36 results on '"*PIPERIDINE"'
Search Results
2. 1‐Azaspiro[3.3]heptane as a Bioisostere of Piperidine.
- Author
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Kirichok, Alexander A., Tkachuk, Hennadii, Kozyriev, Yevhenii, Shablykin, Oleh, Datsenko, Oleksandr, Granat, Dmitry, Yegorova, Tetyana, Bas, Yuliya P., Semirenko, Vitalii, Pishel, Iryna, Kubyshkin, Vladimir, Lesyk, Dmytro, Klymenko‐Ulianov, Oleksii, and Mykhailiuk, Pavel K.
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HEPTANE , *PIPERIDINE , *ISOXAZOLIDINES , *BIOISOSTERES , *ISOCYANATES , *BUPIVACAINE , *DRUG design , *LACTAMS - Abstract
1‐Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with alane produced 1‐azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent‐free analogue with high activity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. The Construction of Highly Substituted Piperidines via Dearomative Functionalization Reaction.
- Author
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Hu, Miao, Ding, Hao, DeSnoo, William, Tantillo, Dean J., and Nairoukh, Zackaria
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DENSITY functional theory , *PIPERIDINE , *NATURAL products , *HETEROCYCLIC compounds - Abstract
Nitrogen heterocycles play a vital role in pharmaceuticals and natural products, with the six‐membered aromatic and aliphatic architectures being commonly used. While synthetic methods for aromatic N‐heterocycles are well‐established, the synthesis of their aliphatic functionalized analogues, particularly piperidine derivatives, poses a significant challenge. In that regard, we propose a stepwise dearomative functionalization reaction for the construction of highly decorated piperidine derivatives with diverse functional handles. We also discuss challenges related to site‐selectivity, regio‐ and diastereoselectivity, and provide insights into the reaction mechanism through mechanistic studies and density functional theory computations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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4. Enantio‐ and Regioselective Copper‐Catalyzed 1,2‐Dearomatization of Pyridines.
- Author
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Pappoppula, Mukesh, Olsen, Kathryn L., Ketelboeter, Devin R., and Aponick, Aaron
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PIPERIDINE , *FUNCTIONAL groups , *PYRIDINE , *ACETYLENE , *ALKYNES , *IMIDAZOPYRIDINES - Abstract
A copper‐catalyzed dearomative alkynylation of pyridines is reported with excellent regio‐ and enantioselectivities. The synthetically valuable enantioenriched 2‐alkynyl‐1,2‐dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three‐component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl P,N‐ ligand, as the catalytic system. Under mild reaction conditions, the desired 1,2‐addition products are delivered in up to 99 % yield with regioselectivity ratios up to 25 : 1 and enantioselectivities values of up to 99 % ee. Activated and non‐activated terminal alkynes containing a wide range of functional groups are well tolerated. Even acetylene gas delivered mono‐alkynylated products in high yield and ee. Application of the methodology in an efficient enantioselective synthesis of the chiral piperidine indolizidine, coniceine, is reported. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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5. Gold‐Catalyzed Amine Cascade Addition to Diyne‐Ene: Enantioselective Synthesis of 1,2‐Dihydropyridines.
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Wei, Jingwen, Xing, Yangyang, Ye, Xiaohan, Nguyen, Bao, Wojtas, Lukasz, Hong, Xin, and Shi, Xiaodong
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AMINES , *PIPERIDINE , *PYRIDINE , *CONDENSATION , *DIHYDROPYRIDINE - Abstract
With the well‐documented chemical and biological applications, piperidine and pyridine are among the most important N‐heterocycles, and a new synthetic strategy, especially one with an alternative bond‐forming design, is of general interest. Using the gold‐catalyzed intermolecular condensation of amine and diyne‐ene, we report herein the first example of enantioselective 1,2‐dihydropyridine synthesis through a formal [3+2+1] fashion (up to 95 % yield, up to 99 % e.e.). [ABSTRACT FROM AUTHOR]
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- 2023
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6. Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4‐Addition of an Organolithium Reagent**.
