We acknowledge financial support from ANR (ANR-15-CE29-0020-01, ACTIV-CF-LAN), CNRS, ICMR, Universit&#233; de Reims Champagne Ardenne, ENSCM and ICGM. We thank Carine Machado and Anthony Robert for help with EI-MS and NMR analysis.

1. Preparation of Starting Material Outside the Glovebox
<ol>
	<li>Prepare necessary equipment: oven-dried Schlenk tube with a magnetic stir bar, vacuum/inert gas line (argon or nitrogen), and magnetic stirrer.</li>
	<li>Prepare trifluoromethylated benzofulvene according to the literature13.</li>
	<li>Weigh out trifluoromethylated benzofulvene (177 mg, 0.65 mmol) and add into an oven-dried Schlenk tube equipped with a magnetic stir bar.</li>
	<li>Close the Schlenk tube with a plastic screw cap with PTFE liner and connect to vacuum line.</li>
	<li>Start stirring and apply vacuum to dry benzofulvene for 10 min. Then, release the vacuum with argon/nitrogen and again apply the vacuum. Repeat this process 3 times. Finally, fill the Schlenk tube with argon/nitrogen and close it tightly.</li>
	<li>Take the Schlenk tube under argon/nitrogen to the glove box.</li>
</ol>
2. Preparation of Freshly Filed Dysprosium Metal Inside the Glovebox
<ol>
	<li>Prepare necessary equipment: glove box under argon/nitrogen with weighing balance, metal file, pliers, aluminum foil, forceps, spatula, test tube, and 2 rubber septa.</li>
	<li>Prepare chemicals: dysprosium metal and anhydrous AlCl3</li>
	<li>Insert Schlenk tube with benzofulvene, a test tube and 2 rubber septa into the glovebox according to your group&#39;s general practice for handling the glovebox, e.g., for a small chamber apply vacuum for 1 min then release with argon/nitrogen three times.</li>
	<li>Put one piece of aluminum foil onto the weighing balance and one onto a plate on the glovebox floor for filing.</li>
	<li>Tightly hold the dysprosium metal with the help of pliers and remove its upper inactive layer by filing with a metal file to obtain a shiny metal surface. Discard this filed metal. 
	NOTE: (1) Use large metal pieces for filing and avoid contact between the pliers and the file in order not to contaminate the dysprosium metal with other metals. (2) Use a different metal file for each lanthanide metal to avoid cross-contamination. (3) Discarded metal powder should be quenched separately outside the glove box, using dil. aq. HCl solution. 
	Caution: The reaction of dysprosium with aq. HCl is exothermic and produces hydrogen gas, therefore quench the dysprosium in an open flask surrounded by ice bath.</li>
	<li>Prepare freshly filed dysprosium metal (82 mg, 0.50 mmol), add to the Schlenk tube, and close the tube with a rubber septum.</li>
	<li>Weigh anhydrous AlCl3 (200 mg, 1.5 mmol) into a test tube and close the tube with a rubber septum.</li>
	<li>Remove the Schlenk tube and the test tube from the glove box.</li>
</ol>
3. Start C-F Activation Reaction Outside the Glovebox
<ol>
	<li>Prepare necessary equipment: vacuum/inert gas line (argon or nitrogen), magnetic stirrer, and dry 2 mL syringe with needle.</li>
	<li>Prepare chemicals: freshly distilled dry THF and iodine.</li>
	<li>Clamp the Schlenk tube in a fume hood above a magnetic stirrer and connect to the vacuum line. Perform three cycles of vacuum/inert gas before opening the Schlenk tube under a positive flow of argon/nitrogen. Start the magnetic stirrer.</li>
	<li>Clamp the test tube with AlCl3 in a fume hood and connect to the inert gas line via a needle under a positive flow of argon/nitrogen.</li>
	<li>Add a catalytic amount of iodine (10 - 12 mg) to the Schlenk tube under a positive argon/nitrogen flow.</li>
	<li>Purge a dry 2 mL syringe with needle under argon/nitrogen</li>
	<li>Take 1.5 mL of freshly distilled dry THF using the purged syringe and add 0.5 mL to the Schlenk tube to obtain a deep brown solution (color of iodine in THF).</li>
	<li>Add the remaining 1.0 mL of THF dropwise to the test tube with AlCl3, which will lead to a slightly yellow solution. 
	NOTE: Depending on the quality of AlCl3, the addition of THF can be more or less exothermic.</li>
	<li>While still warm, transfer this AlCl3 solution from the test tube to the Schlenk tube using the syringe.</li>
	<li>Allow the reaction to stir until the full consumption of benzofulvene. Initially, the deep brown color will disappear to give a yellow solution, which over time will turn to a dark green turbid solution.</li>
	<li>Check the reaction by thin-layer chromatography (TLC) after 1 h by taking a sample of the reaction mixture with a capillary under a positive flow of argon/nitrogen. Use petroleum ether as eluent. 
	NOTE: The starting benzofulvene is bright yellow on the TLC plate and its disappearance can be readily observed.</li>
</ol>
4. Addition of Nitroalkene
<ol>
	<li>Prepare 4-methoxyphenylnitroalkene according to the literature16.</li>
	<li>In a test tube weigh out 4-methoxyphenylnitroalkene (90 mg, 0.50 mmol), close the tube with a rubber stopper, and dry it on the vacuum line via a needle connection.</li>
	<li>After disappearance of benzofulvene in the reaction mixture (confirmed by TLC analysis), add dry nitroalkene to the Schlenk tube under a positive flow of argon/nitrogen. The reaction mixture will change color to yellow-green.</li>
	<li>Monitor the reaction by TLC analysis, until full consumption of nitroalkene (usually 1 hour). Use petroleum ether/ethyl acetate 95/5 as eluent.</li>
</ol>
5. Workup and purification
<ol>
	<li>Dilute the reaction mixture with 20 mL of diethyl ether and quench it with 5 mL of 1 molar aqueous solution of hydrochloric acid in an open Schlenk tube. 
	CAUTION: The reaction of remaining dysprosium with aq. HCl is exothermic and produces hydrogen gas, which may cause pressure build up in Schlenk. Therefore, quench the reaction in open Schlenk under a good fume hood.</li>
	<li>After quenching the reaction, transfer it to a separatory funnel.</li>
	<li>Collect the organic phase in a conical flask. Wash the aqueous phase 2 times with 10 mL of diethyl ether and collect the organic phase in the conical flask.</li>
	<li>Dry the organic phase over MgSO4, filter into a pre-weighed flask, and concentrate under reduced pressure on a rotary evaporator to get the crude product as an orange-brown oil.</li>
	<li>Purify the crude product by silica gel column chromatography starting with petroleum ether as eluent to remove non-polar hydrolyzed product. Increasing the polarity up to 10/1 petroleum ether/ethyl acetate gives the new nitro-containing difluoroalkenes. 
	NOTE: When performing the column chromatography on a long column and by slowly increasing the polarity, it is possible to separate the diastereoisomers for analysis purposes.</li>
</ol>

