Name: preparation of contiguous bisaziridines for regioselective ring-opening reactions
Uploaded: 2022-07-28T14:30:00
Description: Watch this Scientific Journal Video about Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions at JoVE.com

This research was supported by the Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (2022R1A6C101A751). This work was also supported by the National Research Foundation of Korea (NRF) grants (2020R1A2C1007102 and 2021R1A5A6002803).

The details of all the synthesized products (1-5), including the structure, full NMR spectra, optical purity, and HRMS-MALDI data, are provided in Supplementary File 1.
1. Synthesis of 3-(aziridin-2-yl)acryl aldehyde (1a)
<ol>
	<li>Flame dry a 50 mL round-bottomed flask equipped with a stirrer bar and a septum under vacuum conditions. Cool it to room temperature while filling it with argon gas.</li>
	<li>Add anhydrous toluene (19 mL) and (<e...

The formation of an inseparable mixture of diastereomers has occasionally been observed during the course of organocatalytic aziridination of chiral 3-[1-(1-phenylethyl)aziridin-2-yl)]acrylaldehyde, when N-Boc-O-tosyl or N-Ts-O-tosyl hydroxylamine was used as the nitrogen source. Further, the yield of contiguous bisaziridine product decreased when the amount of diaryl silyl ether prolinol as catalyst was increased from 7 mol% to 20 mol%47,<sup class="...

Rational design of small organic molecules with diverse reactive sites that precisely control product selectivity is a key goal in modern organic synthesis and green chemistry1,2,3,4,5,6,7,8. To achieve this goal, we were interested in the modular synthesis of aziridines. Aziridines are of interest to most organic chemists, owing to their structurally important framework9 with an electronically diverse set of N-substituents that can lead to regioselective ring-opening reactions with multiple nucleophiles10,11,12,13,14,15,16,17,18,19, and varied pharmacological activities such as antitumor, antimicrobial, and antibacterial properties. Despite the advances in aziridine chemistry, non-activated aziridine and activated aziridine have independent syntheses and ring-opening reactions in the literature20.
Therefore, we aimed to synthesize contiguous bisaziridines comprising both the non-activated and activated aziridines. These contiguous bisaziridines can be used to systematically rationalize a chemoselective ring-opening pattern based on the following electronic properties of the two different aziridines and their reactivity to nucleophiles20,21,22,23,24: a) activated aziridines, in which the electron-withdrawing substituents conjugatively stabilize the negative charge on the nitrogen, readily react with multiple nucleophiles to allow ring-opened products; b) non-activated aziridines, in which the nitrogen is bound to the electron-donating substituents, are considerably inert toward nucleophiles; hence, a pre-activation step with a suitable activator (mainly Br&#248;nsted or Lewis acids) is required to afford the ring-opened products in high yields20,21,25,26.
The present study describes the rational design of contiguous bisaziridines as chiral building blocks via transition-metal-free organocatalysis and the synthesis of diverse nitrogen-rich molecules utilizing predictive modeling tools for ring-opening reactions of bisaziridines. This study aims to stimulate the advancement of practical methods for the construction of nitrogen-enriched bioactive compounds and natural products and the polymerization of aziridines.

