Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• -Trimethylspiro[indoline-2,3'-naphtho[2,1-b][1,4]oxazine]-5'-yl)vinyl)quinolizinium tetrafluoroborate (3a) [60][62][64][65]: To a solution of 2-methylquinolizinium tetrafluoroborate (2a, 116 mg, 500 µmol) and the 5’-formyl-substituted spirooxazine 1b (214 mg, 600 µmol) in MeCN (15 mL) was added piperidine (42.6

• piperidine (34.1 mg, 400 µmol, 39.6 µL) at 80 °C under an argon atmosphere and exclusion of light, and the reaction mixture was stirred under reflux for 2 h. After cooling to rt, the mixture was added dropwise to Et2O (120 mL) under vigorous stirring. The precipitate was filtered and washed with Et2O (3 × 20

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• significantly higher yield than HBTU. The Fmoc cleavage of the compounds 3–5 was performed with piperidine in DMF (20 vol %) [36]. The reaction products were not isolated and purified but instead immediately used for the succeeding peptide coupling step to give the dipeptides 4 and 5 from the glycosylated

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• with TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl) [25] and ABNO (9-azabicyclo[3.3.1]nonane N-oxyl) radicals [26]. Later reports enlarged the synthetic scope of this methodology and provided access to a wide range of synthetically useful building blocks such as substituted heterocycles, fluorinated

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• -(4'-butenyl)-5-(2'-piperidyl)piperidine) (20) and virgiboidine (3-but-3-en-1-yl)decahydro-6H-1,5-methanopyrido[1,2-a][1,5]diazocin-6-one) (21), two important pharmacologically active compounds containing dipiperidine and piperidino-quinolizidine units in their structure. Starting from the monoacetate

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• groups have used Wittig reactions for the synthesis of 3-alkenylindoles [13][14][15]. Another variant that uses the Doebner condensation was reported by Singh and co-worker, who condensed indole-3-carbaldehyde with phenylacetic acid in the presence of pyridine as the solvent/base and piperidine as the

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• -Methylquinolizinium tetrafluoroborate (1) was synthesized according to published procedures [68]. The piperidine-catalyzed reaction of the latter with the benzaldehyde derivatives 2a–d gave the 2-styrylquinolizinium derivatives 3a–d in 63–79% yield (Scheme 1). The known products 3a and 3c were identified by

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• protecting groups, whereby Fmoc was cleaved by piperidine (20 vol % in DMF), while Lev was removed using hydrazine acetate. Iterative cycles continued until the desired structure was obtained. The oligosaccharide products were cleaved from the solid support using a flow UV photoreactor, followed by a two

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• systems could operate copper-free [25][27][29] and/or auxiliary base-free conditions [30]. Recently, some “designer" ionic liquids were also developed for this purpose [29][30][31][32][33] from which an imidazolium-based piperidine-appended one could act as task specific compound operating either as a

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• , relaxation of a spirocyclohexane-substituted nitroxide [10] is also shown in Figure 5. The Tm vs T dependence generally shows consistent trends in frozen solutions. For 2,5-tetramethyl-substituted pyrrolidine and piperidine nitroxides, a local maximum appears in their phase relaxation (1/Tm) at T > 100 K as

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• pyridinium fragments have been described as bright, photostable stains for double-stranded DNA, although their interaction with G4 structures has not been assessed [68][69][70]. All dyes, except for distyryl derivative 6a and mono-styryl derivative 19a, were obtained through a piperidine-catalyzed

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• corresponding dipyrromethenium chloride, which was then converted into its BODIPY analogue 2 through complexation by BF3·OEt2 in basic media. Regioselective introduction of distyryl substituents is achieved via Knoevenagel-type condensation in the presence of piperidine using aldehyde derivatives 3 and 4 whose

• dehalogenation side-product. Finally, a Knoevenagel condensation in the presence of cyanoacetic acid and piperidine is performed to lead to the targeted compounds BOD-TTPA-alk and BOD-TTPA. 3. Optical properties The optical properties of compounds BOD-TTPA-alk and BOD-TTPA were first evaluated in diluted (≈10−6

• dyes. Synthetic scheme of the selected materials. a) hydroxylamine hydrochloride, NaHCO3, DMSO, 60 °C then acetylene, KOH, DMSO, 110 °C, 24% over the two steps; b) 4-iodobenzoyl chloride, DCM, rt then DDQ, DCM, rt then NEt3, BF3·OEt2, 0 °C to rt, 35%; c) piperidine, cat. PTSA, toluene, 130 °C, 5: 35

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• to synthesize the natural (2S,3R,4R,5R)-184 the lactone 186b was subjected to Mitsunobu reaction followed by the ester reduction and the hydrogenolytic cleavage of the 1-phenylethyl group. Piperidines: A cis-disubstituted piperidine scaffold was identified in several piperidine alkaloids of diverse

