3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• selected because it would run smoothly at room temperature, and a mild solvent mixture such as methanol and water (MeOH/water) could be used with the less solvent-compatible parts. Differences between the UV–vis spectra of the starting material and the product can be used to follow the reaction

• optimization. Reactor design 1 (RD1) By mimicking the internal dimensions of the DAD compartment within an Agilent HPLC system, an inline spectroscopic flow cell could be realised (Figure 1). RD1 was therefore fabricated using a 3D Systems Viper si2 SL system from Accura 60 photoresin, with external geometries

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• reaction conditions their enantiomeric ratios did not change, indicating that the reaction is not reversible. During reaction optimization the authors found that the addition of a large excess of brine improved the enantioselectivity of the transformation. Additionally, they found that by using saturated

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• propargyl alcohol. With a convenient route towards these enyne substrates in hand, we set our sights on optimizing the asymmetric enyne bicycloisomerization reaction. Initial experiments and reaction optimization Due to the similarity of 14 to the triple-uptake inhibitor GSK1360707 (see Scheme 2), we

• decided to initiate our efforts on 1,7-enyne sulfonamide 13 for reaction optimization. Table 1 showcases our initial experiments. With 3 mol % of CpRu-sulfoxide catalyst 1 in THF at 40 °C, 14 could be obtained in a 69% yield and a promising 26.5:73.5 er (Table 1, entry 1). This important first experiment

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• . Metathesis reaction optimization In 2003, Grubbs published a classification system for cross-metathesis catalysts and substrates, defining the substrates by type ranging from I to IV depending on their level of homodimerization observed in a metathesis reaction [20]. Type I substrates are defined as

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

• in due course. Overall strategy. Boc-protected aminoalcohols used as inputs in a diastereoselective Ugi reaction. Optimization of the synthesis of 6a. Scope of the synthesis of Ugi adducts 6. Supporting Information Supporting Information File 232: General remarks, experimental procedures and

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

• isoindolinones 9 via retro-Michael process. Asymmetric synthesis of (S)-PD172938. Coupling of chiral acid 9 with p-tolylpiperazine and CuI arylation of chiral isoindolinones. Catalyst screening in asymmetric cascade reactions of 2-cyanobenzaldehyde. Optimization of the asymmetric cascade reaction. Optimization

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• -membered carbocycle was realized via a B-alkyl Suzuki–Miyaura cross-coupling reaction. Optimization studies of this key ring closure with different protecting groups on the lactol functionality revealed methyl acetal 135 as the most efficient substrate for this transformation. The challenging key step was

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• MHz,CDCl3) δ 29.2, 33.8, 41.5, 55.4, 110.4, 114.5, 117.9, 120.4, 127.0, 139.1, 145.3, 157.2; GC–MS (m/z) 176.1. Ligands used for reaction optimization. Proposed catalytic cycle. Optimization of reaction conditionsa. Coupling of triarylaluminum reagents with alkyl iodides and bromidesa

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• anesthetic that is 100 times as powerful as morphine (Figure 2) [29]. By creating a tetrasubstituted variant, the activity is increased two orders of magnitude: carfentanil is over 10,000 times as active as morphine. Results and Discussion Reaction optimization The two-step/three-reaction sequence shown in

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• -acetamidoacetophenone. Cross carboxylative cyclization reaction. Optimization of the reaction conditions.a Carboxylative cyclization of various o-hydroxyacetophenones with carbon dioxide.a Carboxylative cyclization of various o-acetamidoacetophenones with carbon dioxide.a Supporting Information Supporting Information

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• -promoted synthesis of 2,2'-bisbenzofuran derivatives. Intramolecular competition experiments. Copper-promoted synthesis of benzo[b]thiophenes. Proposed mechanism for the annulation reaction. Optimization of the reaction conditions.a Supporting Information Supporting Information File 518: Full experimental

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• frameworks. Results and Discussion Reaction optimization We began our investigation into endoperoxidation conditions with diene 2a as the substrate as it contained both a styene and an aliphatic alkene. Using catalyst 1c in DCM at −41 °C under irradiation with 470 nm LEDs afforded endoperoxide 3a in 40

• intermediates are trapped by O2 and furnish the shown bicyclic products after reduction. Diversification strategy for endoperoxide synthesis by single electron transfer. E*red vs SCE [20]. Proposed mechanism for endoperoxide synthesis from tethered dienes. Competing formal [3,3] pathway. Reaction Optimization

