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

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• ’ regioselectivity, creating a new stereogenic center [59][60]. In 1995, Bäckvall et al. reported the first example of an asymmetric allylic substitution reaction catalyzed by a chiral copper complex, giving a moderate enantioselectivity (42% ee) in Grignard reactions with allylic acetates. The enantiomeric excess

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

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• ethyl 2-nitrobutanoate (1b) as Michael donor also led to good results for three representative nitroalkenes (Table 2, entries 15–17), although in the case of nitroalkene 2e a somewhat lower enantiomeric excess was obtained. Finally, and as it happened in the reaction catalyzed by 4, β-alkyl-substituted

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• concentration, temperature and catalyst loading were also investigated (not shown) with no improvement on the enantioselectivity. After extensive optimization, the highest enantiomeric excess obtained was only 83% ee and so we decided to examine other leaving groups (Table 2). Like allyl chloride 2a, allyl

• became clear that when using alkylzirconocene nucleophiles and Cu catalysis, derivatised 3,6-dihydro-2H-pyrans are difficult to obtain in high enantiomeric excess. Moreover, both optimised systems gave poor yield; 25% yield with 100% conversion from allyl chloride 2a and 17% yield with 31% conversion

• quite robust so that we could also determine its enantiomeric excess during the course of the reaction. Initially 2a is racemic but it becomes scalemic to slowly reach 34% ee when the reaction is complete (~12 hours). From these observations and our experimental demonstration that 2a is much more stable

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• the 1,4-adduct 47, and the ethyl moiety was inserted with 74% enantiomeric excess in 78% yield (Scheme 13). Very recently, a new study dealing with the reactivity of unsaturated acyl-N-methylimidazole substrates in copper-catalyzed ACA was released by Mauduit, Campagne and co-workers [33

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• solvents, and yielded products with high enantiomeric excess (ee). The results where comparable to previously reported results for molybdenum-catalyzed systems [57], although the latter was used under inert conditions. In 2003, Blechert et al. reported the first systematic example of olefin metathesis in

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• highest enantiomeric excess 95%, but with only 26% chemical yield (Table 1, entry 6). Subsequently other catalysts were tested in order to improve the efficiency of the reduction. The catalyst 12, which is based on N-tosyl-(1S,2S)-1,2-diphenylethane-1,2-diamine (TsDPEN), gave amine 7 with 72–73% ee

• amine developed by us [16] was tested. This catalyst possesses similar activity to catalyst 12 and gave the product with 75% enantiomeric excess and 52% yield. Applying dimethylformamide as a solvent led to lower asymmetric induction and to significant reduction of the yield to 21%. The