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	<tbody>
		<tr>
			<td>(R)-(+)-&#945;,&#945;-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether</td>
			<td>Sigma-Aldrich</td>
			<td>677191</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>(R)-1-((R)-1-phenylethyl)aziridine-2-carbaldehyde</td>
			<td>Imagene Co.,Ltd.</td>
			<td></td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>(S)-(&#8211;)-&#945;,&#945;-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether</td>
			<td>Sigma-Aldrich</td>
			<td>677183</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>(S)-2-(diphenyl((trim ethylsilyl)oxy)methyl)pyrrolidine</td>
			<td>Sigma-Aldrich</td>
			<td>677183</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>(Triphenylphosphoranylidene) acetaldehyde</td>
			<td>Sigma-Aldrich</td>
			<td>280933</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>1,2-Dichloroethane</td>
			<td>Sigma-Aldrich</td>
			<td>284505</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>AB Sciex 4800 Plus MALDI TOFTM (2,5-dihydroxybenzoic acid (DHB) matrix</td>
			<td>Sciex</td>
			<td></td>
			<td>High resolution mass spectra</td>
		</tr>
		<tr>
			<td>Acetic acid</td>
			<td>Sigma-Aldrich</td>
			<td>A6283</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Ammonium chloride</td>
			<td>Sigma-Aldrich</td>
			<td>254134</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>aniline</td>
			<td>Sigma-Aldrich</td>
			<td>132934</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Autopol III digital polarimeter</td>
			<td>Rudolph Research Analytical</td>
			<td></td>
			<td>polarimeter</td>
		</tr>
		<tr>
			<td>AVANCE III HD (400 MHz) spectrometer</td>
			<td>Bruker</td>
			<td></td>
			<td>NMR spectrometer</td>
		</tr>
		<tr>
			<td>Bruker Ascend 500 (500 MHz)</td>
			<td>Bruker</td>
			<td></td>
			<td>NMR spectrometer</td>
		</tr>
		<tr>
			<td>Celite 535</td>
			<td>Sigma-Aldrich</td>
			<td>22138</td>
			<td>For Celite pad</td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>Sigma-Aldrich</td>
			<td>270997</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>Di-tert-butyl dicarbonate</td>
			<td>Sigma-Aldrich</td>
			<td>361941</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Ethyl Acetate</td>
			<td>Sigma-Aldrich</td>
			<td>270989</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>Ethyl nitroacetate</td>
			<td>Sigma-Aldrich</td>
			<td>192333</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Imidazole</td>
			<td>Sigma-Aldrich</td>
			<td>I2399</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>INOVA 400WB (400 MHz)</td>
			<td>Varian</td>
			<td></td>
			<td>NMR spectrometer</td>
		</tr>
		<tr>
			<td>JMS-700</td>
			<td>JEOL</td>
			<td></td>
			<td>High resolution mass spectra</td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Sigma-Aldrich</td>
			<td>322415</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>N-Boc-O-tosylhydroxylamine</td>
			<td>Sigma-Aldrich</td>
			<td>775037</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>P-2000</td>
			<td>JASCO</td>
			<td></td>
			<td>polarimeter</td>
		</tr>
		<tr>
			<td>Palladium hydroxide on carbon</td>
			<td>Sigma-Aldrich</td>
			<td>212911</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Phenyl-1H-tetrazole-5-thiol</td>
			<td>TCI</td>
			<td>P0640</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Silica gel</td>
			<td>Sigma-Aldrich</td>
			<td>227196</td>
			<td>For flash clromatography</td>
		</tr>
		<tr>
			<td>Silica gel on TLC plates</td>
			<td>Merck</td>
			<td>60768</td>
			<td>TLC plate</td>
		</tr>
		<tr>
			<td>Sodium acetate</td>
			<td>Sigma-Aldrich</td>
			<td>S8750</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Sodium azide</td>
			<td>Sigma-Aldrich</td>
			<td>S2002</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Sodium borohydride</td>
			<td>Sigma-Aldrich</td>
			<td>452882</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Sodium carbonate</td>
			<td>Sigma-Aldrich</td>
			<td>S2127</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>tert-Butyldimethylsilyl chloride</td>
			<td>Sigma-Aldrich</td>
			<td>190500</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Tetrahydrofuran</td>
			<td>Sigma-Aldrich</td>
			<td>401757</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>Toluene</td>
			<td>Sigma-Aldrich</td>
			<td>244511</td>
			<td>solvent</td>
		</tr>
		<tr>
			<td>Zinc bromide</td>
			<td>Sigma-Aldrich</td>
			<td>230022</td>
			<td>reagent</td>
		</tr>
		<tr>
			<td>Zinc chloride</td>
			<td>Sigma-Aldrich</td>
			<td>429430</td>
			<td>reagent</td>
		</tr>
	</tbody>
</table>

preparation of contiguous bisaziridines for regioselective ring-opening reactions

