The authors thank the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Canada Foundation for Innovation (CFI) for funding and scholarship support.

NOTE: Deuterated solvents were dried according to literature procedure when necessary, and all other solvents were dried over a series of Grubbs&#39;-type columns12 and degassed prior to use. Potassium 1,2,4-tris(diphenylphosphino)cyclopentadiene [K][(Ph2P)3C5H2] and the N-heterocyclic carbene 1,3,4,5-tetramethylimidazole-2-ylidene (MeNHCMe) were synthesized according to literature procedures and the latter was sublimed prior to use.9,13 Cyclohexene was dried over CaH2, distilled and degassed prior to use. Acetonitrile-d3 (CD3CN) and dichloromethane-d2 (CD2Cl2) were dried over phosphorus pentoxide and degassed prior to use. Diatomaceous earth was dried in an oven at 150 &#186;C overnight prior to use. All other reagents were used as received.
1. Synthesis of [dppeP][Br]
<ol>
	<li>Dissolve 1.00 g of 1,2-bis(diphenylphosphino)ethane (dppe) in approximately 40 ml of anhydrous, degassed dichloromethane (DCM) in a 250 ml Schlenk flask, under inert gas, equipped with a rubber septum.</li>
	<li>By syringe or cannula transfer, add 2.53 ml of dry, degassed, cyclohexene to the Schlenk flask containing the stirring solution of dppe.</li>
	<li>To this solution, add 0.26 ml of PBr3 via syringe, dropwise with vigorous stirring. The solution should immediately turn pale yellow, and white precipitate forms after stirring the solution for 20 min. Allow the reaction to stir for several hours or overnight.</li>
	<li>After stirring for several hours or overnight, filter the reaction mixture through a fritted flask topped with a one-inch thick diatomaceous earth plug to remove the precipitate.</li>
	<li>Collect the resulting solution and remove the DCM under vacuum on a Schlenk line.</li>
	<li>To the resulting oil, add approximately 75 ml of tetrahydrofuran (THF) while stirring vigorously (or sonicating) to precipitate the product as a white solid.</li>
	<li>Immediately after the white precipitate forms, collect it via filtration with a fritted flask under an inert atmosphere. Collect the solid immediately, and do not leave the suspension to stir for more than 30 min.</li>
	<li>Once collected, dissolve a small amount of [dppeP][Br] in CD2Cl2 or CDCl3 to obtain 31P, 1H and 13C NMR to confirm purity. [dppeP][Br] can be stored indefinitely in an inert atmosphere, or for several weeks on the benchtop.6</li>
</ol>
2. Synthesis of [dppeP][BPh4]
<ol>
	<li>Dissolve 0.5 g of [dppeP][Br] salt in 5 ml of DCM, in a Schlenk flask. Stir the solution under nitrogen gas. Then, add 0.35 g of sodium tetraphenylborate in 5 ml of THF.</li>
	<li>Allow the solution to stir for several hours or overnight, until a fine precipitate forms.</li>
	<li>Centrifuge the suspension to eliminate the precipitate (KBr) and remove the solvent under reduced pressure to yield [dppeP][BPh4] as a white powder.</li>
</ol>
3. Synthesis of [MeNHCMe2P][BPh4]
<ol>
	<li>Load a 100 ml Schlenk flask with 0.200 g of MeNHCMe and a stir bar under an inert atmosphere.</li>
	<li>Load a 100 ml round bottom flask with 0.603 g of [dppeP][BPh4] under an inert atmosphere.</li>
	<li>Cannula transfer 20 ml of THF to the Schlenk flask containing 0.200 g of MeNHCMe and begin magnetic stirring.</li>
	<li>Cannula transfer 20 ml of THF to the 100 ml round bottom flask with 0.603 g of [dppeP][BPh4] and stir until dissolved.</li>
	<li>Cannula transfer the solution of [dppeP][BPh4] in THF to the stirring solution of MeNHCMe in THF and allow the yellow solution to stir for 1 hr.</li>
	<li>Concentrate the yellow solution to a third of the original volume (13 ml) under reduced pressure.</li>
	<li>Add diethyl ether (Et2O) (40 ml) to the stirring concentrated solution to initiate precipitation of the yellow product and allow the resultant suspension to stir for 20 min.</li>
	<li>Place a sealed frit fitted attached to a 100 ml Schlenk flask on the Schlenk line and create an inert atmosphere by evacuating the flask using vacuum and refilling the flask with nitrogen from the Schleck line. Evacuate for 5 min and refill with nitrogen 3 times to insure an inert atmosphere.</li>
	<li>Cannula transfer the Et2O suspension into the apparatus and filter the precipitate.</li>
	<li>Wash the precipitate with 10 ml of Et2O three times and allow the precipitate to dry under reduced pressure for 2 hr.</li>
	<li>Optional) Allow the filtrate and washings to evaporate slowly under nitrogen to recrystallize dppe. Wash the crystals with a minimal amount of hexanes, dry, and collect the crystals for re-use.</li>
</ol>
4. Synthesis of (Ph2P)C5H2(Ph2P)2P
<ol>
	<li>To a 150 ml Schlenk flask containing 0.484g [dppeP][Br] in an inert atmosphere, add 40 ml of dry, degassed THF.</li>
	<li>Place the Schlenk in a dry-ice/acetone bath to cool the suspension to -78 &#176;C.</li>
	<li>Cannula transfer a THF solution of 0.625g [K][(Ph2P)3C5H2] in a round bottom flask, to the Schlenk flash containing [dppeP][Br].</li>
	<li>When the addition is complete, remove the Schlenk flask from the acetone bath and allow to warm to room temperature. After stirring for 2 hr, the solution will be light yellow with a white precipitate present.</li>
	<li>Transfer the suspension to an air-free fritted filter equipped with a 150 ml Schlenk flask, to remove the white precipitate (KBr).</li>
	<li>Collect the yellow solution and remove the THF under vacuum.</li>
	<li>Add an 80:20 mixture of dry and degassed diethyl ether:pentane to the resulting oil and allow to stir for 20 min.</li>
	<li>Collect the product (Ph2P)C5H2(Ph2P)2P as a pale yellow precipitate by filtering the suspension through an air-free, fritted flask. The remaining ether/pentane solution contains the dppe impurity and may be discarded or the solvent may be removed under vacuum and the dppe collected for further use.</li>
</ol>

