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

Strategies in asymmetric catalysis

• Tehshik P. Yoon

Beilstein J. Org. Chem. 2017, 13, 63–64, doi:10.3762/bjoc.13.8

• Tehshik P. Yoon Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, WI 53706, USA 10.3762/bjoc.13.8 Keywords: asymmetric catalysis; enantioselectivity; stereoselectivity; The stereochemistry of an organic compound can have a profound influence on many of

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• derivatization can be used to alter the solubility, binding properties of substrates, and ultimately enantioselectivity properties of the CDs. The cavity of CDs has the secondary hydroxy groups at one opening and the primary ones at the other and the opening to the cavity at the secondary side is larger than

• often difficult if not impossible to derivatize all of the hydroxy groups. Whether the functionalization takes place preferentially at the primary or secondary hydroxy groups can have a significant impact on the enantioselectivity of the resulting derivative. Carboxymethyl- and trimethylammonio

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

• catalysts for aza-Diels–Alder reactions of Danishefsky’s diene with imines (Scheme 5) [52]. A variety of ammonium salts (L7–L10) including chiral cinchonidine derivatives L7 and catalyst L10 were found to promote the reaction in low-to-good yields albeit with no enantioselectivity. Although it is perhaps

Chromium(II)-catalyzed enantioselective arylation of ketones

• Gang Wang,
• Shutao Sun,
• Ying Mao,
• Zhiyu Xie and
• Lei Liu

Beilstein J. Org. Chem. 2016, 12, 2771–2775, doi:10.3762/bjoc.12.275

• -catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol. Keywords: arylation

• with high enantioselectivity (up to 95% ee) [38][39][40][41]. After that, the Chen group also disclosed enantioselective allylation of ketones using spirocyclic chiral borate and chiral bipyridyl alcohol ligands with the ee value ranging from 27% to 97% [42][43]. However, as far as we know, a Cr

• -dimethoxyethane (DME) was identified to be the best choice (Table 1, entries 8–10). Lowering the reaction temperature was found to be beneficial for improving the enantioselectivity, and when the reaction was performed at −20 °C, expected 2a was isolated in 81% yield with 97% ee (Table 1, entries 10–13). Aryl

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• catalysts provide a mild and highly effective sp3 C–H asymmetric arylation of THIQs. Keywords: C–H arylation; copper catalyst; enantioselectivity; visible light; Introduction Functionalization of sp3 C–H bonds is a unique and powerful transformation in modern organic synthesis, which remains a challenging

• interest in terms of atom economy, nevertheless enantioselectivity is difficult to control due to often-required harsh reaction conditions. Therefore, the development of simple and facile processes to functionalize sp3 C–H bonds under mild conditions in the absence of directing groups is of great interest

• acceptable yield and good enantioselectivity. However, this methodology has shown limitations in terms of substrate scope: only phenylboronic esters with electron-donating substituents yielded the corresponding products. We herein report the first visible light-mediated asymmetric cross-coupling arylation of

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

• synthesis of enantiomerically enriched products by testing different experimental set-ups. L-Proline-catalysed cross-aldol reactions were efficiently performed in continuo, with high yield (99%), anti-stereoselectivity, and enantioselectivity (up to 97% ee). Moreover, using two different DES mixtures, the

• diastereoselectivity of the process could be tuned, thereby leading to the formation, under different experimental conditions, to both the syn- and the anti-isomer with very high enantioselectivity. The excess of cyclohexanone was recovered and reused, and the reaction could be run and the product isolated without the

• interaction, nitrogen was used as a diffusor, thus realizing in set-up III a better mixing of the two phases (Figure 1, III). By monitoring the transformations performed with the above-described different set-ups, it was observed that both the diastereoselection and the enantioselectivity were constant during

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• /bjoc.12.222 Abstract A dipeptide-based urea-amide tertiary amine (DP-UAA) was shown to be an effective Brønsted base catalyst for the first asymmetric annulation reaction between 5H-thiazol-4-ones and N-itaconimides. High levels of enantioselectivity (up to 99% ee) and diastereoselectivity (>19:1 dr

• devised and demonstrated as a competent catalyst to furnish excellent chemo- and stereoselectivity [10]. Therefore, we examined catalyst III for this reaction (Table 1, entry 3); annulation adduct 3a was obtained in 60% yield with 70% ee. The increased in enantioselectivity indicates the potential of

• dipeptide-based tertiary amine for this type of reaction. By modifying the thiourea moiety of III to urea lead us to catalyst DP-UAA IV, which could further increase the enantioselectivity (Table 1, entry 4). Subsequently, we screened the solvent effect with IV as the catalyst (Table 1, entries 5–7), and

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• the key step (right, Scheme 8) [79]. After reduction of the ester 26, a Sharpless asymmetric dihydroxylation (AD) [86][87][88] reaction furnished diol 31 with a high degree of both regio- and enantioselectivity. Osmium-promoted oxidative type B cyclization of 31 proceeded in high yield (81%) and with

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• . Conclusion In summary, we have clearly demonstrated that chiral ammonium betaine 1c acts as a uniquely effective catalyst in promoting a Mannich-type reaction between 3-aryloxindoles and N-Boc aldimines with high levels of diastereo- and enantioselectivity under mild conditions. This study greatly expands

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• %. Three mechanistically distinct approaches to effecting enantioconvergent catalysis are identified, and recent examples of each are highlighted. These processes are compared to related, non-enantioconvergent methods. Keywords: asymmetric catalysis; enantioselectivity; synthetic methods; Review

• . Additionally, there must be a significant difference in the rates of product formation (i.e. k3 > k4). If this condition is not met, enantioselectivity will suffer. Stoltz and co-workers have reported an approach for the preparation of enantioenriched oxindole derivatives from racemic oxindole halides using a

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• enantioselectivity encouraged the Inomata group to further investigate the reaction [152]. Their investigation of enantioselective hetero-Diels–Alder reactions resulted in an enantioselectivity of up to 92% ee, when nitrosobenzene and a dienol were reacted in the presence of tartaric acid ester as a chiral auxiliary

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• -phenylmaleimide (22). For the remaining combinations (20 + 23; 20 + 24; 21 + 24) only the Michael products 29–31 could be observed (0.1 equiv of 10, CH2Cl2, −15 °C). To determine the enantioselectivity of guanidine 10 we started with the structurally simplest case, the reaction of anthrone 20 and N

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

• reaction time, and low temperature required for good enantioselectivity. Thus, new approaches for the organocatalytic enantioselective addition of diphenyl phosphonate to isatin imines are highly desired. In connection with our ongoing research program on the design and application in asymmetric catalysis

• 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

• methanol were used as the solvent (Table 1, entries 7–11). Under low catalyst loading of 2.5 mol %, this enantioselective addition reaction proceeded successfully to give 3a without compromising the reactivity and enantioselectivity (Table 1, entries 3 and 12–14). Finally, lowering the reaction temperature

Stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)”s: functionalization, rotational barriers and non-covalent interactions

• Golo Storch,
• Sebastian Pallmann,
• Frank Rominger and
• Oliver Trapp

Beilstein J. Org. Chem. 2016, 12, 1453–1458, doi:10.3762/bjoc.12.141

• long as their chirality can be controlled by chiral additives or auxiliaries. In addition, the simultaneous presence of both axially chiral BIPHEP enantiomers can be beneficial as this allows bidirectional control of enantioselectivity depending on temperature [14][15]. In this approach, both product

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

• (SiMe3)2 (CuHMDS) and the FeSulphos ligand, with the latter being related to the system reported by Carretero et al. [15]. The reaction produced 3aa smoothly with 3 mol % catalyst loading at −40 °C, and high endo selectivity and high enantioselectivity were obtained (Table 1, entry 1). On the other hand

• loading (Table 1, entry 3), and similar results were obtained in other solvents such as Et2O and toluene, although the reactivity and enantioselectivity both decreased slightly in dichloromethane (DCM, Table 1, entries 4–6). It was found that the use of the chiral CuHMDS catalyst also afforded the product

• with high enantioselectivity at lower catalyst loadings of 0.1 mol % (Table 1, entry 7). The effect of the amide part of the structure was then examined. Copper dialkylamides were not as reactive as CuHMDS, and lower yields were obtained (Table 1, entries 8 and 9). Interestingly, mesitylcopper also