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

• product 5a in 86% yield up to 35% ee (Scheme 4). In order to assess the effect of the calixarene backbone on the catalytic activity and enantioselectivity, they also performed the reaction in the presence of a chiral monoamide and an achiral calix[4]arene-tetramide. The results obtained in the presence of

• the Henry (nitroaldol) reaction between 4-nitrobenzaldehyde (21) and nitromethane (22, Scheme 6). Excellent yields (up to 99%) were obtained in CH3CN and THF when H2O was added. The best enantioselectivity (7.5%) was achieved in a mixed protic solvent (EtOH/H2O, 3:1, v/v) with a yield of 54% when 5

• asymmetric Tsuji–Trost allylic alkylation of 1,3-diphenylprop-2-enyl acetate (33) with dimethyl malonate (34, Scheme 9). Both, good catalytic activity and enantioselectivity (ee values up to 86%) were obtained with the potassium cation. This was due to the more strongly interaction of the dimethyl malonate

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

• high yields (89–99%) and enantioselectivities (92–99% ee). A lower yield (78%) albeit combined with a high enantioselectivity (94% ee) was obtained in the reaction of a dihalogenated isatin imine (R1 = 4,7-Cl2). The scope of the process was also extended to 1,3-dicarbonyl compounds other than

• symmetrical pentane-2,4-dione, such as 1,3-diphenylpropane-1,3-dione (R2 = R3 = Ph), that also led by reaction with the unsubstituted isatin imine (R1 = H) to the corresponding product in high yield (93%) and enantioselectivity (96% ee). Furthermore, unsymmetrical 1,3-dicarbonyl compounds, such as methyl

• good yields (42–81%), low to moderate diastereoselectivities (4–44% de), and low to excellent enantioselectivities (15–96% ee) for the major diastereomers formed (Scheme 4). In general, most of the isatin imines underwent the reaction smoothly with a good level of enantioselectivity (88–96% ee) and

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• enantioselectivity [24]. Later, Kita et al. used chiral tartaric acid derivatives to synthesize chiral I(V) reagents 2 from PhIO2. This represented the first example of the catalytic use of chiral hypervalent reagents in the oxidation of sulfides to sulfoxides with decent enantioselectivities (ees, Scheme 2a). The

• sulfides to sulfoxides with good yields but with poor enantioselectivity (Scheme 2b) [27]. Later, Zhdankin et al. synthesized different classes of chiral I(V) reagents 4 based on various amino acids as sources of chirality. The oxidation of the readily available 2-iodobenzamides (synthesized from amino

• with excellent enantioselectivity (Scheme 2d). Another class of chiral I(V) reagents 6 was synthesized by Wirth et al. who synthesized the desired compounds through esterification between chiral alcohols and the I(I)-substituted aromatic acids followed by oxidation with dimethyldioxirane (Scheme 2e

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• performing catalytic reactions with high enantioselectivity and efficiency [13][14]. As a result, a wide range of chiral catalysts have been established [15][16]. Chiral catalysts are, however, not only incompatible with aqueous solutions, but also expensive due to the structural complexity of the ligands

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• are utilised. The employment of a variety of different ligands such as phosphines, amines and carbenes allows precise tuning of the properties of homogeneous Pd catalysts, which led to significant improvements in turn over number (TON), reaction rates, enantioselectivity as well as catalyst robustness

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• ) groups in good-to-high yields and enantioselectivities. Axial backbones and substituents on phosphorus atoms of chiral phosphine ligands critically influence the enantioselectivity. Moreover, the methylation of simple perfluoroalkylated ketones is found to be facilitated by only chiral phosphines without

• have so far been reported [7][28][29][30]. In 2007, Gosselin and Britton et al. reported that treatment of ethyl trifluoropyruvate (1a) with (R)-BINOL-mediated organozincate as a chiral methylating regent provided the corresponding methylated tertiary alcohol 2a in moderate enantioselectivity (Scheme 1

• , reaction 1) [31]. Kinetic resolution of racemic α-trifluoromethylated tertiary alcohols 2a by an enzyme is also reported to give the corresponding alcohols 2a in high enantioselectivity (Scheme 1, reaction 2) [32]. However, there has been no report for catalytic asymmetric methylation of trifluoropyruvate