<ol>
	<li>Macdonald, C. L. B., Ellis, B. D., Swidan, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-Oxidation-State+Main+Group+Compounds.">Low-Oxidation-State Main Group Compounds.</a> Encyclopedia of Inorganic and Bioinorganic Chemistry. , (2011).</li><li>Coffer (n&#233;e Monks), P. K., Dillon, K. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cyclic+triphosphenium+ions+and+related+species.">Cyclic triphosphenium ions and related species.</a> Coord. Chem. Rev. 257 (5-6), 910-923 (2013).</li><li>Schmidpeter, A., Lochschmidt, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+Products+from+PCl3,+P(NMe2)3,+and+AlCl3.">New Products from PCl3, P(NMe2)3, and AlCl3.</a> Angew. Chem. Internat. Ed. in Engl. 25 (3), 253-254 (1986).</li><li>Schmidpeter, A., Lochschmidt, S., Karaghiosoff, K., Sheldrickb, W. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Triphosphane-l,3-di-ium+Ions.">Triphosphane-l,3-di-ium Ions.</a> J. Chem. Soc. Chem. Commun. , 1447-1448 (1985).</li><li>Ellis, B. D., Carlesimo, M., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stabilised+phosphorus(I)+and+arsenic(I)+iodide:+readily-synthesised+reagents+for+low+oxidation+state+main+group+chemistry.">Stabilised phosphorus(I) and arsenic(I) iodide: readily-synthesised reagents for low oxidation state main group chemistry.</a> Chem. Commun. 15 (15), 1946-1947 (2003).</li><li>Norton, E. L., Szekely, K. L. S., Dube, J. W., Bomben, P. G., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+convenient+preparative+method+for+cyclic+triphosphenium+bromide+and+chloride+salts.">A convenient preparative method for cyclic triphosphenium bromide and chloride salts.</a> Inorg. Chem. 47 (3), 1196-1203 (2008).</li><li>Ellis, B. D., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phosphorus(I)+iodide:+a+versatile+metathesis+reagent+for+the+synthesis+of+low+oxidation+state+phosphorus+compounds.">Phosphorus(I) iodide: a versatile metathesis reagent for the synthesis of low oxidation state phosphorus compounds.</a> Inorg. Chem. 45 (17), 6864-6874 (2006).</li><li>Kosnik, S. C., Farrar, G. J., Norton, E. L., Cooper, B. F. T., Ellis, B. D., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-Valent+Chemistry:+An+Alternative+Approach+to+Phosphorus-+Containing+Oligomers.">Low-Valent Chemistry: An Alternative Approach to Phosphorus- Containing Oligomers.</a> Inorg. Chem. 11 (53), 13061-13069 (2014).</li><li>Kosnik, S. C., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+zwitterionic+triphosphenium+compound+as+a+tunable+multifunctional+donor.">A zwitterionic triphosphenium compound as a tunable multifunctional donor.</a> Dalton Trans. 45 (14), 6251-6258 (2016).</li><li>Binder, J. F., Swidan, A., Tang, M., Nguyen, J. H., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remarkably+stable+chelating+bis-N-heterocyclic+carbene+adducts+of+phosphorus(I)+cations.">Remarkably stable chelating bis-N-heterocyclic carbene adducts of phosphorus(I) cations.</a> Chem. Commun. 51 (36), 7741-7744 (2015).</li><li>Binder, J. F., Corrente, A. M., Macdonald, C. L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+route+to+phosphamethine+cyanines+from+S,N-heterocyclic+carbenes.">A simple route to phosphamethine cyanines from S,N-heterocyclic carbenes.</a> Dalton Trans. 45 (5), 2138-2147 (2016).</li><li>Pangborn, A. B., Ma Giardello, ., Grubbs, R. H., Rosen, R. K., Timmers, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safe+and+Convenient+Procedure+for+Solvent+Purification.">Safe and Convenient Procedure for Solvent Purification.</a> Organometallics. 15 (5), 1518-1520 (1996).</li><li>Smaliy, R. V., Beaup&#233;rin, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hexaphosphine:+A+multifaceted+ligand+for+transition+metal+coordination.">Hexaphosphine: A multifaceted ligand for transition metal coordination.</a> Eur. J. Inorg. Chem. (9), 1347-1352 (2012).</li><li>Klebach, T. C., Lourens, R., Bickelhaupt, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+mesityldiphenylmethylenephosphine:+a+stable+compound+with+a+localized+phosphorus:carbon+bond.">Synthesis of mesityldiphenylmethylenephosphine: a stable compound with a localized phosphorus:carbon bond.</a> J. Amer. Chem. Soc. 100 (15), 4886-4888 (1978).</li><li>Alcarazo, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&#945;-Cationic+Phosphines:+Synthesis+and+Applications.">&#945;-Cationic Phosphines: Synthesis and Applications.</a> Chem. Eur. J. 20 (26), 7868-7877 (2014).</li></ol>

