This work was funded by the Spanish Ministerio de Econom&#236;a y Competitividad (CTQ 2013-41067-P). H.B. acknowledge with thanks a MEC-FPI grant.

1. Functionalization of 2,15-Dimethylhexahelicene
<ol>
	<li>Dibromination of 2,15-dimethylhexahelicene
	<ol>
		<li>Weigh 0.356 g (1.0 mmol) of 2,15-dimethylhexahelicene, 0.374 g (2.1 mmol) of freshly recrystallized N-bromosuccinimide (NBS) and 24 mg (0.07 mmol) of benzoyl peroxide (BPO) (70% wt with 30% of water as stabilizer). Place all solids in a 100 ml Schlenk flask with a magnetic stir bar. Put under nitrogen atmosphere by three cycles of gas evacuation followed by refilling with inert gas in the Schlenk line.</li>
		<li>Add 21 ml of carbon tetrachloride (CCl4). Degas the solution by the same evacuation/refilling process (step 1.1.1) with vigorous stirring and carefully in order to prevent massive loss of solvent.</li>
		<li>Heat at reflux (77 &#176;C) the mixture with an oil bath for 4 hours. Check the reaction by 1H-nuclear magnetic resonance (NMR). Doublets between 3.7 ppm and 4.0 ppm should appear. They indicate the presence of diastereotopic -CH2- groups (Figure 1).</li>
		<li>Once finished, cool the mixture to room temperature and remove the solvent under vacuum. Set up a trap filled with liquid nitrogen to avoid pump contamination.</li>
		<li>Redissolve the crude in 30 ml of dichloromethane (DCM), transfer to a round-bottom flask and mix with 4 g of silica gel (typically add 5-fold the crude weight). Concentrate the mixture in a rotary evaporator.</li>
		<li>In the meantime, fill a column (length around 20 cm and a thickness of 4.5 cm) with SiO2 gel mixed previously with hexane/ethyl acetate (95:5) as the mobile phase. Add the mixture to the top of the column and then add a layer of sand (2 cm).</li>
		<li>Carefully pour in the new mobile phase and perform the chromatography by collecting fractions in test tubes (typically 20 ml per tube and 4 ml near the expected product elution). Check fractions by thin layer chromatography (TLC) with the same mobile phase (hexane/ethyl acetate 95:5) and image under UV light. The expected product (4b) should elute at a Retention factor (Rf) of 0.35 as a yellow oil after combining all wanted fractions and removing off the solvent in the rotary evaporator. 334 mg should be obtained (yield 65%). 
		NOTE: All Schlenk techniques, the use of an oil bath for heating and column chromatography settings will be widely utilized in most of the protocols, so from now on, they will not be covered in detail and only a few comments, when necessary, will be given.</li>
	</ol>
	</li>
</ol>
<img alt="Figure 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> 
Figure 1. 1H-NMR spectra (500 MHz, CDCl3) of 2,15-dimethylhelicene (top) and an aliquot taken after 2 hr. New signals, corresponding to -CH2-, are depicted in a red circle (bottom). <a href="https://www.jove.com/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<ol start="2">
	<li>Synthesis of 2,15-bis(azidomethyl)hexahelicene
	<ol>
		<li>Weigh 0.103 g (0.2 mmol) of 2,15-bis(bromomethyl)hexahelicene and 0.390 g (6 mmol) of sodium azide. Place both solids in a 50 ml Schlenk flask equipped with magnetic bar and put under nitrogen atmosphere.</li>
		<li>Mix 8.6 ml of tetrahydrofuran (THF) with 5.2 ml of water (H2O) and pour the mixture of solvents into the Schlenk flask. Degas the solution.</li>
		<li>Heat at reflux (65 &#176;C) for 3 hr. Check the reaction by 1H-NMR. -CH2- signals should shift to 3.75 ppm (Figure 2).</li>
		<li>Afterwards, cool down the mixture to room temperature and remove THF under vacuum. Dilute with 50 ml of H2O.</li>
		<li>Transfer the mixture to a separatory funnel and extract three times with 40 ml of DCM. Combine all organic phases and wash with pure H2O (50 ml).</li>
		<li>Purify the crude by column chromatography on silica gel using hexane/ethyl acetate (85:15) as the mobile phase to give a yellow oil at Rf=0.38 corresponding to 2,15-bis(azomethyl)hexahelicene (5b). 70 mg should be obtained (yield 80%).</li>
	</ol>
	</li>
</ol>
<img alt="Figure 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> 
Figure 2: 1H-NMR spectra (500 MHz, CDCl3) of 4b (top) and an aliquot taken after 3 hr (bottom). Note the changes in the aliphatic region. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
2. Functionalization of Corannulene
<ol>
	<li>Monobromination of Corannulene
	<ol>
		<li>Weigh 0.125 g (0.5 mmol) of corannulene, 89 mg (0.5 mmol) of freshly recrystallized NBS and 17 mg of gold(III) chloride hydrate.</li>
		<li>Place all compounds into a 10 ml vial specially designed for microwave reactions equipped with a magnetic bar and then put into a nitrogen atmosphere with the help of a 2-necked round-bottom flask.</li>
		<li>Add 7 ml of 1,2-dichloroethane (DCE) and degas the solution.</li>
