Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ether using Pd/C and ammonium formate (Scheme 21). With this synthetic route, the authors achieved the total synthesis of combretastatin D-4, after 12 reaction steps with an overall yield of 11%, highlighting the efficient formation of the diaryl ether 102 in 61% yield without the use of metallic

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• hydrogenation of N3-β-CD (3) in the presence of Pd/C under a H2 atmosphere. In CD chemistry, this method was first described by Petter et al. [8] in the early 1990s. This method is very popular with small-scale syntheses because only gaseous N2 is formed as a byproduct and no purification is required when pure

• N3-β-CD (3) is used as substrate. However, for large-scale syntheses, mixing hydrogen with the Pd/C catalyst can be dangerous if an inert atmosphere is not properly maintained. In addition, Pd/C is pyrophoric and tends to ignite when it is separated from the reaction mixture by filtration. However

• , these two drawbacks are not a problem for large-scale flow synthesis when using an H-Cube system with an incorporated electrolytic cell producing H2 in situ from ultrapure water [47]. The Pd/C catalyst is placed in a stainless steel cartridge, so it is not necessary to separate it from the solution

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• ) BnNH2, 120 °C, 7 h, quant.; (c) PTSA·H2O, CH2Cl2/MeOH 30:1, rt, 24 h, 69%; (d) TsCl, DMAP, CH2Cl2, 0 °C–rt, overnight, 88%; (e) LiBHEt3, THF, 0–40 °C, overnight, 83%; (f) 20% HCl, MeOH, rt, 72 h, 70%; (g) 1. H2, Pd/C, MeOH, rt, 48 h; 2. conc. HCl, 0–40 °C, 2 h, 3. ArCH2Br, K2CO3, DMF, 0 °C–rt, overnight

• .; (h) 1. H2, Pd/C, MeOH, rt, 2 h; 2. conc. HCl, 0–40 °C, 2 h, 68%. Synthesis of the intermediate 13 and the target pyrrolidines 17–20. Reagents and conditions: (a) 1. H2, Pd/C, MeOH, rt, 48 h; 2. CbzCl, Et3N, CH2Cl2, 0 °C–rt, 2 h, 91% over two steps, (b) PTSA·H2O, CH2Cl2/MeOH 30:1, rt, 20 min, 90%; (c

• ) 1. DMP, CH2Cl2, rt, 1 h; 2. MeMgBr, Et2O, 0 °C–rt, 1 h, 63% over two steps; (d) 1. H2, Pd/C, MeOH, rt, 2 h; 2. ArCH2Br, K2CO3, DMF, 0 °C–rt, overnight; (e) 20% HCl, MeOH, rt, 72 h; (f) H2, Pd/C, MeOH, rt, 5 h, then, conc. HCl, 0 °C, 76%. Synthesis of the target pyrrolidines 26–29. Reagents and

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• (dba)3, SPhos, and Et3N in 86% yield. Reduction of the double bond with Pd/C followed by dual Stille coupling for the introduction of two methyl groups and Mukaiyama hydration utilizing Mn(dpm)3 and PhSiH3 furnished the misassigned structure for dysiherbol A (79). A revised structure was finally

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• was further confirmed through X-ray crystallographic analysis. With the key intermediate 10 in hand, we were in a position to test the planned two-step transformation including the palladium-catalyzed reductive cross coupling with HCO2H followed by Pd/C-catalyzed hydrogenation. To our surprise, the

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• under Pd/C-catalyzed hydrogenation to provide 1-deazaguanine (11) in six steps and 6% overall yield. A total of 120 mg of 11 were obtained in the course of this study. At this point, we note that N9-tert-butyloxycarbonyl-protected 6-iodo-1-deazapurine was successfully synthesized but not stable during

• -Deazaguanine (11) Compound 22 (111 mg, 462 µmol) and palladium on carbon 10% (Pd/C, 180.56 mg) were suspended in H2O/methanol 1:1 (7 mL). A rubber septum was applied and hydrogen gas (balloon with syringe) was bubbled through the solution for 10 minutes. The mixture was stirred under hydrogen atmosphere for

• )), 157.10 (H-C(6)); ESIMS (m/z): [M + H]+ calcd for 226.10; found, 226.10. 1-Deazahypoxanthine (30) Compound 31 (230 mg, 1.02 mmol) was dissolved in methanol (15 mL), then palladium on charcoal 10% (Pd/C, 400 mg, 337 µmol) was added and hydrogen (balloon with syringe and septum) was bubbled through the

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• shown in Scheme 2b and c. To access mixed oxime-hydrazone 5a, benzylamine was reacted with two equivalents of α-chlorohydrazone 9c to give bishydrazone 10, which was debenzylated by hydrogenolysis with Pd–C catalyst. The subsequent introduction of the oximinoalkyl unit was selectively achieved by