The authors have nothing to disclose.

Crystal structures and multi-nuclear NMR (31P, 1H, and 13C) were obtained for all products reported to confirm connectivity. Electrospray-ionization mass spectrometry was used to confirm presence of the cations and elemental analysis was used to confirm analytical purity of the samples.
It is imperative that all reactions are done in an air-free and dry environment to ensure that no unexpected by-products or decomposition products are formed. Using a slight excess of dppe as well as an excess (10 equivalents) of cyclohexene is necessary, to ensure good yields of [dppeP][Br].
There are no major limitations of the techniques described herein. The ligand displacement reactions with [dppeP][Br] are only limited to ligands of sufficient donor ability to displace the dppe from the [dppeP][Br] molecule. Notwithstanding, the significant advantage to this methodology is the controlled release of &#34;P+&#34; without the generation of unanticipated by-products or the use of harsh reagents. Thus, this methodology can be employed in the future to generate novel molecules containing PI moieties.

The chemistry of main group elements in unusually low oxidation or valence states has been an area of significant interest over the last two decades.1 Aside from the fundamental interest arising from their unique bonding and structure, such compounds often display reactivities that are very different from those of their more typical oxidation state counterparts. In this sense, they offer significant potential as reagents to build more complex main group-element containing materials.
A landmark class of low-valent phosphorus containing molecules are &#34;triphosphenium&#34; cations which were first reported by Schmidpeter in the 1980s.2 These ions feature a dicoordinate phosphorus(I) ion ligated by two phosphonio substituents, with the more stable variants built from a chelating framework.3,4 Our group has optimized the syntheses of triphosphenium halide salts5-7 and has demonstrated that these stable compounds are versatile P+ transfer agents that are useful for the controlled synthesis of phosphorus(I)-containing oligomers,8 zwitterions,9 and phosphamethine cyanine dyes.10,11 While the original syntheses of such compounds often involve dangerous phosphorus-containing reagents and/or highly reducing conditions, the controlled route we present is safe, P-atom efficient, and convenient. The method results in high purity materials which may be used as dyes, ligands for transition metal complexes and precursors for more complex phosphorus-containing species.

