Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• applying biphasic conditions (using either K2CO3 or Cs2CO3 as solid bases) in the presence of 10 mol % A1, they were able to achieve enantiomeric ratios up to 85:15 under operationally simple room temperature conditions. After this pioneering report, it took around eight years until Maruoka’s group

• substrate scope when using just 2 mol % of phosphonium salt F1 under liquid/liquid biphasic conditions (Scheme 3). As already stated before, the use of chiral anionic PTCs became increasingly important over the last years and especially asymmetric fluorine-transfer reactions have been very extensively

• alkaloid-based PTC A3, the chiral products 16 were obtained in high enantioselectivities under operationally simple biphasic reaction conditions, as outlined in Scheme 7. Rather surprisingly, despite this pioneering early report almost 20 years passed until this methodology became more systematically

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• for N,N´-diacylation. To avoid this, the reaction was performed employing a diluted solution of the amine in a biphasic system (CHCl3/aqueous NaOH), low temperature (0 °C) and the use of anhydrides as acylating agents, if commercially available. The results are shown in Table 1. For R3 = H, products

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• pre-transitions are detectable below the main transition. In the corresponding DSC cooling scans (Figure 5B), a biphasic transition appears in most mixtures. Starting with the 1:10 mixture, the DSC scan depicts a peak at T = 23.1 °C, slightly below Tm of pure DMPC. With increasing amount of the

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• biphasic system was kept under stirring and the organic layer was continuously collected into a flask. Removal of CH2Cl2 gave pure amino compound 2a in 94% yield. This system allowed to easily obtaining almost 1 g of pure 2a in about 4 hours (see Supporting Information File 1 for further details

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• )porphyrinate), and ethyl diazoacetate (11) to generate arsonium ylide 12 for use in biphasic catalytic Wittig-type reactions (Scheme 3) [11]. In these reactions sodium hydrosulfite replaced triphenylphosphite as the reducing reagent to convert the byproduct Ph3As=O (13) back into 9 in the aqueous phase of the

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• -tetra(prop-2-yn-1-yl)-1,4,8,11-tetraazacyclotetradecane diperchlorate is reported. Keywords: azamacrocycles; biphasic system; cyclam; cyclen; N-alkylation; Findings The tetraazamacrocycles cyclam (1) and cyclen (2) have been the subject of considerable interest over many years [1][2][3][4][5][6][7

• electrophiles and excess sodium bicarbonate in anhydrous DMF, but the yields were generally poor (60% in the privileged case of ethyl bromoacetate, 25–40% in all other examples) [35]. Some success has been reported using direct alkylation in biphasic solvent systems which combine an alkaline aqueous phase with

• in achieving N-alkylation with a range of substituted aromatic groups, affording the N-tetraalkyl products in generally good to excellent yields. In some instances the products were found to be partially soluble in the biphasic solvent system, which made isolation slightly less straightforward

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• a reasonable time scale [13]. HPCCC relies on the combination of a biphasic immiscible solvent system and a high centrifugal force field. The centrifugal force immobilizes one of the phases in the coiled column (stationary phase), while the remaining phase can be pumped through the column (mobile

• phase). The rotation and the coiled structure of the column induce multiple sequential extractions between these two phases and thus the compounds are eluted from the column according to their partition coefficients. Most of the biphasic solvent systems contain different combinations of hexane, ethyl

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• in a biphasic reaction mixture – and the slow hydrolysis of 6 under the reaction conditions according to LC–MS (not shown). The conversion of 6 was complete in ethanol. However, in addition to the expected cyano compound 13, significant amounts of side products 14 (resulting from ethanolysis of 6

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• transfer synthesis’ in micro-chips for a diazo-coupling reaction [23]. The authors did not however employ a phase transfer catalyst, but rather the principle to increase the reaction selectivity in the diazo coupling of 5-methylresorcinol (10) to p-nitrobenzene diazonium tetrafloroborate (11) in a biphasic

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• Josef Schachtner Patrick Bayer Axel Jacobi von Wangelin Institute of Organic Chemistry, University of Regensburg, Universitaetsstr. 31, 93040 Regensburg, Germany 10.3762/bjoc.12.170 Abstract A home-built microreactor system for light-mediated biphasic gas/liquid reactions was assembled from