• for the aziridine ring opening and the removal of the 1-phenylethyl group and also for the reduction of the intermediate cyclic imine which appeared stereospecific. Two other piperidine alkaloids, (+)-deoxocassine ((2S,3S,6R)-190a) and (+)-spectaline ((2S,3S,6R)-190b) were synthesized as hydrochloride

• salts in a similar way [33]. However, to introduce the hydroxy group at C3 of the piperidine ring addition of a lithium acetylide to the aziridine aldehyde (2S,1'R)-6 was performed (Scheme 51) instead of alkylation (Scheme 50). Two diastereoisomeric acetylenic alcohols were formed in the reaction with

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the resin linker in an efficient four-step procedure compatible with Fmoc-based SPPS. In the first step the Fmoc group was cleaved by treatment with 20% piperidine in DMF giving the free amino function on the resin linker. Then the resin was washed with DCM, DMF and NMP. In the next step the free

• , combined with HOAt. Loading of the resin was determined spectrophotometrically by measuring the absorption of the piperidine-dibenzofulvene adduct formed during Fmoc deprotection (20% v/v piperidine in DMF) at wavelength 290 nm. The obtained loadings were ranging from 0.36–0.60 mmol/g, while the original

• Fmoc-Sieber-PS resin was N-methylated. Firstly, the Fmoc group was cleaved with 20% piperidine in DMF from the resin linker (3 × 10 min shaking). After washing the resin three times with DCM, DMF and 1-methyl-2-pyrrolidone (NMP), the free amino groups of the resin were o-NBS protected. A mixture of 4

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• condensation in detail. Results and Discussion The catalyzed Knoevenagel condensations of mono-fluorinated benzaldehydes 1a–c with malonodinitrile (2) are depicted in Scheme 1. In contrast to previous work, which reported the uncatalyzed reaction [19], piperidine was used as a basic catalyst. This was done as

• performed (Figure 3). The relative intensity of the peak corresponding to piperidine (Figure 3 red box) decreases systematically with respect to that of 3a (Figure 3 blue box). Hence, this suggests that the catalyst is indeed present in the solid product. Further analysis is required to understand the

• (1a) contain spectral properties belonging to PMMA (shaded areas in Figure S3, Supporting Information File 1). The mechanochemical catalyzed reactions of 1b and 1c with 2 performed with 2 µL piperidine did not exhibit the same polymorphic transformations as with 1a. Instead, reactions using 1b and 1c

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• ]. Considering that the widely used Fmoc protecting group, of which the H-9 has a pKa of ≈22 [42], can be readily removed with a weak base such as piperidine, we hypothesized that the oxidized Dmoc groups and linkers could be cleaved under weakly basic and non-nucleophilic conditions via β-elimination. Indeed

Precious metal-free molecular machines for solar thermal energy storage

• Meglena I. Kandinska,
• Snejana M. Kitova,
• Vladimira S. Videva,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• Stanislav B. Baluschev,
• Silvia E. Angelova and
• Aleksey A. Vasilev

Beilstein J. Org. Chem. 2019, 15, 1096–1106, doi:10.3762/bjoc.15.106

• excess of crown ether 3 was easily removed. In general the zwitterionic salts 2a–d reacted to complete depletion in ethanol and in the presence of piperidine as catalyst with the crown ether benzaldehyde 3 (TLC monitoring, ethyl acetate/ethanol 4.5:0.5). After the addition of ethyl acetate the

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• most of the cases, the Z-isomer as the sole or main product, while tert-butyl derivatives gave the E-isomer selectively. On the secondary amine side, morpholine, piperidine, pyrrolidine and dibutylamine all rendered the reaction efficiently. A plausible explanation for the mechanism of this

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• obtain an aldehyde that could then be used in a reductive amination. Beginning with the commercially available 4-(4-bromophenyl)butanoic acid, an alkene was installed with a Suzuki reaction, which in turn underwent ozonolysis to give 21, shown in Scheme 4. In parallel, a commercially available piperidine

• the same linker as HF-4, its lengthy epitope actually required a different, but parallel synthetic strategy. The same commercially available piperidine used to obtain 24 was instead acylated with phthaloyl-protected aminopropanoyl chloride, deprotected, and reductively aminated with 21 to give 33

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of polystyrene resin 3 as the amine component. After resin removal with piperidine in DMF, a combinatorial strategy of replacing the carboxylic acid component with trimethylsilyl azide (TMSN3) (azido-Ugi reaction) or cyanic acid, followed by Fmoc removal (TFA), allowed the formation of the tetrazole

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• character, 2,2,6,6-tetramethyl-1-(1-(2-(4-nitrophenyl)benzofuran-6-yl)ethoxy)piperidine (2a) and its regioisomer 2b, were designed and synthesized. The one-photon (OP) (365 ± 10 nm) and TP (710–760 nm) triggered release (i.e., uncaging) of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical under air

