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

• . Moreover, TMS-substituted alkyne was suitable for this Huisgen reaction to achieve the desired triazole product. Next, some triazene scaffolds, such as dimethylamino-, pyrrolidine-, piperidine-, morpholine-, and piperazine-derived triazenes were screened. Aryl azides containing Br, I, Me, and MeO as well

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ). Asymmetric synthesis of piperidines The six-membered nitrogen-containing rings are the most common heterocycles among natural products and also synthetic pharmaceutical drugs [107][108]. For this reason, the piperidine unit has attracted great attention among organic chemists [109]. Due to that, a large

• reaction intermediate that was not isolated. Treatment of 115 with potassium hexamethyldisilazide (KHMDS) led to the sulfinyl piperidine derivative 116, and final deprotection under acidic conditions produced enantioenriched 2-allylpiperidine (117) as its hydrochloride (Scheme 32) [121]. Compound 117 has

• led to (−)-pelletierine (112) alkaloid. Yus and co-workers developed the synthesis of the piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b), (+)-isosolenopsin A (122c) and (2R,6R)-6-methylpipecolic acid hydrochloride by oxidation of the aromatic ring of (2R,6R)-2-methyl-6

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

• presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• columns. Initially, fluorenylmethyloxycarbonyl (Fmoc) group removal from the Rink linker was achieved by applying 20% piperidine in DMF (2 × 30 min). Preactivation of Fmoc amino acid (4 equiv) prior each coupling was performed with 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide

• deprotection was achieved via 20% piperidine in DMF (1 × 2 min and 1 × 18 min) to prepare the resin for the next coupling step. The resin was washed three times with each solvent in the given order DMF, DCM, and DMF after every reaction step. Peptide sequences T7: H-HAIYPRH-NH2 Modified T7: dipalmitoyl-Dap

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• pyridopyrimidines 94 utilizing a piperidine-catalyzed microwave-assisted four-component reaction by employing 1,1-dimethylthio-2-nitroethylene (91), 1,3-propanediamine (92), phenylsulfonyl acetonitrile 93 and aldehyde 5 in ethanol as solvent (Scheme 34). The crucial role of time was realized when the yield of the

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• . As can be seen from Scheme 2 the yields of the amination products 5 and 6 were dependent on the nature of the amine as well as on the used phthalazinone. Efficient results of coupling were received using, inter alia, cyclic, aromatic or benzylamines. The reaction of 3a with piperidine gave a higher

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• ), piperidine, acetic anhydride, trifluoroacetic acid (TFA), triisopropylsilane (TIS), Rink Amide AM resin (4-(2’,4’-dimethoxyphenyl-Fmoc-aminomethyl)phenoxyacetamido-aminomethyl resin, 100–200 mesh), and Tube-O-DIALYZER™ mini dialysis system (MWCO 1K) from Merck (Darmstadt, Germany). 1,2

• mL column was suspended in 5 mL of DMF and swollen overnight. After washing with DMF (3 × 2 mL), the Fmoc groups of the Rink amide AM resin were activated with 20% of piperidine in DMF (2 mL) for 20 min. After washing with DMF (3 × 2 mL), Fmoc-Ser(t-Bu)-OH (3 equiv) as the first Fmoc-amino acid and

• terminal amino acid, the Fmoc groups of Fmoc-Lys(Fmoc)-OH were activated with 2 × 20% of piperidine in DMF (2 mL) for 20 min, and the coupling reaction with perfluoroalkylated acids (3 equiv) or alkyl acid (3 equiv) was performed 3 times with HBTU/HOBT/DIPEA (6 equiv/6 equiv/12 equiv) for 3 h. After

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• chlorination. After the treatment of compound 39 with piperidine, the N-terminal free dipeptide was obtained and acylated with hexanedioic anhydride to afford the designed hapten 40 (Scheme 7) [11]. Phosphonodepsioctapeptide 41 was prepared as a variation of the partial sequence of a gene product of erb B-2

• hydrogenolysis and reaction with Fmoc-OSu, the N-protected phosphonodepsipeptide 145 was transformed to the N-Fmoc-protected phosphonodepsidipeptide 147, which was then coupled with the resin-loaded Cys(Trt)-NH-resin 148. The resin-loaded tripeptide 149 was deprotected with piperidine, coupled with Fmoc-Tyr(Ot

