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

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• ) was treated with the Wittig reagent Ph3P=CHCO2Et and the resulting unsaturated ester was then hydrogenated with Pd–C and H2 at room temperature to obtain compound 11 in 91% yield over two steps (Scheme 2). DIBAL-H (1.1 equiv, –78 °C) reduction of the ester group of 11 followed by Wittig olefination of

• subjected to a Sharpless asymmetric dihydroxylation with AD-mix-α in t-BuOH/H2O (1:1) at 0 °C for 24 h furnishing syn-2,3-dihydroxy ester 19 in a high yield of 92%. For the synthesis of syn-2,3-dihydroxy ester 20, AD-mix-β was employed. Debenzylation of diol 20 with Pd–C and H2 at room temperature produced

• test this hypothesis, first compound 24 was subjected to the debenzylation reaction with 10% Pd–C in EtOH under an H2 atmosphere (Scheme 8) at room temperature. After completion of the debenzylation process, K2CO3 was added to the reaction mixture in the same reaction vessel. The reaction mixture

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -1-indanone. New 1-indanone derivatives that may be used as multi-functional drugs for the treatment of Alzheimer's disease have been synthesized by Li et al. [8]. In this synthesis, ferulic acid (23) was hydrogenated in the presence of Pd/C catalyst to give the saturated derivative 24 and then

• -Benzylidene-1-indanones 126a–o were obtained by a Knoevenagel condensation of 1-indanone 125 with various aromatic aldehydes. Hydrogenolysis of 2-benzylidene-1-indanone 126b using Pd/C allowed to obtain 2-benzyl substituted 1-indanone 127 (Scheme 40). 2-Bromo-6-methoxy-3-phenyl-1-indanone 130, as an

• -chloropropionyl chloride 174 followed by a intramolecular Friedel–Crafts alkylation afforded 1-indanones 178 (Scheme 51) [80]. A direct reaction of the latter with n-butylnitrite led to the formation of keto-oximes 179 which underwent a Pd/C catalytic reduction to give 2-amino substituted 1-indanones 180. Both

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• the reduction sequence at room temperature (Scheme 7). The synthesis of praziquantel from intermediate 11h was accomplished through N-debenzylation at 80 °C under 1 atmosphere of H2 in the presence of Pd/C [40]. The present synthetic protocol involves the debenzylation reaction under milder conditions

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• , Pd/C, MeOH, rt, 96%; (c) Ac2O, Et3N, DMAP, Et2O, rt, 88% (4), 88% (6); (d) TBAF (1 M), THF, 0 °C, 2 h, 85% (5), 76% (7). Reagents and conditions: (a) N6-bis-Boc-adenine or 2-amino-6-chloropurine, PPh3, DIAD, THF, 0 °C to rt, 42% (8), 54% (9); (b) for 10: i) 8, TFA, Cl(CH2)2Cl, rt; ii) K2CO3, MeOH, rt

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• conditions, 3 h, 76%; d) for 7a: NaOEt, EtOH, 0 °C to rt, 30 min, 76%, for 7b: H2NEt, THF, rt, 16 h, 75%; e) for 8a: isobutyl chloroformate, NMM, 4, DMF, −15 °C to rt, 2 h, 69%, for 8b: HBTU, Et3N, 4, DMSO, rt, 3 h, 69%; f) Pd/C, H2, MeOH, rt, 1 h, 74% 9a, 97% 9b; g) iPr2EtN, DMAP, propionic anhydride, DCM

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• employing a more nucleophilic and less basic reagent such as a lithium hydroxide/hydrogen peroxide mixture did not provide relief from the problem, but instead also produced a mixture of undesired products. Adjustments in the sequence of deprotection steps by first carrying out hydrogenolysis using Pd/C in

• (0.5 M in MeOH) in MeOH, ii. NaOH (4 M, 2 M, 1 M, 0.5 M, 0.1 M) solution in THF, iii. H2O2, LiOH, THF, H2O; successful sequence (d) Pd/C, AcOH, H2O, t-BuOH (e) H2O2, LiOH, THF, H2O, 37% over two steps. Supporting Information Supporting Information File 44: Experimental details and full

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• mild hydrogen source with Pd/C gave chroman-4-one 8 in a clean reaction with a good yield of 76% whereas the direct use of H2 with Pd/C gave mainly the fully reduced 2-heptylchromane. Compound 8 can be applied for the synthesis of 1-O-PQS (13) as described in [33]. A new, direct way in which 1-O-HHQ (4

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• ). Then, glycosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-ß-D-ribofuranose gave the desired nucleoside 2 in high yield. Unfortunately, all our attempts to find appropriate conditions to reduce the 6-azido group to the corresponding amine failed. In short, these trials included i) hydrogenation under Pd/C

• catalysis at elevated pressure (30 psi) in ethanol or N,N-dimethylacetamide, ii) ammonium formiate, Pd/C, in methanol [28], iii) tin(II) chloride, in ethanol [29], iv) thioacetic acid, lutidine, in CH2Cl2 [30], v) triphenylphosphine, in CH2Cl2, aqueous work-up, and finally vi) Mg0 in methanol. Efficient 5

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• derivative. The reaction time and the hydrogen pressure had to be optimized. By heterogeneous catalytic hydrogenation at 5 bar with a Pd/C catalyst, aminotriazine 16d was obtained in 77% yield after 5 days. Hydrolyses of all three methyl esters 16b–d provided the tricarboxylic acids 17b–d in 96% to

• acid 15 and subsequent hydrolyses of the esters 16. Conditions: a) Pd(PPh3)4, K3PO4, dioxane, H2O, 48 h, reflux, 16b: 90%, 16c: 73%, b) Pd/C, H2, 5 bar, CH2Cl2, 5 d, room temperature, 16d: 77%. c) 17b: LiOH/H2O/dioxane, 48 h, room temp, 96%; 17c: LiOH/H2O/THF, 24 h, 60 °C, quant.; 17d: H2O/THF, 24 h