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Mauger, Audrey, Jarret, Maxime, Tap, Aurélien, Perrin, Rémi, Guillot, Régis, Kouklovsky, Cyrille, Gandon, Vincent, and Vincent, Guillaume
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PINACOL rearrangement , *INDOLE alkaloids , *MOIETIES (Chemistry) , *PIPERIDINE , *ORGANOLITHIUM compounds , *AMMONIUM , *ALKALOIDS - Abstract
We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C‐fluorocurine, C‐profluorocurine, C‐mavacurine, normavacurine, 16‐epi‐pleiocarpamine and taberdivarine H. We designed a strategy involving late‐stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2‐indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4‐addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C‐profluorocurine and C‐fluorocurine were finalized by the dihydroxylation of C‐mavacurine and a pinacol rearrangement, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen.
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Ng, Teng Wei, Tao, Ran, See, Willy Wei Li, Poh, Si Bei, and Zhao, Yu
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HYDROGEN , *AROMATIZATION , *OXIDATION-reduction reaction , *ALCOHOL , *PIPERIDINE - Abstract
We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one‐pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3‐amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N‐protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di‐ and tri‐substituted piperidines, which ranks the topmost frequent N‐heterocycle in commercial drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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8. Production of Piperidine and δ‐Lactam Chemicals from Biomass‐Derived Triacetic Acid Lactone.
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Chen, Bingfeng, Xie, Zhenbing, Peng, Fangfang, Li, Shaopeng, Yang, Junjuan, Wu, Tianbin, Fan, Honglei, Zhang, Zhaofu, Hou, Minqiang, Li, Shumu, Liu, Huizhen, and Han, Buxing
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BIOMASS chemicals , *PIPERIDINE , *LIGNOCELLULOSE , *RUTHENIUM catalysts , *CATALYST supports , *METALS - Abstract
Piperidine and δ‐Lactam chemicals have wide application, which are currently produced from fossil resource in industry. Production of this kind of chemicals from lignocellulosic biomass is of great importance, but is challenging and the reported routes give low yield. Herein, we demonstrate the strategy to synthesize 2‐methyl piperidine (MP) and 6‐methylpiperidin‐2‐one (MPO) from biomass‐derived triacetic acid lactone (TAL) that is produced microbially from glucose. In this route, TAL was firstly converted into 4‐hydroxy‐6‐methylpyridin‐2(1H)‐one (HMPO) through facile aminolysis, subsequently HMPO was selectively transformed into MP or MPO over Ru catalysts supported on beta zeolite (Ru/BEA‐X, X is the molar ratio of Si to Al) via the tandem reaction. It was found that the yield of MP could reach 76.5 % over Ru/BEA‐60 in t‐BuOH, and the yield of MPO could be 78.5 % in dioxane. Systematic studies reveal that the excellent catalytic performance of Ru/BEA‐60 was closely correlated with the cooperative effects between active metal and acidic zeolite with large pore geometries. The related reaction pathway was studied on the basis of control experiments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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9. The Existence of a N→C Dative Bond in the C60–Piperidine Complex.
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Lamanec, Maximilián, Lo, Rabindranath, Nachtigallová, Dana, Bakandritsos, Aristides, Mohammadi, Elmira, Dračínský, Martin, Zbořil, Radek, Hobza, Pavel, and Wang, Weizhou
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COORDINATE covalent bond , *FULLERENES , *COVALENT bonds , *HYDROGEN bonding , *MOLECULAR dynamics , *FOURIER transform infrared spectroscopy - Abstract
The complexes formed between carbon allotropes (C20, C60 fullerenes, graphene, and single‐wall carbon nanotubes) and piperidine have been investigated by means of computational quantum chemical and experimental IR and NMR techniques. Alongside hydrogen bonds, the C⋅⋅⋅N tetrel bond, and lone‐pair⋅⋅⋅π interactions, the unexpected N→C dative/covalent bond has been detected solely in complexes of fullerenes with piperidine. Non‐planarity and five‐member rings of carbon allotropes represent the key structural prerequisites for the unique formation of a dative N→C bond. The results of thermodynamics calculations, molecular dynamics simulations, and NMR and FTIR spectroscopy explain the specific interactions between C60 and piperidine. The differences in behavior of individual carbon allotropes in terms of dative bonding formation brings a new insight into their controllable organic functionalization. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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10. Hexafluoroisopropanol‐Promoted Haloamidation and Halolactonization of Unactivated Alkenes.
