Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• interface populated by catalyst particles. They deposited metallic Pd onto carbon nanotube–inorganic oxide hybrid nanoparticles and used them in emulsions for the hydrodeoxygenation of a phenolic compound and the hydrogenation and etherification of an aldehyde. The advantages of such a system include a high

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• chemistry; hydrogenation; hydroiodic acid; hydroxychloroquine; Introduction Our research group has been focused on the development of new synthetic methods for the preparation of a variety of active pharmaceutical ingredients for global health applications by employing the principles of process

• ). Continuous flow hydrogenation was performed using a FlowCAT instrument. Synthesis of 5-iodopentan-2-one (10) Two solutions, 2-acetylbutyrolactone (8, 1.176 mL, 10.35 mmol, 1.0 equiv) and hydroiodic acid (55% aqueous solution) were pumped at 1.0 mL min−1 using peristaltic pumps through a 10 mL coil

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• Cristina Mozo Mulero Alfonso Saez Jesus Iniesta Vicente Montiel Instituto de Electroquímica, Universidad de Alicante, Apartado 99, 03080 Alicante, Spain 10.3762/bjoc.14.40 Abstract The electrocatalytic hydrogenation of benzophenone was performed at room temperature and atmospheric pressure using

• electrochemically hydrogenated in EtOH/water (90/10 v/v) plus 0.1 M H2SO4. Current densities of 10, 15 and 20 mA cm−2 were analysed for the preparative electrochemical hydrogenation of benzophenone and such results led to the highest fractional conversion (XR) of around 30% and a selectivity over 90% for the

• synthesis of diphenylmethanol upon the lowest current density. With regards to an increase by ten times the Pd electrocatalytic loading the electrocatalytic hydrogenation led neither to an increase in fractional conversion nor to a change in selectivity. Keywords: benzophenone; diphenylmethanol

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

• used for the hydrogenation of fatty acids). In comparison to the Wolff–Kishner reaction, the use of hydrazine is replaced by the use of hydrogen gas, which can be seen as a double-bladed knife. The reduction step can also be performed with NaBH4 or other reductants. At the moment, a complete and clear

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• conditions for their cleavage. Secondly some glycosyl oxazolines are also prone to reductive cleavage by catalytic hydrogenation [41], presenting a significant further limitation as to which OH-protecting groups may be employed. Most of the reports in the literature have therefore used a protecting group

• removed. Treatment with UDP-Gal and a β(1–4)-galactosyl transferase led to the addition of galactose residues to all of the 4-hydroxy groups of the GlcNAcs. Deprotection of the remaining benzyl protecting groups and removal of the SPh at the reducing terminus by catalytic hydrogenation gave the completely

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• detritylation and coupling of the third monomer. The release of the trimer in fully protected form from the support was achieved by hydrogenation with Pd/C (10%) in tetrahydrofurane (THF) for 40 h at room temperature. Three fully protected trimers were prepared this way with isolated yields in the range of 44

• reductive conditions (disulfide cleavage or hydrogenation) or under mild basic conditions leaving all protecting groups at the trimer undamaged. In particular, soluble support strategies have great potential for an efficient large scale synthesis of fully protected trinucleotides. The essential feature here

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• of this transformation are underway in our laboratory. Arylations of pyrrole derivatives with diaryliodonium salts. Formation of N-phenylamine derivatives 4 and 5 via ring opening reactions. Preparation of product 6 by hydrogenation. Optimization of reaction conditions.a Scope of diaryliodonium salts

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• the condensation of 5-aminopyrazole derivative 16 and sodium nitromalonaldehyde 171 followed by reduction of the nitro group by hydrogenation to give 6-aminopyrazolo[1,5-a]pyrimidines 172. 6-Aminopyrazolo[1,5-a]pyrimidines 172 thus obtained were coupled with variously substituted benzoic acids 173 to

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• : through dehydration in the case of 1 or radical reduction through the corresponding bisxanthate derivative in the case of 2. The required diol 3 could be obtained through a simultaneous hydrogenation of both, the cyclohexene and vinyl moieties of 1-aryl-4-vinyl-5,5,6,6-tetrafluorocyclohex-2-ene-1,4-diol 4

• steps less than the previous method. In addition, the present synthetic protocol involves several standard organic transformations, such as hydrogenation and dehydration, which are advantageous for a large-scale synthesis of the target compounds. Thus, we attempted a detailed examination of the short