• -Bu) 150, deprotected again with piperidine, and cleaved with TFA and trapping agents. The free phosphonodepsipeptide 151 was obtained in 45% yield after HPLC purification (Scheme 25) [38]. A general and high yielding synthesis of phosphonodepsidipeptides 152 was realized via a Mitsunobu reaction of

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• common nitrogen-containing compounds such as pyridine, pyrazine, 1H-pyrazole, 1H-indole, 1-methyl-1H-indole, piperidine, and piperazine were subjected to screening. Pyridine and piperidine slightly hamper the reaction of 1g (Table 2, entries 2 and 7, 80–82%). Other nitrogen-containing compounds have more

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• , HOAt, NMM, DMF, 0 °C to rt, 15 h, 93%; iv) SPPS using HBTU, HOBt, DIPEA for coupling (HATU for BTA coupling), 20 vol % piperidine in DMF for Fmoc cleavage, DCM/TFA/TIS 20:20:1 (v/v/v) for final cleavage, 68%; v) azidoacetic acid NHS ester, NMM, DMF, rt, 4 h, 81%; vi) 4, PyBOP, HOAt, NMM, DMF, 0 °C to

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

• piperidine (17). The synthetic sequence performed by the authors is described in Scheme 3. Oxidation of 17 in the presence of hydrogen peroxide, catalyzed by selenium dioxide provided tetrahydropyridine N-oxide 18 in 88% yield. 18 was treated with (R)-p-tolylsulfinylmethyllithium 25 in THF at −78 °C to

• tricyclic adduct (+)-23b, a precursor to (−)-adaline (1). This methodology, based on the synthesis of optically active β-sulfinyl nitrones, was proved to be efficient in the synthesis of (+)-euphococcinine (2) in 7 steps from piperidine (17), in an overall yield of 2.1%. Specific rotation for (+)-2 was [α

• desired homotropane. Ikeda synthesis – 2002 Ikeda et al. prepared azabicycle (±)-42, a protected form of (±)-euphococcinine (2) [45]. The author’s method focused on the radical reaction of 2-(but-3-ynyl)piperidine (±)-34 mediated by Bu3SnH. This "6-exo-dig" cyclization occurred in a regioselective way to

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• heterocyclic compounds play an important role in pharmaceutical industry and related areas [1][2]. Among the variety of aromatic and saturated structures, the piperidine ring has a special role, as it is the most widely occurring form of nitrogen in FDA-approved drugs [3]. The ability of fluorine atoms to

• iodine by treatment with zinc, followed by the reaction with iodine monochloride. The iodide 2b reacted quite rapidly with the nitrone but the expected fluoroalkylation product was not observed. Instead, the tetrafluorinated piperidine 3a was obtained in a moderate yield (Table 1, entry 2). Apparently

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy 10.3762/bjoc.16.255 Abstract The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The

• piperidine derivatives 1 because of the accelerating effect of the nitrogen atom that stabilizes the oxyallyl cation intermediate 4 formed upon the ring closure. This was in analogy to that found for the classical Brønsted or Lewis acid-catalyzed Nazarov reaction involving N-heterocycles [27][28][29][30][31

• of the accuracy of the computational method we have used for the comparison of the isomeric complexes I and V. Our previous experience in this area taught us that seven-membered azepane-derived enynyl acetates react faster than the corresponding piperidine analogues 1, prompting us to prepare enynyl

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• between the states was accomplished by the addition of twice 2-ferrocenyl-1,10-phenanthroline (69) followed by the addition of copper(I) ions (Figure 19). In the state SelfSORT-I, representing an incomplete self-sorted mixture of ten components, piperidine (70) was firmly bound at the zinc porphyrin

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• HeLa cells treated with a mixture of RPE (8 μg/mL) and A) 1 (400 μM) or B) 2 (400 μM) after 2 h and 4 h of incubation. Blue: nucleus, red: RPE. Synthetic route to the branched peptides. (i) HBTU, DIPEA, DMF, 12 h, rt, (ii) TFA, 2 h, rt, and (iii) 20% piperidine in DMF, 2 h, rt. Supporting Information