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Qi, Chenxiao, Force, Guillaume, Gandon, Vincent, and Lebœuf, David
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FUNCTIONAL groups , *PYRROLIDINE , *PIPERIDINE , *HALIDES - Abstract
Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post‐modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While progress has been made in this field, notably with the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal‐ and oxidant‐free protocol to achieve the haloamidation of olefins, promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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11. Total Synthesis of (−)‐Himeradine A.
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Burtea, Alexander, DeForest, Jacob, Li, Xinting, and Rychnovsky, Scott D.
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MANNICH reaction , *SUZUKI reaction , *RING formation (Chemistry) , *PIPERIDINE , *SECONDARY amines , *ISOQUINOLINE alkaloids - Abstract
(−)‐Himeradine A is a complex lycopodium alkaloid with seven rings and ten stereogenic centers that shows anticancer activity against lymphoma L1210 cells. A total synthesis has been developed that builds off prior work on (+)‐fastigiatine. A 2,4,6‐trisubstitited piperidine ring forms the core of the quinolizidine segment, and was prepared by diastereoselective reduction of a pyridine and classic resolution of an intermediate. The remaining secondary amine was introduced with a catalyst‐controlled Overman rearrangement. The piperidine segment was coupled in a B‐alkyl Suzuki reaction with a bicyclic bromoenone, which was a key intermediate for the synthesis of (+)‐fastigiatine. The final transformation featured a transannular Mannich reaction and cyclization to complete the quinolizidine. Five bonds and four new rings were generated in this one‐pot procedure. (−)‐Himeradine A was prepared in 17 steps in the longest linear sequence. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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12. A Local‐Desymmetrization‐Based Divergent Synthesis of Quinine and Quinidine.
- Author
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Lee, Jaehoo and Chen, David Y.‐K.
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ORGANIC synthesis , *QUININE , *QUINIDINE , *STEREOCHEMISTRY , *PIPERIDINE , *NATURAL products - Abstract
Herein we report a novel synthetic entry to the legendary quinuclidine natural products quinine and quinidine. The developed strategy is based on the use of a symmetrical and nonstereogenic precursor to access quinine and quinidine through a "local‐desymmetrization" approach, in stark contrast conceptually to the preparation of stereodefined disubstituted piperidines (or their acyclic precursors) as featured in all past syntheses. The developed strategy also provided quinine and quinidine derivatives that could not be readily obtained through previous total syntheses or by modification of the naturally occurring substances. Seeing old friends in a new light: A divergent synthesis of quinine and quinidine (see structures) was designed on the basis of a symmetrical and nonstereogenic intermediate, conceptually different from the stereodefined piperidine precursors used in past syntheses. Complementary late‐stage local‐desymmetrization reactions were developed to access the two targets. The strategy also enabled the synthesis of novel quinine and quinidine derivatives. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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13. Mannich‐type Reactions of Cyclic Nitrones: Effective Methods for the Enantioselective Synthesis of Piperidine‐containing Alkaloids.
- Author
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Lisnyak, Vladislav G., Lynch‐Colameta, Tessa, and Snyder, Scott A.
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MANNICH reaction , *NITRONES , *PIPERIDINE , *ENANTIOSELECTIVE catalysis , *AMINO ketones , *ALKALOIDS - Abstract
Even though there are dozens of biologically active 2‐substituted and 2,6‐disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich‐type additions to nitrones, one using β‐ketoacids under catalyst‐free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2‐substituted materials, as well as other ring variants, in the form of β‐N‐hydroxy‐aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98 %). The combination of these methods, along with other critical steps, has enabled 8‐step total syntheses of the 2,6‐disubstituted piperidine alkaloids (−)‐lobeline and (−)‐sedinone. Just Mannich enough: Despite their prevalence, 2‐ and 2,6‐disubstituted piperidines are challenging to prepare enantioselectively, particularly when they possess β‐functionalization. Two new approaches based on the use of cyclic nitrones provide the means to readily fashion an array of such materials, one of which proceeds with high enantioselectivity (up to 98 % ee) using a chiral thiourea promoter. Their sequential use has enabled 8‐step total syntheses of both (−)‐lobeline and (−)‐sedinone from a common intermediate. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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14. The True Fate of Pyridinium in the Reportedly Pyridinium‐Catalyzed Carbon Dioxide Electroreduction on Platinum.
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Olu, Pierre‐Yves, Li, Qi, and Krischer, Katharina
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CARBON dioxide , *ELECTROLYTIC reduction , *OXIDATION-reduction reaction , *ELECTROLYSIS , *CARBONATION (Chemistry) - Abstract
Protonated pyridine (PyH+) has been reported to act as a peculiar and promising catalyst for the direct electroreduction of CO2 to methanol and/or formate. Because of recent strong incentives to turn CO2 into valuable products, this claim triggered great interest, prompting many experiments and DFT simulations. However, when performing the electrolysis in near‐neutral pH electrolyte, the local pH around the platinum electrode can easily increase, leading to Py and HCO3− being the predominant species next to the Pt electrode instead of PyH+ and CO2. Using a carefully designed electrolysis setup which overcomes the local pH shift issue, we demonstrate that protonated pyridine undergoes a complete hydrogenation into piperidine upon mild reductive conditions (near 0 V vs. RHE). The reduction of the PyH+ ring occurs with and without the presence of CO2 in the electrolyte, and no sign of CO2 electroreduction products was observed, strongly questioning that PyH+ acts as a catalyst for CO2 electroreduction. Hey pyridinium, you are not doing your assigned job! The protonated pyridine cation was believed to be a promising although peculiar catalyst for CO2 electroreduction reaction on platinum surfaces. By using an electrolysis setup—carefully designed to overcome the misleading issue of local pH shift—it was shown that protonated pyridine is not the catalyst. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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15. Ligand‐Enabled Enantioselective C –H Activation of Tetrahydroquinolines and Saturated Aza‐Heterocycles by RhI.
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Greßies, Steffen, Klauck, Felix J. R., Kim, Ju Hyun, Daniliuc, Constantin G., and Glorius, Frank
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QUINOLINE , *HETEROCYCLIC compounds , *RHODIUM , *CARBON-hydrogen bonds , *PIPERIDINE , *LIGANDS (Chemistry) - Abstract
Abstract: The first rhodium(I)‐catalyzed enantioselective intermolecular C sp 3 –H activation of various saturated aza‐heterocycles including tetrahydroquinolines, piperidines, piperazines, azetidines, pyrrolidines, and azepanes is presented. The combination of a rhodium(I) precatalyst and a chiral monodentate phosphonite ligand is shown to be a powerful catalytic system to access a variety of important enantio‐enriched heterocycles from simple starting materials. Notably, the C sp 3 –H activation of tetrahydroquinolines is especially challenging due to the adjacent C sp 2 −H bond. This redox‐neutral methodology provides a new synthetic route to α‐N‐arylated heterocycles with high chemoselectivity and enantioselectivity up to 97 % ee. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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16. The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular “Inside‐Out” Approach.
- Author
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Scharnagel, Dagmar, Goller, Jessica, Deibl, Nicklas, Milius, Wolfgang, and Breuning, Matthias
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ALKALOIDS , *ENANTIOSELECTIVE catalysis , *PIPERIDINE , *PYRIDONE , *CHIRALITY - Abstract
Abstract: Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7‐diazabicyclo[3.3.1]nonane) to which combinations of an α,N‐fused 2‐pyridone, an endo‐ or exo‐α,N‐annulated piperidin(on)e, and an exo‐allyl substituent are attached. We developed a modular “inside‐out” approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C2‐symmetric 2,6‐dioxobispidine by desymmetrization of a 2,4,6,8‐tetraoxo precursor, the construction of the α,N‐fused 2‐pyridone by using an enamine‐bromoacrylic acid strategy, and the installation of endo‐ or, optionally, exo‐annulated piperidin(on)es. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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17. Ultrafast Light-Driven Substrate Expulsion from the Active Site of a Photoswitchable Catalyst.
- Author
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Pescher, Manuel D., van Wilderen, Luuk J. G. W., Grützner, Susanne, Slavov, Chavdar, Wachtveitl, Josef, Hecht, Stefan, and Bredenbeck, Jens
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PIPERIDINE , *CATALYSTS , *CATALYSIS , *AZOBENZENE , *HYDROGEN bonding - Abstract
The photoswitchable piperidine general base catalyst is a prototype structure for light control of catalysis. Its azobenzene moiety moves sterically shielding groups to either protect or expose the active site, thereby changing the basicity and hydrogen-bonding affinity of the compound. The reversible switching dynamics of the catalyst is probed in the infrared spectral range by monitoring hydrogen bond (HB) formation between its active site and methanol (MeOH) as HB donor. Steady-state infrared (IR) and ultrafast IR and UV/Vis spectroscopies are used to uncover ultrafast expulsion of MeOH from the active site within a few picoseconds. Thus, the force generated by the azobenzene moiety even in the final phase of its isomerization is sufficient to break a strong HB within 3 ps and to shut down access to the active site. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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18. Stereoselective Synthesis of Piperidines by Iridium-Catalyzed Cyclocondensation.
- Author
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Sandmeier, Tobias, Krautwald, Simon, and Carreira, Erick M.
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STEREOSELECTIVE reactions , *PIPERIDINE , *ALIPHATIC amine synthesis , *IRIDIUM catalysts , *CONDENSATION , *RING formation (Chemistry) , *AMINO alcohols - Abstract
An iridium-catalyzed cyclocondensation of amino alcohols and aldehydes is reported. Intramolecular allylic substitution by an enamine intermediate and subsequent in situ reduction furnishes 3,4-disubstituted piperidines with high enantiospecificity and good diastereoselectivity. The modular approach and the broad functional group tolerance provide access to diverse piperidine derivatives, which were further functionalized to give a versatile set of products. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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19. Thermally Adjustable Dynamic Disulfide Linkages Mediated by Highly Air-Stable 2,2,6,6-Tetramethylpiperidine-1-sulfanyl (TEMPS) Radicals.
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Takahashi, Akira, Goseki, Raita, and Otsuka, Hideyuki
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DISULFIDES , *PIPERIDINE , *RADICALS (Chemistry) , *DISSOCIATION (Chemistry) , *ATMOSPHERIC chemistry - Abstract
Intrinsically exchangeable dynamic covalent bonds that can be triggered by readily usable stimuli offer easy incorporation of their dynamic properties in various molecular systems, but the library of such bonds is still being developed. Herein, we report the dynamic covalent chemistry of 2,2,6,6-tetramethylpiperidine-1-sulfanyl (TEMPS) dimers derived from thermally reversible homolytic dissociation of disulfide linkages. High air stability of TEMPS was observed even at 100 °C, affording facile employment of thermal dissociation-association equilibria and adjustable bond exchange properties under atmospheric conditions. We also established an efficient synthetic route for a modifiable derivative of the dimer that enabled incorporation of dynamic properties into linear and network polymer structures. The obtained polymers showed controllable molecular weights, temperature-dependent swelling properties, healing ability, and recyclability, reflecting the thermally tunable dynamics of the dimer. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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20. Strong Evidence of a Phosphanoxyl Complex: Formation, Bonding, and Reactivity of Ligated Phosphorus Analogues of Nitroxides.
- Author
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Heurich, Tobias, Schnakenburg, Gregor, Streubel, Rainer, Nesterov, Vitaly, Qu, Zheng-Wang, Grimme, Stefan, Hazin, Khatera, Gates, Derek P., and Engeser, Marianne
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NITROXIDES , *STYRENE , *PIPERIDINE , *CHEMICAL bonds , *PHOSPHINES - Abstract
Facile access to [W(CO)5(Ph2P-OTEMP)] is used to initiate a study on the generation, properties, and reactions of transient phosphanoxyl complexes [ML n(R2PO)], the first example of which could be trapped via heterocoupling with the trityl radical. It is also demonstrated that the phosphorus nitroxyl complex acts as radical initiator in the polymerization of styrene. The quest for P−O versus O−N bond homolysis, as well as the initial steps of the polymerization were studied by DFT methods. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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21. A Chemical Probe for the ATAD2 Bromodomain.
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Bamborough, Paul, Chung, Chun‐wa, Demont, Emmanuel H., Furze, Rebecca C., Bannister, Andrew J., Che, Ka Hing, Diallo, Hawa, Douault, Clement, Grandi, Paola, Kouzarides, Tony, Michon, Anne‐Marie, Mitchell, Darren J., Prinjha, Rab K., Rau, Christina, Robson, Samuel, Sheppard, Robert J., Upton, Richard, and Watson, Robert J.
