of

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

• , 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

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

• 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

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• the repeating (CHF)n motif within the target molecule via an iterative synthetic approach (Scheme 1, boxed). We reasoned that an aldehyde such as 7 could undergo electrophilic fluorination, mediated by a chiral organocatalyst [18][19][20], to generate the fluorinated aldehyde 8 as a single

• the method developed by Jørgensen and co-workers (Scheme 1) [20]. Thus, the aldehyde 7a (or 7b) was treated with N-fluorobenzenesulfonimide in the presence of the chiral organocatalyst 10, and after a certain period the fluorinated aldehyde product 8 was reduced in situ. Initial studies with substrate

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

• dots [107] and used as anchoring group for dye-sensitized solar cells [108][109][110] or for the immobilization of organocatalyst [111][112]. Phosphonic acid was also used for coating superparamagnetic iron oxide (e.g., magnetite) assessed as contrast agent in magnetic resonance imaging [113] or to

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

• -free conditions were performed using a combination of (S)-binam-L-Pro (A, 5 mol %) and benzoic acid (10 mol %) as organocatalyst [49]. Juaristi and co-workers investigated the mechanistic aspects of α,α-dipeptide derivatives of a (S)-proline- (A′)-catalyzed asymmetric aldol reaction (Scheme 2b) under

• -poor aromatic aldehydes and aromatic ring of the organocatalyst plays a crucial role for excellent yield and selectivity. Apparently the solvent-free system enhances the rigidity of the transition state for more selective reactions under mechanochemical activation. Michael addition Generally strong

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• 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

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

• . 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

• mechanism was proposed in Scheme 3. The multifunctional organocatalyst d has a chiral scaffold including a thiourea moiety and an amino group. Both the 3-substituted oxindoles 1 and nitrovinylacetamide (2a) that participate in this reaction are activated simultaneously via multiple hydrogen bonds. In

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• have been used for this cycloaddition reaction [20][21][22][23][24][25][26][27][28][29]. Organocatalytic approaches based on β-enamine–azide or enolate–azide cycloadditions have been employed to synthesize 1,2,3-triazole scaffolds [30][31][32]. Depending on the organocatalyst employed, different

• 1,2,3-triazoles [33][34][35][36][37]. Selanyltriazoyl carboxylates, carboxamides, carbonitriles or sulfones were synthesized in good to excellent yields using catalytic amounts of an organocatalyst. Organoselenium compounds are attractive synthetic targets because of their selective reactions [38][39

• temperature in the presence of 1 mol % of Et2NH as organocatalyst, providing an excellent yield (98%) of the desired product 3a after 2 h (conditions A, Scheme 2). With the aim to compare the effect of different energy sources in this β-enamine–azide cycloaddition, the reaction between substrates 1a and 2a in

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

• 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

• immediately treated with iodine to yield N-benzylpyrrolidine 2 in 69% isolated yield. The subsequent exposure of compound 2 to molecular hydrogen in the presence of Pd(OH)2/C as a catalyst afforded the desired organocatalyst OC1 in 73% yield (Scheme 1). The same reaction sequence led to organocatalyst OC2 in

• catalytic Pd/C. In this way organocatalysts OC3–OC10 were obtained (Scheme 3 and Scheme 4). In addition another new organocatalyst, OC11, with a different bulky substituent at C2 in the pyrrolidine moiety was prepared. Reacting diol 7 with 1,3-dichlorotetraisopropyldisiloxane in the presence of imidazole

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

• hydrogen bonds or halogen bonding (C–X···X or C–X···A interactions) in organocatalyst design. Such non-covalent interactions have been traditionally viewed as “weak” when compared to classical A–H···A hydrogen bonds. However, in some cases the term “weak” may be misleading as an increasing number of

• examples demonstrate the effectiveness of such interactions for organocatalyst design. While C–H···A hydrogen bonds have been invoked in biological processes, halogen bonding is not commonly observed in natural enzyme-catalyzed reactions. Therefore, application of these new interactions for small molecule

• dominated the field of organocatalysis, numerous recent examples highlight the importance of other types of non-covalent interactions for electrophilic substrate activation. The use of C–H and C–X bonds with halogens or electron-rich heteroatoms has been particularly useful in new organocatalyst design

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

• when using an apparently simple organocatalyst such as L-proline. These observations have important implications in the future design of chiral catalysts, thereby opening the floodgates to new intriguing opportunities for organocatalysis in unconventional reaction media. Experimental set-up I: test

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

• reported results for the synthesis of esters from the reaction of nitriles and alcohols [48]. 4-(3-Methyl-1-imidazolium)-1-butanesulfonic acid triflate ([HSO3-BMIM][CF3SO3]) has been chosen as a model organocatalyst to explore the kinetics of the transesterification of methyl acetate with ethanol [49][50

