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

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• , 6 h, rt; (c) 1 N NaOH, EtOH, 3 h, 45 °C; (d) L-Selectride, THF, −75 °C, 4 h. Conversion of methyl ester (+)-6 into rosaprostol (−)-1a. Reagents and conditions: (a) L-Selectride, THF, −45 °C, 3 h; (b) O2 (air), Pd/C, NaBH4, KOH, H2O/MeOH 2:1. Synthesis of rosaprostol stereoisomers 1b and 1d. Reagents

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• (Scheme 9). Treatment of 14 with 2 mol % Pd/C (10%) and trimethylamine in ethanol under hydrogen pressure, gave the desired debrominated product 29 in almost quantitative yield. Conclusion In summary, we report here that the use of a 2-bromo-substituent on thiophenes acts as a blocking group, allowing

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• , CH2Cl2, 0 °C, 10 min, 24 °C, 2 h, 87%; (i) H2, Pd/C, MeOH, overnight, 84%; (k) 1 equiv 17, THF, 48 h, 2 equiv NaBH4; MeOH, 96 h, 58%; (l) 10 equiv TFA, CH2Cl2, 40 °C, 24 h, 100%; (m) 1.3 equiv dimethyl trithiocarbonate, MeNO2, 101 °C, 2 h, 4 equiv AcOH, 2 equiv MeI, 101 °C, 3 h, 67% as iodide salt 10a

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• including solvent, Lewis acid, and protecting groups on the nucleobase or sugar; we thought of synthesizing the peracylated anhydrosugar to alter its reactivity towards glycosylation [22]. In this regard, anhydrosugar 15 was subjected to 10% Pd/C and Et3SiH (for deprotection of the benzyl functionality and

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• -BuLi, THF, −78 °C to 0 °C, 2 h; m) TFA, CH2Cl2, 0 °C to rt, 1 h; n) L-phenylalanine benzyl ester DIEA, triphosgene, CH2Cl2, rt, 1 h, 60% over three steps; o) H2, Pd/C, EtOAc, rt, 2 h, 77%. Synthesis of compound 17. Reagents and conditions: a) Oxalyl chloride, DMSO, CH2Cl2, TEA, −78 °C to 0 °C, 2 h, 60

• %; b) n-nonyltriphenylphosphonium bromide, n-BuLi, THF, −78 °C to 0 °C, 2 h, 74%; c) L-phenylalanine benzyl ester, DIEA, triphosgene, CH2Cl2, rt, 72 h, 49%; d) H2, Pd/C, EtOAc, rt, 2 h, 50%. Supporting Information Supporting Information File 461: General experimental methods, synthetic procedures and

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• the desired β-lactam product, anti-3Bj, in 58% yield. Fortunately, since 2j was stable compared to 2h under the reaction conditions, the yield of β-lactam anti-3Bj was somewhat improved. After deprotection using Pd/C and H2 the target product, (±)-ezetimibe was obtained in 80% yield and its overall

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• by Cross et al. (Figure 2) [18]. The molecular structure of 1 comprises of a palladium atom with near perfect square planar geometry with a slight out of plane displacement of Br and C(1) where the Br–Pd–C(1) angle is 170.9°. As a whole, the molecule has approximate Cs symmetry with the PPh3 ligands

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -oxazolopiperidines 52 with 58% yield and 79:21 dr. Further reduction and hydrogenolysis of 52 in the presence of Pd/C led to aminoester 53 which was converted to (S)-piperidin-2-phosphonic acid (54) through acidic hydrolysis and subsequent treatment with propylene oxide in 42% overall yield and 58% ee (Scheme 13

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp³)–H arylation

• Yunyun Liu,
• Yi Zhang,
• Xiaoji Cao and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2016, 12, 1122–1126, doi:10.3762/bjoc.12.108

• PdCl2, Pd/C, Pd(PPh3)4 did not show better results (entries 4–6, Table 1). The screening on the effect of base and solvent species demonstrated that K2CO3 and p-xylene were the best base additive and reaction medium, respectively (entries 7–15, Table 1). On the other hand, final optimization on the

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• (Ph2PCH2CH2CH2PPh2)(dppp)) (angle of P–Pd–P: 90.58°) having a six-membered ring conformation [217], and palladacycles reported previously [73][206][215]. The length of the Pd–N4 bond, (2.126 Å), is slightly longer than those of Pd–N(3), Pd–C(5), Pd–O(2) bonds, likely due to a trans effect of the strong σ-donor aryl

• level. BF4 and hydrogen atoms were omitted for clarity. Selected bond length (Å): Pd–C(5) = 1.980, Pd–N(3) = 1.995, Pd–N(4) = 2.126, Pd–O(2) = 1.988. Selected angles (°): C(5)–Pd–N(3) = 94.15, N(3)–Pd–N(4) = 87.81, N(4)–Pd–O(2) = 86.07, O(2)–Pd–C(5) = 91.98. NMR studies. A: The reaction of [Pd(MeCN)4