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BROMODOMAIN-containing proteins , *SULFONES , *FLUORINE , *PIPERIDINE , *NUCLEAR proteins - Abstract
ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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22. Harnessing the Electrophilicity of Keteniminium Ions: A Simple and Straightforward Entry to Tetrahydropyridines and Piperidines from Ynamides.
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Lecomte, Morgan and Evano, Gwilherm
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IMINIUM compounds , *ELECTROPHILES , *YNAMIDES , *PYRIDINE derivatives , *PIPERIDINE , *ALKYLATION , *RING formation (Chemistry) - Abstract
An efficient, modular and straightforward entry to tetrahydropyridines and piperidines is reported. This reaction is based on a formal intramolecular hydroalkylation of readily available, properly substituted ynamides which, upon simple activation under acidic conditions, generate highly reactive activated keteniminium ions whose reactivity can be finely controlled to induce a remarkably efficient [1,5]-hydride shift from unactivated C−H bonds and trigger a cationic cyclization which is complete within minutes. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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23. Synthesis and Utility of Dihydropyridine Boronic Esters.
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Panda, Santanu, Coffin, Aaron, Nguyen, Q. Nhu, Tantillo, Dean J., and Ready, Joseph M.
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DIHYDROPYRIDINE , *BORONIC esters , *PIPERIDINE , *ALIPHATIC amine synthesis , *INTERMEDIATES (Chemistry) , *HETEROCYCLIC compounds synthesis , *SUBSTITUENTS (Chemistry) - Abstract
When activated by an acylating agent, pyridine boronic esters react with organometallic reagents to form a dihydropyridine boronic ester. This intermediate allows access to a number of valuable substituted pyridine, dihydropyridine, and piperidine products. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
24. Highly Stereoselective Synthesis of Natural-Product-Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence.
- Author
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Echemendía, Radell, de La Torre, Alexander F., Monteiro, Julia L., Pila, Michel, Corrêa, Arlene G., Westermann, Bernhard, Rivera, Daniel G., and Paixão, Márcio W.
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ALDEHYDES , *ORGANIC compounds , *STEREOSELECTIVE reactions , *STEREOCHEMISTRY , *ORGANOCATALYSIS , *PIPERIDINE , *PEPTIDOMIMETICS , *HETEROCYCLIC compounds - Abstract
In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of 1,3-dicarbonyls to α,β-unsaturated aldehydes followed by an intramolecular isocyanide-based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity-generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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25. Cation-Cation Pairing by NCH⋅⋅⋅O Hydrogen Bonds.
- Author
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Gamrad, Waltraud, Dreier, Angelika, Goddard, Richard, and Pörschke, Klaus-Richard
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CATIONS , *ION pairs , *HYDROGEN bonding , *PIPERIDINE , *ALUMINATES - Abstract
The pairing of ions of opposite charge is a fundamental principle in chemistry, and is widely applied in synthesis and catalysis. In contrast, cation-cation association remains an elusive concept, lacking in supporting experimental evidence. While studying the structure and properties of 4-oxopiperidinium salts [OC5H8NH2]X for a series of anions X− of decreasing basicity, we observed a gradual self-association of the cations, concluding in the formation of an isolated dicationic pair. In 4-oxopiperidinium bis(trifluoromethylsulfonyl)amide, the cations are linked by NH⋅⋅⋅OC hydrogen bonds to form chains, flanked by hydrogen bonds to the anions. In the tetra(perfluoro- tert-butoxy)aluminate salt, the anions are fully separated from the cations, and the cations associate pairwise by NCH⋅⋅⋅OC hydrogen bonds. The compounds represent the first genuine examples of self-association of simple organic cations based merely on hydrogen bonding as evidenced by X-ray structure analysis, and provide a paradigm for an extension of this class of compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