• . Hydrazinium dihydrochloride was isolated in some cases (confirmed by X-ray, mp, and FT-IR data) demonstrating the degradation of the heteroadamantane cage. Deprotection of Cbz derivatives by hydrogenation over Pd–C was more productive. Thus, hydrogenolysis of product 8b delivered the 1N,2O-TAAD derivative 15

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• deprotection with concomitant azide reduction was completed using hydrogen and Pd/C and Pd(OH)2/C catalysts, affording 13 as the disodium salt in 90% yield, after anion exchange chromatography. Synthesis of 6-deoxy-6-thio-ᴅ-mannose 1-phosphate (18) was completed from 14 via C6 substitution with thioacetate and

• if GMD activity fully restored (or probe 19 was not an inhibitor). Syntheses of C6-modified mannose 1-phosphates 13 and 17. Conditions a) PPh3, CBr4, DCM, rt, 75%; b) NaN3, DMF, 75 °C, 64%; c) HO(O)P(OBn)2, NIS, AgOTf, DCM, rt, 65%; d) Pd/C, Pd(OH)2, H2, HCl, EtOH, THF, 24 h, 90%; e) NH4OAc, DMF, 30

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• proton-exchange membrane reactor is described. The reduction of enones proceeded smoothly under mild conditions to afford ketones or alcohols. The reaction occurred chemoselectively with the use of different cathode catalysts (Pd/C or Ir/C). Keywords: enone; hydrogenation; iridium; palladium; PEM

• ]. For instance, they recently reported a stereoselective reduction of alkynes to Z-alkenes using a PEM reactor. The use of a Pd/C cathode catalyst and the appropriate cathode potential realize the selective synthesis of Z-alkenes [22][23][24]. They also reported the stereoselective hydrogenation of α,β

• should be controllable by the cathode catalyst and electrochemical parameters. Fortunately, we found that chemoselective reduction of enones 1 can be carried out using different cathode catalysts (Pd/C or Ir/C). Results and Discussion Electroreduction of enones to ketones First, we chose cyclohex-2-en-1

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• obtained from compound 26 by a conventional procedure [7][8]. Several methods have then been tried to convert 27 to the N-amino derivative 23 (Zn dust, AcOH [8]; Zn dust, NH4Cl [15]; H2, Pd/C [16]; Na2S2O4 [17][18]; Mg, TiCl4 [19]), but to our regret, in all cases the N-nitroso group was removed and

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• attempted starting from the known dioctyloxydinitro derivative DN (Scheme 1) [33]. Reduction of the nitro groups with hydrazine, in the presence of catalytic amounts of Pd/C (10 mol %) led to the corresponding diamino intermediate. This latter could be subsequently reacted with the desired phosphino benzoic

• identifies the phenolic ring substituted with the octyloxy chains, while the circle identifies those with methoxy groups. Stacked plot 1H NMR (tetrachloroethane-d2) of A(AuCl)2 at variable temperature. i) NH2NH2∙H2O, Pd/C in EtOH, 80 °C (quant.); ii) diphenylphosphinobenzoic acid, EDC∙HCl, DMAP (cat

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• led exclusively to the desired isomer 5 with the nitrophenyl group in position 3, most likely due to the steric effect. Then, the nitro group in 5 was reduced by hydrogenation under 4 bar using Pd/C as catalyst to yield the desired amine 6 in 78% yield. Subsequently, the desired chloroacetyl

• methyl 4-(2-nitrophenyl)-3-oxobutanoate [36] and 1-benzyl-1-(4-bromophenyl)hydrazine in the presence of sodium acetate and sulfuric acid in glacial acetic acid affording 1b in 55% yield. It is of note that the treatment of 1b with hydrogen in the presence of Pd/C as catalyst led not only to reduction of

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• could be converted into N-acetates upon reduction with tributyltin hydride and azobisisobutyronitrile (AIBN), and the N-Cbz groups were removed to liberate the free amino groups during hydrogenolysis over Pd/C [259]. A collection of well-defined COS with defined DP and PA was prepared by AGA [93][157

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• reductive elimination occurs in the presence of base to achieve the desired product 119 (Scheme 36) [59]. Direct arylation of disubstituted triazoles 123 with aryl halides 124 using a Pd/C catalyst under solvent-free conditions to give fully decorated triazoles 125 was reported by Farinola et al. Different

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• -phosphate 21. Deprotection utilised 0.6 equiv of Pd/C (0.1 equiv per benzyl group) and 0.6 equiv of Pd(OH)2/C to afford 21 in 72% yield after 24 h. NMR analysis of 21 confirmed the presence of a C6-tetrazole (δC = 160.8 ppm), alongside an anomeric phosphate (δP = −2.15 ppm), and 1H coupling constant data (δ

• °C, 55%; e) PMBCl, KI, K2CO3, DMF, 76% for 18 and 19; f) 3-(benzyloxycarbonylamino)-propan-1-ol, NIS, AgOTf, CH2Cl2, −40 to −10 °C, 3 h, 34%; g) H2(g), Pd/C, Pd(OH)2/C, HCl, EtOH, THF, rt, 56 h, 96%; h) dibenzyl phosphate, NIS, AgOTf, CH2Cl2, −30 to 0 °C, 3.5 h, 72%; i) H2(g), Pd/C, Pd(OH)2/C, 5