• compound 4a in hand, the successive hydrogenation in the presence of 20 mol % of Pd/C in methanol was performed for 1 d and generated the corresponding tetrafluorinated cyclohexane-1,4-diol 3a in quantitative yield. Compound 3a could be converted to the cyclohexadiene 1a in 82% isolated yield under the

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• material 3. Due to the very similar polarities of 3 and 4, chromatographic separation was very tedious, and only 34% of methyl compound 4 was isolated, accompanied by about 30% of starting material 3 and mixed fractions. Debenzylation of 4 by catalytic hydrogenation in methanol solution under palladium

• hydrogenolysis experiments with 5, which were aimed at simultaneous O-debenzylation at the 7-position and conversion of the N,N-dimethylaminomethyl group at C1 into a methyl group. Hydrogenation in presence of palladium as catalyst at 1 bar in the presence or absence of small amounts of sulfuric acid gave the

• highly reactive benzylammonium residue still takes place, but O-debenzylation is predominantly suppressed by this catalyst poison. Finally, poisoning of the catalyst was prevented by simply passing a solution of the methoiodide 7 through a chloride-loaded ion exchanger prior to catalytic hydrogenation

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• deprotection by catalytic hydrogenation furnished lipid A 31. Alternatively, the lactol 30 was phosphitylated by application of the phosphoramidite procedure with (benzyloxy)[(N-Cbz-3-aminopropyl)oxy](N,N-diisopropylamino)phosphine in the presence of 1H-tetrazole and subsequent oxidation with dimethyldioxirane

• (DMDO) [91] to furnish protected lipid A derivative 32. Global deprotection by hydrogenation over Pd(OH)2/C in the presence of acetic acid afforded ethanolamine-modified H. pylori lipid A 33. To get deeper insight into the immunomodulatory potential of H. pylori lipid A, an access to synthetic H. pylori

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• -catalyzed selective hydrogenation, and oxidation. Zeng et al. described the synthesis of the enantiomer (2R,3S)-Boc-CF3-Thr(Bzl) in four steps from the (S)-Garner’s aldehyde [17][18]. The enantiomer (2S,3R)-Boc-CF3-Thr(Bzl) was not described by Zeng et al. However, we decided to follow this more

• with TFA and then performing the coupling reaction with Boc-L-Ala-OH in the presence of HBTU/HOBt/DIPEA or DMTMM(Cl−)/NMM. Catalytic hydrogenation, using 10% Pd/C or Pd(OH)2, under H2 atmosphere, gave pentapeptides 1a–3a in moderate to quantitative yield. After acidic removal of the Boc group, the

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• can be converted into saturated (2-oxohexahydropyrimidin-4-yl)acetic acid derivatives by mild hydrogenation of the endocyclic C=C double bond in the presence of Pd/C as catalyst. The cis-stereoisomers selectively formed upon reduction of the Michael-type products were structurally determined by X-ray

• derivative 9d was synthesized from 9c in a good yield by using the general procedure for N1-PMB cleavage. Likewise, regioisomeric acids 5a,g,i and their phenyl esters 6a,g,i were reduced to the respective saturated compounds 10a–c and 11a–c. In this case a high hydrogenation cis-stereoselectivity is provided

• hydrolysis has also confirmed the cis-geometry for acids 10a–c obtained by direct hydrogenation of compounds 5a,g,i (see Supporting Information File 1). N3-Unsubstituted compounds 10d and 11d with the preserved cis-configuration of the substituents were readily prepared from the corresponding N3-PMB

A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• and trichloroacetonitrile with Cs2CO3 as catalyst. Finally, 3'-O-ethyl-5,6-dihydrospinosyn J was obtained through the selective hydrogenation of 12 catalyzed by 10% Pd/C. During the final reduction step, as ascertained by NMR and mass spectrometry, only the 5,6-double bond was reduced, and the other

• semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on spinosyn A with high yields in each step. With this synthetic route, we achieved a chemoselective hydrogenation of the 5,6-double bond under mild conditions, which is of great significance for future studies on the chemical modification of spinosyns

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

• chemistry; heterocycle; hydrogenation; indole; multistep; Introduction Indoles are amongst the most important bioactive heterocyclic structures being commonly encountered in the amino acid tryptophan (1), the related neurotransmitter serotonin (2) as well as numerous complex alkaloid natural products and

• subjected to heterogeneous hydrogenation conditions to produce the indole product 12 through a reductive cyclisation sequence. From the corresponding ester functionalised indole 12 we anticipated that condensation with hydrazine would furnish the corresponding acyl hydrazine 13 which could be cyclised to

