Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• ; ii. TBDPSCl, imidazole, DCM, 0 °C to rt; iii. MeI, Ag2O, DMF, 0 °C to rt; (g) i. Pd/C, H2, EtOAc; ii. I2, PPh3, imidazole, DCM, 0 °C to rt; (h) vinylmagnesium bromide, CuI, HMPA, THF, −30 °C; (i) OsO4, (DHQ)2PYR, 0 °C; (DHQ)2PYR: hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether. Synthesis of 27

• , DMAP, DCM, rt; (h) i. OsO4, NaIO4, 2,6-lutidine, 1,4-dioxane, rt; ii. ʟ-proline, MeOH, −10 °C; iii. NaBH4, MeOH, 0 °C; (i) i. PivCl, pyridine, DMAP, DCM, rt; ii. H2, Pd/C, MeOH, EtOAc, rt; iii. (iPr)2SiHCl, imidazole, DMAP, DCM, rt; (j) BF3·OEt2, DCM, −20 to −10 °C; (k) i. Mg(OMe)2, MeOH, rt; ii. 2,2

• ; (f) i. TBAF, THF, 0 °C; ii. pyridinium p-toluenesulfonate, DCM, 0 °C; (g) acrylic acid, DIC, DMAP, DCM, rt; (h) i. Grubbs cat 2nd generation, toluene, reflux; ii. Pd/C, H2, EtOAc; (i) i. DIBAL-H, THF/toluene, 10 °C ; ii. triethyl phosphonoacetate, t-BuOK, THF, 60 °C; iii. AcOH, 40 °C; (j) i. NaIO4

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• complex. The probe was absent in side-view classes. Synthesis of CI-994 and the Au–(CI-994) conjugate. Conditions: a) Boc2O, NEt3, THF, 0 °C to rt, 19 h, 70%; b) 4-nitrobenzoyl chloride, DIPEA, DCM, 0 °C to rt, 16 h, 74%; (c) H2, 10% Pd/C, MeOH/THF 1:1, rt, 17 h, 95%; d) AcCl, NEt3, THF, 0 °C to rt, 21 h

• , 67%; e) TFA, DCM, 0 °C to rt, 20 h; (f) MP-carbonate resin, MeOH, rt, 3 h, 95%; g) benzyl bromide, 1,4-dioxane/DMF 1:1, 90 °C, 19 h, 45%; h) 3, 5, HATU, DIPEA, DMF, 0 °C to rt, 40 h, 59%; i) H2, 10% Pd/C, THF, rt, 19 h, 99%; j) N-hydroxysuccinimide, EDC, DMF, 0 °C to rt, 16 h, 90%; k) TFA, DCM, 0 °C

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• hydrogenation of the aromatic core of highly substituted benzocyclobutenes using simple Pd/C under ambient conditions [38]. The pronounced substituent effects on the hydrogenation rate highlight the key role of small-ring strain in this generally challenging transformation. Complementary to these strictly

• -arene complexes illustrates this perfectly (Figure 8B): Os(II) coordination partially localizes the π-system of the arene while protecting the coordinated double bond, enabling selective hydrogenation of the diene portion even under ambient conditions [53][54]. Reduction in the presence of a simple Pd/C

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• aromatic rings (Scheme 4) [48]. Using [Rh(nbd)Cl]2 and Pd/C as catalysts, aromatic hydrocarbons with various functional groups can be hydrogenated at room temperature and 1 atmosphere of hydrogen, thus simplifying the reaction operation and cost. Hydrogenation of fused aromatic rings Hydrogenation of the

• . Three subsequent steps (74% overall yield) then provided the key hydrogenation precursor 161. Hydrogenation of 161 under heterogeneous catalytic conditions (Pd/C, Pt/C, Raney Ni, Rh/C, Ru/C) proved inefficient, giving complex mixtures that included partially or fully hydrogenated pyridines, over-reduced

• the cyano group to an amide (162) under acidic conditions, which then allowed successful Pd/C-mediated hydrogenation to 163. Subsequent dehydration with POCl3 and chiral resolution using ᴅ-DBTA provided the optically enriched compound 165 (Scheme 22). While this approach rendered catalytic

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• C14 β-OH group. The revised synthetic route is described in Scheme 2. At first, 4 was subjected to a Pd/C-catalyzed hydrogenation to afford the desired A/B-cis fused intermediate 7 along with its C5 epimer as a 2:1 separable mixture in a quantitative yield. By treating 7 with the Bestmann ylide

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• discovered back in 1881 [35]. Furthermore, this rearrangement positioned a chloride handle at the desired site for the next C–H arylation. Part of 68 was then converted to pyridine N-oxide via Pd/C-catalyzed dechlorination and mCPBA oxidation. While a similar C–H arylation strategy was used in the Tsukano

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -metathesis reaction smoothly in the presence of the Hoveyda–Grubbs second-generation catalyst to afford the enone 13 in 63% yield with the desired trans-configuration. Enone 13 was then subjected to the Pd/C-catalyzed hydrogenation to give the thermodynamically favored bicyclic hemiketal 21 in 92% yield as

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• ) and dissolved in ethanol (3 mL). A catalytic amount of Pd/C was then added and hydrogenolysis was conducted for 4 h with stirring under an H2-filled balloon. The reaction was monitored by TLC and, after completion of the reaction, the mixture was filtered through Celite, followed by washing of the