<table border="0" cellpadding="0" cellspacing="0" width="968">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">bis(diphenyl)phosphino ethane (dppe)</td>
			<td style="width:99px;">Strem</td>
			<td style="width:119px;">1663-45-2</td>
			<td style="width:468px;">98% Stored in gloved box, used as is.&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Anhydrous Dichloromethane (DCM)</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">270997</td>
			<td>Purified through solvent purification system, or standard methods</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Anhydrous Cyclohexene&#160;</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">29240</td>
			<td>Dried over calcium hydride and distilled.&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Phosphorus Tribromide (PBr3)</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">157783</td>
			<td>99% Stored in glove box, used as is. Air sensitive</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Anyhydrous Tetrahydrofuran (THF)</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">401757</td>
			<td>Purified through solvent purification system, or standard methods</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Methylene Chloride-D2 (CD2Cl2)</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td style="width:119px;">DLM-23-25</td>
			<td>Dried over phosphorus pentoxide, vacuum transferred or distilled</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Acetonitrile</td>
			<td style="width:99px;">Alfa Aesar</td>
			<td align="right" style="width:119px;">5/8/1975</td>
			<td>Stored in glove box, used as is</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Sodium Tetraphenylborate</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td style="width:119px;">T25402</td>
			<td>Stored in glove box, used as is</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Anyhydrous Diethyl Ether&#160;</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">673811</td>
			<td>Purified through solvent purification system, or standard methods</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:283px;">Anhydrous Pentane</td>
			<td style="width:99px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">236705</td>
			<td>Purified through solvent purification system, or standard methods</td>
		</tr>
	</tbody>
</table>

preparation and reactivity of a triphosphenium bromide salt: a convenient and stable source of phosphorus(i)

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable low-valent-phosphorus-containing compound acts as a useful P+ transfer agent. Unlike traditional methods employed to access low-coordinate phosphorus species which usually require pyrophoric phosphorus-containing precursors (white phosphorus, Tris(trimethylsilyl)phosphine, etc.), or harsh reducing agents (alkali metals, potassium graphite, etc.), the current approach does not involve pyrophoric or explosive reagents and can be done on large scales (&#62;20 g) in excellent yields by undergraduates with basic air-free synthetic training. The bromide counter ion is readily exchanged with other anions such as tetraphenyl borate (described herein) using typical salt metathesis reagents to obtain materials with desired properties and reactivities. The versatility of this P+ transfer approach is exemplified by the reactions of these triphosphenium precursors with an N-heterocyclic carbene and an anionic bisphosphine, each of which readily displace the neutral bisphosphine to give an NHC-stabilized phosphorus(I) cation and a phosphorus(I) containing zwitterion, respectively.