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<li>Girard, P., Namy, J. L., Kagan, H. B. <a target="_blank" href="https://pubs.acs.org/doi/pdf/10.1021/ja00528a029">Divalent Lanthanide Derivatives in Organic Synthesis. 1. Mild Preparation of SmI2 and YbI2 and Their Use as Reducing or Coupling Agents.</a> J. Am. Chem. Soc. 102 (8), 2693-2698 (1980).</li>
<li>Wu, S., Li, Y., Zhang, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((%CE%B1-Regioselective+Barbier+Reaction+of+Carbonyl+Compounds+and+Allyl+Halides+Mediated+by+Praseodymium%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">α-Regioselective Barbier Reaction of Carbonyl Compounds and Allyl Halides Mediated by Praseodymium.</a> J. Org. Chem. 81 (17), 8070-8076 (2016).</li>
<li>Umeda, R., Ninomiya, M., Nishino, T., Kishida, M., Toiya, S., Saito, T., Nishiyama, Y., Sonoda, N. <a target="_blank" href="https://www.sciencedirect.com/science/article/pii/S0040402014018055">A Novel Lanthanum Metal-assisted Reaction of Diaryl Ketones and Electrophiles.</a> Tetrahedron. 71 (8), 1287-1291 (2015).</li>
<li>Chen, W., Li, K., Hu, Z., Wang, L., Lai, G., Li, Z. <a target="_blank" href="https://pubs.acs.org/doi/abs/10.1021/om200080f">Utility of Dysprosium as a Reductant in Coupling Reactions of Acyl Chlorides: The Synthesis of Amides and Diaryl-Substituted Acetylenes.</a> Organometallics. 30 (7), 2026-2030 (2011).</li>
<li>Concellón, J. M., Rodríguez-Solla, H., Concellón, C., del Amo, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Stereospecific+and+Highly+Stereoselective+Cyclopropanation+Reactions+Promoted+by+Samarium%5BTitle%5D)+AND+%22Chem.+Soc.+Rev%22%5BJournal%5D)">Stereospecific and Highly Stereoselective Cyclopropanation Reactions Promoted by Samarium.</a> Chem. Soc. Rev. 39 (11), 4103-4113 (2010).</li>
<li>Bousrez, G., Dechamps, I., Vasse, J. -L., Jaroschik, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reduction+of+Titanocene+Dichloride+with+Dysprosium%3A+Access+to+a+Stable+Titanocene%28II%29+Equivalent+for+Phosphite-free+Takeda+Carbonyl+Olefination%5BTitle%5D)+AND+%22Dalton.+Trans%22%5BJournal%5D)">Reduction of Titanocene Dichloride with Dysprosium: Access to a Stable Titanocene(II) Equivalent for Phosphite-free Takeda Carbonyl Olefination.</a> Dalton. Trans. 44 (20), 9359-9362 (2015).</li>
<li>Bousrez, G., Jaroschik, F., Martinez, A., Harakat, D., Nicolas, E., Le Goff, X. F., Szymoniak, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reactivity+Differences+Between+2%2C4-+and+2%2C5-Disubstituted+Zirconacyclopentadienes%3A+A+Highly+Selective+and+General+Approach+to+2%2C4-Disubstituted+Phospholes%5BTitle%5D)+AND+%22Dalton.+Trans%22%5BJournal%5D)">Reactivity Differences Between 2,4- and 2,5-Disubstituted Zirconacyclopentadienes: A Highly Selective and General Approach to 2,4-Disubstituted Phospholes.</a> Dalton. Trans. 42 (30), 10997-11004 (2013).</li>
