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

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• reagent feed time) in order to evaluate this hydrogenation process. The process proved robust allowing reproducible and safe generation of the desired product in both high yield and enantiomeric excess. Additionally, semi-continuous liquid–liquid extraction, in-line distillation and product

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• mixture. As reported in the literature, immobilization of chiral imidazolidin-4-ones on polymeric support might affect the formation of the desired products and lead to decreased enantioselectivities [58]. Indeed, in all the experiments reported in Table 1 the enantiomeric excess of 13 was lower compared

• ). Nevertheless, the observed enantiomeric excess of the product 13 is still low when compared with those (93% ee, at −30 °C) originally reported in the case of the traditional (S)-phenylalanine-based imidazolidin-4-one [53]. Using the optimized solvent system (Table 1), we then turned our attention to study the

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• iodoarenes in the presence of peroxides. Chiral iodoarenes, such as 197, served as the catalysts in the asymmetric C–O coupling of sulfonic acids with ketones. The enantiomeric excess of the product was not higher than 58% due, in particular, to instability of the configuration of the products, α-sulfonyloxy

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• bromo derivative, which conducted in toluene gives mainly the product of single inversion, whereas carried out in methanol it provides exclusively the product of net retention. Enantiomeric excess of optically active promethazine and ethopropazine were established by HPLC measurements with chiral

• analytical HPLC separation studies of the corresponding pairs of enantiomers and for the measurement of the enantiomeric excess values of the compounds prepared in the biocatalyzed reactions, the afore-prepared alcohol (±)-3 was reacted with the appropriate acyl chloride in dry dichloromethane in the

• obtained with excellent enantiomeric excess (>99% ee), while the remaining alcohol (S)-(+)-5 was recovered only with 96% ee due to the fact that the reaction definitely stopped at 49% conversion being reached after two weeks. The specificity of this lipase for the (R)-alcohol was evident since even after

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• a Varian 3900 gas chromatograph equipped with a WCOT fused-silica column (25 m × 0.25 mm). This allowed to determine the b:l ratio. In order to determine the enantiomeric excess, a sample of the reaction mixture (toluene) was treated with LiAlH4 for 0.5 h. After filtration, the toluene solution

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

• Helmut Ritter,
• Antonia Stöhr and
• Philippe Favresse

Beilstein J. Org. Chem. 2014, 10, 2361–2366, doi:10.3762/bjoc.10.246

• monomeric residual of each oligomerization was measured twice. The obtained enantiomeric excess (ee) values of the monomeric residual are given in Table 1. Because of the rapid conversion of the monomer 1 during the oligomerization with highly active peroxidase–H2O2 system at room temperature, the reaction

• of the oligomers synthesized with laccase from the racemate 1. Oligomerization of N-(4-hydroxyphenyl)mandelamide (1). Enantiomeric excess values (ee) of the monomeric residual of the enzymatic oligomerization of 1.

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• cyclic dipeptide [5]. In these reactions, N-substituted imines react with HCN to yield (S)-α-aminonitriles with remarkably high enantiomeric excess (ee). One example is shown in Scheme 3. However, when benzaldehyde and NH3 instead of the N-substituted imine were employed as the substrates, the reaction

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• determination of the enantiomeric excess of a chiral amine based on the use of phosphorinanes derivatives. Two synthetic pathways i) the AT reaction and ii) the direct use of chlorophosphate were evaluated for the derivatization of chiral amine (or alcohol) as reported in Scheme 6. For the AT reaction (i) [23

• reduction of a prochiral ketone. The phosphoramidate (Scheme 32-iii) was the most efficient catalyst for these two reactions (ee: 95–98%, conversion 87–98%). In relation with asymmetric synthesis, the determination of the enantiomeric excess (ee) is usually achieved by different methodologies including

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• preparative HPLC or recrystallization. Nucleophilic substitution of pure diastereomer (RP)-2a with methyllithium afforded the phosphine–borane (S)-4 with 94% enantiomeric excess. The substitution resulted in inversion of the configuration at the phosphorus center. Deboranation of the air stable borane adduct

• favored by the spartein auxiliary. The enantioselectivity was found to be time and temperature dependent. Simple stirring of the intermediate (−)-sparteine–lithium complex of 13a for 1 h at 25 °C prior to alkylation resulted in an increase in enantiomeric excess of 14a. The organocatalyst 16 has also been

• alkenylphosphine 81c was formed. The highest enantiomeric excess measured by chiral HPLC was 56%. No reaction was observed without the palladium catalyst [165]. Gillaizeau and co-workers have demonstrated the use of α-amido enol phosphates 88 as vinylic coupling partners in the palladium-catalyzed C–P cross

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

• substituents have been constructed [20]. Starting from 3, the first conjugate addition using (R,SFe)-L1 afforded 4, as expected in high yield and excellent enantiomeric excess (Scheme 1). Reduction with DIBALH, followed by Horner–Wadsworth–Emmons olefination and again asymmetric conjugate addition gave 6 in 77

• from 6. Both the enantiomeric excess and the diastereomeric excess of 8 were excellent which is important as the response of insects to their pheromones can be highly sensitive to the stereoisomeric composition. A number of procedures exist to reduce ketones to their corresponding methylene groups

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• show any racemisation at all, not even after a longer time of storage. For the latter three the enantiomeric excess was not determined on this step: Further conversion as depicted in Scheme 4 and Table 2 delivered piperidinols 11a, 11b and 11d in ≥99% ee. As no intermediate in the conversion of 7 to 11

• File 1). Indeed, under optimized conditions (1.2 equiv I2, P(OEt)3, Et3N (5–6 equiv)/CH2Cl2 1:2; −78 °C then warming to rt) the piperidinols 11a–d were isolated after saponification (during work up) of triethylphosphate and chromatographic purification in 68–82% yield and high enantiomeric excess (90

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• equiv of rac-12 based on NFSI afforded the corresponding product 13 in higher enantioselectivity than that obtained in the reaction with 2 equiv of NFSI, along with 27% ee of 14; however the enantiomeric excess of 13 was not sufficiently high (47% ee). These results suggested that the reaction proceeded

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• quinine, gives modest yields (60%) albeit with low enantiomeric excess (13% ee). Lowering the reaction temperature with catalyst 4 results in a slightly higher enantiomeric excess (27% ee, Table 2), however the yield drops to only 30%. We anticipated an increase in enantioselectivity for the epimer 5 as

• motifs. Indeed cis-catalyst 14a exhibited an excellent efficacy with 98% isolated yield and a good enantioselectivity of up to 75% ee (Table 4). It is noteworthy, that the enantiomeric excess can easily be increased to >99% by recrystallization. While enantioselectivities with 14a are slightly higher in

• -hydroxynaphthoquinone to β-nitrostyrene. The open-chain triamide catalyst 7a performs with nearly quantitative yields (98%) and moderate enantiomeric excess of 51%, even at 2% catalyst loading (Table 2). Cyclodiphosphazane cis-14a shows the same efficiency with 98% isolated yields and an even improved enantiomeric

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• kinetic resolution [156], albeit with unsatisfactory enantiomeric excess. The undesired enantiomer was then selectively cleaved using another enzyme with reversed selectivity to give enantiopure pyranone 181. Cyclopropanation was achieved using a Michael addition initiated ring closure yielding diester