26. A Toggle Nanoswitch Alternately Controlling Two Catalytic Reactions.
- Author
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De, Soumen, Pramanik, Susnata, and Schmittel, Michael
- Subjects
- *
CATALYSIS synthesis , *BENZALDEHYDE , *ETHYNYL benzene , *PIPERIDINE , *CATALYSTS - Abstract
Reversible switching between two states of the triangular nanoswitch [Cu( 1)]+ was accomplished by alternate addition of 2-ferrocenyl-1,10-phenanthroline ( 2) and copper(I) ions. The two switching states regulate the binding and release of two distinct catalysts, piperidine and [Cu( 2)]+, in a fully interference-free manner and allow alternating on/off switching of two orthogonal catalytic processes. In switching state I, piperidine is released from the nanoswitch and catalyzes a Knoevenagel addition between 4-nitrobenzaldehyde and diethyl malonate (ON-1 and OFF-2), while in state II the released [Cu( 2)]+ catalyzes a click reaction between 4-nitrophenylacetylene and benzylazide (OFF-1 and ON-2). Upon addition of one equivalent of 2 to the (OFF-1 and ON-2)-state, both catalytically active processes are shut down (OFF-1 and OFF-2). [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
27. Enantioselective Synthesis of Piperidines through the Formation of Chiral Mixed Phosphoric Acid Acetals: Experimental and Theoretical Studies.
- Author
-
Sun, Zhankui, Winschel, Grace A., Zimmerman, Paul M., and Nagorny, Pavel
- Subjects
- *
PIPERIDINE , *ALIPHATIC amine synthesis , *ENANTIOSELECTIVE catalysis , *ACETAL resins , *PHOSPHORIC acid , *RING formation (Chemistry) , *ENOL ethers , *STEREOSELECTIVE reactions , *SULFUR compounds - Abstract
An enantioselective intramolecular chiral phosphoric acid-catalyzed cyclization of unsaturated acetals has been utilized for the synthesis of functionalized chiral piperidines. The chiral enol ether products of these cyclizations undergo subsequent in situ enantioenrichment through acetalization of the minor enantiomer. A new computational reaction exploration method was utilized to elucidate the mechanism and stereoselectivity of this transformation. Rather than confirming the originally postulated cyclization proceeding directly through a vinyl oxocarbenium ion, simulations identified an alternative two-step mechanism involving the formation of a mixed chiral phosphate acetal, which undergoes a concerted, asynchronous SN2′-like displacement to yield the product with stereoselectivity in agreement with experimental observations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
28. A Multifaceted Secondary Structure Mimic Based On Piperidine-piperidinones.
- Author
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Xin, Dongyue, Perez, Lisa M., Ioerger, Thomas R., and Burgess, Kevin
- Subjects
- *
PIPERIDINE , *PROTEIN-protein interactions , *HETEROCYCLIC compounds , *IMINO acids , *ADAPTOR proteins - Abstract
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld- 1 faf crystallized in a conformation that is estimated to be 0.91 kcal mol−1 above the minimum energy solution state. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
29. Total Synthesis of the Monoterpenoid Indole Alkaloid (±)-Aspidophylline A.
- Author
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Teng, Mingxing, Zi, Weiwei, and Ma, Dawei
- Subjects
- *
MONOTERPENOIDS , *NATURAL products , *PIPERIDINE , *HETEROCYCLIC compounds , *RING formation (Chemistry) ,INDOLE alkaloid synthesis - Abstract
Aspidophylline A belongs to the akuammiline alkaloid family, the members of which possess intriguing cagelike structures and diverse biological activities. Herein we report a 15-step synthesis of this alkaloid from conveniently available starting materials. The key elements of the synthesis include an intramolecular oxidative coupling to create the tetracyclic furoindoline motif of the natural product and a [Ni(cod)2]-mediated cyclization to install its piperidine ring. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
30. Gold(I)-Catalyzed Diastereoselective Hydroacylation of Terminal Alkynes with Glyoxals.
- Author
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Shi, Shuai, Wang, Tao, Weingand, Vanessa, Rudolph, Matthias, and Hashmi, A. Stephen K.
- Subjects
- *
ALKYNES , *GLYOXAL , *PIPERIDINE , *ENAMINES , *HYDROLYSIS , *ISOMERIZATION - Abstract
The reaction of an α-ketoaldehyde and a terminal alkyne in the presence of piperidine and a catalytic amount of AuCl delivers 1,2-dicarbonyl-3-enes, products of the formal hydroacylation of the triple bond. The scope of the method is broad; different aryl substituents on the dicarbonyl unit and on the alkyne are well tolerated. The products can be transformed selectively into vinylquinoxalines. Mechanistic studies, including isotope-labeling experiments, indicate that after an initial A3-type conversion to propargylic amines, a subsequent base-mediated alkyne-to-allene isomerization and a hydrolysis of the enamine substructure during the workup deliver the formal hydroacylation products. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
31. Nickel-Catalyzed Enantioselective Arylation of Pyridinium Ions: Harnessing an Iminium Ion Activation Mode.
- Author
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Chau, Stephen T., Lutz, J. Patrick, Wu, Kevin, and Doyle, Abigail G.