A stable salt ([dppeP][Br]) containing a low valent phosphorus(I) source can be synthesized easily by the addition of PBr3 to diphenylphosphinoethane (dppe) in the presence of excess cyclohexene (Figure 1)6.
Upon work up of the reaction, 31P NMR spectra show the presence of a triplet signal that is significantly shielded at -220 ppm, and a doublet signal at 50 ppm. Strong coupling between the nuclei is observed on the order of 500 Hz (Figure 2).
Single crystals can be grown from concentrated acetonitrile or dichloromethane solutions and single crystal X-ray diffraction analysis reveals that [dppeP][Br] has an ion-separated structure with two formula units present in the asymmetric unit (Figure 4). The bromide ion may be exchanged for a less reactive anion, such as trifluoromethane sulfonate (triflate, OTf) or tetraphenylborate (BPh4). The 31P NMR spectrum of this product is almost identical to that of the starting material [dppeP][Br] (Figure 3).
Addition of [dppeP][BPh4] to a solution containing two equivalents of the carbene MeNHCMe results in displacement of the chelating bis-phosphine by the more strongly donating NHC ligands and generates the yellow phosphamethine cyanine dye [MeNHCMe2P][BPh4] (Figure 1). Because [MeNHCMe2P][BPh4] is soluble in THF but insoluble in diethyl ether, the latter is used to remove the bisphosphine byproduct, which is highly soluble in most solvents. Once separated by filtration, washed and dried, [MeNHCMe2P][BPh4] is obtained as an analytically pure yellow powder. The 31P NMR spectrum of this material dissolved in acetonitrile-d3 features a singlet signal at -113 ppm, which is significantly shielded relative to typical phosphaalkenes (cf. 31P NMR &#948; for P-mesityldiphenylmethylenephosphine = 233.06 ppm14) which is consistent with the phosphorus(I) assignment (Figure 5).
Likewise, the relatively long C-P bond lengths, the acute C-P-C angle and twisting of the heterocycles from the C-P-C plane observed in the crystal structure of [MeNHCMe2P][BPh4] (Figure 6) are also most consistent with the phosphorus(I) description. In addition to its potential applications as a dye, compounds such as [MeNHCMe2P][BPh4] have also proven to be useful ligands and reagents for the preparation of cationic phosphines of a type that are useful components in catalytic applications.15
The reaction of potassium 1,2,4-tris(diphenylphosphino)cyclopentadiene in a 1:1 stoichiometric ratio with [dppeP][Br] yields (Ph2P)C5H2(Ph2P)2P in quantitative yield (Figure 1)9. The only byproducts from this reaction, namely KBr and dppe, can be removed by filtrations in THF and diethyl ether/pentane respectively. The 31P NMR spectrum obtained from a concentrated solution of (Ph2P)C5H2(Ph2P)2P in CD2Cl2 (Figure 7) reveals the presence of a triplet signal at -174 ppm, attributable to the dicoordinate phosphorus(I) center, a singlet signal at -16.9 ppm for the Ph2P fragment on the backbone, and a doublet signal attributable to the two Ph2P groups that chelate the phosphorus(I) center.
This structure of this molecule obtained from a single crystal X-ray diffraction analysis is shown in Figure 8. Crystals can be grown via slow evaporation of a concentrated solution of DCM, THF, or even a dilute solution of diethyl ether. The ligand chemistry of (Ph2P)C5H2(Ph2P)2P is of interest because the molecule features three different types of donor sites with which it may interact with metals: it features a phosphine site, a phosphide-like site, and a cyclopentadienide site.9
<img alt="Figure 1" src="/files/ftp_upload/55021/55021fig1.jpg" /> 
Figure 1. Reaction of dppe with PBr3 and cyclohexene, [dppeP][BPh4] with MeNHCMe, and dppeP][Br] with [K][(Ph2P)3C5H2]. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/55021/55021fig2.jpg" /> 
Figure 2. 31P (A), 1H (B), and 13C (C) NMR spectra of [dppeP][Br] collected in CD2Cl2 prepared as described in the protocol. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/55021/55021fig3.jpg" /> 
Figure 3. 31P (A), 1H (B), 11B (C), and 13C (D) [dppeP][BPh4] collected in CD2Cl2 prepared as described in the protocol. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" src="/files/ftp_upload/55021/55021fig4.jpg" /> 
Figure 4. Molecular Structure of [dppeP][Br] (A) and [dppeP][BPh4] (B). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" src="/files/ftp_upload/55021/55021fig5.jpg" /> 
Figure 5. 31P (A), 1H (B), 11B (C) and 13C (D) NMR spectra of [MeNHCMe2P][BPh4] collected in CD3CN prepared as described in the protocol. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" src="/files/ftp_upload/55021/55021fig6.jpg" /> 
Figure 6. Molecular Structure of [MeNHCMe2P][BPh4]. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 7" src="/files/ftp_upload/55021/55021fig7.jpg" /> 
Figure 7. 31P (A), 1H (B), and 13C (C) NMR spectra of (Ph2P)C5H2(Ph2P)2P collected in CD2Cl2 prepared as described in the protocol. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig7large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 8" src="/files/ftp_upload/55021/55021fig8.jpg" /> 
Figure 8. Molecular Structure of (Ph2P)C5H2(Ph2P)2P. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55021/55021fig8large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI at JoVE.com

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI

The synthesis of a triphosphenium bromide salt is described and its use as a P+ transfer agent is outlined by reactions with an N-heterocyclic carbene and an anionic bisphosphine, yielding an NHC-stabilized P(I) cation and a P(I) containing zwitterion, respectively.

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I)

We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable ...

preparation-reactivity-triphosphenium-bromide-salt-convenient-stable

Nanyang Technological University

Research

JoVE Journal

Chemistry

7.7K Views.  University of Windsor. The synthesis of a triphosphenium bromide salt is described and its use as a P+ transfer agent is outlined by reactions with an N-heterocyclic carbene and an anionic bisphosphine, yielding an NHC-stabilized P(I) cation and a P(I) containing zwitterion, respectively.