<li>Klahn, M., Rosenthal, U. <a target="_blank" href="https://pubs.acs.org/doi/abs/10.1021/om200978a">An Update on Recent Stoichiometric and Catalytic C-F Bond Cleavage Reactions by Lanthanide and Group 4 Transition-Metal Complexes.</a> Organometallics. 31 (4), 1235-1244 (2012).</li>
<li>Deacon, G. B., Junk, P. C., Kelly, R. P., Wang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Exploring+the+Effect+of+the+Ln%28III%29%2FLn%28II%29+Redox+Potential+on+C-F+Activation+and+on+Oxidation+of+Some+Lanthanoid+Organoamides%5BTitle%5D)+AND+%22Dalton+Trans%22%5BJournal%5D)">Exploring the Effect of the Ln(III)/Ln(II) Redox Potential on C-F Activation and on Oxidation of Some Lanthanoid Organoamides.</a> Dalton Trans. 45 (4), 1422-1435 (2016).</li>
<li>Träff, A. M., Janjetovic, M., Ta, L., Hilmersson, G. <a target="_blank" href="https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201306104">Selective C-F Bond Activation: Substitution of Unactivated Alkyl Fluorides using YbI3.</a> Angew. Chem. Int. Ed. 52 (46), 12073-12076 (2013).</li>
<li>Deacon, G. B., Jaroschik, F., Junk, P. C., Kelly, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+Divalent+Heteroleptic+Lanthanoid+Fluoride+Complex+Stabilised+by+the+Tetraphenylcyclopentadienyl+Ligand%2C+Arising+From+C-F+Activation+of+Pentafluorobenzene%5BTitle%5D)+AND+%22Chem.+Commun%22%5BJournal%5D)">A Divalent Heteroleptic Lanthanoid Fluoride Complex Stabilised by the Tetraphenylcyclopentadienyl Ligand, Arising From C-F Activation of Pentafluorobenzene.</a> Chem. Commun. 50 (73), 10655-10657 (2014).</li>
<li>Kumar, T., Massicot, F., Harakat, D., Chevreux, S., Martinez, A., Bordolinska, K., Preethanuj, P., Kokkuvayil Vasu, R., Behr, J. -B., Vasse, J. -L., Jaroschik, F. <a target="_blank" href="https://www.ncbi.nlm.nih.gov/pubmed/28980352">Generation of ε,ε-Difluorinated Metal-Pentadienyl Species through Lanthanide-Mediated C-F Activation.</a> Chem. Eur. J. 23 (65), 16460-16465 (2017).</li>
<li>Philips, F., Maria, A. <a target="_blank" href="http://www.eurekaselect.com/134899">Organocatalytic Asymmetric Nitro-Michael Reactions.</a> Curr. Org. Synth. 13 (5), 687-725 (2016).</li>
<li>Zhang, X., Cao, S. <a target="_blank" href="https://www.sciencedirect.com/science/article/pii/S0040403916317026">Recent Advances in the Synthesis and CF Functionalization of Gem-difluoroalkenes.</a> Tetrahedron Lett. 58 (5), 375-392 (2017).</li>
<li>Kodukulla, R. P. K., Trivedi, G. K., Vora, J. D., Mathur, H. H. <a target="_blank" href="https://www.tandfonline.com/doi/abs/10.1080/00397919408011304">Synthesis, Chemical Transformation and Antimicrobial Activity of a Novel Class of Nitroolefins: 1,3-Diaryl-2-nitroprop-1-enes.</a> Synth. Commun. 24 (6), 819-832 (1994).</li>
</ol>