• ), 126.43 (C), 125.01 (CH), 124.33 (CH), 124.07 (CH), 121.22 (CH), 110.42 (CH), 105.12 (CH), 29.25 (CH2), 15.84 (CH3); HRMS–ESI (m/z): [M−] calcd. for C16H13NO3, 267.09009; found, 267.09064. 2,2,6,6-Tetramethyl-1-(1-(2-(4-nitrophenyl)benzofuran-6-yl)ethoxy)piperidine (2a). Under air, TEMPO (0.23 g, 1.5 mmol

• -(1-(2-(4-nitrophenyl)benzofuran-5-yl)ethoxy)piperidine (2b). Under air, TEMPO (46.8 mg, 0.3 mmol), 5-ethyl-2-(4-nitrophenyl)benzofuran (5b, 267 mg, 1 mmol), Cu(OAc)2 (3.6 mg, 0.02 mmol), bpy (3.1 mg, 0.02 mmol), TBHP (aqueous 70%, 0.086 mL, 0.6 mmol) were added into a Schlenk tube in the dark. The

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• Fmoc group removal and coupling steps. The Fmoc group was removed using piperidine/DMF (3:7). The coupling of amino acids was mediated by N,N’-diisopropylcarbodiimide (DIPCDI) and ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) in DMF, except for Fmoc-Glu-OpNB and Fmoc-Phe(4-I)-OH, which were coupled

• biaryl bicyclic peptide 1. Synthesis of the biaryl bicyclic peptide 1 incorporating a Phe-Phe linkage. Reagents and conditions: (i) Piperidine/DMF (3:7). (ii) Fmoc-βAla-OH, DIPCDI, Oxyma, DMF. (iii) Fmoc-Phe(4-I)-OH, COMU, Oxyma, DIPEA, DMF, overnight. (iv) Fmoc-Gln(Tmob)-OH, DIPCDI, Oxyma, DMF. (v) Fmoc

• . Synthesis of the biaryl bicyclic peptide 2 incorporating a Phe-Tyr linkage. Reagents and conditions: (i) Piperidine/DMF (3:7). (ii) Fmoc-βAla-OH, DIPCDI, Oxyma, DMF. (iii) Fmoc-Phe(4-I)-OH, COMU, Oxyma, DIPEA, DMF, overnight. (iv) Fmoc-Gln(Tmob)-OH, DIPCDI, Oxyma, DMF. (v) Fmoc-Gly-OH, DIPCDI, Oxyma, DMF

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• reported that 2,6-diazidopurine nucleosides exhibit opposite regioselectivity with aliphatic thiols, which do SNAr reactions at C(2) position of purines [50][51]. Taking this information into account, we performed an SNAr reaction between 2,6-diazidopurine 2a and piperidine and obtained the C(2

• or piperidine were more regioselective than in the purine series. In the latter case the purine products 6a–c had to be chromatographically separated to remove the 2-azido-6-amino isomer as the purification at the stage of final products was not effective. The observed C(2)-selectivity in the 7

• (piperidine or pyrrolidine) substituents did not significantly influence fluorescent properties. The preliminary study showed that introduction of other aliphatic amines at C(2) does not significantly affect the photophysical properties of the target substances either. On the other hand, the present synthetic

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• and in particular compounds with an amino functional group such as 3-aminopiperidine are valuable intermediates for the production of a large number of bioactive compounds with pharmacological properties. In this paper, the synthesis of both enantiomers of 3-amino-1-Boc-piperidine by amination of the

• intermediates for the synthesis of a large number of biologically active compounds used for the treatment of obesity, type-I and II diabetes mellitus or as psychotropic drugs against depression and schizophrenia [15][16][17][18][19]. In particular (R)-3-amino-1-Boc-piperidine is a useful precursor of compounds

• reaction parameters were studied to optimize the protocol for further scaling-up purposes. Results and Discussion In order to obtain enantiomerically pure (R)- and (S)-3-amino-1-Boc-piperidine (2), the transamination reaction was studied by using commercially available immobilized TAs (TAs-IMB) and

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• –al led to the substituted malonates 3a–al. A simple and general procedure was adopted for the condensation using fairly concentrated ethanolic solutions of diethyl malonate (4) and aldehydes 5a–al along with catalytic amounts of piperidine and acetic acid as well as some 4 Å molecular sieves to trap

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• has been adapted from an earlier work reported by Moroder et al. in which trifluoroacetyl (Tfa) moiety was deprotected during a peptide synthesis [44] using 1 M aqueous piperidine at ice cold temperature. The polypeptide chain 10 was thus subjected to 1 M aqueous piperidine at 0 °C to deprotect the ε

• -amino trifluoroacetyl moiety. The literature reported conditions, however, failed to deprotect the Tfa group from polypeptide chain 10. We have tested few reaction conditions and after optimization, we have successfully deprotected ε-amino Tfa protecting group from the side chain using 2 M aq piperidine

• -(trifluoroacetyl) group does not give positive Kaiser test (see Experimental section). Using 2 M aqueous piperidine we successfully cleaved the Tfa protecting group from the side chain of 15 to give a polypeptide chain 16 that is still intact with the resin. The successful cleavage of the Tfa group from the lysine