A new approach to functionalized spiropiperidines through tandem RCM and nitrogen-directed reactions

The synthesis of a functionalized spiropiperidine via a tandem ring closing metathesis strategy is described, furthermore, the regio- and stereoselective functionalization of this compound has been achieved through a novel nitrogen-directed epoxidation reaction.     

Formal synthesis of (±)-perhydrohistrionicotoxin via a stepwise [3+3] annelation strategy

A formal synthesis of (±)-perhydrohistrionicotoxin is described that includes a highly diastereoselective modified Sharpless aziridination and a stepwise [3+3] annelation reaction for the stereoselective construction of the key spiropiperidine motif.     

Novel route to spiropiperidines using N-methyl-4-piperidone,malononitrile and electrophiles

A new pathway to spiropiperidine rings via sequential one pot reaction of N-methyl-4-piperidone, malononitrile, and electrophiles or Michael acceptor in the presence of triethyl amine in ethanol under reflux condition is reported.     

Flow synthesis of tricyclic spiropiperidines as building blocks for the histrionicotoxin family of alkaloids

A domino cyclization reaction of the bis-unsaturated ketone 3 with hydroxylamine proceeds with good yield and high stereoselectivity, in a flow reactor system. The tricyclic spiropiperidine products 5 and 2 obtained are valuable building blocks for the synthesis of analogues of the histrionicotoxin alkaloids.     

Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold

The synthesis of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold has been achieved in five steps with an overall yield of 47%. The versatility of the spiropiperidine scaffold in the context of library synthesis is exemplified by selective and sequential derivatisation of the amino and aryl bromide functional groups, including the development of multi-step telescope reaction matrices.     

N-Boc 4-nitropiperidine: preparation and conversion into a spiropiperidine analogue of the eastern part of maraviroc

Previously unreported N-Boc 4-nitropiperidine was prepared in two steps from N-Boc-piperidone. The synthetic utility of this new intermediate was demonstrated by the development of a new and simple route to spirolactam piperidines. Further synthetic work involving a challenging triazole cyclisation allowed the preparation of a spiropiperidine analogue of the eastern part of maraviroc.     

Diasteroselective synthesis of new spiropiperidine scaffolds from the CN(R,S) building block

A methodology allowing the construction of spiropiperidine scaffolds similar to those found in naturally occurring alkaloids has been developed. This approach begins with the well-established CN(R,S) strategy, the spiro-center being built by way of an intramolecular attack of a nitrile function by an organolithium species obtained by a halogen/lithium exchange reaction mediated by either t-BuLi or lithium naphthalenide.     

Intramolecular N to N acyl migration in conformationally mobile 1′-acyl-1-benzyl-3′,4′-dihydro-1′<Emphasis Type="Italic">H</Emphasis>-spiro[piperidine-4,2′-quinoline] systems promoted by debenzylation conditions (HCOONH<Subscript>4</Subscript>/Pd/C)

We report an efficient and useful synthesis of new attractive spiropiperdine scaffolds 4 based on an intramolecular acyl transfer process in 1′-acyl-1-benzyl-3′,4′-dihydro-1′H-spiro[piperidine-4,2′-quinolines] 3 using simple and mild debenzylation reaction conditions (HCOONH₄/Pd/C). The compounds 3 were prepared by acylating 1-benzyl-4′-methyl-3′,4′-dihydro-1′H-spiro[piperidine-4,2′-quinolines] 2 that are easily available from 1-benzyl-4-piperidone 1. The intramolecular character of this process was proven primarily through a crossover experiment technique. Through an examination of all spectroscopic information (¹H, ¹³C NMR, VT-¹H NMR, and ²D NMR) it was possible to correctly predict amide configurations and piperidine ring conformations of starting and final spiropiperidine compounds.      

Diastereoselective preparation of 2,4,6-trisubstituted-2'-cyanopiperidines: application to the construction of the carbon framework of perhydrohistrionicotoxin

The anodic cyanation of methanolic solutions of the 2-alkyl-N-phenylpiperidines 6b-d was performed in a flow cell equipped with a graphite felt anode. The reaction led to the formation of the 2-cyano-6-alkyl-N-phenylpiperidines 2b-d and proceeded with a high degree of regioselectivity. The 1H NMR spectra of the aminonitriles 2b-d showed an epimeric mixture at C-6. The major isomer has a trans configuration in which the cyano group is axial and the alkyl substituent is equatorial. Conversely, electrochemical oxidation of the 4-methyl-6-pentyl-N-phenylpiperidine 6e afforded the trisubstituted aminonitrile 2e as a single diastereomer (> 98% de). The 4-cyanobutyl side chain was incorporated in a two-step procedure to yield dinitrile 4e. This latter compound was directly converted into spiropiperidine 5e by using the Thorpe-Ziegler annulation procedure. The overall sequence (4 steps, 43%) allows the construction of the basic carbon framework of perhydrohistrionicotoxin.     

