Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• derivative was employed for the asymmetric dioxytosylation of styrene and its derivatives. The electrophilic addition of the hypervalent iodine(III) compound toward styrene proceeded with high enantioface selectivity to give 1-aryl-1,2-di(tosyloxy)ethane with an enantiomeric excess of 70–96% of the (S

• . [15][16][17] reported the dioxytosylation of styrene (1a, Scheme 1). Chiral hypervalent iodine reagents 2 bearing a 1-methoxyethyl side chain were used for enantiocontrol of the dioxytosylation, and the maximum enantiomeric excess (ee) of the product 3a reached 65%. Despite recent rapid progress in

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

• under reduced pressure. The residue was purified by silica gel column chromatography to give p-nitrobenzoylated alcohol 2’. The enantiomeric excess was determined by chiral HPLC analysis. (S)-3-Ethoxy-1,1,1-trifluoro-2-methyl-3-oxopropan-2-yl 4-nitrobenzoate (2a’) The yield of alcohol 2a (86%) was

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

• preparation of β-amino acids, especially protocols leading to products with high enantiomeric excess (ee), which are required to test the pharmacological activity of each enantiomer [11][12][13]. In this regard, several methods for the asymmetric synthesis of β-amino acids have been documented [14][15][16][17

• 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

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

• 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

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 the privileged pyrrolidine motif. When used in the asymmetric Michael addition of aldehydes to nitroolefins, diastereoselectivities of up to 93:7 and enantioselectivities of up to 85% enantiomeric excess for the syn-adduct were obtained in the presence of the most effective organocatalyst OC4

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

• process. The stereochemistry of the adduct can be simply switched to the opposite enantiomer, by using the enantiomeric supported catalyst PS–(R)-pybox–calcium chloride. The enantiomeric excess of the products was about 96%. Two more steps consisting in a Pd-catalyzed hydrogenation reaction and a

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

• % enantiomeric excess (Scheme 33). 2-Methylbenzil (108) has been converted to 2-hydroxy-2-phenylindan-1-one (109) as a result of photochemical isomerization, in 90% yield (Scheme 34) [59]. Wagner et al. have reported that hexaisopropyl-, hexaethyl- and hexamethylbenzils 110a–c photocyclized to the corresponding

• % enantiomeric excess) from bis(α-diazo-β-keto ester) 205 [86]. The key step of this synthesis was a double intramolecular C–H insertion process catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate]. The resulting spiroindanone derivative 207 obtained from the intermediate 206, underwent

• rhodium(II) complex 220 followed by the carboxylic methyl ester hydrolysis/decarboxylation in DMSO/H2O at 120 °C with up to 72% enantiomeric excess (Scheme 60) [89]. 1.7 From epoxides and cyclopropanes The chalcone epoxides 221 ring opening catalyzed by indium(III) chloride, followed by a intramolecular

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

• arylation of THIQ using phenylboronic acid with 44% enantiomeric excess (ee), but very poor yield of the optically active products. Lowering the reaction temperature, in order to increase the corresponding ee, resulted in inhibition of the reaction. More recently, Liu et al. have demonstrated the arylation

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

• hours and with high conversion (≥95%) in all tested DESs (A–E, Table 2, entries 1–5). While low diastereoselectivity was observed in DES A (Table 2, entry 1), anti-stereoselectivity (up to 85:15) and high enantiomeric excess in favour of the anti isomer (up to 92% ee) were instead detected running the

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• commercially available) of (1-2H)geranial to (R)- and (S)-(1-2H)geraniol that were obtained with high enantiomeric excess (>95% ee) as determined by Mosher ester analysis (Figure S1, Supporting Information File 1). The alcohols were subsequently converted into the corresponding diphosphates using

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

• diastereomeric ratio was moderate (dr = 7.3:1), the enantiomeric excess (ee) of the major isomer was determined to be 98% (Table 1, entry 1). The investigation then focused on the effects of the catalyst structure, primarily on diastereocontrol, which revealed the importance of steric bulk at the periphery of

