Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• -donating or electron-withdrawing groups, work well under these conditions. However, the amine component does not react when primary or aromatic secondary amines are used. It works very well with cyclic or acyclic aliphatic secondary amines, such as piperidine or dibutylamine. In all cases, the yields are

• . This result suggests the generation of the Fe acetylide intermediate type A. On the other hand, Tang et al. prepared a derivative of intermediate C and subjected it to reaction with piperidine under optimized reaction conditions (DBU in MeOH at 80 °C) and obtained the propargylamine product D [66

• secondary amines such as piperidine or pyrrolidine afford an aminal or an iminium ion, in general under high temperature or pressure conditions, which is not the case for the AHA coupling [69][70]. Despite these cases, the absence of evidence in terms of iminium ion generation confirms that the AHA coupling

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

• chloride, DMAP, NEt3, THF, 0 °C or 0 °C to rt, 3h, tetrahydrofuran, 77% (for 20)/88% (for 21); d) 1. piperidine, N,N-dimethylformamide, rt, 1.5 h; 2. unit B (11 for 20 and 13 for 21), HOAt, NEt3, EDC·HCl, CH2Cl2, 0 °C to rt, 18 h, 49% (for 22)/38% (for 23); e) 1. TFA, CH2Cl2, 0 °C to rt, 2.5 h; 2. HATU

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• the C=S bond. The subsequent elimination of H2S afforded the final product (Scheme 30) [48]. Analogously, piperazinylthiazoloquinolines 40 and thiazolocoumarins 41 were obtained using piperazine or piperidine, CS2 and substituted quinolines or coumarins [49]. The synthesis of furo[3,4-b]pyrazolo[4,3-f

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

• like the azetidine in compound 16 (56%) and the piperidine in compound 17 (67%) also resulted in good yields. Concerning tertiary alkyl substrates, acyclic alkyl substrates used in compound 19 (68%) and 20 (53%) as well as cyclic alkyl substrates like bromomethylcyclohexane used in compound 21 (61

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• further investigate the potential utility of this methodology, a gram scale experiment was conducted affording product 16f in a good yield and a slight decrease of the enantioselectivity. Additionally, a derivatization of product 16f by hydrogenation was carried out to yield the tricyclic piperidine 17

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• -coupling to give 32 or chemoselective Negishi coupling to give 33 [74]. Finally, BPin 21 could be oxidised to the phenol derivative 34 or cross-coupled with piperidine under Chan–Lam conditions to give the aniline derivative 35 in good yield [75]. Conclusion In summary, we have developed a general method

• equiv), MeCN, air, 70 °C, 24 h. (vii) Cu(OAc)2·H2O (30 mol %), B(OH)3 (2.0 equiv), piperidine (2.0 equiv), MeCN, air, 70 °C, 24 h. See Supporting Information File 1 for full details. Supporting Information The research data supporting this publication can be accessed at https://doi.org/10.17630

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

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• delight, we found that the subsequent multicomponent coupling of the organozinc bromide with piperidine and benzaldehyde was possible, although it required the additional presence of lithium chloride to furnish a satisfactory result. We attributed the beneficial role of LiCl to the formation of more

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

• shaken for 15 min and then placed in an oven at 100 °C until the silica gel was completely dried. The impregnated silica gel was stored in the dark until use. Syntheses 1-(1-Propen-1-yl)piperidine (2): In a manner analogous to [27], potassium carbonate (2 g, 15 mmol), piperidine (10 mL, 0.1 mol), and

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• benzoyl group on the nitrogen atom preventing equilibration to the thermodynamic piperidine product [21]. Basic workup hydrolyzes the trifluoroacetoxy ester in 14 to alcohol 7a. Consideration of the literature NMR data for the three possible isomeric products (i.e., pyrrolidine, piperidine, and

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

• approach was also used to synthesize pyrazoles since the intermediary-formed diketone 18 forms the corresponding pyrazoles 17 in a Knorr reaction with 2-hydrazinyl-4-phenylthiazoles 15 in a one-pot process (Scheme 4) [52]. Piperidine was used as a catalyst for the Knoevenagel condensation. Remarkably