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• successfully developed a rhodium-catalyzed asymmetric arylation process leading to triarylmethanes 25. With the application of mild reaction conditions (40 °C, 15 h), a high enantioselectivity (≥90% ee) was reached with good to excellent yields. (Scheme 2). Starting from 2-naphthol, 2,2-disubstituted 3

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• yet sufficiently understood, if properties like solvent or temperature stability need to be optimized, or regio-, chemo- or enantioselectivity and substrate specificity shall be changed. Thus, the optimization and variation of proteins, in particular of enzymes, by random mutagenesis and subsequent

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• based on the use of chiral substrates and enantioselective catalytic procedures. Keywords: asymmetric (aza)-Reformatsky reaction; asymmetric synthesis; chirality; diastereoselectivity; enantioselectivity; total synthesis; Introduction The Reformatsky reaction involves the formation of β

• alcohols and BINOL (1,1’-bi-2-naphthol) derivatives, ligand 53 was selected as optimal ligand when used at a stoichiometric amount in THF at −40 °C. As shown in Scheme 21, the corresponding fluorinated chiral β-amino alcohol 54 was formed in both moderate yield (60%) and enantioselectivity (37% ee

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

• bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S

• 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

• decreased the reactivity and enantioselectivity and required diluted concentrations with low temperatures [47]. With the new chloramphenicol base amide organocatalysts we envisioned that the presence of a bulky oxygen group could avoid the intermolecular aggregation of the catalyst, while keeping the

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

•  2, entries 3–5). By employing catalyst 9b, the reaction proceeded at −60 °C to give phthalide 1a in 51% yield with 12% ee (Table 2, entry 4). To improve the enantioselectivity of the present nucleophilic trifluorometylation/lactonization, we surveyed suitable conditions for the catalytic asymmetric

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• . These methods have often the drawback of generating mixtures of regioisomers. Future efforts will be focus on developing efficient and less expensive reagents, along with a better understanding of mechanisms, improving the regioselectivity and enantioselectivity in these trifluoromethylation processes

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• , followed by the intramolecular Wittig reaction gave the corresponding 3,6-dihydropyran derivatives 44 in yields of 34–56% and a high enantioselectivity of 95–98% (Scheme 30) [43]. Pyran derivatives are structural elements of many natural biologically active compounds [44][45][46][47]. 2.2.2. Reactions with

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

• near quantitative synthesis with >95% ee at 60 min (Scheme 33) [134]. However, aldehydes having strong electron-withdrawing or -donating groups yielded the product with lesser enantioselectivity. The silica-supported catalyst could be recovered from the reaction mixture by washing with DCM. They have

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

• alone does not sufficiently catalyse and control the reaction. However, addition of Na2CO3 (leading to formation of the sodium enolate of 1 and the sodium phosphate of H) had a very pronounced effect on both, yield and enantioselectivity when using NFSI as the fluorinating agent. Again, the exact

• success in terms of enantioselectivity as under no conditions any asymmetric induction could be observed and the same was the case when we tested the use of N-bromosuccinimide under PTC conditions with a variety of different chiral catalysts, thus illustrating rather well some of the major present

• reaction has so far only been successful in a racemic fashion, whereas the use of chiral PTCs like A7 gave very little enantioselectivity only (er = 56:44, Scheme 12). Nevertheless, this inspiring report very nicely demonstrated the potential of phase-transfer catalysis for such dearomatization reactions

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

• 2M2B was replaced with other LAG additives a lower yield was observed (Table 1, entries 4–6). Nevertheless, the enantioselectivity of the process is maintained (95% ee), except when hexane was used (Table 1, entry 7), where a higher yield was observed (60%) although with a lower enantiomeric excess (86

• mechanochemical conditions was demonstrated. The reaction proceeds with an excellent yield (up to 49% of the theoretical 50% maximum) and high enantioselectivity (up to 98% ee). The method proved to be efficient in the resolution of racemic mixtures of β3-amino esters with aliphatic chains of different lengths

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• 10.3762/bjoc.13.157 Abstract The enantioselectivity of β-cyclodextrin (β-CD) towards L- and D-N-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that β-CD forms complexes of very similar but not identical geometry with both L- and D