- Subjects
- *
BORONIC acids , *CARBON , *OXYGEN , *ENANTIOSELECTIVE catalysis , *PYRIDONE , *NUCLEOPHILES , *REACTIVITY (Chemistry) , *PIPERIDINE - Abstract
A nickel for your thoughts …︁ An enantioselective nickel‐catalyzed cross‐coupling between N‐acylpyridinium salts and organozinc reagents is reported. The catalytic system, which is comprised of an air‐stable NiII source and a chiral phosphoramidite ligand, affords 2‐substituted‐2,3‐dihydro‐4‐pyridones with up to >99 % ee. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
32. General Entry to Aspidosperma Alkaloids: Enantioselective Total Synthesis of (−)-Aspidophytine.
- Author
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Yang, Rongwen and Qiu, Fayang G.
- Subjects
- *
ENANTIOSELECTIVE catalysis , *ASPIDOSPERMA , *PIPERIDINE , *PYRROLIDINE , *CYCLOHEXANE - Abstract
A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a CH bond activation with a Heck‐type coupling, and the stereo‐controlled formation of piperidine and pyrrolidine rings as key steps. The feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4‐disubstituted cyclohexanedione and 2,3‐dimethoxyaniline (see scheme). [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
33. Highly Enantioselective Catalytic [6+3] Cycloadditions of Azomethine Ylides.
- Author
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Potowski, Marco, Bauer, Jonathan O., Strohmann, Carsten, Antonchick, Andrey P., and Waldmann, Herbert
- Published
- 2012
- Full Text
- View/download PDF
34. Oxygenase-Catalyzed Desymmetrization of N, N-Dialkyl-piperidine-4-carboxylic Acids.
- Author
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Rydzik, Anna M., Leung, Ivanhoe K. H., Kochan, Grazyna T., McDonough, Michael A., Claridge, Timothy D. W., and Schofield, Christopher J.
- Subjects
- *
ALIPHATIC amines , *PIPERIDINE , *ACIDOLYSIS , *CARBOXYLIC acids , *NEUTRALIZATION (Chemistry) , *OXYGENASES - Abstract
γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate dependent oxygenase that catalyzes the final hydroxylation step in the biosynthesis of carnitine. BBOX was shown to catalyze the oxidative desymmetrization of achiral N, N-dialkyl piperidine-4-carboxylates to give products with two or three stereogenic centers. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
35. Frontispiece: Intramolecular Metalloamination of N, N-Dimethylhydrazinoalkenes: A Versatile Method to Access Functionalized Piperidines and Pyrrolidines.
- Author
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Sunsdahl, Bryce, Smith, Adrian R., and Livinghouse, Tom
- Subjects
- *
PIPERIDINE , *PYRROLIDINE , *MOLECULAR structure - Abstract
Heterocycle Synthesis In their Communication on page 14352 ff., T. Livinghouse et al. describe the direct metalloamination/cyclization of hydrazinoalkenes by Et2Zn. Electrophilic capture of the chelated organozinc intermediates drives the subsequent cascade. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
36. Corrigendum: Highly Enantioselective Catalytic [6+3] Cycloadditions of Azomethine Ylides.
- Author
-
Potowski, Marco, Bauer, Jonathan O., Strohmann, Carsten, Antonchick, Andrey P., and Waldmann, Herbert
- Subjects
- *
ENANTIOSELECTIVE catalysis , *RING formation (Chemistry) , *SCHIFF bases - Abstract
A correction is presented to the article "Highly Enantioselective Catalytic [6+3] Cycloadditions of Azomethine Ylides" by M. Potowski, J. O. Bauer, C. Strohmann and others, published in volume 51, 2012.
- Published
- 2013
- Full Text
- View/download PDF
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