Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -Protecting group optimization for the asymmetric Mannich reaction. All yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. aReaction conducted for 24 h. Catalyst screening using 7b as a substrate. All yields were determined by 1H NMR spectroscopy using 1,3,5

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

• ] to obtain free acid 11. Exchange of the Boc protecting group of dimethylaniline 8 to an acryloyl substituent and subsequent saponification furnished dimethylamine building block 13. For the macrocycle assembly, especially the ring closure, we decided on two different routes. While the cryptophycin

• containing a dimethylamino motif did not require an additional protecting group, ring closure was performed through alkene cross metathesis, which has been accomplished reliably and with good yields for other cryptophycins [11][26][27]. However, for the synthesis of a cryptophycin with a monomethylated amino

• group in unit B a suitable protecting group, i.e., allyloxycarbonyl (Alloc), must be used. Since the presence of this allylic double bond would most likely interfere with a clean reaction outcome after alkene cross metathesis, we decided for a more classical ring-closure strategy through

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• host catalysis – (i) using the host as a “protecting group” to direct reactivity external to the host [187][346], and (ii) confinement of a transition-metal catalyst to take advantage of the restricted environment of the host [51][52] – neither of which resembles the enzyme-like possibility of a true

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

• depicted in the review may assist the readers to plan their synthetic protocols in oligosaccharide synthesis. Neighbouring group participation In glycosylation reactions the protecting group at the vicinal C-2 position may be either participating or non-participating in nature. Participating functional

• groups interact with the anomeric carbon and thereby help in the formation of a specific stereocentre. So, modulating the neighbouring protecting group in the C-2 position of glycosyl donors helps in improving the stereoselectivity of the produced glycoside bonds. Ester-type participating protecting

• inversion in carbohydrates was illustrated extensively by Frush and Isbell [75] with silver carbonate as the promoter, drawing analogy with an SN2-type substitution mechanism with the formation of the acetoxonium ion intermediate [76]. An acyl protecting group in the vicinal C-2 position is widely accepted

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• thermodynamically more stable than its 5-exo counterpart 13. Thirdly, the 2,3-diaminobenzofuran would be utilized as a temporary protecting group for both the phenolic hydroxy group and the nitrile moiety. These functional groups are necessary for the aromatic A-ring to interact with DNA and for synthetic

• manipulation to install the C1 sidechain for saframycins, respectively [14][39]. The alkyne segment 8 was prepared by protecting group manipulations in three steps from the known starting material, 2-ethynyl-6-hydroxybenzaldehyde (15), which can be readily synthesized from commercially available 1-bromo-3

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• tertiary amide on the same position. Alternatively, the use of a double Boc-protected Dha resulted in a rather low yield of compound 25 (32%), while varying one Boc-protecting group with a Cbz-protecting group increased the yield substantially to 86% for compound 26. In addition, the use of a cyclic, N-Cbz

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• intramolecular SNAr reactions. Ugi-4CR/deprotection/cyclization (UDC) strategy: In the UDC approach a protected amine and an electrophilic functional group like esters or ketones are used. Convertible isocyanides can also be employed. Once the Ugi reaction is completed, the protecting group is removed, and the

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• = protecting group. Synthesis of β-fluorinated piperidines. Intramolecular fluoroaminations of unsaturated amines published by Li. Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12). PG = protecting group. 3-fluoropyrrolidine synthesis. aDiastereomeric ratio

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , Ballester and co-workers reported on the preparation of an octapyridinium-based water-soluble superaryl-extended calix[4]pyrrole molecular container and used it as a capsule for desymmetrization reactions [41], where the reported compound acts both as sequestering and supramolecular protecting group. All of

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• in Fe-catalyzed difunctionalization of alkenes with TBHP resulting in δ-peroxy ketones 126 and δ-peroxy esters 129 (Scheme 43a and 43b). In the case of siloxy cyclopropanes 128 the authors used TBAF as the additive to remove the TMS-protecting group. Oxidation of the resulting anion A with TBHP and

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

• converted into the methyl esters 10 (54%), 11 (52%), and 12 (46%). The benzyl-protecting group was removed hydrogenolytically to give products 13 (85%), 14 (65%), and 15 (99%). The alcohols were then converted to the triflates 16 (28%), 17 (41%), and 18 (63%). We have chosen 3,4,5-trimethoxybenzaldehyde (19

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• 11. It was proposed, that the internal hydrogen bond between the catalyst 11 and the P=O fragment of the protecting group of imine 9 is responsible for the observed high enantioselectivities (76–98% ee). The scope included a wide range of substrates, such as aromatic, heteroaromatic, aliphatic, and α

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• give 1,5-diacyl-5-hydroxypyrazolines 131. Cleavage of the protecting group with potassium carbonate in methanol finally provides the corresponding 5-acyl NH-pyrazoles 132 (Scheme 46) [149]. A novel approach to synthesizing pyrazoles via the initial formation of isoxazoles 138 through (3 + 2