• operation of various other reactions at light/liquid/gas interfaces in student, research, and industrial laboratories. Keywords: biphasic reactions; flow chemistry; gas phase; microreactor; oxygen; photochemistry; Introduction The recent developments of microreactor technologies have significantly

• photooxidations of citronellol [35][40][41][42], indanes [43], monoterpenes [36], furans [42], furfurals [44], thiols [37] and amines [45] as well as the syntheses of ascaridol [46] and artemisinin [47]. Related microreactor setups were applied to biphasic gas/liquid mixtures in the photochlorination of

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• , acetonitrile, or ether at 0 °C or −78 °C. To each was added nitric acid (16 M) and concentrated sulfuric acid (18 M), a biphasic organic/inorganic reaction mixture formed [25]. Unfortunately after work-up all of these reactions afforded complex mixtures. Thus although the 1H NMR and mass spectrometry indicated

• the moderate yield was not problematic as rac-68 and rac-69 were readily separable, allowing rac-68 to be recycled (based on recovered starting material the yield was almost quantitative). Oxidative O-PMB deprotection of rac-69 using DDQ in biphasic dichloromethane/water generated 1° alcohol (±)-2

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• sellowii was investigated using liquid–liquid partition and centrifugal partition chromatography (CPC), which is related to the counter-current chromatography (CCC) [22]. The chromatographic behavior of the butanol fraction of the leaves of J. sellowii was evaluated in six different biphasic systems

• optimized biphasic system composed by EtOAc/EtOH/H2O, 9:2:10, v/v/v, shaken in a separatory funnel and kept until the phase separation. The separation was then conducted in isocratic ascending mode at room temperature, using the lower phase of the previously prepared mixture as stationary phase and the

• volume was determined as 320 mL. The butanol fraction was injected after dissolution in 20 mL of a mixture 1:1 of the selected biphasic system. 70 fractions of 50 mL were collected in the ascending mode. After switching to descending mode, 20 additional fractions of 50 mL were collected. Extrusion

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• solutions of N,N-dialkyl-N-chloramines is described using either a bespoke meso-scale tubular reactor with static mixers or a continuous stirred tank reactor. Both reactors promote the efficient mixing of a biphasic solution of N,N-dialkylamine in organic solvent, and aqueous sodium hypochlorite to achieve

• phase require longer reaction times, provided by the CSTR, to compensate for low mass transfer rates in the biphasic system. The green metrics of the reaction have been assessed and compared to existing procedures and have shown the continuous process is improved over previous procedures. The organic

• solutions of N,N-dialkyl-N-chloramines produced continuously will enable their use in tandem flow reactions with a range of nucleophilic substrates. Keywords: amine; biphasic; chloramine; chlorination; continuous flow chemistry; CSTR; static mixer; sodium hypochlorite; tube reactor; Introduction N

Grubbs–Hoveyda type catalysts bearing a dicationic N-heterocyclic carbene for biphasic olefin metathesis reactions in ionic liquids

• Maximilian Koy,
• Hagen J. Altmann,
• Benjamin Autenrieth,
• Wolfgang Frey and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2015, 11, 1632–1638, doi:10.3762/bjoc.11.178

• , H2ITapMe2 = 1,3-bis(2’,6’-dimethyl-4’-trimethylammoniumphenyl)-4,5-dihydroimidazol-2-ylidene, OTf− = CF3SO3−) based on a dicationic N-heterocyclic carbene (NHC) ligand was prepared. The reactivity was tested in ring opening metathesis polymerization (ROMP) under biphasic conditions using a nonpolar organic

• solvent (toluene) and the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate [BDMIM+][BF4−]. The structure of Ru-2 was confirmed by single crystal X-ray analysis. Keywords: biphasic catalysis; ionic initiators; recycling; ROMP; ruthenium; Introduction Ionic metathesis catalysts offer

• access to metathesis reactions in either aqueous solution [1][2][3][4][5][6][7][8][9][10] or under biphasic conditions [11][12][13][14]. Particularly the latter aspect is of utmost relevance in case of ionic liquids (ILs) can be used as the phase in which the catalyst is dissolved. The ionic character of

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• (Scheme 48). Ohsima and co-workers [182] have reported a rhodium-catalyzed [2 + 2 + 2] cyclotrimerization of triynes 283 in a water-organic biphasic system. The biphasic system provides dilute reaction conditions suitable for macrocyclization. Selective cross-annulation between hydrophobic diynes and