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

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

• organocatalyst; ketimines; organocatalysis; squaramide; Introduction α-Aminophosphonate derivatives are important compounds as structural mimics of natural α-amino acids [1][2][3]. Chiral α-aminophosphonates have been shown a wide range of biological activities including antibacterial [4] and anticancer

• 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

• at room temperature (Table 1, entries 1–6). Catalyst III, which is a binaphthyl-modified squaramide bifunctional organocatalyst, was the best catalyst for this enantioselective addition reaction (90% ee, Table 1, entry 3). In order to improve the selectivity, different solvents were tested in the

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• system were also tested in this reaction [45]. Unfortunately, the reactions proceeded slowly to afford the cycloaddition products in less than 10% yield. We then selected the use of co-catalysts of Pd2(dba)3 and organocatalyst I in CHCl3 at room temperature to evaluate the generality of this [3 + 2

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

• nitroalkenes Organocatalysts In the first reported example of the enantioselective protonation of a nitronate, Ellman and co-workers demonstrated that an N-sulfinylurea organocatalyst could be used to catalyze the addition of α-substituted Meldrum’s acids to terminally unsubstituted nitroalkenes (Scheme 37

• ) [65]. Interestingly, the optimal organocatalyst for the transformation was chiral only at sulfur, when chiral amine motifs were explored, e.g., 1,2-cyclohexanediamine, poor enantioselectivity was observed (≤75:25 er). A variety of R1 substituents on Meldrum’s acid 156 were compatible with the reaction

• yields and with high enantioselectivity to α,β,β-trisubstituted nitroalkenes 161 using a thiourea organocatalyst 101b (Scheme 38) [66]. This report was the first example of enantioselective addition to a trisubstituted nitroalkene and was the first example of conjugate addition–enantioselective

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• pronucleophile to a substituted furanyl nitroolefin catalysed by a bifunctional cinchonine-derived thiourea has been used as the key stereocontrolling step in a new synthetic strategy to the heavily functionalised piperidine core of keramaphidin B. Keywords: bifunctional organocatalyst; enantioselective Michael

• nitroolefin 9 under the control of a cinchona-derived bifunctional Brønsted base/H-bond donor organocatalyst developed in our group and others [16][17][18][19]. Bifunctional organocatalysed Michael addition studies In our previous total syntheses of nakadomarin A [5][7][20] and manzamine A [10] the

• hydroxypropyl chain attached to the quaternary stereocentre, poised for further functionalisation. Having established that the cinchonine-derived bifunctional Brønsted base/thiourea organocatalyst 12 was effective for installing two stereocentres including the quaternary carbon in a model system, we next

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

• reaction was performed under mild conditions using PTSA·H2O as the additive. Subsequently, the asymmetric aldol reaction of aliphatic aldehydes with isatins was achieved by the same group by using a structurally slightly modified organocatalyst (cat. 5, Scheme 18) [34]. Malonic acid as the additive and

• hydrogen bonds with organocatalyst (cat. 5) and isatin substrate. A novel N-prolinylanthranilamide-based pseudopeptide organocatalyst (cat. 6) was designed by Bunge et al. for the enantioselective aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one with isatins, affording the products in good yield and with

• designed another DACH-derived organocatalyst cat. 12 bearing an additional phenolic hydroxy group for the asymmetric aldol reactions of isatins with ketones. Cat. 12 can efficiently catalyze the reactions, affording the final compounds in excellent yields (up to 98% yield) and with good

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

• increased to 50% ee for diastereoisomer 7a when using chlorobenzene as the solvent at room temperature (Table 2, entry 5). It is worth noting that bifunctional organocatalyst VII appears to be more effective in terms of diastereocontrol than previously employed Brønsted base/Lewis acid system TMG/ZnI2

• 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

• , homologous to V, was used as organocatalyst. Taking the supported thiourea V as the catalyst of choice, the effects of the catalyst loading, the temperature, the ratio of nucleophile, and the use of different solvents were studied for the reaction of 1a and 3a. Fortunately, the reduction of the amount of

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

• have exhibited efficient catalytic activity in the asymmetric Mannich reaction. In fact, the use of simple trans-(1R,2R)-aminoindanol (1c) as an efficient organocatalyst in the enantioselective synthesis of natural products as the TMC-954 core [12][13], has been recently reported. These examples show

• the high catalytic potential that this versatile motif exhibits [14]. The concept of bifunctionality has been extensively explored in organocatalysis in the last decade [15][16]. The bifunctional organocatalyst contains two chemical groups that interact simultaneously with the substrates. This mode of

• -type alkylation reaction of indoles To the best of our knowledge, the first example of an aminoindanol-containing bifunctional organocatalyst was reported by Ricci and co-workers in 2005 [18]. In this pioneering study, the authors used the easily prepared cis-(1R,2S)-aminoindanol-based thiourea