• remaining Pd/C with ethanol (3 × 5 mL). The solvent was removed by evaporation under reduced pressure and the resulting crude compound was purified by chromatography on silica gel (hexane/EtOAc; 90:10) to afford 25c as a white solid (41 mg, 73%); mp 154–156 °C (lit. mp 164 °C [22]; 150–152 °C [35]; 157–158

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• , usage of classical reducing agents – H2 on Pd/C or NaBH4 did not show similar chemoselectivity [26]. Additionally, the NaH2PO2 usability is engaging due to fine green chemistry metrics, e.g., an E-factor less than 1 was reached, moreover the main wastes of this process were safe and useful as

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• product 4 (Scheme 5a). The transformation of the enamine had to be carried out by reduction of the N-acyliminium ion by NaBH3CN in the presence of TFA, as Pd/C with H2 would lead also to the reduction of the triple bond. The products (2R,6S)-13 and (2R,6R)-13 were obtained in a 1:1 ratio (Scheme 5b

• given by switching one in an equatorial position. Using Pd/C and H2 for hydrogenation reactions usually leads to reduction of double or triple bonds, while aromatic systems tend not to be affected [58]. However, 3m and 3p undergo hydrogenation in the aromatic moiety, while 3p displays a complete

• )-9 are generated in a 1:1 ratio, while a hydrogenation of the N-formyl enamine with Pd/C and H2 favours the (2R,6S)-9 diastereomer. Moreover, an in-depth NMR analysis, focusing on coupling constants and subsequent dihedral angles of diastereomers (2R,6S)-9 and (2R,6R)-9, as well as selected

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• aldol condensation of 5 provided the tetracyclic α,β-unsaturated enone 6 in 57% yield. Subsequent catalytic hydrogenation using Pd/C conditions delivered the hydrogen to the alkene from the less hindered face, producing ketone 7 with high diastereoselectivity. Final reduction of both the amide and

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• : the formation of compound 31 was always observed, and brevicolline ((±)-1) was not formed. Interestingly, our attempts made for the transformation of compound 31 by dehydrogenative aromatization to brevicolline ((±)-1) by using several reagents (DDQ, Pd/C, MnO2, CuCl2, I2, elemental sulfur, KMnO4

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• scaffolds (Scheme 6) [64][65]. First, we attempted heterogeneous hydrogenation of the alkene functionality in compound 16a under 1 atm hydrogen pressure using Pd/C as a catalyst. Although the reaction proved sluggish, we were able to drive it to completion over a prolonged reaction time of 14 days

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• reorganization likely involves the cleavage and re-formation of the dynamic Ctriazine–OAr bonds, and the presence of an excess of base could facilitate the formation of the thermodynamic-favored reorganized products [29][31]. The benzyl groups were subsequently removed under Pd/C and H2 conditions to afford the

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• % yield under basic conditions using sodium hydroxide and tert-butanol. The reduction of nitrile 3q with lithium aluminum hydride generated amine 7 in an 85% yield, whereas the selective hydrogenation of the alkene moiety of 3q using a Pd/C catalyst in a H2 gas environment smoothly produced product 8 in a

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• formation and N-Boc-protection [24] provided nitroarene 5 in 40% yield over three steps. Reduction of the nitro group was performed with Pd/C and hydrogen to obtain aniline 6 in 98% yield, which served as a precursor for mono- and dimethylated unit B derivatives 7 and 8, respectively. While dimethylaniline

• control of equivalents and pH, or Leuckart–Wallach-like reaction with ammonium formate and Pd/C [25] provided monomethylaniline 7 in 37% and 35% yield, respectively. The absolute structure of monomethylaniline 7 was confirmed by single-crystal X-ray diffraction measurements (Figure 2). Compound 7

• % probability. Synthesis of modified unit B derivatives. a) HNO3, H2SO4, 0 °C, 5 h, 48% (isolated as monohydrate); b) SOCl2, MeOH, 0 °C, 90 min, then reflux, 17 h, 95%; c) Boc2O, NEt3, MeCN, H2O, rt, 22 h, 88%; d) H2, Pd/C, MeOH, rt, 25 h, 98%; e) either: formalin, NaBH3CN, HOAc, MeOH, rt, 20 min, 37%, or

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• the presence of Pd-C. This deprotection protocol also facilitates an orthogonal deprotection strategy in multistep oligosaccharide syntheses in the presence of benzyl (OBn) groups (Scheme 6). The benzyl and cyanopivaloyl-protected hexarhamnoside derivative 37 was completely deprotected by a single

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• ether synthesis with 2-hydroxy-3,4,5-trimethoxybenzaldehyde (21). Conditions: a) K2CO3, benzyl bromide, abs. MeCN, N2, reflux, 18 h; b) TEMPO, KBr, NaOCl, NaHCO3, MeCN, rt, 76 h; c) MeOH, H2SO4, reflux, 18 h; d) Pd/C, H2, EtOH, rt, 24 h; e) Tf2O, pyridine, DCM, rt, 18 h. Synthesis of perfluoroalkyl

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• concentrated under a stream of N2. Hydrogenation: The solvent of the natural extract (100 µL) was removed with a stream of N2 and taken up in pentane (100 µL) and a catalytic amount of Pd/C was added. The reaction was then stirred for 1 h under a H2 atmosphere. The catalyst was filtered and rinsed with pentane

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• of 10% Pd/C and 5% Pd/CaCO3 yielded reduced compound 19. Cleavage of the THP group with Amberlist-15® resin and a final Jones oxidation of the primary alcohol to the carboxylic acid, led to cyclization with the 17β-OH group affording the lactone 20 in a moderate overall yield (Scheme 6). Biological

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine