Name: preparation of a corannulene-functionalized hexahelicene by copper(i)-catalyzed alkyne-azide cycloaddition of nonplanar polyaromatic units
Uploaded: 2016-09-18T14:00:00.000+00:00
Duration: 9 min 35 s
Description: 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

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. Funzionalizzazione di 2,15-Dimethylhexahelicene <ol><li> Dibromination di 2,15-dimethylhexahelicene <ol><li> Pesare 0,356 g (1,0 mmol) di 2,15-dimethylhexahelicene, 0,374 g (2,1 mmoli) di -bromosuccinimide appena ricristallizzato N (NBS) e 24 mg (0,07 mmoli) di perossido di benzoile (BPO) (70% in peso con il 30% di acqua come stabilizzatore). Mettere tutti i solidi in un pallone da 100 ml Schlenk con ancoretta magnetica. Mettere in atmosfera di azoto da tre cicli di evacuazione gas seguita da riempimento con gas inerte nella linea Schlenk. </li><li> Aggiungere 21 ml di tetracloruro di carbonio (CCL 4). Degassare la soluzione dallo stesso evacuazione / processo di riempimento (fase 1.1.1) sotto vigorosa agitazione e con attenzione per evitare perdita massiccia di solvente. </li><li> Calore a riflusso (77 ° C) la miscela con un bagno di olio per 4 ore. Controllare la reazione mediante risonanza magnetica 1 H-nucleare (NMR). Doppietti tra 3,7 ppm e 4,0 ppm shoULD appaiono. Essi indicano la presenza di -CH diastereotopici 2 - gruppi (Figura 1). </li><li> Una volta terminato, raffreddare la miscela a temperatura ambiente e rimuovere il solvente sotto vuoto. Impostare una trappola piena di azoto liquido per evitare la contaminazione della pompa. </li><li> Riprendere il grezzo in 30 ml di diclorometano (DCM), trasferire in un pallone a fondo rotondo e mescolare con 4 g di gel di silice (tipicamente aggiungere 5 volte il peso grezzo). Concentrare la miscela in un evaporatore rotante. </li><li> Nel frattempo, riempire una colonna (lunghezza circa 20 cm ed uno spessore di 4,5 cm) con SiO 2 gel miscelato in precedenza con esano / acetato di etile (95: 5) come fase mobile. Aggiungere la miscela al superiore della colonna e quindi aggiungere uno strato di sabbia (2 cm). </li><li> Versare con cautela nella nuova fase mobile e eseguire la cromatografia attraverso la raccolta di frazioni in provette (in genere 20 ml per provetta e 4 ml vicino l&#39;eluizione del prodotto atteso). Controllare frazioni di cromatografia su strato sottile(TLC) con la stessa fase mobile (esano / acetato di etile 95: 5) e l&#39;immagine sotto luce UV. Il prodotto atteso (4b) dovrebbe eluire con un fattore di ritenzione (Rf) di 0,35 come olio giallo dopo aver combinato tutti frazioni voluto e rimuovendo il solvente in evaporatore rotante. 334 mg dovrebbero essere ottenuti (resa 65%). NOTA: Tutte le tecniche Schlenk, l&#39;uso di un bagno d&#39;olio per riscaldamento e di colonna impostazioni cromatografiche saranno ampiamente utilizzati nella maggior parte dei protocolli, così da ora in poi, non verrà descritta in dettaglio e solo poche osservazioni, quando necessario, essere dato. </li></ol></li></ol><img alt="Figura 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> . Figura 1 1 H-NMR (500 MHz, CDCl 3) di 2,15 -dimethylhelicene (in alto) e una aliquota scattata dopo 2 ore nuovi segnali, corrispondenti a -CH 2 -.., sono raffigurati in un cerchio rosso (in basso) <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <ol start="2"><li> Sintesi di 2,15-bis (azidomethyl) hexahelicene <ol><li> Pesare 0,103 g (0,2 mmol) di 2,15-bis (bromometil) hexahelicene e 0,390 g (6 mmoli) di sodio azide. Posizionare entrambi i solidi in un matraccio da 50 ml dotato di Schlenk barra magnetica e posto sotto atmosfera di azoto. </li><li> Mescolare 8,6 ml di tetraidrofurano (THF) con 5,2 ml di acqua (H 2 O) e versare la miscela di solventi nel pallone Schlenk. Degassare la soluzione. </li><li> Calore a riflusso (65 ° C) per 3 ore. Controllare la reazione 1 H-NMR. -CH 2 - segnali dovrebbero trasferire al 3,75 ppm (Figura 2). </li><li> In seguito, cool giù la miscela a temperatura ambiente e rimuovere THF sotto vuoto. Diluire con 50 ml di H 2 O. </li><li> Trasferire la miscela in un imbuto separatore ed estrarre tre volte con 40 ml di DCM. Unire tutte le fasi organiche e lavare con puro H 2 O (50 ml). </li><li> Purificare il grezzo mediante cromatografia su colonna su gel di silice usando esano / acetato di etile (85:15) come fase mobile per dare un olio giallo a Rf = 0,38 corrispondente a 2,15-bis (azomethyl) hexahelicene (5b). 70 mg dovrebbe essere ottenuto (resa 80%). </li></ol></li></ol><img alt="figura 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> Figura 2: 1 H-NMR (500 MHz, CDCl 3) 4 b (in alto) e un&#39;aliquota presa dopo 3 ore(in basso). Notare i cambiamenti nella regione alifatici. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> 2. Funzionalizzazione di corannulene <ol><li> Monobromination di corannulene <ol><li> Pesare 0,125 g (0,5 mmoli) di corannulene, 89 mg (0,5 mmol) di appena ricristallizzato NBS e 17 mg di oro (III) cloruro idrato. </li><li> Mettere tutti i composti in un flaconcino da 10 ml appositamente progettati per le reazioni a microonde dotati di una barra magnetica e poi messo in atmosfera di azoto, con l&#39;aiuto di un pallone a 2 colli. </li><li> Aggiungere 7 ml di 1,2-dicloroetano (DCE) e degassare la soluzione. </li><li> Sonicare la miscela per 2 minuti per disperdere particelle di sale d&#39;oro. </li><li> Il calore all&#39;interno del reattore a microonde a 100 ° C per 2 ore. </li><li> Al termine, trasferire il grezzo in un pallone a fondo rotondo e rimuovere il solvente dal rotarevaporazione y. </li><li> Purificare il grezzo mediante cromatografia su colonna su SiO 2 gel usando esano come fase mobile. NOTA: Bromocorannulene (4a) è ottenuto come solido giallo a Rf = 0.38. 99 mg dovrebbe essere ottenuto (resa 60%). Corannulene non reagito (3a) può essere recuperato e conservato per ulteriori usi. Sembra a Rf = 0,29. </li></ol></li><li> Sonogashira Accoppiamento di Bomocorannulene e Ethynyltrimethylsilane <ol><li> Pesare 49 mg (0,15 mmol) di bromocorannulene, 11 mg (0,015 mmol) di [PdCl 2 (dppf)] 49,50 (dppf essere 1,1-&#39;bis (diphenylphsphino) ferrocene, 3 mg (0,015 mmol) di cui. 51 </li><li> Mettere tutti i solidi in un matraccio da 50 ml Schlenk assieme con una barra magnetica e posto sotto atmosfera di azoto. </li><li> Aggiungere 5,0 ml di trietilammina (Net 3) e degassare la miscela. </li><li> Infine, aggiungere 104 ml (0,75 mmol) di ethynyltrimethylsilane. </li><li> Sonicare la miscela per 2 minuti perdisperdere le particelle di sale di metallo. </li><li> Riscaldare a 85 ° C per 24 ore con sonicazione periodica per evitare la deposizione di sali metallici. NOTA: Il colore della miscela acceso al nero presto, indicando la presenza di palladio (0). </li><li> Raffreddare a temperatura ambiente ed evaporare NEt 3 sotto vuoto. </li><li> Riprendere in 20 ml di DCM e purificare mediante cromatografia in colonna su gel di silice eluendo con esano per dare un solido giallo a Rf = 0,28 corrispondente a 5a. 41 mg dovrebbe essere ottenuto (resa 78%). NOTA: Se il grezzo viene filtrato attraverso un tampone di Celite in DCM, un campione puro ragionevole potrebbe essere ottenuto, comunque derivati ​​fosfinici non vengono rimossi completamente. </li></ol></li><li> Preparazione di Ethynylcorannulene da TMS deprotezione <ol><li> Pesare 35 mg (0,10 mmoli) di 5a e 7,3 mg (0,125 mmoli) di fluoruro di potassio anidro. </li><li> Mettere tutti i solidi in un matraccio da 50 ml Schlenk attrezzato con una barra di magneticad Mettere in atmosfera di azoto. </li><li> Mescolare 4 ml di THF e 4 ml di metanolo (MeOH) e versare il composto nel pallone Schlenk. Degas a fondo. </li><li> Lasciar reagire a temperatura ambiente, Mantenere il matraccio lontano dalla luce coprendolo con una pellicola opaca. Controllare la reazione 1 H-NMR, cercando in 3,48 ppm. Un segnale corrispondente -CCH deve emergere (Figura 3). NOTA: Anche se questo composto ha una alkyne terminale che è reattivo e si decompone facilmente, abbiamo riscontrato problemi durante il lavoro fino descritto di seguito. È stata effettuata sotto la luce naturale. </li><li> Una volta terminato, rimuovere THF sotto vuoto e diluire con 10 ml di acqua, trasferire tutto in un imbuto separatore. </li><li> Estrarre con DCM (3 x 15 ml), combinare tutte le fasi organiche in un pallone a fondo rotondo e concentrato in un evaporatore rotante a temperatura ambiente per ottenere finalmente un solido giallo corrispondente 6a. 27 mg dovrebbe essere ottenuto (resa quantitativa). </li></ol></li></ol><img alt="Figura 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> Figura 3:.. 1 H-NMR (500 MHz, CDCl 3) di 5 A (in alto) e 6 bis (basso) singoletto -CCH è raffigurato in un cerchio rosso <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> 3. Montaggio finale da Click Chimica <ol><li> Pesare 15,3 mg (0,035 mmoli) di 5b, 20,0 mg (0,073 mmoli) di 6a, 1,4 mg (0,007 mmoli) di sale sodico dell&#39;acido ascorbico, 1,7 mg (0,007 mmoli) di CuSO 4 · 5H 2 O. </li><li> Mettere tutti i solidi in un matraccio da 50 ml dotato di Schlenk ambar agnetica e messo in atmosfera di azoto. </li><li> Mescolare 3 ml di H 2 O e 12 ml di THF e versare il composto nel pallone Schlenk. Degassare bene la soluzione. </li><li> Riscaldare a 65 ° C per 3 giorni con un condensatore collegato alla sommità del pallone e controllare periodicamente la reazione per controllare la temperatura, agitazione e volume di solvente. Controllare la reazione 1 H-NMR. Il segnale a 3.48 ppm dovrebbe scomparire e essere spostato a 7.27 ppm indicante il consumo di etinil corannulene e l&#39;esistenza del gruppo triazolo (Figura 4). </li><li> Al termine, rimuovere THF sotto vuoto e diluire con 20 ml di acqua, trasferendo la miscela in un imbuto separatore. </li><li> Estrarre con DCM (3 x 20 ml), combinare tutte le fasi organiche in un pallone a fondo rotondo e concentrato in un evaporatore rotante. </li><li> Purificare il grezzo mediante cromatografia su colonna su gel di SiO 2 eluendo con esano / acetato di etile (1: 1) per dare un solido giallo pallido a Rf = 0,59corrispondente al 7. 27 mg dovrebbe essere ottenuto (resa 75%). </li></ol><img alt="Figura 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> Figura 4: 1 H-NMR (500 MHz, CDCl 3) di 5 B (in alto), 6 bis (al centro) e una aliquota prelevata dopo 2 giorni (in basso) Si noti la scomparsa del segnale di -CCH nel greggio.. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Si prega clicca qui per vedere una versione più grande di questa figura.</a>

The authors have nothing to disclose.

Composto finale 7 è stato preparato dopo 6 passi da precursori poliaromatici non planari 3 A e 3 B da moderata a molto buone rese in ogni reazione. La limitazione principale osservata in questo percorso è stata la bromurazione di composti poliaromatici non planari. Tuttavia, nel caso del composto 4 bis, una quantità importante di corannulene libero può essere recuperato per altri usi. La sintesi di ...

Grazie alla loro particolare geometria, corannulene e helicenes sono molecole che possono adottare una struttura lontano dalla planarità e dar luogo a proprietà interessanti. 1-15 Negli ultimi anni, la ricerca dei recettori molecolari per nanotubi di carbonio e fullereni è una zona molto attiva 16-19 a causa, principalmente, alle loro potenziali applicazioni come materiali per le celle organiche solari, transistor, sensori e altri dispositivi. 20-28 l&#39;ottima complementarietà di forma tra il corannulene e un fullerene hanno attirato l&#39;attenzione di numerosi ricercatori, con l&#39;obiettivo di progettare recettori molecolari in grado di stabilire un&#39;associazione supramolecolare da parte delle forze di dispersione. 29-39 La chimica dei composti poliaromatici non planari suddetti è simile a quella descritta per le molecole totalmente planari, ma a volte è difficile trovare condizioni adatte per raggiungere le selettività e le rese desiderati. 40 </sup&gt; In questo lavoro presentiamo la sintesi di una molecola (7) avente tre unità poliaromatici in pochi passi con buone rese applicando tecniche semplici e tipiche presenti in ogni laboratorio di ricerca. La molecola è di grande importanza perché può adottare una conformazione tenaglia per stabilire buone interazioni con C 60 37 in soluzione; e può aprire una linea di ricerca come potenziale recettore per maggiori fullereni chirali grazie al linker eliceni, che è una molecola chirale a causa dell&#39;esistenza di un asse stereogenico. 41-45 Tuttavia, solo eliceni racemico saranno utilizzati in questo lavoro. A questo punto, l&#39;unica limitazione per sintetizzare questi recettori è la preparazione di helicenes e corannulenes, dal momento che non sono disponibili in commercio. Ma, secondo i nuovi metodi pubblicati altrove 46-48 possono essere ottenuti in quantità adatte in un breve periodo di tempo ragionevole.

<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 (3 a) e 2,15-dimethylhexahelicene (3 b) può essere preparato secondo i metodi attuali 46-48 in modo semplice con ottime rese (Figura 5). Entrambi condividono una molecola comune, 2,7-dimetilnaftalene, come materiale di partenza, dando luogo a una divergente alla sintesi convergente della molecola finale. <img alt="F...

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

Qui, vi presentiamo un protocollo per sintetizzare un complesso composto organico composto da tre unità poliaromatici non planari, montato facilmente con rendimenti ragionevoli.

Preparazione di un Hexahelicene corannulene-funzionalizzati da rame (I) -catalyzed Acetilene-azide cicloaddizione di unità non planare policiclici aromatici

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 ...

preparation-corannulene-functionalized-hexahelicene-copper-i

Universidad de Cartagena UDEC

Research

Education

JoVE Core

JoVE Journal

Organic Chemistry

Chemistry

Unit 1

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

Aromatic Compounds

SCIENTISTS IN ACTION

11.4K Views.  Universidad de Valladolid.  Qui, vi presentiamo un protocollo per sintetizzare un complesso composto organico composto da tre unità poliaromatici non planari, montato facilmente con rendimenti ragionevoli. 

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.

Sintesi di hypervalent iodonio Alchinile triflati per l&#39;applicazione di Generazione Cyanocarbenes

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

Ricerca

Chimica

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.

Accesso prezioso Ligand Supporti per metalli di transizione: una versione modificata, Intermedio Scala Preparazione di 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 ...

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.

Preparazione di stabile biciclico Aziridinium ioni e loro anello-apertura per la sintesi di Azaheterocycles

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

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Chemoselective preparazione di 1-Iodoalkynes, 1,2-Diiodoalkenes e 1,1,2-Triiodoalkenes basato sull'iodurazione ossidativo degli alchini terminali

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC&#8211;NHC &#8220;Wanzlick&#8221; dimer and the synthesis of the related stable organic &#8220;olefin&#8221; radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick&#8217;s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed &#8220;Wanzlick dimer&#8221; and the reduced stable organic radical.

Isolando gratis carbeni, loro misto dimeri e radicali organici

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, 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.

Sintesi efficiente dei centri quaternari All-Carbon tramite l'aggiunta di coniugato di Monoorganozinc di bromide funzionalizzati

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 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.

Preparazione di bisaziridine contigue per reazioni regioselettive di apertura dell'anello

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

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs used to manage and treat pain and inflammation. In 2016, a new class of boron functionalized NSAIDs (bora-NSAIDs) was synthesized under mild conditions via the copper-catalyzed regioselective boracarboxylation of vinyl arenes using carbon dioxide (CO2 balloon) and a diboron reductant at room temperature. This original method was performed primarily in a glovebox or with a vacuum gas manifold (Schlenk line) under rigorous air-free and moisture-free conditions, which often led to irreproducible reaction outcomes due to trace impurities. The present protocol describes a simpler and more convenient benchtop method for synthesizing a representative bora-NSAID, bora-ibuprofen. A Suzuki-Miyaura cross-coupling reaction between 1-bromo-4-isobutylbenzene and vinylboronic acid pinacol ester produces 4-isobutylstyrene. The styrene is subsequently boracarboxylated regioselectively to provide bora-ibuprofen, an &#945;-aryl-&#946;-boryl-propionic acid, with good yield on a multi-gram scale. This procedure allows for the broader utilization of copper-catalyzed boracarboxylation in synthetic laboratories, enabling further research on bora-NSAIDs and other unique boron-functionalized drug-like molecules.

The present protocol describes a detailed benchtop catalytic method that yields a unique borylated derivative of ibuprofen.&#160;

Sintesi di un derivato dell'ibuprofene borilato mediante reazioni di cross-coupling Suzuki e alchene boracarbossilazione

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs used to manage and treat pain and inflammation. In 2016, a new class 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="Figure1" src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" />
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="Figure2" src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" />
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C&#8211;C bond.
<img alt="Figure3" src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" />
<h4>Reaction Mechanism &#8212;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="Figure4" src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" />
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="Figure5" src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" />

Preparazione degli alchini: reazione di alchilazione

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 ...

Didattica

Chimica Organica

Unità 1

Alchini

TERMINI E CONCETTI CHIAVE

Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Figure1" src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" />
<h4>Reaction Mechanism &#8211; E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Figure2" src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" />
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Figure3" src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" />
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Figure4" src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" />
<img alt="Figure5" src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" />
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Figure6" src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" />
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Figure7" src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" />
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane &#8211; a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Figure8" src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" />
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane &#8211; a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Figure9" src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" />

Preparazione degli alchini: deidroalogenazione

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...