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of functionalized nitrogen-containing target compounds through the regiocontrolled ring-opening of C-substituted aziridines. Despite the tremendous progress in aziridine synthesis over the past decade, accessing contiguous bisaziridines efficiently remains difficult. Therefore, we were interested in synthesizing contiguous bisaziridines bearing an electronically diverse set of N-substituents beyond the single aziridine backbone for regioselective ring-opening reactions with diverse nucleophiles. In this study, chiral contiguous bisaziridines were prepared by organocatalytic asymmetric aziridination of chiral (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde with N-Ts-O-tosyl or N-Boc-O-tosyl hydroxylamine as the nitrogen source in the presence of (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as a chiral organocatalyst. Also demonstrated here are representative examples of regioselective ring-opening reactions of contiguous bisaziridines with a variety of nucleophiles such as sulfur, nitrogen, carbon, and oxygen, and the application of contiguous bisaziridines to the synthesis of multi-substituted chiral pyrrolidines by Pd-catalyzed hydrogenation.

To investigate the achievability of preparing a contiguous bisaziridine, (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde (1a) was first synthesized as a model substrate according to the procedure mentioned in step 1 (Figure 1)28.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/64019/64019fig01.jpg" /> 
Figu...

Watch this Scientific Journal Video about Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions at JoVE.com

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Contiguous bisaziridines containing non-activated and activated aziridines were synthesized by asymmetric organocatalytic aziridinations and then subjected to chemoselective ring-opening reactions under acidic or basic conditions. The non-activated aziridine ring opens with less reactive nucleophiles under acidic conditions, whereas the activated aziridine ring opens with more reactive nucleophiles under basic conditions.

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of ...

The significance of our protocol is rational design of contiguous bisaziridine containing both activated and non-activated aziridines, and subject it to regioselective ring-opening reactions with diverse nucleophiles. The advantage of this technique is that it allows the synthesis of nitrogen-rich molecules using predictive modeling tools for selective ring openings. The current protocol can be used to develop practical methods for the synthesis of nitrogen-enriched bioactive compounds and natural products.To begin, flame dry a 50-milliliter round-bottomed flask with a stirrer bar and a septum under vacuum conditions. After cooling it to room temperature, fill it with argon gas. Then add anhydrous methanol and aldehyde to the flask, and stir the solution for a minute.Next, add sodium borohydride to the stirred solution, and stir the reaction mixture at zero degrees Celsius for one hour. Monitor the reaction progress by TLC, using ethyl acetate and hexanes as an eluent. After one hour, quench the reaction mixture with distilled water, and extract with ethyl acetate in a separatory funnel.Dry the combined organic layer over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify the crude residue by silica gel flash chromatography with ethyl acetate and hexanes as the eluent, to isolate pure products as a yellow liquid. Afterward, confirm the product by NMR and polarimeter measurements.First, flame-dry a five-milliliter round-bottomed flask with a stirrer bar and a septum under vacuum conditions. Then cool it to room temperature while filling it with argon gas. Next, add the previously synthesized bisaziridine and acetic acid to the flask.Stir the mixture at room temperature for five hours, and monitor the reaction progress by TLC, using ethyl acetate and hexanes as an eluent. After five hours, remove the acetic acid in vacuo, and purify the crude residue by silica gel flash chromatography with ethyl acetate and hexanes as the eluent, to isolate the pure product as a yellow liquid. Confirm the product by NMR and polarimeter measurements.The proton NMR spectrum revealed a peak at 1.42 ppm, corresponding to the alcohol hydrogen in the ethyl alcohol adjacent to the aziridine, indicating the reduction of an aldehyde into ethyl alcohol. Moreover, the peaks at 4.00 and 3.54 ppm represent the methylene hydrogens in ethyl alcohol. The peak observed at 2.13 ppm corresponds to the methyl hydrogens of acetate, whereas peaks at 4.43 and 4.15 ppm correspond to the methylene hydrogens adjacent to acetate formed after the aziridine ring-opening reaction.Reduction involving NaBH4 have found to be exothermic, and thus, maintain the reaction temperature at zero degrees Celsius. Also, care is required during the quenching of NaBH4 by H2O. We believe that this technique will stimulate further research toward the development of practical methods for the construction of nitrogen-enriched complex molecules having biological activities.