The authors have nothing to disclose.

This protocol involves work with highly reactive, air and moisture sensitive lanthanide metals. Therefore, the whole reaction procedure must be carried out under dry inert gas, and all starting materials, including solvents, must be very clean and dried before use.
There are two advantages for the preparation of freshly filed metals over the purchase of already filed metals: (i) the purchase of pieces or ingots is considerably more economic and (ii) freshly filed metal is more reactive because...

Lanthanide metals have been sporadically used in organic synthesis since the late 1970s1. Initially, these strong reducing agents, with a redox potential Ln3+/Ln&#160;of approximately -2.3 V, were employed mainly in Birch-type reductions of aromatic compounds and pinacol coupling reactions. An increased availability and purity of lanthanide metals from the 1980s on, as well as the development of methodologies and equipment to handle air and moisture sensitive compounds led to new applications of lanthanide metals. The preparation of the widely used SmI2 directly from Sm metal and diiodoethane or iodine was a breakthrough in lanthanide chemistry2. In recent years, new reactivity patterns of lanthanide metals have been described, for example, the Barbier-type reaction of allylic halides with carbonyl compounds3, the reductive coupling reactions involving diaryl ketones4 or acyl chlorides5, selective cyclopropanation reactions6, and the combination of lanthanide metals with group 4 metallocenes7,8. These studies showed that lanthanide metals display a promising functional group tolerance and that their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic transformations.
Organolanthanide complexes and inorganic lanthanide salts have been studied in C-F activation reactions with aromatic and aliphatic carbon-fluorine bonds for over 40 years9,10,11. In 2014, the first report on C-F activation using elemental ytterbium metal appeared12. It showed the regioselective reaction of Yb with pentafluorobenzene to afford p-tetrafluorobenzene and YbF2. More recently, we have shown that various lanthanide metals can react with trifluoromethylated benzofulvenes in the presence of aluminum chloride to obtain &#949;,&#949;-difluoropentadienylmetal complexes that reacted selectively with a wide range of aldehydes to new difluoroalkenes (Figure 1)13. It turned out that the combination of dysprosium metal and aluminum chloride gave the highest yields and best selectivities. We herein present an extension of this work using nitroalkenes as electrophiles14, leading regioselectively to a new class of difluoroalkenes15.

<table><tbody><tr><td>Dysprosium ingot</td><td>Strem</td><td>93-6637</td><td>Store under nitrogen/argon</td></tr><tr><td>Anhydrous aluminum chloride</td><td>Alfa Aesar</td><td>88488</td><td>Store under nitrogen/argon</td></tr><tr><td>Iodine 99.5% for analysis</td><td>Across Organics</td><td>212491000</td><td></td></tr><tr><td>THF GPR Rectapur</td><td>VWR Chemicals</td><td>28552.324</td><td>Dried and distilled over Na/benzophenone before use</td></tr><tr><td>Glovebox</td><td>MBraun</td><td></td><td>Under nitrogen atmosphere</td></tr></tbody></table>

application of elemental lanthanides in the selective c-f activation of trifluoromethylated benzofulvenes providing access to various difluoroalkenes

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln&#160;of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg&#160;redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.