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• the reference standard for our optimization study, 3-bromo-5-phenyl-2,4,6-trimethylpyridine (3) was dehalogenated into 2 in a usual manner by means of ethanol under hydrogen atmosphere in the presence of Pd/C. Unsymmetrically substituted 3,5-diaryl-4-chloro-2,6-dimethylpyridines Finally, we needed to

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• deoxofluoro derivatives of 2-azido-1,6-anhydrohexopyranoses in hand, we examined their conversion to the target acetylated hexosamine analogs. Initially, compound 19 was hydrogenated (Pd/C) and acetylated to afford acetamide 40 in modest yield (37%). Sulfuric acid-catalyzed [35] cleavage of the internal

• , TESOTf-catalyzed acetolysis and subsequent hydrogenation (Pd/C in a mixture of ethanol and acetic anhydride) was applied to obtain the target acetylated fluoro analogs (Table 1). Compound 21 was acetolyzed to 43 which was obtained as a mixture of anomers and characterized by NMR and finally hydrogenated

• , MeOC2H4OH, 79%; (b) i) BzCl, py; ii) NaBrO3, Na2S2O4, AcOEt, H2O, 47% over 2 steps; (c) Pd/C, H2, EtOH, 96%; (d) Tf2O, then (Bu)4NNO2, 69%; (e) (i) NaH, BnBr, THF, 79%; (ii) LiN3, NH4Cl, MeOC2H4OH, 100 °C, 81%; (f) (i) TsCl, py, (ii) AcOH, H2O; (iii) IRA 410 (OH−), MeOH, 78% over 3 steps; (g) (i) Tf2O, py

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• . The catalytic hydrogenation of 6I-azido-6I-deoxy-β-CD using Pd/C was achieved under US irradiation in MeOH/H2O in 20 min (20.4 kHz, 80 W, yield: 88%); hydrogen was supplied at 1 bar pressure [15]. Sonochemical metals depassivation in organometallic reactions is well established [17]. A typical example

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• produced low yields (for details, see Supporting Information File 2). Ethyl linker: Synthesis of 3-(2,5-dimethoxyphenethyl)-1H-pyrrole (3b) Compound 3b was prepared by reduction of 4d with H2 over Pd/C catalyst (Scheme 4). The N-protected 4d was used instead of 3d to minimize the risk of decomposition

• , 0.5 h, 90%; iii) Pd(PPh3)2Cl2, CuI, triethylamine, 3-iodo-1-(triisopropylsilyl)-1H-pyrrole, THF, rt, overnight, 50%; iv) TBAF, THF, rt, 0.5 h, 85%. Synthesis of 3-(2,5-dimethoxyphenethyl)-1H-pyrrole (3b). Conditions: i) Pd/C, MeOH/acetone, rt, 1.5 h, 98%; ii) TBAF, THF, rt, 0.5 h, 85%. Calculated and

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• on commercially available palladium on carbon (10 wt % Pd/C) [62]. The resulting bimetallic Ru–Pd heterogeneous catalyst 8-Pd/C exhibited the same activity in metathesis as catalyst deposited on activated carbon. Interestingly, the E/Z selectivity in reaction carried out with 8-C* was significantly

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• TFA/H2O (9:1), 100 °C, 24 h. Synthesis of benzaldehyde derivatives 14 and 15: i. Pd(PPh3)4, Bu3SnH, THF, CO (1 atm), 50 °C, 2–3 h, 70%. Olefination reactions of 15 and the X-ray structure of 17 (CCDC number 1432194): i. Zn, TiCl4, THF, 0 °C to reflux, 12 h; ii. Pd/C, H2, EtOAc, 20 °C, 16 h, 76% over 2

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• protecting groups to yield N6-hydroxy-3’-fluoro-3’-deoxyadenosine (3). Hydrogenation of compound 26 under hydrogen pressure (50 psi) over 10% Pd/C resulted in the de-chlorinated compound 27, which was further deprotected in a saturated solution of ammonia in methanol providing the desired 6-deaminated 3

• . Deprotection of compound 48 with a saturated solution of ammonia in methanol at 0 °C resulted in the desired product 22 in 85% yield. In addition, the 6-chlorine atom was left untouched during the deprotection. Compound 48 was hydrogenated over 10% Pd/C under hydrogen pressure (50 psi) giving the de

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• ][33][34][35][36][37][38][39]. The two Pd centers are bound to three carbon atoms of the bridging Cp ligand. Two of the three carbon atoms are bound to only one Pd center, while the central carbon atom binds to both Pd centers. Pd–C bond distances of almost 3 Å clearly indicate that there is no

• -systems [40]. Strong evidence for a Pd–Pd single bond is provided by the Pd–Pd distance of 2.5669(4) Å [41]. Presumably for steric reasons the NHC ligands are bent away from the bridging Cp ligand and the C–Pd–Pd (C of IPr) bond angles are significantly less than 180° (Pd(1)–Pd(2)–C(7) 164.9(1) and Pd(2