The spiropiperidine-3,3′-oxindole scaffold: a type II β-turn peptide isostere

An unprecedented chiral spiropiperidine oxindole system was synthesized starting from enantiopure quaternary 3-aminooxindole and relying on a ring closing metathesis as the key step. This compound acts as an highly constrained Freidinger γ-lactam, adopting a type II β-turn conformation in solution, as assessed by modelling and spectroscopical studies.     

Allenic and acetylenic spiropiperidine alkaloids from the neotropical frog, Dendrobates histrionicus

Four analogs of the acetylenic alkaloid, histrionicotoxin (C₁₉H₂₅NO) and the allenic alkaloid, isodihydrohistrionicotoxin have been isolated from extracts of skins of the arrow poison frog, Dendrobates histrionicus and characterized as neodihydrohistrionicotoxin, tetrahydrohistrionicotoxin, isotetrahydrohistrionicotoxin and octahydrohistrionicotoxin. These spiropiperidine (8-hydroxy-1-azaspiro[5.5]undecane) alkaloids differ only in the degree of unsaturation in the five carbon atoms (position 2) and four carbon atoms (position 7) side chains. A fifth compound, HTX-D, corresponds in empirical formula to a tetrahydrohistrionicotoxin with a 7-(cis-1-butenyl-3-ynyl) side chain, but the major mass spectral fragmentation with loss of C₂H₅O is not characteristic of the histrionicotoxins. Reduction of histrionicotoxin with hydrogen and Lindlar catalyst affords an isomeric dihydrohistrionicotoxin with the terminal acetylene of the five carbon atoms side chain reduced, tetrahydrohistrionicotoxin and hexahydrohistrionicotoxins, while reduction with hydrogen and palladium on charcoal affords dodecahydrohistrionicotoxin which is readily methylated to the tertiary amine by methyl iodide.     

Diphenylphosphorylated PEG (DPPPEG) as a new support for generation of nano-Pd(0) as catalyst for carbon–carbon bond formation via copper-free Sonogashira and homocoupling reactions of aryl halides in PEG

In this study, synthesis and application of diphenylphosphorylated PEG₂₀₀ (DPPPEG₂₀₀) are described. Herein, we report a very simple procedure for the preparation of DPPPEG₂₀₀ as a stable solid through the reaction of PEG₂₀₀ with ClPPh₂. This compound was used as a very suitable ligand for the in situ generation of nano-Pd(0) particles through its reaction with PdCl₂ as a pre-catalyst. Isolation of this catalyst is very simple through addition of diethyl ether to the reaction mixture and centrifugations. Full characterization of the nano-Pd(0)/DPPPEG200 was performed by XRD spectra, UV–Vis spectra, and also by TEM image. This nano-complex was used as an efficient catalyst for copper-free Sonogashira and homocoupling reactions of aryl halides. The sonogashira reaction of aryl halides was conducted at 80 °C in PEG. However, the homocoupling reaction was performed at 100 °C for aryl iodides and activated aryl bromides and at 130 °C for deactivated aryl bromides and aryl chlorides in PEG. The catalyst was recovered and recycled for four consecutive runs.     

Characteristics of the Decomposition of CO2 in a Dielectric Packed-Bed Plasma Reactor

The decomposition of CO₂ in a dielectric packed-bed plasma reactor has been studied. It was found that the dielectric properties and morphology of packing dielectric pellets play important roles in the reaction due to their influence on the electron energy distribution in the plasma. The acid–base properties of the packing materials also affect the reaction through the chemisorption of CO₂ on basic sites of the materials. Heterogeneous reactions on the solid surfaces of the dielectric materials also play a role in the reaction, which was also confirmed through the investigation of the influence of the discharge length on the reaction. The reverse reaction of CO₂ decomposition, the oxidation of CO, was also investigated to further understand the role of dielectric materials in the plasma and their effect on plasma reactions. Both the decomposition of CO₂ and the oxidation of CO in non-packed or dielectric packed reactors are first-ordered.     

Al2O3与BN在氩气中合成AlN粉末

氮化铝是一种具有许多优异性能的被认为具有广泛应用前景的无机材料,普遍受到国内外材料学家和化学家的关注。目前制备ＡｌＮ粉末主要有氧化物还原氮化法,等离子化学法,熔炼法,裂解法和直接氮化法,但由Ａｌ２Ｏ３与ＢＮ直接合成单相ＡｌＮ粉末尚未见报道［１,２］。...     