		<li>Sonicate the mixture for 2 min to disperse gold salt particles.</li>
		<li>Heat inside the microwave reactor at 100 &#176;C for 2 hr.</li>
		<li>When finished, transfer the crude to a round-bottom flask and remove solvent by rotary evaporation.</li>
		<li>Purify the crude by column chromatography on SiO2 gel using hexane as mobile phase. 
		NOTE: Bromocorannulene (4a) is obtained as a yellow solid at Rf=0.38. 99 mg should be obtained (yield 60%). Unreacted corannulene (3a) can be recovered and stored for further uses. It appears at Rf=0.29.</li>
	</ol>
	</li>
	<li>Sonogashira Coupling of Bomocorannulene and Ethynyltrimethylsilane
	<ol>
		<li>Weigh 49 mg (0.15 mmol) of bromocorannulene, 11 mg (0.015 mmol) of [PdCl2(dppf)]49,50 (dppf being 1,1-&#39;bis(diphenylphsphino)ferrocene, 3 mg (0.015 mmol) of CuI.51</li>
		<li>Place all solids in a 50 ml Schlenk flask along with a magnetic bar and put under nitrogen atmosphere.</li>
		<li>Add 5.0 ml of triethylamine (NEt3) and degas the mixture.</li>
		<li>Finally, add 104 &#181;l (0.75 mmol) of ethynyltrimethylsilane.</li>
		<li>Sonicate the mixture for 2 min to disperse metal salt particles.</li>
		<li>Heat at 85 &#176;C for 24 hr with periodic sonication to prevent deposition of metal salts. 
		NOTE: The mixture color turned to black soon, indicating the presence of palladium(0).</li>
		<li>Cool down to room temperature and evaporate NEt3 in vacuo.</li>
		<li>Redissolve in 20 ml of DCM and purify by column chromatography on silica gel eluting with hexane to give a yellow solid at Rf=0.28 corresponding to 5a. 41 mg should be obtained (yield 78%). 
		NOTE: If the crude is filtered through a Celite pad in DCM, a reasonable pure sample might be obtained, however phosphine derivatives are not removed totally.</li>
	</ol>
	</li>
	<li>Preparation of Ethynylcorannulene by TMS Deprotection
	<ol>
		<li>Weigh 35 mg (0.10 mmol) of 5a and 7.3 mg (0.125 mmol) of anhydrous potassium fluoride.</li>
		<li>Place all solids in a 50 ml Schlenk flask equipped with a magnetic bar and put under nitrogen atmosphere.</li>
		<li>Mix 4 ml of THF and 4 ml of methanol (MeOH) and pour the mixture into the Schlenk flask. Degas thoroughly.</li>
		<li>Allow to react at room temperature, Keep the flask away from light by covering it with an opaque film. Check the reaction by 1H-NMR by looking at 3.48 ppm. A signal corresponding to -CCH must emerge (Figure 3). 
		NOTE: Although this compound bears a terminal alkyne that is reactive and decomposes easily, we found no problems during the work up described below. It was carried out under natural light.</li>
		<li>Once finished, remove THF under vacuum and dilute with 10 ml of water, transferring everything to a separatory funnel.</li>
		<li>Extract with DCM (3 x 15 ml), combine all organic phases in a round-bottom flask and concentrate in a rotary evaporator at room temperature to finally get a yellow solid corresponding to 6a. 27 mg should be obtained (quantitative yield).</li>
	</ol>
	</li>
</ol>
<img alt="Figure 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> 
Figure 3: 1H-NMR spectra (500 MHz, CDCl3) of 5a (top) and 6a (bottom). -CCH singlet is depicted in a red circle. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
3. Final Assembly by Click Chemistry
<ol>
	<li>Weigh 15.3 mg (0.035 mmol) of 5b, 20.0 mg (0.073 mmol) of 6a, 1.4 mg (0.007 mmol) of ascorbic acid sodium salt, 1.7 mg (0.007 mmol) of CuSO4&#183;5H2O.</li>
	<li>Place all solids in a 50 ml Schlenk flask equipped with a magnetic bar and put under nitrogen atmosphere.</li>
	<li>Mix 3 ml of H2O and 12 ml of THF and pour the mixture into the Schlenk flask. Degas the solution thoroughly.</li>
	<li>Heat at 65 &#176;C for 3 days with a condenser connected to the top of the flask and check periodically the reaction to control temperature, stirring and solvent volume. Check the reaction by 1H-NMR. The signal at 3.48 ppm should disappear and be shifted to 7.27 ppm indicating the consumption of ethynyl corannulene and the existence of the triazole unit (Figure 4).</li>
	<li>When finished, remove THF under vacuum and dilute with 20 ml of water, transferring the mixture to a separatory funnel.</li>
	<li>Extract with DCM (3 x 20 ml), combine all organic phases in a round-bottom flask and concentrate in a rotary evaporator.</li>
	<li>Purify the crude by column chromatography on SiO2 gel eluting with hexane/ethyl acetate (1:1) to give a pale yellow solid at Rf = 0.59 corresponding to 7. 27 mg should be obtained (yield 75%).</li>
</ol>
<img alt="Figure 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> 
Figure 4: 1H-NMR spectra (500 MHz, CDCl3) of 5b (top), 6a (middle) and an aliquot taken after 2 days (bottom). Note the disappearance of -CCH signal in the crude. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

The authors have nothing to disclose.

Final compound 7 has been prepared after 6 steps from nonplanar polyaromatic precursors 3a and 3b with moderate to very good yields at each reaction. The main limitation observed in this route was the bromination of both nonplanar polyaromatic compounds. However, in the case of compound 4a, an important amount of free corannulene can be recovered for further uses. The synthesis of 4<stro...

Due to their special geometry, corannulene and helicenes are molecules that can adopt a structure far from planarity and give rise to interesting properties.1-15 In the last few years, the search of molecular receptors for carbon nanotubes and fullerenes is a very active area16-19 due, mainly, to their potential applications as materials for organic solar cells, transistors, sensors and other devices.20-28 The excellent complementarity in shape between corannulene and a fullerene have attracted the attention of several researchers with the aim of designing molecular receptors capable of establishing supramolecular association by dispersion forces.29-39
The chemistry of the above mentioned nonplanar polyaromatic compounds is similar to that described for totally planar molecules, but it is sometimes difficult to find suitable conditions to achieve desired selectivities and yields.40 In this work we present the synthesis of a molecule (7) having three polyaromatic units in a few steps with good yields by applying easy and typical techniques found in every research laboratory. The molecule is of great importance because it can adopt a pincer-like conformation to establish good interactions with C6037 in solution; and it may open a research line as a potential receptor for higher chiral fullerenes thanks to the helicene linker, which is a chiral molecule due to the existence of a stereogenic axis.41-45 However, only racemic helicene will be used in this work.
At this point, the only limitation to synthesize these receptors is the preparation of helicenes and corannulenes, since they are not commercially available. But, according to new methods published elsewhere46-48 they can be obtained in suitable amounts in a reasonable short period of time.