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Chemistry

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable.
The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts.
The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Microwave-assisted intramolecular dehydrogenative Diels-Alder (DA) reactions provide concise access to functionalized cyclopenta[b]naphthalene building blocks. The utility of this methodology is demonstrated by one-step conversion of the dehydrogenative DA cycloadducts into novel solvatochromic fluorescent dyes via Buchwald-Hartwig palladium-catalyzed cross-coupling reactions.

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to ...

Retropinacol/Cross-pinacol Coupling Reactions - A Catalytic Access to 1,2-Unsymmetrical Diols

Unsymmetrical 1,2-diols are hardly accessible by reductive pinacol coupling processes. A successful execution of such a transformation is bound to a clear recognition and strict differentiation of two similar carbonyl compounds (aldehydes &#8594; secondary 1,2-diols or ketones &#8594; tertiary 1,2-diols). This fine-tuning is still a challenge and an unsolved problem for an organic chemist. There exist several reports on successful execution of this transformation but they cannot be generalized. Herein we describe a catalytic direct pinacol coupling process which proceeds via a retropinacol/cross-pinacol coupling sequence. Thus, unsymmetrical substituted 1,2-diols can be accessed with almost quantitative yields by means of an&#160;operationally simple performance under very mild conditions. Artificial techniques, such as syringe-pump techniques or delayed additions of reactants are not necessary. The procedure we describe provides a very rapid access to cross-pinacol products (1,2-diols, vicinal diols). A further extension of this new process, e.g. an enantioselective performance could provide a very useful tool for the synthesis of unsymmetrical chiral 1,2-diols.

A novel account for the synthesis of unsymmetrical 1,2-diols based on a retropinacol/cross-pinacol coupling mechanism is described. Due to the catalytic execution of this reaction a considerable improvement compared to conventional cross-pinacol couplings is achieved.

Unsymmetrical 1,2-diols are hardly accessible by reductive pinacol coupling processes. A successful execution of such a transformation is bound to a clear ...

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible to ensure consistent product quality over time using this technique. We here show how to interface a commercially available flow unit with a Raman spectrometer. The Raman flow cell is placed after the back-pressure regulator, meaning that it can be operated at atmospheric pressure. In addition, the fact that the product stream passes through a length of tubing before entering the flow cell means that the material is at RT. It is important that the spectra are acquired under isothermal conditions since Raman signal intensity is temperature dependent. Having assembled the apparatus, we then show how to monitor a chemical reaction, the piperidine-catalyzed synthesis of 3-acetylcoumarin from salicylaldehyde and ethyl acetoacetate being used as an example. The reaction can be performed over a range of flow rates and temperatures, the in-situ monitoring tool being used to optimize conditions simply and easily.

Real-time monitoring allows for fast optimization of reactions performed using continuous-flow processing. Here the preparation of 3-acetylcoumarin is used as an example. The apparatus for performing in-situ Raman monitoring is described, as are the steps required to optimize the reaction.

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible ...

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.

The safe and proper use of organolithium reagents is described.