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• 13, which only needed to be oxidised to the carboxylic acid 14 then coupled to piperidine in order to deliver the target compound, 2. However, the oxidation of 13 proved to be unexpectedly troublesome. Mild oxidising agents caused incomplete consumption of 13, while vigorous conditions led to the

• difluorinated acid 20. Finally, coupling of the acid 20 with piperidine afforded the target compound 2 in moderate yield (Scheme 3). The enantiopurity of 2 was investigated using chiral HPLC. From a spectroscopically pure sample of 2, two HPLC peaks were observed, with an integral ratio of 99:1. It is assumed

• conformational mimic of 1. The next-higher energy structure (2b, Figure 2) is related to 2a through a ring-flip of the piperidine moiety (equivalent to a 180° rotation of the amide bond). The structures 2a,b are close in energy, suggesting that both puckers of the piperidine moiety would be substantially

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• molar extinctions of both species were determined by adding a strong axial ligand such as piperidine (to achieve almost complete coordination) and acid (TFA) (protonation of the pyridine unit to prevent coordination, completely diamagnetic). At concentrations of ≈10 µM, intermolecular coordination is

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• atmosphere. Then, water (100 mL) was added and the yellow precipitate was filtered, and washed with ether. After Boc and Fmoc deprotection by using TFA and piperidine, respectively, crude compound 4 was obtained. The crude product was further purified by column chromatography (1% methanol in chloroform

• , ii) GCP, A, DIPEA, HCTU, iii) 20% piperidine in DMF, iv) TFA/CH2Cl2 1:1. Thermal stabilisation (∆Tma/°C) of ds-DNA and ds-RNA upon the addition of compound 4 at various ratios rb at pH 5 (buffer sodium cacodylate, I = 0.05 M). Binding constants (log Ka)a, ratios n = [4]/[polynucleotide] of 4 with ds

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• . reported on the photoswitching of the basicity of a piperidine nitrogen by reversible steric shielding of the nitrogen lone pair. The photoswitchable base was applied as a nucleophilic catalyst in the nitroaldol (Henry) reaction. Attached to a sterically demanding azobenzene unit, the lone pair was

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• Micromonospora [5]. Dipeptide analogs with phosphonoproline 2 and piperidine-2-phosphonic acid 3 are potent inhibitors of dipeptidyl peptidase IV [6][7]. Oxygen-containing heterocycles containing a phosphoryl group are also of interest in the development of new drugs. It is known that phosphorylated carbohydrate

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• resin was washed with DMF (10 mL × 4). Subsequently, 10 mL of 20% piperidine in DMF were added to the preswollen resin, and the resulting mixture was stirred for 30 minutes under a nitrogen gas atmosphere. After washing the resin with DMF, the deprotection procedure was repeated, and the resin was

• different concentrations at pH 7.4. Detailed synthetic scheme for PEP-1. (i) 20% piperidine in DMF, (ii) HBTU, (iii) NMM, (iv) Ac2O/Py/DMF 1:2:3 and (v) TFA/phenol/water/TIPS 88:5:5:2. Supporting Information Supporting Information File 374: Materials and methods as well as additional figures. Funding G. G

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• facilitates the synthesis of cyclopentenone-fused ring systems, which tend to be difficult to construct. The Pauson–Khand reaction has also been used as a key step in the synthesis of a number of biologically-relevant compounds, including fluorine-containing piperidine-fused cycles. Of course, where the

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• chromatography. Pleasingly, the sequence proceeded in high yields (63–83%) for all substrates with no chromatography required. Despite relatively high yields, significant racemisation was seen in the synthesis of piperidine 20 and pyrrolidine cores 23. Pyrrolidine 23 was obtained with an ee of only 30

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• ), the 1-ethyl derivative 20 did not react at all with the anhydrides 5–7. The structures of compounds 25 and 26 were confirmed by 2D NMR spectroscopy and singe-crystal X-ray analysis (Figure 3). The piperidine moiety is planar to a significant extent due to the combined influence of the aromatic ring

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• copper-catalysed asymmetric conjugate addition (ACA) of dialkylzinc reagents to N-substituted 2,3-dehydro-4-piperidones 1 in order to access useful chiral piperidine derivatives (Scheme 1A) [15]. They found the catalytic system based on the chiral phosphoramidite L1 and a copper salt to be the most