• Sonogashira coupling is conducted under basic conditions, it is important to remove the protecting group with stoichiometric amounts of PTSA in this consecutive three-component synthesis. The process tolerates both electron-rich and electron-poor aryl substituents. However, it is not possible to introduce

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• condensation of 73 and 74, followed by highly-diastereoselective vinylogous Mukaiyama aldol reaction and subsequent protecting group manipulations [81][82][83]. The separately synthesized left and right segments, 72 and 75, were then assembled via Horner–Wadsworth–Emmons (HWE) olefination to give carboxylic

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• . Key to the successful development of this two-step process is the identification of a benzhydryl-protecting group, which orchestrates the photochemical Norrish–Yang cyclization and facilitates the subsequent ring opening. Keywords: azetidine; Norrish–Yang cyclization; ring-opening reaction; ring

• ). The corresponding protecting group (PG) was thought to control the conformation of the 1,4-biradical 2, which is known to be important for efficient Norrish–Yang cyclizations [27][28]. Furthermore, the PG was deemed crucial for the development of further functionalizations of the azetidinols (vide

• ) protecting group (entries 5–7 in Table 1). When changing to phenyl substitution at the nitrogen, azetidinol 3h was formed in 12% yield with a substantial amount of unselective side reactions (Table 1, entry 8). By introducing an ethyl group (1i), only 27% conversion were achieved, with 2% product formation

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• protecting group afforded the cyclic disaccharide exclusively. Cyclic oligosaccharides up to the trisaccharide were obtained using the monomer with a 2-azido-2-deoxy group. Keywords: cyclic oligosaccharide; electrochemical glycosylation; glucosamine; polyglycosylation; Introduction Electrochemical

• (R3 = Ac, R4 = Bn) were obtained in 13% and 6% yield, respectively. The protecting group R3 of 3-OH was changed from an acetyl to a benzyl group. However, conversion and yield of linear oligosaccharides 9c and 10c decreased, and the corresponding cyclic disaccharide 8c was not obtained at all (Table 1

• , entry 4). The reasons for the lower conversion and yield are unclear. However, the lower yield may stem from the lower stability of glycosylation intermediates with a benzyl protecting group at C-3. In all cases, the major product was 1,6-anhydrosugar 7, which was the intramolecular glycosylation

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• yield (92%) and formed the diol 77, after the removal of the Boc-protecting group, where the prochiral hydroxymethyl groups ultimately paved the way towards the natural products (Scheme 22). Bernhardson and coworkers developed a simple scalable route towards ertugliflozin (80), a C-glycoside containing

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• obtained in 84% yield after silica gel purification. Removal of the Boc protecting group from 6 in the presence of trifluoroacetic acid in DCM at room temperature overnight, followed by cyclisation in boiling pyridine/triethylamine, led to 4-hydroxy-1,4-azaphosphinan-2,4-dione (7) in 84% yield. The free

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• us to try another protecting group for the formyl function, namely arylhydrazone. Thus, reactions of compounds 7a–c with a number of arylhydrazines afforded the corresponding hydrazones 11 which were not isolated and subjected to cyclization under the action of K2CO3 (Scheme 5). In most cases the

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• circumvent this side reaction, we envisioned that a more electron-withdrawing protecting group could reduce the tendency of the starting olefin to oxidation. Therefore, the N-tosylated 2,5-dihydro-1H-pyrrole 1b was evaluated under the same reaction conditions with the same three aryldiazonium salts used

• -nitrophenyl)sulfonyl (2-Ns) as alternative protecting groups of 2,5-dihydro-1H-pyrrole (Scheme 5). Although the results with the 2-Ns protecting group were somewhat disappointing, the results with 4-Ns group were more promising, even with a welcome increase in the enantiomeric ratio in some cases (4dd and 4de

• methanolysis, the hemiaminal ether product 3 is formed. We hypothesize that the enantioselectivity-determining step consists of the migratory insertion of the aryl group bonded to palladium to the pyrroline. The steric effect of the t-Bu group favors the coordination of the pyrroline with the protecting group

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• , ii) HBTU, DIPEA, in DMF, rt, overnight, and iii) trifluoroacetic acid (TFA)/triisopropylsilane (TIPS)/H2O, rt, 1.5–2 h. AA and PG stand for amino acid and protecting group, respectively. All AAs in 1a–c, 2a–c, and 4a–c were protected. Structure of C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• then transformed into aldehyde 31 through several protecting group adjustments and the corresponding alcohol and Ley oxidation. After the preparation of 33 using Evans syn-aldol condensation as a critical step, 34 was produced by thioester formation, desilylation, and allylic oxidation. Incubating 34

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• partial conversion of the starting material was observed. We postulated that the presence of two Boc protecting groups on the nitrogen makes the oxidation of the C-centered radical challenging. By using 1o only bearing one protecting group the desired product could be obtained, albeit in only 17% yield