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

• led to asymmetric versions of this reaction. Vasella synthesized the hetero-Diels–Alder product 118 with >96% enantiomeric excess from an α-chloro-α-nitroso ether 115, prepared from mannose, and 1,3-cyclohexadienes 116 (Scheme 23) [56]. A similar work was reported by the Streith group in 1998 [106

• reaction carried out using a catalytic amount (20 mol %) of the di-tert-butyl tartrate and 1.4 equiv of n-propylzinc bromide resulted in an enantiomeric excess of up to 83% for the product. It should be noted that 4 Å molecular sieves, to provide extremely anhydrous conditions, were vital for the

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

• , batches larger than 15 g of the S-configurated acid 13 could be isolated in 90% yield (45% based on rac-12). In a two-step procedure 13 was converted into amino alcohol 14 without recrystallization in order to keep the enantiomeric excess unchanged. It was determined at this stage to be better than 99

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

•  1 for images). Under optimized conditions, bromochloroalcohol 6 was produced in 57% yield and 89% enantiomeric excess (ee) with small amounts of undesired bromochloride 7 (6%) and other brominated byproducts (8 + others, 22% combined) (Table 1, entry 4). The trace dibromide 8 was quantitatively and

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• hydrogenation of alkenes S1–3. It also outperformed the most efficient serine-derived PHOX catalysts ser-PHOX-OAc and ser-PHOX-OBz. In terms of activity and enantiomeric excess the performance of this catalyst was comparable to the tert-leucine-derived complex Ir-1b. The analogous serine-based complex Ir-20

• cyclohex-2-en-1-yl benzoate a notable enantiomeric excess of 70% was achieved using ligand 14-TES, in striking contrast to the extremely low enantioselectivities reported for analogous PHOX ligands [4]. Using ligand 14 with a free hydroxy group the result was less satisfying. Not only the yield dropped to

• 53% but also the ee was substantially lower than with the triethylsilyl analog 14-TES. For NeoPHOX ligand 1b the enantiomeric excess was even lower (5%). These results demonstrate that the 2nd generation NeoPHOX ligands possess potential for palladium-catalyzed allylic substitutions. Conclusion The

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• the C(sp3)–H bond of the asymmetric carbon to yield ketoester 7 in 67% yield. This latter compound was converted to (+)-α-cuparenone (8) in 26% yield and 96% enantiomeric excess. In the late 1980s, many studies have been published by Taber [35], Sonawane [36], Doyle [37] and their respective coworkers

• carbenoid insertion into C(sp3)–H [40]. In this work, the authors introduced the enantiomeric rhodium(II) carboxamides complexes (R)-18 and (S)-18 (Figure 4). The authors could observe the enantioselective formation of the lactones 20 with high enantiomeric excess (Table 2). The carbenoid formed by (S)-18

• dimers of α-substituted α-diazoacetates as the main products of this reaction. This issue was circumvented when low temperatures, −50 °C, were used and the insertion reaction occurred with considerable yields and good enantiomeric excess (Table 8). According to the authors, the low temperature could

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

• enantiomeric excess was determined by chiral-phase HPLC analysis using mixtures of hexane/isopropanol as eluent. Method B, under ball-milling conditions: Catalyst VI (15 mg, 0.015 mmol, 0.05 equiv), 2-nitrocyclohexanone (43 mg, 0.3 mmol) and nitroalkene (0.45 mmol, 1.5 equiv) were transferred to a clean, dry

• enantiomeric excess was determined by chiral-phase HPLC analysis using mixtures of hexane/isopropanol as eluent. Parent and supported bifunctional thioureas used in this work. Reaction of nitrostyrene with diethyl malonate and 2-ethoxycarbonyl cyclopentanone. Reaction of nitrostyrenes with malonates and β

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

• significant increase of conversion and enantiomeric excess (Scheme 2) [23]. Experimental proofs exploring different catalysts and acids suggested that it is the thiourea which provides the sense of the enantioinduction. Therefore, the authors assumed the bifunctional transition state TS2, similar to the above

• % of this compound was employed in the enantioselective conjugate addition of the hydroxylamine derivatives 31 to the enoates 30, affording the final products 32 with good yield (up to 98%) and high enantiomeric excess (up to 98% ee). This provided an efficient method that allows the preparation of

• catalyst, the hydroxy group of the squaramide 43 was methylated (43'). Its catalytic activity was tested in the reaction of acetylacetone (36a) and β-nitrostyrene (3a), leading to very low enantiomeric excess (24% ee). This fact suggested the important role played by the hydroxy group in the activation and

(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

• formation of substituted dihydro-2H-pyran-6-carboxylate 3 (Scheme 4) [16]. It was observed, that by employing PhCOOH as an additive, the yield (%) and the ee (%) increased, in comparison to the use of 4-dimethylaminopyridine (DMAP). A single example was shown leading to 82% yield and an enantiomeric excess

• and high enantiomeric excess. It has been observed that a nucleophilic 2π-reactant is needed for the successful conversion of the reactants into the desired products, following a mechanism which involves a cationic, electron-poor amino-pyrylium intermediate. In addition, for the achievement of high ee

• yields up to 94% and enantiomeric excess up to >99%. A proposed mechanism for this reaction is shown below, where the formation of the s-trans-enamine occurs and then attacks the electrophilic double bond of the nitroallyl acetate (Scheme 15). Among the same lines, Tsakos and Kokotos reported an

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• synthesis of buphanidrine (104) and powelline (105) led to the bespoke development of another cupreidine catalyst CPN-107. Unfortunately, although the resulting adduct 108 (after alkylation of the catechol) was produced in a 70% enantiomeric excess (Scheme 24b), subsequent steps that had worked with the

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• the enantiomeric excess of the original scalemic mixture of binol (diol) or amine (Figure 15). The three-component system was very versatile and we could use the complexes to determine the enantiomeric excess (ee) of amines [69][70], diamines [71], amino alcohols [72], hydroxylamines [73] and diols

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R)-enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess. Keywords: asymmetric catalysis

• stereo-differentiating potential of carbohydrate ligands in this type of reaction where their gluco-PHOX ligand, derived from glucosamine, resulted in a high enantiomeric excess of up to 98% [14]. Recently, Vidal et al. reported on a spiro-bis(isooxazoline) ligand A (Figure 1) [15] prepared via 1,3

• as a benchmark for new chiral ligands and examined in great detail [9][10][11][12][13][14][27][28]. In all cases investigated here, the alkylated product 14 was isolated after purification by chromatography and its enantiomeric excess was determined via chiral HPLC using a Reprosil chiral-NR column

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , the usefulness of this approach relies on an efficient and diversity-oriented preparation of the required amines in high enantiomeric excess. Chiral aminoalcohols can be ideal substrates for diastereoselective Ugi reactions: the additional hydroxy group can both help in modulating diastereoselectivity

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• of 16, however, was found to be difficult due to competitive bromination of the electron-rich aromatic ring, and thus the desired bromide 17 was obtained in only 14% yield. We then investigated an alternative route from adduct 5, even though the enantiomeric excess of 5 (86% ee) was a little lower

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• –7.48 (m, 1H), 5.09–4.99 (m, 1H), 2.97–2.89 (m, 1H), 2.68–2.48 (m, 1H); 13C NMR (100 MHz, CD3OD) δ 172.6, 171.2, 146.8, 131.9, 131.3, 128.1, 122.9, 122.6, 53.4, 38.3. The enantiomeric excess was determined by derivatization of the compound into methyl ester 12 or amide 16. Some chiral, bioactive