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• 25 at 4 atm whilst incorporating Pd/C as a catalyst furnished the desired amine 26 in quantitative yield. Performing the reaction at a lower pressure resulted in the recovery of starting material only. With the two C5 fragments in hand, convergent coupling of aldehyde 23 and amine 26 was achieved via

• intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C, 30 min; ii) K2CO3, rt, 30 min, 99%; b) benzylamine, DCE, THF, sodium triacetoxyborohydride, N2, rt, 24 h, 60%; c) ethanol, 10% Pd/C, H2, rt, 24 h, 84%; d) Boc anhydride, DMAP, THF, rt, overnight, 100%; e) Na, NH3, THF, -60 °C, 1 h, 81

• %. Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, quantitative yield; b) TsCl, DMAP, DCM, rt, 24 h, 83%; c) NaN3, DMF, 80 °C, 3 h, 75% yield; d) 10% Pd/C, H2, ethanol, rt, 12 h, quantitative yield; e) sodium triacetoxyborohydride, 1,2-DCE, THF, rt, 24 h, 95

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• authors screened several other 3D printed reactors evaluating materials (PTFE, PLA or Nylon), volumes (1 or 10 mL), and channel shape (circular, square, or rectangular). The process was then merged with a hydrogenation step using the H-Cube® apparatus (Pd/C, 30 °C, 15 bar) for the continuous preparation

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• Minnaard group reported a protocol for the addition of boronic acids to enones [37]. At first, they tested the combination of Pd(OAc)2 with triflic acid (TfOH) to obtain a Pd(II) complex with a weakly coordinating anion that is necessary for a fast Pd–C bond cleavage and thus avoiding the undesired β

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• unknown compounds 14–16 opens many synthetic possibilities for the preparation of novel fused derivatives of 1-aza-9-oxafluorene. The nitro compounds 14 and 15 were reduced to the corresponding aniline derivatives using hydrogen and Pd/C as a catalyst. The resulting aminophenols 17 and 18 were further

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• h, 44%. Synthesis of intermediate 2. Reagents and conditions: (i) Pd/C (wet), EtOAc/CH2Cl2, H2, 45 psi, rt, 2 h, 95%; (ii) imidazole, CH2Cl2, rt, 16 h, 46%; (iii) Al(Me)3, NH4Cl, CH2Cl2, 0 °C-rt, 40 h, 23%. Synthesis of intermediates 3–5. Reagents and conditions: (i) (Ac)2O, CH2Cl2, rt, 24 h, 95–99

• %; (ii) aqueous NaOH, 0 °C, 2 h, 85–99%; (iii) (Ac)2O, H2O, rt, 3 h, 68%. Synthesis of compounds A1–21. Reagents and conditions: (i) acetyl chloride, TEA, CH2Cl2, rt, 16 h, 97% (for B1), HATU, DIPEA or DCC, DMAP, DMF or THF, rt, 16–24 h, 43–98%. (ii) Pd/C (wet), THF or EtOAc/TEA, H2, rt, 16 h, 22–96

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• , K2CO3, DMF/acetone 1:2, 80 °C, 43 h (98%). Final steps in the synthesis of biaryl 1. Conditions: h) Pd(OAc)2, SPhos, Cs2CO3, dioxane/H2O 7:1, 70 °C, 18 h, (R = TBS: 98%, containing non-separable impurities; R = Bn: 89%) ; i) R = Bn: Pd/C (10%), H2, THF, 8 bar, 24 h, 40 °C (88%). NMR data of natural and

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• acetal, cat. (CH2OH)2, BF3·Et2O, 85%; x) 1. Luche reduction, 98%; 2. a) NaH; b) CS2, c) MeI, 88%; 3. Bu3SnH, AIBN, heat, 75%; xi) 1. cat. Pd(MeCN)2Cl2, wet acetone, 95%; 2. H2, Pd-C, 90%. Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-menthyl-3

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• -dibromopyridine it was the only way for us to synthesize the target [4]helicenes [70]. Unfortunately, the coupling of 2,3-dichloroquinoxaline (3a) with 9-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole in the 5% Pd-C/PPh3/K2CO3/toluene/H2O catalytic system at 100 °C for 24 h (method A) gave the

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• °C, 60 min → 25 °C, 80 min, 94%; ii) NaN3, acetone/water 5:1 (v/v), reflux 20 h, 95%; iii) H2, Pd/C (10%), 1 mol/L HCl (1 equiv), methanol, 25 °C, 8 d, 86%; iv) rac-lipoic acid (for rac-1) or (R)-lipoic acid (for (R)-1), TBTU, DIPEA, DMF, 25 °C, 6 d, rac-1: 51%, (R)-1: 44%. Synthesis of ligand 2