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• protection of the more nucleophilic 4’-phenol and subsequent glucosylation or sulfation should lead to the desired products. For the development of a reliable protective group strategy and subsequent reaction optimization, 2,4-dihydroxybenzoic acid isopropyl ester (9) [29] was used as a RAL mimic. For

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• 455 °C. At the outlet of the reaction section, the reaction mixture was diluted with water by an integrated caterpillar micro mixer and subsequently sparged through an ice-water filled flask to condense volatile nitric compounds outside the integrated microreactor. Reaction optimization was conducted

Iron-catalyzed decarboxylative alkenylation of cycloalkanes with arylvinyl carboxylic acids via a radical process

• Jincan Zhao,
• Hong Fang,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2013, 9, 1718–1723, doi:10.3762/bjoc.9.197

• alkenylation of cyclopentan, cycloheptane and cyclooctane. Catalytic conditions: cinnamic acid (1) (0.3 mmol), cycloalkanes (2.0 mL), Fe(acac)3 (20 mol %), DTBP (2 equiv), 120 °C, 24 h, N2. Yields are isolated yields based on cinnamic acid. A plausible pathway for the reaction. Optimization of typical reaction

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• are not labeled for clarity). The transformation of Friedel–Crafts alkylation product 4a to cycloadduct 3a. Effect of ligands on the asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction. Optimization of reaction conditions. Effect of additives on asymmetric tandem Friedel–Crafts

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• addition of acid due to decomposition [36]. Additionally, we have shown a broad application of the quinolinium [44][45][46][47][48] and isoquinolinium [49] salts for the synthesis of a wide variety of alkaloid-like frameworks. Results and Discussion Reaction optimization During the course of the above

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• -azaindole with amides, amines, amino acid esters and phenols. Reaction optimization for coupling of 1e with benzamide (2a) under various conditionsa. C–N-bond-formation cross coupling of N-protected 4-bromo-7-azaindoles 1 with amides 2. Optimization of the coupling reaction of 4-bromo-1-ethyl-1H-pyrrolo[2,3

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• by thio-Ugi reaction. Synthesis of the bottromycin ring system 12 by thio-Ugi reaction. Optimization of amidine formation. Supporting Information Supporting Information File 436: Detailed experimental procedures, NMR and analytical data of all compounds. Acknowledgements This work was supported by

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• of substituted polymer-bound nitroarenes 1{a–k} are available (Scheme 1, Figure 1). Reaction optimization In order to optimize the reaction conditions, the temperature for the Bartoli reaction on solid supports was systematically changed. For the reaction of (4-chloro-3-nitrophenyl)carboxymethyl

Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis

• Magnus Rueping,
• Teerawut Bootwicha and
• Erli Sugiono

Beilstein J. Org. Chem. 2012, 8, 300–307, doi:10.3762/bjoc.8.32

• fast read out of reaction progress as the intensity of substrate and product peaks can be directly related to the conversion. Thus, as exemplified above, applying the inline analysis to different reaction parameters provides a fast and convenient method for reaction optimization. By using the optimized

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• drop in chemical yield was observed when the flow rate increased from 0.5 mL min−1 to 1.0 mL min−1 (Table 1, entry 2 versus entry 8), indicating that the flow rate should be 0.5 mL min−1. Further reaction optimization was accomplished by varying the substrate concentration. While the chemical yields

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• the present gold-catalyzed oxaallylic alkylation reaction. Gold-catalyzed synthesis of γ-lactones 4 from the corresponding monoesters 3. Mechanistic sketch of the gold-promoted oxaallylic alkylation reaction. Optimization of the reaction conditions for the lactonization of 1a.a Proving the scope of

The Eschenmoser coupling reaction under continuous-flow conditions

• Sukhdeep Singh,
• J. Michael Köhler,
• Andreas Schober and
• G. Alexander Groß

Beilstein J. Org. Chem. 2011, 7, 1164–1172, doi:10.3762/bjoc.7.135

• minimum residence time. For small scale synthesis flow chemistry is of great advantage to realize these conditions on the laboratory bench safely [18]. Results and Discussion For the reaction optimization we have focused on a straightforward procedure that finally prevents the isolation of the S-alkylated

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• run-to-run reproducibility of the H-Cube® reactor for screening and reaction optimization is discussed. Keywords: catalyst leaching; CatCart®; H-Cube®; packed bed flow hydrogenation; Introduction The potential advantages of heterogeneous catalytic flow hydrogenation over traditional batch reactor