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes

Here, we describe an effective protocol that combines photoredox Ni/Ir catalysis with the use of a Zn-alkoxide for efficient ring-opening polymerization, allowing for the synthesis of isotactic poly(&#945;-hydroxy acids) with expected molecular weights (&#62;140 kDa) and narrow molecular weight distributions (Mw/Mn &#60; 1.1). This ring-opening polymerization is mediated by Ni and Zn complexes in the presence of an alcohol initiator and a photoredox Ir catalyst, irradiated by a blue LED (400 - 500 nm). The polymerization is performed at a low temperature (-15 &#176;C) to avoid undesired side reactions. The complete monomer consumption can be achieved within 4 - 8 hours, providing a polymer close to the expected molecular weight with narrow molecular weight distribution. The resulted number-average molecular weight shows a linear correlation with the degree of polymerization up to 1000. The homodecoupling 1H NMR study confirms that the obtained polymer is isotactic without epimerization. This polymerization reported herein offers a strategy for achieving rapid, controlled O-carboxyanhydrides polymerization to prepare stereoregular poly(&#945;-hydroxy acids) and its copolymers bearing various functional side-chain groups.

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes

A protocol for the controlled photoredox ring-opening polymerization of O-carboxyanhydrides mediated by Ni/Zn complexes is presented.

Here, we describe an effective protocol that combines photoredox Ni/Ir catalysis with the use of a Zn-alkoxide for efficient ring-opening polymerization, ...

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. Their synthesis by conventional organic chemistry often requires tedious multi-step synthesis processes, with difficult control of the stereochemical outcome. We present a protocol to enzymatically synthetize amino alcohols starting from the readily available L-lysine in 48 h. This protocol combines two chemical reactions that are very difficult to conduct by conventional organic synthesis. In the first step, the regio- and diastereoselective oxidation of an unactivated C-H bond of the lysine side-chain is catalyzed by a dioxygenase; a second regio- and diastereoselective oxidation catalyzed by a regiodivergent dioxygenase can lead to the formation of the 1,2-diols. In the last step, the carboxylic group of the alpha amino acid is cleaved by a pyridoxal-phosphate (PLP) decarboxylase (DC). This decarboxylative step only affects the alpha carbon of the amino acid, retaining the hydroxy-substituted stereogenic center in a beta/gamma position. The resulting amino alcohols are therefore optically enriched. The protocol was successfully applied to the semipreparative-scale synthesis of four amino alcohols. Monitoring of the reactions was conducted by high performance liquid chromatography (HPLC) after derivatization by 1-fluoro-2,4-dinitrobenzene. Straightforward purification by solid-phase extraction (SPE) afforded the amino alcohols with excellent yields (93% to &#62;95%).

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. ...

Preparation and Characterization of C60/Graphene Hybrid Nanostructures

Physical thermal deposition in a high vacuum environment is a clean and controllable method for fabricating novel molecular nanostructures on graphene. We present methods for depositing and passively manipulating C60 molecules on rippled graphene that advance the pursuit of realizing applications involving 1D C60/graphene hybrid structures. The techniques applied in this exposition are geared towards high vacuum systems with preparation areas capable of supporting molecular deposition as well as thermal annealing of the samples. We focus on C60 deposition at low pressure using a homemade Knudsen cell connected to a scanning tunneling microscopy (STM) system. The number of molecules deposited is regulated by controlling the temperature of the Knudsen cell and the deposition time. One-dimensional (1D) C60 chain structures with widths of two to three molecules can be prepared via tuning of the experimental conditions. The surface mobility of the C60 molecules increases with annealing temperature allowing them to move within the periodic potential of the rippled graphene. Using this mechanism, it is possible to control the transition of 1D C60 chain structures to a hexagonal close packed quasi-1D stripe structure.

Preparation and Characterization of C60/Graphene Hybrid Nanostructures

Here we present a protocol for the fabrication of C60/graphene hybrid nanostructures by physical thermal evaporation. Particularly, the proper manipulation of deposition and annealing conditions allow the control over the creation of 1D and quasi 1D C60 structures on rippled graphene.