Video: Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of molecular iodine to samarium metal in THF.1,2-3 It is a mild and selective single electron reductant and its versatility is a result of its ability to initiate a wide range of reductions including C-C bond-forming and cascade or sequential reactions. SmI2 can reduce a variety of functional groups including sulfoxides and sulfones, phosphine oxides, epoxides, alkyl and aryl halides, carbonyls, and conjugated double bonds.2-12 One of the fascinating features of SmI-2-mediated reactions is the ability to manipulate the outcome of reactions through the selective use of cosolvents or additives. In most instances, additives are essential in controlling the rate of reduction and the chemo- or stereoselectivity of reactions.13-14 Additives commonly utilized to fine tune the reactivity of SmI2 can be classified into three major groups: (1) Lewis bases (HMPA, other electron-donor ligands, chelating ethers, etc.), (2) proton sources (alcohols, water etc.), and (3) inorganic additives (Ni(acac)2, FeCl3, etc).3
Understanding the mechanism of SmI2 reactions and the role of the additives enables utilization of the full potential of the reagent in organic synthesis. The Sm-Barbier reaction is chosen to illustrate the synthetic importance and mechanistic role of two common additives: HMPA and Ni(II) in this reaction. The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot.1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported,1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products.16,17 Previous studies on the effect of additives on SmI2 reactions have shown that HMPA enhances the reduction potential of SmI2 by coordinating to the samarium metal center, producing a more powerful,13-14,18 sterically encumbered reductant19-21 and in some cases playing an integral role in post electron-transfer steps facilitating subsequent bond-forming events.22 In the Sm-Barbier reaction, HMPA has been shown to additionally activate the alkyl halide by forming a complex in a pre-equilibrium step.23
Ni(II) salts are a catalytic additive used frequently in Sm-mediated transformations.24-27 Though critical for success, the mechanistic role of Ni(II) was not known in these reactions. Recently it has been shown that SmI2 reduces Ni(II) to Ni(0), and the reaction is then carried out through organometallic Ni(0) chemistry.28
These mechanistic studies highlight that although the same Barbier product is obtained, the use of different additives in the SmI2 reaction drastically alters the mechanistic pathway of the reaction. The protocol for running these SmI2-initiated reactions is described.

Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

A straightforward procedure for the preparation of samarium diiodide (SmI2) in THF is described. The role of two main additives namely hexamethylphosphoramide (HMPA) and Ni(acac)2 in Sm mediated reactions is demonstrated in the Sm-Barbier reaction.

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of ...

Preparing Adherent Cells for X-ray Fluorescence Imaging by Chemical Fixation

X-ray fluorescence imaging allows us to non-destructively measure the spatial distribution and concentration of multiple elements simultaneously over large or small sample areas. It has been applied in many areas of science, including materials science, geoscience, studying works of cultural heritage, and in chemical biology. In the case of chemical biology, for example, visualizing the metal distributions within cells allows us to study both naturally-occurring metal ions in the cells, as well as exogenously-introduced metals such as drugs and nanoparticles. Due to the fully hydrated nature of nearly all biological samples, cryo-fixation followed by imaging under cryogenic temperature represents the ideal imaging modality currently available. However, under the circumstances that such a combination is not easily accessible or practical, aldehyde based chemical fixation remains useful and sometimes inevitable. This article describes in as much detail as possible in the preparation of adherent mammalian cells by chemical fixation for X-ray fluorescent imaging.

Here, we present a protocol on how to determine the quantity and distribution of metals in a sample using synchrotron X-ray fluorescence. We focus on adherent cells, and describe the chemical fixation method to prepare this sample. We then describe how to mount and image the sample using synchrotron X-rays.

X-ray fluorescence imaging allows us to non-destructively measure the spatial distribution and concentration of multiple elements simultaneously over ...

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N-triphosPh ligand precipitates from the solution after approximately 1 hr of reflux and can be isolated analytically pure via simple cannula filtration procedure under nitrogen. Reaction of the N-triphosPh ligand with [Ru3(CO)12] under reflux affords a deep red solution that show evolution of CO gas on ligand complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-&#954;3P] (2) were isolated on cooling to RT. The 31P{1H} NMR spectrum showed a characteristic single peak at lower frequency compared to the free ligand. Reaction of a toluene solution of complex 2 with oxygen resulted in the instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}-&#954;3P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under 15 bar of hydrogen in a high-pressure reactor gave the dihydride complex [RuH2(CO){N(CH2PPh2)3}-&#954;3P] (4), which was fully characterized by X-ray crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful catalyst precursors for a range of hydrogenation reactions, including biomass-derived products such as levulinic acid (LA). Complex 4 was found to cleanly react with LA in the presence of the proton source additive NH4PF6 to give [Ru(CO){N(CH2PPh2)3}-&#954;3P{CH3CO(CH2)2CO2H}-&#954;2O](PF6) (6).

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Ruthenium phosphine complexes are widely used for homogeneous catalytic reactions such as hydrogenations. The synthesis of a series of novel tridentate ruthenium complexes bearing the N-triphos ligand N(CH2PPh2)3 is reported. Additionally, the stoichiometric reaction of a dihydride Ru&#8211;N-triphos complex with levulinic acid is described.

Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N-triphosPh) (1) via a phosphorus based Mannich reaction of the ...