This lanthanide-mediated C-F activation procedure followed by reaction with nitroalkenes provides readily access to new difluoroalkenes containing a nitro group. A plausible reaction mechanism is depicted in Figure 2. In contrast to our previous work using aldehydes as electrophiles (Figure 1)13, nitroalkenes afford the 1,3-disubstituted indene products regioselectively. This may be explained by the greate...

Watch this Scientific Journal Video about Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes at JoVE.

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

This protocol describes the preparation of elemental lanthanides under inert atmosphere and their application in a selective C-F activation process involving trifluoromethylated benzofulvenes.

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the ...

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6.4K Views.  Université de Reims Champagne Ardenne. Dit protocol beschrijft de bereiding van elementaire lanthaniden onder inerte atmosfeer en hun toepassing in een selectieve C-F-activeringsproces waarbij trifluoromethylated benzofulvenes.

Video: Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

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 ...

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

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 ...

Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high atomic and step economy. However, this functionality-directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required, producing a large amount of waste. Due to our interest in novel 1,3-butadiene synthesis, we describe the ruthenium-catalyzed olefination of electron-deficient alkenes using allyl acetate and without external oxidant. The reaction of 2-phenyl acrylamide and allyl acetate was chosen as a model reaction, and the desired diene product was obtained in 80% isolated yield with good stereoselectivity (Z,E/Z,Z = 88:12) under optimal conditions: [Ru(p-cymene) Cl2]2 (3 mol %) and AgSbF6 (20 mol %) in DCE at 110 &#186;C for 16 h. With the optimized catalytic conditions in hand, representative &#945;- and/or &#946;-substituted acrylamides were investigated, and all reacted smoothly, regardless of aliphatic or aromatic groups. Also, differently N-substituted acrylamides have proven to be good substrates. Moreover, we examined the reactivity of different allyl derivatives, suggesting that the chelation of acetate oxygen to the metal is crucial for the catalytic process. Deuterium-labeled experiments were also conducted to investigate the reaction mechanism. Only Z-selective H/D exchanges on acrylamide were observed, indicating a reversible cyclometalation event. In addition, a kinetic isotope effect (KIE) of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic C-H metalation step is probably involved in the rate-determining step.

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

The ruthenium-catalyzed olefination of electron-deficient alkenes with allyl acetate is described here. By using aminocarbonyl as a directing group, this external oxidant-free protocol has high efficiency and good stereo- and regioselectivity, opening a novel synthetic route to (Z,E)-butadiene skeletons.

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

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.

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

Easy Access to Aliphatic Sulfonamides using Sulfamoyl Chlorides Under Visible Light Activation

Sulfonamides are prevalent motifs in marketed drugs and natural products. Their synthesis represents a great interest to the pharmaceutical industry, due to their unique biological properties. Recently, several methods for the synthesis of aryl sulfonamides have been developed, but little effort has focused on developing one-step methodologies to access sulfonamides flanked by two alkyl groups. This protocol describes a practical and facile method for the net hydrosulfamoylation of electron-deficient alkenes using sulfamoyl chlorides as radical precursors under blue-light activation. This practical and cost-effective methodology is performed in the presence of the metal-free photocatalyst Eosin Y and uses light as a clean and traceless energy source. The procedure is scalable, displays a broad functional group tolerance, and can be applied for late-stage functionalization. All reagents used in this protocol are commercially available. Simple reaction set-up, the absence of work-up and easy purification, demonstrate the convenience of this protocol. The reaction is best applied to electron-deficient alkenes.

Presented here is a protocol for the easy synthesis of aliphatic sulfonamides using sulfamoyl chlorides, (TMS)3SiH and Eosin Y under blue-light irradiation.

Sulfonamides are prevalent motifs in marketed drugs and natural products. Their synthesis represents a great interest to the pharmaceutical industry, due ...

Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
<img alt="Figure1" src="/files/ftp_upload/12875/12875_PT_Figure_1.svg" style="text-align: center; height: 90px;" />
Unlike fluorine, iodine is highly unreactive for electrophilic aromatic substitution reactions. The iodination of benzene is achieved in the presence of an oxidizing agent such as nitric acid, hydrogen peroxide, or a copper salt. These agents oxidize iodine to iodine cation, which behaves as a powerful electrophile, and follows the standard mechanism of the electrophilic aromatic substitution to yield the iodinated product.
<img alt="Figure2" src="/files/ftp_upload/12875/12875_PT_Figure_2.svg" style="text-align: center; height: 70px;" />

Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are ...

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

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