<table><tbody><tr><td>2,15-Dimethylhexahelicene</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 5b,c in the main text.</td></tr><tr><td>Corannulene</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 5a in the main text.</td></tr><tr><td>&lt;em&gt;N&lt;/em&gt;-Bromosuccinimide (NBS)</td><td>Sigma Aldrich</td><td>B8.125-5</td><td>ReagentPlus&amp;reg;, 99%. Recrystallized from hot water.</td></tr><tr><td>Benzoyl peroxide (BPO)</td><td>Sigma Aldrich</td><td>B-2030</td><td>~70% (titration). 30% water as stabilizer.</td></tr><tr><td>Sodium azide</td><td>Sigma Aldrich</td><td>S2002</td><td>ReagentPlus&amp;reg;, &amp;ge;99.5%.</td></tr><tr><td>Gold(III) chloride Hydrate</td><td>Sigma Aldrich</td><td>50778</td><td>puriss. p.a., ACS reagent, &amp;ge;49% Au basis.</td></tr><tr><td>Ethynyltrimethylsilane</td><td>Sigma Aldrich</td><td>218170</td><td>98%</td></tr><tr><td>[PdCl&lt;sub&gt;2&lt;/sub&gt;(dppf)]</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 6 in the main text.</td></tr><tr><td>CuI</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 7 in the main text.</td></tr><tr><td>KF</td><td>Sigma Aldrich</td><td>307599</td><td>99%, spray-dried.</td></tr><tr><td>(+)-Sodium L-ascorbate</td><td>Fluka</td><td>11140</td><td>BioXtra, &amp;ge;99.0% (NT).</td></tr><tr><td>Copper(II) Sulphate 5-hydrate</td><td>Panreac</td><td>131270</td><td>For analysis.</td></tr><tr><td>Carbon tetrachloride (CCl&lt;sub&gt;4&lt;/sub&gt;)</td><td>Fluka</td><td>87030</td><td>For IR spectroscopy, &amp;ge;99.9%.</td></tr><tr><td>Dichloromethane (DCM)</td><td>Fisher Scientific</td><td>D/1852/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>Hexane</td><td>Fisher Scientific</td><td>H/0355/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>Ethyl acetate</td><td>Scharlau</td><td>AC0145025S</td><td>Reagent grade. Distilled prior to use.</td></tr><tr><td>Tetrahydrofuran (THF)</td><td>Fisher Scientific</td><td>T/0701/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>1,2-Dichloroethane (DCE)</td><td>Sigma Aldrich</td><td>D6,156-3</td><td>ReagentPlus&amp;reg;, 99%.</td></tr><tr><td>Methanol (MeOH)</td><td>VWR</td><td>20847.36</td><td>AnalaR NORMAPUR.</td></tr><tr><td>Triethyl amine (NEt&lt;sub&gt;3&lt;/sub&gt;)</td><td>Sigma Aldrich</td><td>T0886</td><td>&amp;ge;99%</td></tr><tr><td>Silica gel</td><td>Acros</td><td>360050010</td><td>Particle size 40-60 mm.</td></tr><tr><td>Sand - low iron</td><td>Fisher Scientific</td><td>S/0360/63</td><td>General purpose grade.</td></tr><tr><td>TLC Silica gel 60 F&lt;sub&gt;254&lt;/sub&gt;</td><td>Merck</td><td>1.05554.0001</td><td></td></tr><tr><td>Monowave 300 (Microwave reactor)</td><td>Anton Para</td><td></td><td></td></tr><tr><td>Sonicator</td><td>Grupo Selecta</td><td>3000513</td><td>6 Litres.</td></tr></tbody></table>

preparation of a corannulene-functionalized hexahelicene by copper(i)-catalyzed alkyne-azide cycloaddition of nonplanar polyaromatic units

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds.

Corannulene (3a) and 2,15-dimethylhexahelicene (3b) could be prepared following current methods46-48 in a straightforward fashion with very good yields (Figure 5). Both share a common molecule, 2,7-dimethylnaphthalene, as the starting material, giving rise to a divergent to convergent synthesis of the final molecule.
<img alt="Fi...

Watch this Scientific Journal Video about Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units at JoVE.com

Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Here, we present a protocol to synthesize a complex organic compound comprised of three nonplanar polyaromatic units, assembled easily with reasonable yields.

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar ...

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11.4K Views.  Universidad de Valladolid. Here, we present a protocol to synthesize a complex organic compound comprised of three nonplanar polyaromatic units, assembled easily with reasonable yields.

Video: Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

1,3,5-Triphenylbenzene and Corannulene as Electron Receptors for Lithium Solvated Electron Solutions

The authors report on conductivity studies carried out on lithium solvated electron solutions (LiSES) prepared using two types of polyaromatic hydrocarbons (PAH), namely 1,3,5-triphenylbenzene and corannulene, as electron receptors. The solid PAHs were first dissolved in tetrahydrofuran (THF) to form a solution. Metallic lithium was then dissolved into these PAH/THF solutions to yield either blue or greenish blue solutions, colors which are indicative of the presence of solvated electrons. Conductivity measurements at ambient temperature carried out on 1,3,5-triphenylbenzene-based LiSES, denoted by LixTPB(THF)24.7 (x = 1, 2, 3, 4), showed an increase of conductivity with increase of Li:PAH ratio from x = 1 to 2. However, the conductivity gradually decreased upon further increasing the ratio. Indeed the conductivity of LixTPB(THF)24.7 for x = 4 is even lower than for x = 1. Such behavior is similar to that of the previously reported LiSES prepared from biphenyl and naphthalene. Conductivity versus temperature measurements on corannulene-based LiSES, denoted by LixCor(THF)247 (x = 1, 2, 3, 4, 5), showed linear relationships with negative slopes, indicating a metallic behavior similar to biphenyl and naphthalene-based LiSES.

The authors report on conductivity studies carried out on lithium solvated electron solutions (LiSES) prepared using 1,3,5-triphenylbenzene (TPB) and corannulene as electron receptors.

The authors report on conductivity studies carried out on lithium solvated electron solutions (LiSES) prepared using two types of polyaromatic ...

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that derive from initial 2-bromo-2-butene lithiation followed by acid mediated dienol cyclization. The revised synthesis and purification of the ligand avoids the use of mechanical stirring while still permitting access to significant quantities (39 g) of Cp*H in good yield (58%). The procedure offers other additional benefits, including a more controlled quench of excess lithium during the production of the intermediate heptadienols and a simplified isolation of Cp*H of sufficient purity for metallation with transition metals. The ligand was subsequently used to synthesize [Cp*MCl2]2 complexes of both iridium and ruthenium to demonstrate the utility of the Cp*H prepared and purified by our method. The procedure outlined herein affords substantial quantities of a ubiquitous ancillary ligand support used in organometallic chemistry while minimizing the need for specialized laboratory equipment, thus providing a simpler and more accessible entry point into the chemistry of 1,2,3,4,5-pentamethylcyclopentadiene.

Reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented. The revised protocol for the synthesis and purification of the ligand minimizes the need for specialized laboratory equipment while simplifying reaction workups and product purification. Use of Cp*H in the synthesis of [Cp*MCl2]2 complexes (M = Ru, Ir) is also described.

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that ...

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 ...

[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF6 as a general copper-based photoredox catalyst which proved efficient to promote the activation of a broad variety of organic halides, including unactivated ones. These can then participate in various radical transformations such as reduction and cyclization reactions, as well as in the direct arylation of several (hetero)arenes. These transformations provide a straightforward access to a range of small molecules of interest in synthetic chemistry, as well as to biologically active natural products. Altogether, [(DPEPhos)(bcp)Cu]PF6 acts as a convenient photoredox catalyst which appears to be an attractive, cheap and complementary alternative to the state-of-the-art iridium- and ruthenium-based photoredox catalysts. Here, we report a detailed protocol for the synthesis of [(DPEPhos)(bcp)Cu]PF6, as well as NMR and spectroscopic characterizations, and we illustrate its use in synthetic chemistry for the direct arylation of (hetero)arenes and radical cyclization of organic halides. In particular, the direct arylation of N-methylpyrrole with 4-iodobenzonitrile to afford&#160;4-(1-methyl-1H-pyrrol-2-yl)benzonitrile and the radical cyclization of N-benzoyl-N-[(2-iodoquinolin-3-yl)methyl]cyanamide to afford natural product luotonin A are detailed. The scope and limitations of this copper-based photoredox catalyst are also briefly discussed.

[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Detailed and general protocols are presented for the synthesis of [(DPEPhos)(bcp)Cu]PF6, a general copper-based photoredox catalyst, and for its use in synthetic chemistry for the direct arylation of C-H bonds in (hetero)arenes and radical cyclization of organic halides.

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF6 as a general copper-based photoredox catalyst which proved efficient to promote the ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.

New routes for the synthesis of nitrogen-containing heterocycles utilizing cercosporin as a metal-free photocatalyst were developed.

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. ...

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.

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 ...

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Alkyne alkylation reaction using NaNH2 and ethyl bromide, chemical equation diagram." src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Alkyne ionization reaction equation NaNH2, diagram shows acetylene converting to acetylide ion." src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure2">
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C–C bond.
<img alt="Organic reaction mechanism, Na+ and Br- ion exchange, illustrates chemical synthesis process." src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure3">
<h4>Reaction Mechanism —SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Nucleophilic substitution reaction mechanism diagram with alkynes, NaBr formation, chemical process." src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" data-altupdatedat="1747908711000" data-alt="Figure4">
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Alkyne chain elongation via NaNH₂, CH₃Br; reaction equation diagram for organic synthesis." src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure5">

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

Alkynes

KEY TERMS AND CONCEPTS

Aromatic Hydrocarbon Cations: Structural Overview

Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 &#960; electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 &#960; electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group with both or one or no electrons generates cycloheptatrienyl cation, radical, and anion, respectively, thereby converting the sp3 carbon of cycloheptatriene to sp2. As a result, the generated empty 2p orbital in cycloheptatrienyl cation and the p orbitals of other carbons in the ring forms a continuous loop of overlapping p orbitals. Therefore, compared to radical and anion, the cycloheptatrienyl cation with 6 &#960; electrons and a continuous loop of overlapping p orbitals fulfills all Huckel&#8217;s criteria and is aromatic.

Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. ...