Preparation of Mica and Silicon Substrates for DNA Origami Analysis and Experimentation

The designed nature and controlled, one-pot synthesis of DNA origami provides exciting opportunities in many fields, particularly nanoelectronics. Many of these applications require interaction with and adhesion of DNA nanostructures to a substrate. Due to its atomically flat and easily cleaned nature, mica has been the substrate of choice for DNA origami experiments. However, the practical applications of mica are relatively limited compared to those of semiconductor substrates. For this reason, a straightforward, stable, and repeatable process for DNA origami adhesion on derivatized silicon oxide is presented here. To promote the adhesion of DNA nanostructures to silicon oxide surface, a self-assembled monolayer of 3-aminopropyltriethoxysilane (APTES) is deposited from an aqueous solution that is compatible with many photoresists. The substrate must be cleaned of all organic and metal contaminants using Radio Corporation of America (RCA) cleaning processes and the native oxide layer must be etched to ensure a flat, functionalizable surface. Cleanrooms are equipped with facilities for silicon cleaning, however many components of DNA origami buffers and solutions are often not allowed in them due to contamination concerns. This manuscript describes the set-up and protocol for in-lab, small-scale silicon cleaning for researchers who do not have access to a cleanroom or would like to incorporate processes that could cause contamination of a cleanroom CMOS clean bench. Additionally, variables for regulating coverage are discussed and how to recognize and avoid common sample preparation problems is described.

Reproducible cleaning processes for substrates used in DNA origami research are described, including bench-top RCA cleaning and derivatization of silicon oxide. Protocols for surface preparation, DNA origami deposition, drying parameters, and simple experimental set-ups are illustrated.

The designed nature and controlled, one-pot synthesis of DNA origami provides exciting opportunities in many fields, particularly nanoelectronics. Many of ...

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 &#181;g/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 oC over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven.

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar ...

A Simple Method for the Size Controlled Synthesis of Stable Oligomeric Clusters of Gold Nanoparticles under Ambient Conditions

Reducing dilute aqueous HAuCl4 with sodium thiocyanate (NaSCN) under alkaline conditions produces 2 to 3 nm diameter nanoparticles. Stable grape-like oligomeric clusters of these yellow nanoparticles of narrow size distribution are synthesized under ambient conditions via two methods. The delay-time method controls the number of subunits in the oligoclusters by varying the time between the addition of HAuCl4 to alkaline solution and the subsequent addition of reducing agent, NaSCN. The yellow oligoclusters produced range in size from ~3 to ~25 nm. This size range can be further extended by an add-on method utilizing hydroxylated gold chloride (Na+[Au(OH4-x)Clx]-) to auto-catalytically increase the number of subunits in the as-synthesized oligocluster nanoparticles, providing a total range of 3 nm to 70 nm. The crude oligocluster preparations display narrow size distributions and do not require further fractionation for most purposes. The oligoclusters formed can be concentrated &#62;300 fold without aggregation and the crude reaction mixtures remain stable for weeks without further processing. Because these oligomeric clusters can be concentrated before derivatization they allow expensive derivatizing agents to be used economically. In addition, we present two models by which predictions of particle size can be made with great accuracy.

We describe a simple method for producing highly stable oligomeric clusters of gold nanoparticles via the reduction of chloroauric acid (HAuCl4) with sodium thiocyanate (NaSCN). The oligoclusters have a narrow size distribution and can be produced with a wide range of sizes and surface coats.

Reducing dilute aqueous HAuCl4 with sodium thiocyanate (NaSCN) under alkaline conditions produces 2 to 3 nm diameter nanoparticles. Stable grape-like ...

Combining Solid-state and Solution-based Techniques: Synthesis and Reactivity of Chalcogenidoplumbates(II or IV)

The phases of &#34;PbCh2&#34; (Ch = Se, Te) are obtained from solid-state syntheses (i.e., by the fusion of the elements under inert conditions in silica glass ampules). Reduction of such phases by elemental alkaline metals in amines affords crystalline chalcogenidoplumbate(II) salts comprised of [PbTe3]2- or [Pb2Ch3]2- anions, depending upon which sequestering agent for the cations is present: crown ethers, like 18-crown-6, or cryptands, like [2.2.2]crypt. Reactions of solutions of such anions with transition-metal compounds yield (poly-)chalcogenide anions or transition-metal chalcogenide clusters, including one with a &#181;-PbSe ligand (i.e., the heaviest-known CO homolog).
In contrast, the solid-state synthesis of a phase of the nominal composition &#34;K2PbSe2&#34; by successive reactions of the elements and by the subsequent solvothermal treatment in amines yields the first non-oxide/halide inorganic lead(IV) compound: a salt of the ortho-selenidoplumbate(IV) anion [PbSe4]4-. This was unexpected due to the redox potentials of Pb(IV) and Se(-II). Such methods can further be applied to other elemental combinations, leading to the formation of solutions with binary [HgTe2]2- or [BiSe3]3- anions, or to large-scale syntheses of K2Hg2Se3 or K3BiSe3 via the solid-state route.
All compounds are characterized by single-crystal X-ray diffraction and elemental analysis; solutions of plumbate salts can be investigated by 205Pb and 77Se or 127Te NMR techniques. Quantum chemical calculations using density functional theory methods enable energy comparisons. They further allow for insights into the electronic configuration and thus, the bonding situation. Molecular Rh-containing Chevrel-type compounds were found to exhibit delocalized mixed valence, whereas similar telluridopalladate anions are electron-precise; the cluster with the &#181;-PbSe ligand is energetically favored over a hypothetical CO analog, in line with the unsuccessful attempt at its synthesis. The stability of formal Pb(IV) within the [PbSe4]4- anion is mainly due to a suitable stabilization within the crystal lattice.

