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

• a polymer electrolyte membrane electrochemical reactor (PEMER). Palladium (Pd) nanoparticles were synthesised and supported on a carbonaceous matrix (Pd/C) with a 28 wt % of Pd with respect to carbon material. Pd/C was characterised by transmission electron microscopy (TEM), and thermogravimetric

• important to note that, formation of “active hydrogen” is the main step in this process and hydrogen-active powder electrocatalysts such as Pd/C, Pt/C or Raney-nickel have been demonstrated as the optimal choice [16][17]. Moreover, the organic molecule adsorption rate must be faster than that one associated

• water-in-oil (w/o) microemulsion (water/Brij@30/n-heptane). This methodology has been previously used in our laboratory [27][28]. We first explored the morphology, size and dispersion of Pd nanoparticles supported on Vulcan XC72R carbonaceous material (Pd/C electrocatalysts) using TEM micrographs. As

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

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• rearrangement in 75% yield over two steps. After Pd/C-catalyzed hydrogenative deprotection of hydroxy group in methanol under acidic conditions, the corresponding alcohol 12 was transferred to the product 13 via acid-promoted deprotection. A single recrystallization from ethanol allowed 13 to be isolated with

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

• -pyrazolo[3,4-d]pyrimidin-6-yl)aniline 214 by NO2 group reduction with H2, Pd/C followed by Boc protection, coupling with tributyl(3,6-dihydro-2H-pyran-4-yl)stannane (213) and subsequent Boc deprotection with TFA in DCM. Pyrazolo[3,4-d]pyrimidinylaniline 214 was used to synthesize pyrazolo[3,4-d

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

• 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

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

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

• 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

• and a trifluoromethyl group. Thus, the acids 4a,g,i quantitatively yielded reduced products 9a–c under mild catalytic conditions (when reacted with hydrogen at atmospheric pressure and room temperature for 3 hours in the presence of 10% Pd/C catalyst) as shown in Scheme 1. The simplest acetic acid

• when the Pd/C catalyst loading is smaller than 20 weight % (otherwise the reaction proceeds too fast leading to diastereomeric mixtures with a cis- to trans-ratio of up to 3:1). The relative cis-configuration of the CF3 and CH2COOPh substituents in the prepared phenyl (2-oxo-6

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 deprotection steps. Then, with 10% Pd/C as catalyst, the 5,6-double bond of the macrolide was selectively reduced to afford 3'-O-ethyl-5,6-dihydrospinosyn J. In addition, the 3-O-ethyl-2,4-di-O-methylrhamnose is synthesized from rhamnose which is available commercially, while the D-forosamine and

• 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

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

• contained 0.4 M product 11 which was further diluted with EtOH to furnish a 0.2 M stock solution for use in the next reductive cyclisation step. The reduction was performed using a ThalesNano H-cube system [20][21] operating in full hydrogen mode with a 10 mol % Pd/C catalyst cartridge. At a flow rate of

• -carboxylate (12) [23]: A 0.2 M solution of compound 11 in a 1:1 mixture of EtOAc/EtOH with 10 mol % AcOH was passed through a ThalesNano H-cube at 1.3 mL/min containing a 10 mol % Pd/C heated at 50 °C and pressurised at 15 bar. The solvent was removed under reduced pressure and the residue triturated with 9

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• , NaI, DMF, 150 °C (83%); (c) KOH, MeOH, 65 °C (96%). (a) MCPBA, CH2Cl2, 20 °C (90%); (b) NBS, DME, 20 °C; (c) KOH, MeOH, 20 °C (85% over 2 steps). (a) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (94%); (b) PCC, CH2Cl2, 20 °C (84%); (c) H2, Pd/C, 20 °C (99%); (d) NaBH4, EtOH, −25 °C (61%); (e) KOH, MeOH, 65

• °C (96%). (a) TsCl, DMAP, Py, 30 °C (91%); (b) Py, 115 °C (65%); (c) KOH, MeOH, 20 °C (52%). (a) NaBH4, EtOH, −25 °C (49%); (b) KOH, MeOH, 65 °C (85%). (a) Anisaldehyde, TMSCl, MeOH, 20 °C; (b) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (86% over 2 steps); (c) PCC, CH2Cl2, 20 °C (81%); (d) H2, Pd/C, 20

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

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

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

• , 32.2, 31.4, 28.3, 28.1, 23.8 ppm; HRMS (TOF–MS ES+) m/z: [M + Na]+ calcd for C18H31NNaO6, 380.2049; found, 380.2056. Biologically active naturally occurring cyclic tetrapeptide HDAC inhibitors. Reagents and conditions: (i) Triethyl phosphonoacetate, n-Bu4N+I−, aq K2CO3, rt, 18 h, 86%; (ii) H2, Pd/C

• (2.5 mol %), DCM, reflux, 2 h, 14a, 83%; 14b, 90%; 14c, 88% ; (ii) H2, Pd/C, MeOH, rt, 2 h, 15a, 79%; 15b, 82%; 15c, 90%. Supporting Information Supporting Information File 350: Experimental details and analytical data of all new compounds as well as copies of their 1H and 13C NMR spectra

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

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• , AgOTf, then 110, −78 °C to rt; (h) p-TolSCl, AgOTf, then 110, −78 °C to rt; (i) p-TolSCl, AgOTf, then 113, −78 °C to rt; (j) NaOCH3, CH3OH/CH2Cl2 (2:1); (k) Pd/C, H2, EtOAc/THF/1-PrOH/H2O (2:1:1:1). Synthesis of oligo-glucosamines through electrochemical promoted preactivation-based thioglycoside