Physical thermal deposition in a high vacuum environment is a clean and controllable method for fabricating novel molecular nanostructures on graphene. We ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having multifarious bioactivities. Although chemical O-glycosylation is a commonly beneficial strategy to synthesize disaccharide nucleosides, the preparation of substrates such as glycosyl donors and acceptors requires&#160;tedious protecting&#160;group manipulations and a purification at each synthetic step. Meanwhile, several research groups have reported that boronic and borinic esters serve as a protecting or activating group of carbohydrate derivatives to achieve the regio- and/or stereoselective acylation, alkylation, silylation, and glycosylation. In this article, we demonstrate the procedure for the regioselective O-glycosylation of unprotected ribonucleosides utilizing boronic acid. The esterification of 2&#39;,3&#39;-diol of ribonucleosides with boronic acid makes the temporary protection of diol, and, following O-glycosylation with a glycosyl donor in the presence of p-toluenesulfenyl chloride and silver triflate, permits the regioselective reaction of the 5&#39;-hydroxyl group to afford the disaccharide nucleosides. This method could be applied to various nucleosides, such as guanosine, adenosine, cytidine, uridine, 5-metyluridine, and 5-fluorouridine. This article and the accompanying video represent&#160;useful (visual) information for the O-glycosylation of unprotected nucleosides and their analogs for the synthesis of not only disaccharide nucleosides, but also a variety of biologically relevant derivatives.

Regioselective O-Glycosylation of Nucleosides via the Temporary 2&#039;,3&#039;-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

Here, we present protocols for the synthesis of disaccharide nucleosides by the regioselective O-glycosylation of ribonucleosides via a temporary protection of their 2&#39;,3&#39;-diol moieties utilizing a cyclic boronic ester. This method applies to several unprotected nucleosides such as adenosine, guanosine, cytidine, uridine, 5-methyluridine, and 5-fluorouridine to give corresponding disaccharide nucleosides.

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having ...

Photogeneration of N-Heterocyclic Carbenes: Application in Photoinduced Ring-Opening Metathesis Polymerization

We report a method to generate the N-heterocyclic carbene (NHC) 1,3-dimesitylimidazol-2-ylidene (IMes) under UV-irradiation at 365 nm to characterize IMes and determine the corresponding photochemical mechanism. Then, we describe a protocol to perform ring-opening metathesis polymerization (ROMP) in solution and in miniemulsion using this NHC-photogenerating system. To photogenerate IMes, a system comprising 2-isopropylthioxanthone (ITX) as the sensitizer and 1,3-dimesitylimidazolium tetraphenylborate (IMesH+BPh4-) as the protected form of NHC is employed. IMesH+BPh4- can be obtained in a single step by anion exchange between 1,3-dimesitylimidazolium chloride and sodium tetraphenylborate. A real-time steady-state photolysis setup is described, which hints that the photochemical reaction proceeds in two consecutive steps: 1) ITX triplet is photo-reduced by the borate anion and 2) subsequent proton transfer takes place from the imidazolium cation to produce the expected NHC IMes. Two separate characterization protocols are implemented. Firstly, CS2 is added to the reaction media to evidence the photogeneration of NHC through formation of the IMes-CS2 adduct. Secondly, the amount of NHC released in situ is quantified using acid-base titration. The use of this NHC photo-generating system for the ROMP of norbornene is also discussed. In solution, a photopolymerization experiment is conducted by mixing ITX, IMesH+BPh4-, [RuCl2(p-cymene)]2 and norbornene in CH2Cl2, then irradiating the solution in a UV reactor. In a dispersed medium, a monomer miniemulsion is first formed then irradiated inside an annular reactor to produce a stable poly(norbornene) latex.

We describe a protocol to photogenerate N-heterocyclic carbenes (NHCs) by UV irradiation of a 2-isopropylthioxanthone/imidazolium tetraphenylborate salt system. Methods to characterize the photoreleased NHC and elucidate the photochemical mechanism are proposed. The protocols for ring-opening metathesis photopolymerization in solution and miniemulsion illustrate the potential of this 2-component NHC photogenerating system.

We report a method to generate the N-heterocyclic carbene (NHC) 1,3-dimesitylimidazol-2-ylidene (IMes) under UV-irradiation at 365 nm to characterize IMes ...