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• cyclization (Table 1, entry 7) and the six-membered piperidine 3, instead of the five-membered pyrrolidine 2, was obtained in excellent yield without electricity (Table 1, entry 8). Thus, it is proposed that the electrochemical aza-Wacker cyclization under acidic conditions proceeded via radical cations to

• give five-membered pyrrolidine 2, while the six-membered piperidine 3 is formed through ionic cyclization under non-electrochemical conditions. With the optimized conditions in hand, the scope of the electrochemical aza-Wacker cyclization was investigated (Scheme 3). Various aryl sulfonamides 4–6 were

• piperidine 17 were obtained in good mass balance under non-electrochemical conditions. Although the detailed mechanism remains an open question, the electrochemical aza-Wacker cyclizations might be radical reactions rather than ionic ones, since the six-membered piperidine was not obtained from the

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

• on normal human peripheral blood mononuclear cells (PBMC). In 2003, a direct transformation of tetraoxanes to amides via carboxylic acid was also reported by the same research group [68]. Some amides were synthesized using methyl glycinate, di-n-propylamine, and piperidine with significant

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• anilines were obtained. The quinoline reduction was efficiently promoted by adding a catalytic amount of p-toluenesulfonic acid (PTSA) or pyridinium p-toluenesulfonate (PPTS). Pyridine was also reduced to piperidine in the presence of PTSA. Keywords: cyanoarene; nitroarene; PEM reactor; pyridine

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• example, methyl acetoacetate (2a) possesses one CH-acidic methylene carbon which can be deprotonated in equilibrium by weak organic bases, such as triethylamine, piperidine or DBU, under thermodynamic conditions. Dimethyl acetone-1,3-dicarboxylate (3a) contains even two reactive methylene groups which can

• . Conditions: i, 1) DBU (1.3 equiv), 1,4-dioxane, 20 °C, 12 h; 2) I2 (2 equiv), DBU (3 equiv), MeCN or DMF. Then aqueous work-up at the air. Synthesis of 39a–i. Conditions: i, method A: DBU (1.3 equiv), 1,4-dioxane, 20 °C; method B: K2CO3 (4 equiv), DMF, 20 °C. Synthesis of 40. Conditions: i, piperidine, MeOH

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• in moderate to good yields. With the β-ketoesters prepared, we began the synthesis of the Knoevenagel derivatives. To do so, we employed an adapted protocol from the literature. Using 1.00 equiv of β-ketoester, 1.50 equiv of aldehyde, 0.60 equiv of acetic acid, and 0.25 equiv of piperidine, the

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

• NMM (8 equiv) in DMF. Each Fmoc deprotection step of the peptide N-terminus was conducted by the repeated treatment of the peptide on resin with 20% piperidine in DMF (2 × 10 min). After each coupling reaction, the resin was washed with DMF. Synthesis of C60–peptide conjugates 5a–c The synthetic

• was subjected to SPPS with the peptides on trityl resin (i.e., 2a–c) to provide 4a–c. By simultaneous deprotection of peptide side chains and cleavage from resin, C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo-Arg (5c) were obtained. Reagents and conditions: i) 20% piperidine, rt, 2 × 10 min

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• explanation for the present tetrazole form in the solutions. Surprisingly, FTIR and X-ray analyses of 12a in the solid state indicated the existence of 12a in the azide form. In subsequent experiments it was discovered that for less nucleophilic N-nucleophiles (piperidine, morpholine, N-methylpiperazine) C2

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• from the known brocaeloid D by the addition of a methyl group, and there is a change in the relative stereochemistry at C2 and C3. In addition, the conversion of the five-membered pyrrole ring in compound 2 to the six-membered piperidine ring in compound 1 is intriguing. Although there have been many

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• of KMnO4 at 100 °C. The variation of the nucleophile did not give positive results either. For example, the replacement of dimethylamine with higher-boiling piperidine and n-butylamine or using liquid ammonia, which is highly reactive in such transformations, dipyridoacenaphthene 5 still returned

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• properties, so far. Therefore, we have synthesized selected benzo[c]quinolizinium derivatives and studied their DNA-binding and DNA-photodamaging properties. Results and Discussion Synthesis The styrylpyridine derivatives 2a,c,d,f were synthesized by a piperidine- or Ca(OTf)2-catalyzed condensation reaction

• : piperidine, MeOH, reflux (2a,c), ii: Ca(OTf)2, Bu4NPF6, 130 °C (2d,f), iii: N2H4·H2O, Pd/C, MeOH, reflux (2b), iv: NaNO2, CuCl, aq HCl (37%), room temp., 2 h, 60 °C, 30 min (2e), v: acetyl chloride, pyridine, THF, room temp. (2g). Photoinduced formation of styrylpyridine derivatives 2b–g to the benzo[c

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• ). However, piperidine, TMG, and Na2CO3 failed to promote the annulation reaction (Table 1, entries 4–6). When triethylamine was employed as the base, the reaction gave the spiro compound 3a in 71% yield (Table 1, entry 7). The yields of product 3a remained nearly unchanged when the reaction time was either

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• pyridine-3,5-carbonitriles 6–9 were synthesized starting with 4-bromobenzaldehyde (1) (Scheme 1 and Scheme 2). Thus, piperidinium 3,5-dicyano-6-hydroxy-4-(4-bromophenyl)pyridin-2-olate (2) was prepared by cyclocondensation of 1 with cyanoacetamide in methanol in the presence of piperidine. The conversion

• , 2.5 equiv), piperidine (14.81 mL, 0.15 mol, 3 equiv), and MeOH (150 mL) was heated until complete dissolution. The mixture was cooled to rt and 4-bromobenzaldehyde (1, 9.25 g, 0.05 mol, 1 equiv) was added. The mixture was vigorously stirred at 40 °C for 48 h. Then solvents were evaporated to a half of

• (m, 2H), 3.02–2.99 (m, 4H), 1.63–1.51 (m, 6H); MS–ESI− (m/z): 315 ([M − H − piperidine]−, 100). 2,6-Dibromo-4-(4-bromophenyl)pyridine-3,5-dicarbonitrile (3). A mixture of compound 2 (1.16 g, 2.89 mmol, 1 equiv) and POBr3 (2.49 g, 8.68 mmol, 3 equiv) was heated with stirring in an oil bath at 170 °C

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -withdrawing group, such as trifluoromethyl (4h), was obtained in 44% yield. When morpholine was replaced with piperidine (5a) or seven-membered azepane (5b) as a solvent, a decreased yield was observed (30–42%). The addition of piperidine offers an advantage in expanding the substrate scope to medicinal

• chemistry applications. In the reaction with piperidine, we observed unreacted organic azide 2b by TLC and 1H NMR analyses. Based on the 1H NMR analysis, 0.4 equiv of 2b had reacted to form the product, 0.9 equiv of 2b had decomposed to form aniline, and the remaining 0.2 equiv of 2b was unreacted

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• -polar solvents. When using N,N-dimethylamine, N,N-diethylamine, pyrrolidine, piperidine, morpholine and N-methylpiperazine as sec-amine component, the 1H NMR spectra reveal the formation of complexes with a 1:1 stoichiometry. However, for aliphatic amines with longer hydrocarbon chains, like

• the described amines formed a complex with R[4]A, in which the amine molecule is located outside the R[4]A molecule (“out” complex). In the case of small amine molecules such as N,N-dimethylamine, N,N-diethylamine, pyrrolidine, and piperidine, the calculations revealed a structure in which a proton is

• substituents with R[4]A in ethanol were synthesized. The composition of the complexes was determined based on the integration of amine proton signals in the 1H NMR spectra. For small molecule sec-amines such as N,N-dimethylamine, N,N-diethylamine, and cyclic amines (pyrrolidine, piperidine, morpholine, N