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• compounds were generated that were all used without further purification for the following condensation reactions. For example, sulfanilamide reacted with Oxone® in a biphasic DCM/water mixture to its nitroso counterpart, which was condensed with p-toluidine to give methyl azobenzene 1f (Scheme 1c) in 45

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

• yield (76%) by using allyl bromide in biphasic system composed of CH2Cl2/50% NaOH and the additive TBAHS as the catalyst at room temperature. The obtained 10-(prop-2-en-1-yl)-10H-phenothiazine was subsequently conducted into an oxymercuration–demercuration reaction accordingly to the procedure proposed

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

• Jonathan Potier,
• Stéphane Menuel,
• David Mathiron,
• Véronique Bonnet,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2014, 10, 2642–2648, doi:10.3762/bjoc.10.276

• used as additives in Rh-catalyzed hydroformylation of 1-hexadecene. The combined supramolecular and coordinating properties of these polymers allowed increasing the catalytic activity of the reaction without affecting the selectivities. Keywords: biphasic catalysis; cyclodextrin; hydroformylation

• compartments [6]. We especially developed biphasic catalytic systems in which cyclodextrin (CD) derivatives acted as interfacial additives [7][8]. These torus-like macrorings proved to be appropriate to supramolecularly recognize C8–C10 alkenes within their cavity and convert them into their corresponding

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

• also a few reports on AT reactions in water–organic solvent mixtures when reactive nucleophilic species were used (primary amine) and under biphasic conditions with a phase-transfer agent as shown in Scheme 10 [38]. In this study, water and CCl4 were used to produce the biphasic system. NaOH is the

• addition of a base immediately gives rise to the formation of pyrophosphate (31P NMR around −12 ppm alkyl pyrophosphate and −25 ppm tetraaryl pyrophosphate) and to phosphate in the presence of additional water (31P NMR dialkyl phosphate 0.4 ppm and diaryl phosphate −9.6 ppm). With the use of a biphasic

• chains as exemplified by a reaction reported by Taylor et al (Scheme 17-ii) [56]. The phosphorylation of phenol by the AT reaction was also reported under biphasic conditions in the presence of a phase-transfer agent. Interestingly, the study of Ilia et al. [57], reports the use of both liquid/liquid and

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• cameras and computer vision to synthesis procedures. Building on work in which a camera and a float were employed to measure the position of a biphasic (aqueous/organic) mixture within a settling column [5], we manufactured a float containing an air bubble [39] which would float on less dense solvents

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

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

• -dinitroaniline. Under conventional conditions of nitration, oxidation or over-nitration of aniline derivatives is unavoidable, as the reaction rates are strongly limited by interfacial mass transfer due to biphasic conditions. The selectivity of the isomer of interest can be increased by avoiding any pre

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

• and the solid iodine for the large scale preparation of piperidinol 11a (14 g, Table 2, entry 2) mechanical stirring was preferred. For saponification, saturated KOH solution in MeOH (ca. 4 N) was chosen, because aqueous KOH or NaOH solution would result in biphasic mixtures. A quantitative hydrolysis

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

• lactam, together with an acylimine. This was removed under acidic conditions to furnish aldehyde 143. Tebbe olefination [127] installed the missing double bond in 144. Oxymercuration [128] followed by reductive biphasic demercurization [129] furnished the remaining tetrahydropyran ring, yielding 145

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• )-catalyzed click chemistry – one of the most effective conjugation methods [21][22]. Thus, heating the educts with Cu(II)/sodium ascorbate in a biphasic mixture of CH2Cl2/H2O during 1 h provided compounds 6a–g (Scheme 3). According to the 13C NMR spectra, the click reaction proceeds regioselective in all

The difluoromethylene (CF₂) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF₂ groups

• Yi Wang,
• Ricardo Callejo,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2014, 10, 18–25, doi:10.3762/bjoc.10.4

• ketones, to generate difluoromethyleneacetylenes, is methodology developed by Grée et al. [14][15][16][17][18] and it proved to be very reliable in our hands. An efficient hydrogenation generated the C-8 substituted difluoromethylenepentadecabenzene 12. Finally biphasic ruthenium tetroxide-catalyzed aryl