• the enhancement of solubility, bioavailability and stability of drugs [2][3][4][5]. Moreover, being oligomers of α-D-glucopyranose, CDs possess an intrinsic chirality, thus they form diastereomeric inclusion complexes with enantiomeric pairs and frequently they exhibit enantioselectivity in aqueous

• . Moreover, trends in enantioselectivity do not follow trends in association constants, i.e., the association constants for the β-CD complexes of both enantiomers of N-acetyltyrosine, N-acetylphenylalanine and N-acetyltryptophan are in decreasing order, whereas their enantioselectivity (ratio of the binding

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

• 2a was formed enantioselectively (Table 1, entry 1). Although a lower temperature did not improve the enantioselectivity (Table 1, entry 2), lowering the concentration of the reaction mixture was effective (Table 1, entry 3). The screening of solvents identified ethyl acetate as the most suitable

• phenyl group yielded the product with the highest enantioselectivity (Scheme 2, 2f). However, a decrease in enantioselectivity was observed when the phenyl group was replaced by substituted phenyl groups (Scheme 2, 2g and 2h). The substrate bearing a naphthyl group afforded the corresponding product in

• moderate enantioselectivity (Scheme 2, 2i). In addition, a benzamide with a cyclopropyl group also provided the product in good enantioselectivity (Scheme 2, 2j). Furthermore, when the reaction was carried out using 1k and 1l with 2 equiv of NBA (4a), dibromination proceeded in high yields and moderate

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

• 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

• , respectively (Table 1, entries 1 and 2). Further experiments showed that a bifunctional thiourea catalyst d was the most efficient for the synthesis of spirocyclic oxindole derivatives in good yields (80%) with excellent diastereoselectivity (8:92 dr), and moderate enantioselectivity (83% ee, Table 1, entries

• enantioselectivity (3a–j). For example, the protocol showed moderate yields (75–76%), excellent diastereoselectivity (9:91–3:97 dr) and good enantioselectivity (85–94% ee) for substrates containing 5-CH3 or 5-OCH3 groups (3b and 3d). Substrates carrying 5-F, 7-F, 5-Cl and 6-Cl afforded the corresponding products 3f

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• appreciable enantioselectivity was observed. To investigate the feasibility of a convex-facial addition, we subjected 2a to Luche reduction conditions (Scheme 3). We found this transformation to be completely diastereoselective, and an X-ray diffraction study [58] of the product confirmed our hypothesis

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

• lead to high levels of enantioselectivity in asymmetric transformations in which enamine intermediates are formed. The substituent R1 in the 1,3-dioxolane moiety in pyrrolidines C could be varied to modulate the reactivity and selectivity of the new organocatalysts. The sequential hydrozirconation

• stereochemistry of the major compound depended on the stereochemistry of the organocatalyst and Michael adducts of opposite configuration were obtained on using syn or anti-pyrrolidines with similar levels of enantioselectivity for the major syn-diastereoisomer. Next, the effect of the solvent and temperature was

• enantioselectivity reached 85% ee for the major syn-adduct. A further decrease in temperature did not improve these results substantially but did diminish the reaction yield (Table 2). The organocatalysts OC1–OC11 were then screened to reveal the influence of the substituent R attached to the dioxolane moiety on the

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• number of cinchona alkaloid-derived ligands which allow the dihydroxylation of alkenes of almost all substitution patterns with high enantioselectivity. Noteworthy is that the SAD is not limited to only E-allylic alcohols in its choice of substrates as is the SAE process. Moreover, the SAD is much more

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• probe, for monitoring the transformation, and an in line liquid–liquid separator to avoid tedious work-up procedures, thus saving solvents, resources and optimizing work times. This system was demonstrated to work for 11 h with higher conversion and enantioselectivity (er >99.9%) in comparison to the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• obtained by isomerization of racemic α-arylpropargyl alcohols 161 in the presence of a rhodium catalyst. A high enantioselectivity has been achieved by the use of the chiral bisphosphine ligand (R,R)-160 (Scheme 47). A catalytic cycle of this isomerization is shown in Scheme 48. First, alkoxorhodium 163