• -toxic byproducts (base·HCl, H2O) and uses industrially favourable hydrogenation protocols in the key cyclisation step. To commence the study we first conducted a comprehensive screening program to determine flow compatible conditions for the formation of compound 11 optimising for solvent, base

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• bypassing any diazotization process. Hydrogenation of 41 with 10% Pd/C in the presence of acetic anhydride allowed the isolation of acetanilide 43 in moderate yields (Table 2, entries 4−6). It was found that the acetic anhydride solvent needed to be freshly distilled in every case in order for the reaction

• ). Thus, compound 40a was dissolved in freshly distilled acetic anhydride and subjected to hydrogenation over Pd/C (Scheme 4). The reaction was monitored by TLC at short time intervals in order to avoid over-reduction. The starting material was consumed within 5 h, but the expected acetanilide product

• unexpected, it was reasoned that it might still be a suitable substrate for the subsequent oxidation reaction. Accordingly, the product of the hydrogenation reaction was next treated with sodium metaperiodate and ruthenium trichloride (Scheme 4), and gratifyingly this delivered the desired trifluorinated

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• C-6 atom in the total synthesis of (+/-)-perhydrohistrionicotoxin (Scheme 17) [37][38][39]. The key precursor of perhydrohistrionicotoxin, dioxime 51, was prepared by the reaction of α-bromo oxime 49 with 10 equivalents of 1-butyne and 6 equivalents of butyllithium in THF followed by hydrogenation

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• liver esterase (PLE)-catalyzed enzymatic hydrolysis of meso cis-11 provided selectively the N-protected amino acid 17 as one enantiomer [33][44][45]. Mechanocoupling of 17 with pyrrolidine 12 provided the dipeptide 18 in excellent yield. Removal of the benzyl group by hydrogenation in the presence of Pd

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• dilution and increasing the temperature but the reaction is too slow to be useful. The CM product 14a was then hydrogenated to obtain the known Asu derivative 15a [34] under conventional conditions. Similarly, the known N-Boc-L-Asu-OH (15b) [35] was obtained by hydrogenation of the benzyl ester 14b with

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• , but no cyclic ether was observed when this material was subjected to Pd catalyst and base (not shown). Hydrogenation of 24 over Pd/C gave 26, whose 1H NMR spectrum matches that of the benzoxocane prepared by Pettus and co-workers [42] (Scheme 2), which was shown by them to be the now-refuted structure

• established in applying the Buchwald–Hartwig coupling to 15, producing the benzoxocane 24, which contains the carbon skeleton of heliannuol A. Retrosynthetic analysis of heliannuol A. Hydrosilylation of alkynols. Hydrogenation of benzoxocane 24. Pd-catalyzed couplings of oxasilacycloalkenes with aryl iodides

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• liberating the hydroxy group at C-4’ gave the tethered donor–acceptor combination 36. After the NIS/TfOH-promoted glycosylation the desired trisaccharide 37 was obtained in 75% yield as a pure α-linked diastereomer. The per-acetylated maltotriose target was obtained after palladium-catalyzed hydrogenation

• hydrogenation conditions followed by global acetylation. The results obtained with the 6-hydroxyglucopyranosyl acceptor were somewhat mixed [81]. Attaching the template at various positions of the acceptor to achieve either 16- or 17-membered macrocycles resulted in high yields of 90% and 82%, respectively

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

• palladium-catalysed heterogeneous hydrogenation [61]. In continuation of their elegant work on generating electrophilic heteroatom-transfer reagents in situ upon adding a heteroatom nucleophile to trichloroacetonitrile (compare with Scheme 11), Ooi’s group has recently also expanded this powerful concept to

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• –Miyaura coupling reaction [46] and nitroaromatic hydrogenation [48], the PVP-Pd NPs catalytic system exhibited high catalytic activity after five cycles. In the Heck–Mizoroki coupling reaction under MW irradiation, once the reaction was completed, a new batch of reagents was added to the reaction tube and

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• ]. However, chemical complementation with mycolactone restored the typical M. ulcerans pathology for mycolactone-deficient strains [35]. Some chemical modifications were performed on the purified extracts showing that peracetylation or exhaustive double bond saturation by hydrogenation resulted in a total

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• reported. Apart from traditional hydride reducing agents like lithium aluminum hydride and sodium borohydride [1][2], different modifications were applied, using transition metal salts as catalysts or additives to change or enhance the properties of these reagents [3][4][5][6][7][8]. Hydrogenation is