Theoretical study of DABCO-based ionic liquid: synthesis and reaction mechanism

Quaternary ammonium salt obtained from the Menshutkin reaction between DABCO and benzyl chloride has been used in the synthesis of a novel Bronsted acidic ionic liquid (IL), namely 1-benzyl-4-(sulfobutyl)-diaza-bicyclo-octane hydrogen sulfate. The reaction of DABCO with benzyl chloride is a crucial step in the synthesis of this IL. Density functional theory calculations at B3LYP/6-31G(d,p) level have been employed to investigate the mechanism of Menshutkin reaction by calculating the energy barriers through possible transition states i.e., five-membered ring transition state and S_N2 transition state in gas phase and in diethyl ether as a solvent. It was found that while DABCO reacts with benzyl chloride through the well-known S_N2 transition state mechanism, the corresponding reaction with chlorodiphenylmethane can proceed through both S_N2 and five-membered ring transition state mechanism. However, S_N2 transition state mechanism is still the strongly preferred one out of the two possible mechanisms. The electronic structure analysis shows that solvent effects and enhanced resonance stabilization may play a decisive role in guiding the reaction pathway.     

The Effect of Vibrational Excitation of Molecules on Plasmachemical Reactions Involving Methane and Nitrogen

An experimental study of plasmachemical reaction involving CH₄ and N₂ molecules in rf discharge was studied in order to know the effect of vibrational excitation of N₂ molecules. When the relative nitrogen concentration was greater than 0.8, the main product of CH₄ decomposition was HCN, and the rate of methane decomposition at this condition was faster than that one in pure methane. These results could be confirmed through the mass spectroscopic method. The reason for these results is the vibrational energy of N₂ excited by rf discharge. The chain reaction mechanisms of producing HCN by vibrational excitation of N₂ were examined closely through numerical simulation. The rate-controlling step was the dissociation reaction of excited nitrogen molecule to the atomic nitrogen, so the process of HCN synthesis was limited by the value of reaction constant, k^N.     

A Light/Ketone/Copper System for Carboxylation of Allylic C−H Bonds of Alkenes with CO2

A photo‐induced carboxylation reaction of allylic C?H bonds of simple alkenes with CO₂ is prompted by means of a ketone and a copper complex. The unique carboxylation reaction proceeds through a sequence of an endergonic photoreaction of ketones with alkenes forming homoallyl alcohol intermediates and a thermal copper‐catalyzed allyl transfer reaction from the homoallyl alcohols to CO₂ through C?C bond cleavage.     

Stereoselective total synthesis of muconin

An antitumor acetogenin, muconin, was synthesized through a coupling reaction of a THF-THP segment and a terminal butenolide. The key reactions include successive ether-ring formation reaction under acidic and basic conditions or one-pot double cyclization promoted by TBAF and stereoselective reduction of acyclic ketones adjacent to the 2,6-cis THP with Zn(BH₄)₂.     

Imine hydrosilylation using an iron complex catalyst: A computational study

The reaction mechanism for imine hydrosilylation in the presence of an iron methyl complex and hydrosilane was studied using density functional theory at the M06/6-311G(d,p) level of theory. Benzylidenemethylamine (PhCH = NMe) and trimethylhydrosilane (HSiMe₃) were employed as the model imine and hydrosilane, respectively. Hydrosilylation has been experimentally proposed to occur in two stages. In the first stage, the active catalyst (CpFe(CO)SiMe₃, 1 ) is formed from the reaction of pre-catalyst, CpFe(CO)₂Me, and hydrosilane through CO migratory insertion into the Fe Me bond and the reaction of the resulting acetyl complex intermediate with hydrosilane. In the second stage, 1 catalyzes the reaction of imine with hydrosilane. Calculations for the first stage showed that the most favorable pathway for CO insertion involved a spin state change, that is, two-state reactivity mechanism through a triplet state intermediate, and the acetyl complex reaction with HSiMe₃ follows a σ-bond metathesis pathway. The calculations also showed that, in the catalytic cycle, the imine coordinates to 1 to form an Fe C N three-membered ring intermediate accompanied by silyl group migration. This intermediate then reacts with HSiMe₃ to yield the hydrosilylated product through a σ-bond metathesis and regenerate 1 . The rate-determining step in the catalytic cycle was the coordination of HSiMe₃ to the three-membered ring intermediate, with an activation energy of 23.1 kcal/mol. Imine hydrosilylation in the absence of an iron complex through a [2 + 2] cycloaddition mechanism requires much higher activation energies. © 2018 Wiley Periodicals, Inc.