Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• acrylate (1.2 equiv) was pumped at a flow rate of 0.5 mL/min through the K2CO3 column heated to 100 °C. The resulting short residence time (≈5 min) within the column was sufficient to give a high conversion of the substrates tested (Scheme 5, method 1). In a complementary approach a biphasic liquid–liquid

• biphasic plug flow pattern as the material progressed through a tubular flow coil reactor (rt, 33 min residence time). Upon separation of the phases and evaporation of the volatiles, the desired products were obtained in generally high yields. It was found that both approaches worked well for the tested

• immobilized CALB enzyme is reported. This approach enabled the chemoselective derivatization of benzyl alcohol into the readily removable benzyl butyrate thus simplifying the final purification stages. The resulting Cbz-carbamates were furthermore elaborated into derivatives of β-amino acids via biphasic flow

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• tetraoxide and sodium periodate in a biphasic solvent mixture (CCl4/MeCN/H2O), which gave 6-methyloctanoic acid (nat-10). The authentic (S)-6-methyloctanoic acid and (S)-8-methyldecanoic acid were synthesized in our previous studies [22][30]. These anteiso fatty acids were derivatized with a chiral

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• clear biphasic binding. The commonly used binding models usually also do not account for potential ligand-induced formation of aggregates. For supramolecular ligands it is not uncommon that the sample starts to precipitate when excess ligand is added. The neutralization of surface charges upon binding

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• aqueous or mixed water–EtOH solutions [29] or in biphasic water–Et2O mixtures [30] under reflux conditions. An exhaustive analysis of the literature revealed that virtually the same conditions were suitable for the hydrolysis of diethyl 2‐(2,6‐difluoro‐4‐methoxyphenyl)malonate (8) [31], dimethyl 2-(2

• observed under the conditions mentioned above. In preliminary experiments, we tested the mildest system – biphasic 10% KOH aqueous solution–Et2O at reflux temperature (35 °C) and vigorous agitation for the hydrolysis of diethyl 2-(perfluorophenyl)malonate (Scheme 3) No reaction occurred under these

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• obtained in a lower yield (52%) but high diastereoselectivity, similar to those previously reported [59][61]. The authors also explored the PKR in a catalytic version based on a biphasic system of ethylene glycol/toluene, which generally enhanced both yields and stereoselectivities, as well as simplifying

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• caused biphasic separation of the mixture. Antimicrobial assay The antimicrobial activity was evaluated by the method described previously [16]. Antioxidant assay The antioxidant activity was evaluated by the method described in [41]. Briefly, luminol (10 μM), H2O2 (1000 μM), and vehicle solvent with or

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

• Clemens R. Horn and
• Sylvain Gremetz

Beilstein J. Org. Chem. 2020, 16, 871–879, doi:10.3762/bjoc.16.78

• little as possible” [8]. This phrase describes the approach used to scale up flow reactors to an industrial scale [9][10]. This is particularly true when it comes to biphasic reactions, like a gas/liquid reaction as is the case for photooxidations [11]. An interesting aspect of photooxidations is that

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• -alcohols 63 via electrochemical oxidation in an undivided cell under constant current [61]. This time, they used catalytic amount of a different chiral N-oxyl radical mediator 64 (Scheme 25). The authors proposed that in the biphasic CH2Cl2/water medium, [Br+] is initially generated from [Br−] by

• towards asymmetric electroepoxidation of olefins 71 in a biphasic CH2Cl2/aqueous NaCl system (Scheme 28). The constant current epoxidation of 71 in an undivided cell resulted in chiral epoxides 73 in good yields and moderate enantioselectivities [66]. In 2008, Onomura and co-workers described the

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• sulfuric acid under biphasic conditions. (−)-Isopinocamphone (8) was purified by fractional distillation and isolated in 78% yield. Then, 8 was subjected to an analogous reaction sequence that was used for (+)-verbanone (3), i.e., the synthesis of the enone in the first step followed by its 1,2-reduction

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• -[(4-fluorophenyl)diazenyl]nicotinate (10): 4-Fluoroaniline (444 mg, 4.00 mmol, 1.00 equiv) was dissolved in DCM (15 mL) and treated with a solution of oxone (4.92 g, 8.00 mmol, 2.00 equiv) in water (50 mL). The biphasic mixture was vigorously stirred until thin layer chromatography indicated complete

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• . [52] and by Mousavizadeh et al. [53] through the three-component reactions of indole and coumarin, but in all cases, ordinary aliphatic and aromatic aldehydes as the third partner, mediated by a catalyst or by a biphasic system as solvent, respectively, were used. The lack of structural diversity in

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• the presence of TMSOTf [35] furnished target pentasaccharide derivative 20 in 70% yield (Scheme 4). Removal of the benzoyl group from compound 20 using sodium methoxide [24] followed by TEMPO-mediated oxidation [39] of the hydroxy group to a carboxylic group using sodium hypochlorite under biphasic

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• crucial for the intramolecular cyclopropanation reaction in a water/ether biphasic medium. The water-soluble catalyst could be reused at least six times with little loss in yield and enantioselectivity. Keywords: asymmetric synthesis; carbene transfer; cyclopropanation; diazoester; intramolecular

• previous work, we developed Ru(II)-Pheox catalysts for the intramolecular cyclopropanation of trans-allylic diazoacetates in a biphasic medium [29][30][31]. During the course of our continuous study on the development of a series of Ru(II)-Pheox catalysts, we found the introduction of an ammonium group on

• intramolecular cyclopropanation of a variety of diazo compounds such as diazoacetates and diazoacetamides in a biphasic medium. Diazoacetates were tested in our catalytic system because they are widely used for intramolecular cyclopropanation reactions and also the resulted lactones are widely distributed in

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• -grade silica. This was exploited further by Cabrera et al. [17][18] when 5b and related complexes were investigated as heterogeneous precatalysts in biphasic RO-RCM and CM reactions. The substrate and catalyst were adsorbed on a thin layer silica plate and developed in EtOAc/hexane (1:7 v/v) for the CM

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• equiv of Me2SO4 in a biphasic mixture of dichloromethane (CH2Cl2) and 10% sodium hydroxide (NaOH) aqueous solution in the presence of 0.1 equiv of benzyl(triethyl)ammonium chloride [Bn(Et)3NCl] as PTC at room temperature (rt) afforded a mixture of 4 and 1, in which the desired 1 was a minor component

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• several alkylquinolone compounds were investigated in a structure–functionality relationship manner, resulting in four different profiles: (a) agonists, (b) antagonists, (c) inverse agonists and (d) biphasic modulators. These studies revealed that pyocyanin production is only decreased significantly when

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• ovarian cell lines. This kind of biphasic effect could be explained by the presence of different GnRH receptors or depending on the concentration of a GnRH derivative/conjugate it could stimulate a different signaling pathway via a GnRH-R [40]. The opposite chemokinetic effects of the conjugates

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• imine intermediates to produce chiral amines. Results and Discussion N-Chloramine formation N-(Di)alkyl-N-chloramines have been prepared in continuous organic–aqueous biphasic flow using either static mixers or a single-stage CSTR [26]. The choice of reactor and definition of tres for this reaction is

• may be more of a problem in batch with the longer reaction time [48]. Conclusion A continuous-flow approach to prepare and handle unstable N-chloramines is reported. The method exploits the superior mixing of a CSTR compared with classical batch, to enable fast N-chlorination of amines under biphasic

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• aqueous NaOH through pump P4 which is heated to 140 °C through HE1. In-line extraction and purification happen in packed bed column reactor R6 by water and hexane which are pumped through pump P35 and P36. The resulting biphasic solution passes through gravity operated liquid–liquid separator S2 with

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric alkylation of tert-butyl glycinate benzophenone Schiff base 3 with alkyl halides 4 in a toluene–50% KOH biphasic system (Scheme 1). The corresponding α-alkyl-α-amino acid derivatives 5 were obtained in excellent yields with very low enantioselectivities (up to 9%). This is the first example of

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• environmental point of view. A good method for homogeneous catalysts separation and reuse is offered by the use of biphasic liquid–liquid systems. Recycling can be achieved in the reactor when the organic phase is sampled out, while the aqueous phase containing the catalyst is retained into the vessel, enabling

• representation of a Pickering emulsion with the enzyme in the water phase (i), or with the enzyme inside the polymersome lumen (ii). 3b) Chart of the specific activities of CalB dissolved in the water phase of the polymersome Pickering emulsion (left), CalB in a biphasic water/toluene system (middle,) and CalB

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• the protein and makes the system work also at higher concentrations of co-solvent [105]. However, working with a diluted solution, produce a large amount of wastewater that had to be treated. Another option is represented by biphasic systems: In these cases, the organic phase works as reservoir of

• in chloroform are 7.6 and 14.4 mM, respectively [102]). Several attempts to carry out hydroxysteroid transformations in biphasic systems were reported [106][107][108]: good conversions and an increase of reaction rates were observed for 7-OH and 3-OH epimerizations. In these cases the reactions were

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• positioned run-off. At flow rates of 0.5–1.2 mL/min emanating from the main reactor this unit performed reliably giving excellent quenching and separation. However, at higher flow rates issues were encountered with incomplete partitioning (some emulsion formation) of the biphasic mixture resulting in the

• quenching was immediately observed by the transformation of the dark red reaction mixture to a pale yellow biphasic solution which quickly phase separated upon collection. Confirmation of the successful quenching was obtained by 1H NMR and LC analysis of the organic phase which indicated only the product 11

• reactor – Cambridge Reactor Design). The system pressure was controlled using a 75 psi inline back pressure regulator. The flow stream was quenched by mixing with a solution of hydrochloric acid (1 M) at a flow rate of 2 mL/min within a glass microreactor (1 mL, Little Things Factory). The biphasic