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• back to TEMPO which further repeats the catalytic cycle (Scheme 23). In another interesting example 1-substituted-1,2,3,4-tetrahydroisoquinolines were selectively dehydrogenated in the presence of catalytic Pd/C, modified by potassium phosphate trihydrate (K3PO4·3H2O) under oxygen atmosphere [86

• ]. Original Pd/C lead to sluggish reactions compared to the modified form. The catalyst could also be recycled at least thrice (Scheme 24). This facile synthesis demonstrated seamless production of dihydroisoquinolines. They were the predominant products with nearly 3–5% formation of the aromatic isoquinoline

• K-10 and Pd/C as catalysts. The microwave-assisted synthesis of β-carboline 96 from tetrahydro-β-carboline 95 using catalytic Pd/C and lithium carbonate at high temperature is also reported [96]. This high yielding procedure gets completed within a few minutes (Scheme 36). Although the reaction

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• separated by HPLC, the next steps were performed with the mixture. Performing the removal of the Cbz group with H2/Pd-C in THF, we encountered the formation of the N-(4-hydroxybutylated) product 25 resulting from a ring opening reaction of the solvent (Figure 4). This side reaction has been reported for

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• perfect stereoselectivity (Scheme 30). Glycosylation of the resulting DBT-β-glycosides was carried out in various alcohols (selected examples shown in Table 7) under Pd/C-catalyzed hydrogenolysis conditions to liberate the desired 1,2-cis glycoside and cyanuric acid. The reductant was either H2 (non

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• similar system [22], the final hydrogenolysis of the Cbz protecting group with H2 and either Pd/C or Pd(OH)2 (up to 50 mol % catalyst loading) in EtOAc, MeOH or AcOH was attempted, but no trace of the desired lactone 9 was observed. A control experiment with the addition of tosyl chloride after the

• , CH3CN, 50 °C; b) CbzCl, TEA, DCM, 0 °C to rt. v) LiHMDS, THF, −78 °C, 1 h, then ClCO2Et, −78 °C to rt. vi) LiHMDS, THF, −78 °C, 2 h, then ClCO2Et, −78 °C, 1 h. vii) LiI, AcOH, 70 °C. viii) PdCl2(PPh3)2, Ag2CO3, THF, 60 °C. ix) LiOH, H2O, THF, rt. x) BHT (cat.), PhMe, reflux. xi) Pd/C, H2, EtOAc or MeOH

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• remove the Pd catalyst. The nitroaromatic derivative is mixed with triethylsilane and the mixture is passed through a fixed bed reactor with Pd/C catalyst at 40 °C to reduce the nitro group to an amino group. The yield is reported to be quantitative, and the catalyst activity is reported to be lasted for

• ratio using a ratio controller. This mixed stream can be passed through a packed bed reactor containing a Pd/C catalyst and maintained at 40 °C using a heating jacket. The reactor outlet concentration can be monitored inline and controlled by manipulating the jacket fluid flow rate of the reactor. The

• -supported phosphine (20 equiv) as the trapping agent. The imine is further hydrogenated at 25 °C and 20 bar pressure by using an H-cube reactor with 10% Pd/C as a catalyst [72]. Trifluoroacetylation of the amine intermediate is then carried out in a chip reactor with trifluoroacetic anhydride (in DCM) as a

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• in the absence of theoretical or mechanistic studies. Phenylacetylene (7), 1-bromo-4-ethynyl benzene (8) and 1-ethynyl-4-nitrobenzene (9) were hydrogenated using a Pd@C catalyst with trimodal pore-size distribution [152]. The chemoselectivity to the corresponding alkene product showed to follow the

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• pressure. Hydrogenation of 11a over 10% Pd/C in ethyl acetate gave the desired amine 5a but in very low yield (0–15%) [18][19][20]. The structure of 5a was confirmed by X-ray crystallography (Scheme 2). Adding a few drops of formic acid and triethylamine (molar ratio 37:1) to the hydrogenation, furnished

• h, rt, 30%; c) Et3N·3HF (10 equiv), 4 days, 120 °C, 30%; d) NaBH4 (10 equiv)/NiCl2·6H2O (5 equiv), MeOH, 1 h, 0 °C, 18 h, rt, 50%; e) 10% Pd/C (10 mol %), H2, Et3N/CHOOH: molar ratio 1:37, THF, 18 h, rt, 78%. Reagents and conditions: a) Et3N·3HF (8 equiv), 18 h, 140 °C; b) Tf2O (4 equiv), pyridine

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• catalytic Pd/C. In this way organocatalysts OC3–OC10 were obtained (Scheme 3 and Scheme 4). In addition another new organocatalyst, OC11, with a different bulky substituent at C2 in the pyrrolidine moiety was prepared. Reacting diol 7 with 1,3-dichlorotetraisopropyldisiloxane in the presence of imidazole

• and subsequent hydrogenolysis of the benzylcarbamate with molecular hydrogen in the presence of catalytic Pd/C (Scheme 5) afforded OC11 in 43% overall yield for the two steps. With this series of pyrrolidines at hand, the well-established Michael addition of aldehydes to nitroolefins [16][17][18] was

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• were confirmed by single-crystal X-ray diffraction (vide infra). Catalytic hydrogenation of 1,2,4-triazolium-3-aminides 7 with H2 and Pd/C in methanol selectively cleaves the N1–Cbenzyl bond and yields the neutral N-benzyl-N’-(4-benzylamino-4H-1,2,4-triazol-3-yl)benzohydrazides 10 in high yields