Combining Solid-state and Solution-based Techniques: Synthesis and Reactivity of ChalcogenidoplumbatesII or IV

The synthesis of chalcogenidoplumbates(II,IV) via the in situ reduction of nominal "PbCh2" (Ch = Chalcogen) and via a solid-state reaction and subsequent solvothermal reactions is presented. Additionally, reactivities of plumbate(II) solutions are portrayed, which yield the heaviest-known CO homolog known to date: the &#181;-PbSe ligand.

The phases of &#34;PbCh2&#34; (Ch = Se, Te) are obtained from solid-state syntheses (i.e., by the fusion of the elements under inert conditions in silica ...

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the inverse electron demand Diels-Alder (IEDDA) cycloaddition between a radiolabeled tetrazines and trans-cyclooctene (TCO) linked to a biomolecule has proven to be a highly effective bioorthogonal approach to imaging specific biological targets. Despite the fact that technetium-99m remains the most widely used isotope in diagnostic nuclear medicine, there is a scarcity of methods for preparing 99mTc-labeled tetrazines. Herein we report the preparation of a family of tridentate-chelate-tetrazine derivatives and their Tc(I) complexes. These hitherto unknown compounds were radiolabeled with 99mTc using a microwave-assisted method in 31% to 83% radiochemical yield. The products are stable in saline and PBS and react rapidly with TCO derivatives in vitro. Their in vivo pre-targeting abilities were demonstrated using a TCO-bisphosphonate (TCO-BP) derivative that localizes to regions of active bone metabolism or injury. In murine studies, the 99mTc-tetrazines showed high activity concentrations in knees and shoulder joints, which was not observed when experiments were performed in the absence of TCO-BP. The overall uptake in non-target organs and pharmacokinetics varied greatly depending on the nature of the linker and polarity of the chelate.

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Here, we describe a protocol for radiolabeling and in vivo testing of tridentate 99mTc(I) chelate-tetrazine derivatives for pre-targeting and bioorthogonal chemistry.

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the ...

A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and related diseases, but their precise measurement is still a challenge. Many protocols have been described for neurotransmitter measurement by a variety of instruments, including high-pressure liquid chromatography (HPLC). However, there are shortcomings, such as complicated operation or hard-to-detect multiple targets, which cannot be avoided, and presently, the dominant analysis technique is still HPLC coupled with sensitive electrochemical or fluorimetric detection, due to its high sensitivity and good selectivity. Here, a detailed protocol is described for the pretreatment and detection of catecholamines with high pressure liquid chromatography with electrochemical detection (HPLC-ECD) in real urine samples of infants, using electrospun composite nanofibers composed of polymeric crown ether with polystyrene as adsorbent, also known as the packed-fiber solid phase extraction (PFSPE) method. We show how urine samples can be easily precleaned by a nanofiber-packed solid phase column, and how the analytes in the sample can be rapidly enriched, desorbed, and detected on an ECD system. PFSPE greatly simplifies the pretreatment procedures for biological samples, allowing for decreased time, expense, and reduction of the loss of targets. 
Overall, this work illustrates a simple and convenient protocol for solid-phase extraction coupled to an HPLC-ECD system for simultaneous determination of three monoamine neurotransmitters (norepinephrine (NE), epinephrine (E), dopamine (DA)) and two of their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC)) in infants' urine. The established protocol was applied to assess the differences of urinary catecholamines and their metabolites between high-risk infants with perinatal brain damage and healthy controls. Comparative analysis revealed a significant difference in urinary MHPG between the two groups, indicating that the catecholamine metabolites may be an important candidate marker for early diagnosis of cases at risk for brain damage in infants.

We present a convenient solid-phase extraction coupled to high-pressure liquid chromatography (HPLC) with electrochemical detection (ECD) for simultaneous determination of three monoamine neurotransmitters and two of their metabolites in infants' urine. We also identify the metabolite MHPG as a potential biomarker for the early diagnosis of brain damage for infants.

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and ...

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 ...