Financial support by the Z&#252;rich University of Applied Sciences as well as the Swiss National Science Foundation (SNSF) is acknowledged.

1. Ligand Synthesis (1,1',1''-(Phosphinetriyl)tripiperidine)
<ol>
	<li>Add 150 ml of dry diethyl ether and 5 ml of phosphorous trichloride (57.3 mmol) in an oven-dried 500 ml round bottomed flask. Put a stir bar in the round bottomed flask and attach a 250 ml dropping funnel and cover the flask with septa.</li>
	<li>Cool down the solution to 0 &#176;C by placing the round-bottomed flask in an ice bath.</li>
	<li>Prepare a solution of 42.5 ml of piperidine (429.8 mmol, 7.5 equiv. rel. to PCl3) and 100 ml of diethyl ether and add this solution slowly via the dropping funnel into the stirred diethyl ether solution, containing phosphorous trichloride. The piperidine addition is accompanied by the precipitation of piperidinium chloride.</li>
	<li>After complete addition, warm up the reaction mixture to RT. In order to ensure full conversion, stir the solution for additional 30 min at RT.</li>
	<li>Filter the reaction mixture over a glass frit and collect the filtrate in a 500 ml round bottomed flask. In order to increase the yield of 1,1',1''-(phosphinetriyl)tripiperidine wash the filter cake with additional 100 ml of dry diethyl ether.</li>
	<li>Evaporate the solvent of the filtrate on a rotary evaporator to obtain the pure ligand (1,1',1''-(phosphinetriyl)tripiperidine) in &#62;80% yield as an off-white oil, which solidifies with time. Check the product purity by 31P{1H} NMR spectroscopy (&#948; at 117.3 ppm in C6D6)8a.</li>
</ol>
2. Catalyst Synthesis (Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium)
<ol>
	<li>Weigh out [Pd(cod)Cl2] (0.35 mmol, 100 mg) and add to a clean, oven-dried 50 ml round bottomed flask containing 10 ml of dry THF. Add a stir bar, cover the flask with a septum and stir the suspension.</li>
	<li>Weigh out 1,1',1''-(phosphinetriyl)tripiperidine (0.875 mmol, 248 mg) and add to a clean, dry vial containing 10 ml of dry THF. Add the 1,1',1''-(phosphinetriyl)tripiperidine solution via a syringe through the septum to the THF suspension of [Pd(cod)Cl2]. The suspension turns immediately into a dark yellow solution while addition, indicating completion of the reaction.</li>
	<li>In order to remove insoluble solids pass the reaction mixture quickly through an oven-dried glass frit and collect the filtrate in a 25 ml round bottomed flask. Remove the volatiles under reduced pressure. Wash the palladium complex three times with 5 ml of pentane.</li>
	<li>Remove the pentane by decantation. Dry the yellow powder under reduced pressure to quantitatively obtain the analytically pure palladium complex [(P(C5H10N)3)2PdCl2] (1). Check the purity of 1 by 31P{1H} NMR spectroscopy (&#948; at 92.5 ppm in C6D6)30.</li>
</ol>
3. Heck Reaction Catalyzed by [(P(C5H10N)3)2PdCl2] (1)
<ol>
	<li>Weight out [(P(C5H10N)3)2PdCl2] (0.05 mmol, 37.15 mg) and add to an oven-dried 25 ml Schlenk. Cover the Schlenk with a septum; evacuate the Schlenk and backfill with dinitrogen. Add 10 ml of dry and degassed THF via syringe through the septum into the flask.</li>
	<li>Weight out tetrabutylammonium bromide (1.0 mmol, 322.4 mg) and potassium carbonate (20 mmol, 2.77 g) and add them in a clean, oven-dried 25 ml round-bottomed Schlenk flask. Add 20 ml of N-methyl-2-pyrrolidone (NMP) through a syringe into the Schlenk flask36, 37. Add a stir bar and cover the flask with septa. Evacuate and backfill the Schlenk flask with dinitrogen.</li>
	<li>Dissolve 1-bromo-4-phenoxybenzene (10 mmol, 1.75 ml) and styrene (15 mmol, 1.72 ml) in 5 ml of NMP and add this solution via syringe into the Schlenk flask. Attach a reflux condenser by applying a dinitrogen stream. Connect the reflux condenser with an oil bubbler and set a slight overpressure of dinitrogen.</li>
	<li>Heat up the reaction solution to 100 &#176;C and stir the solution for 5 min on this temperature. Add the catalyst solution (0.05 mol%, 0.005 mmol, 1 ml of THF) to the hot reaction mixture via syringe and stir it vigorously for the indicated time (3 hr in this example). Check the product formation by GC/MS.</li>
	<li>Remove the Schlenk from the oil bath, expose the reaction mixture to air and quench with 50 ml of 1 M hydrochloric acid. Add the cooled reaction mixture into a 500 ml separation funnel and add ethyl acetate (50 ml). Separate the Heck product by extraction and combine all organic phases in an Erlenmeyer flask. Add magnesium sulfate to soak up any last amount of water present in the solution.</li>
	<li>Filter the combined organic layers over a paper filter into a round bottomed flask. Wash the filter cake with additional 50 ml ethyl acetate. Concentrate the solution on a rotary evaporator to obtain the crude coupling product.</li>
	<li>Separate the Heck product via column chromatography, using a mixture of hexane and diethyl ether (5:1) as eluent. Evaporate the solvent on a rotatory evaporator. Check the product purity by 1H and 13C{1H} NMR spectroscopy35.</li>
</ol>

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The authors have nothing to disclose.

Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium (1) is a very cheap and easy accessible, air stable and highly active Heck catalyst with an excellent functional group tolerance that efficiently operates under mild reaction conditions to give the coupling products cleanly in very high yields. The excellent catalytic activity (and general applicability) of 1 is due to the unique properties of aminophosphines: while the steric bulk as well as the &#963;-donor strength of aminophosphines is essentially the same when compared to their phosphine-based analogues, comparable levels of activity were found for complexes of type [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-3; Figure 3) in cross-coupling reactions where molecular mechanisms are operative. On the other hand, the labile character of P-N bonds in aminophosphines (sensitivity towards protons; in form of water e.g.) offers the possibility to effectively control the formation of palladium nanoparticles: increasing numbers of P-N bonds in the ligands successively eases their water-induced degradation and consequently the formation of nanoparticles from the respective complexes. Accordingly, since palladium nanoparticles are the catalytically active form of 1 in the Heck reaction35, as indicated by sigmoidal-shaped kinetics36, 37 or the efficient inhibition of catalysis after addition of a large excess of metallic mercury to reaction mixtures of aryl bromide, olefin and catalyst, for example38, as well as their detection by analysis of reaction mixtures of exemplary Heck cross-coupling reactions by a transmission electron microscopy (TEM) equipped with an energy dispersive X-ray (EDX) analysator35, substitution of 1,1',1''-(phosphinetriyl)tripiperidine by 1,1&#39;-(cyclohexylphosphinediyl)dipiperidine), 1-(dicyclohexylphosphinyl)piperidine) or tricyclohexylphosphine, which successively increases the complex stability and hence, retards the (water-induced) formation of nanoparticles thereof. As a consequence, while dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palladium, is the catalyst of choice in the Heck reaction performed at 140 &#176;C, the highest catalytic activity was obtained for dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) at 100 &#176;C, the least stable complex within this series.
<img alt="Figure 5" fo:content-width="6in" fo:src="/files/ftp_upload/51444/51444fig5highres.jpg" src="/files/ftp_upload/51444/51444fig5.jpg" /> 
Figure 5. The effect of ligand composition of dichloro{bis(aminophosphine)}palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2) on the complex stability and hence, on the ease of (water-induced) nanoparticle formation and hence, their catalytic performance under mild reaction conditions in the Heck cross-coupling reaction. <a href="https://www.jove.com/files/ftp_upload/51444/51444fig5highres.jpg" target="_blank">Click here to view larger image.</a>
Even though the above described syntheses as well as the Heck reaction protocols are straight forward, some of the common troubleshooting procedures are: (a) make sure that the tetrabutylammonium bromide is newly purchased or properly stored (tetrabutylammonium bromide is hygroscopic), (b) make sure that dry solvents are used for the ligand synthesis when small amounts of ligand were prepared, (c) make sure that 1 is either freshly prepared or stored under an inert atmosphere, (d) make sure that the NMP or DMF are newly purchased, (e) make sure that the chemicals are either newly purchased or properly stored, (f) oven-dry all glassware and cool under vacuum.

Palladium-catalyzed C-C cross-coupling reactions, which were acknowledged by the award of the Nobel Prize in chemistry in December 2010, nowadays belong to an indispensable tool for the target oriented synthesis of complex organic molecules across all research fields and industrial segments. The Mizoroki-Heck reaction for example, allows the coupling of olefins with aryl halides in the presence of a base and is nowadays the most popular method for the preparation of vinylbenzenes (Figure 1). The Heck reaction has been demonstrated to find wide utility in both, total syntheses of natural products in academia and synthesis in pharmaceutical and agrochemical industry1-10.
<img ALT="Figure 1" fo:content-width="6in" fo:src="/files/ftp_upload/51444/51444fig1highres.jpg" src="/files/ftp_upload/51444/51444fig1.jpg" /> 
Figure 1. General Heck cross-coupling reaction between an aryl bromide and an olefin. <a HREF="https://www.jove.com/files/ftp_upload/51444/51444fig1highres.jpg" target="_blank">Click here to view larger image.</a>
Taxol, a mitotic inhibitor used in cancer chemotherapy, Singulair, an asthma drug and the herbicide prosulfuron as well as Cyclotene, a monomer for high performance electronic resins are examples that have been successfully prepared including a Heck-Mizoroki cross-coupling step in their syntheses (Figure 2)11-14.
<img ALT="Figure 2" fo:content-width="6in" fo:src="/files/ftp_upload/51444/51444fig2highres.jpg" src="/files/ftp_upload/51444/51444fig2.jpg" /> 
Figure 2. Examples of industrially relevant organic compounds involving a palladium-catalyzed Heck cross-coupling reaction as key step in their synthesis. <a HREF="https://www.jove.com/files/ftp_upload/51444/51444fig2highres.jpg" target="_blank">Click here to view larger image.</a>
Even though recent developments have considerably increased the activity of Heck catalysts15-29, a typical reaction protocol with aryl bromides as substrates still requires high reaction temperatures (140 &#176;C), catalyst loadings in the range of 1 mol% and reaction times of up to 24 hr. Moreover, modified reaction conditions, including the reaction temperature, catalyst loadings, bases, solvents, and additives, e.g. are often reported, implying that these protocols will rarely find their application in organic syntheses due to lack of generality. Furthermore, most catalysts require multiple reaction steps for their synthesis and hence, are time-consuming and low-yielding. Additionally, inert-atmosphere techniques and expensive starting materials of poor stability are often used for their preparation. This refers to the need of new and improved, cheap and easy accessible, stable and green but reactive and general applicable Heck catalysts with high functional group tolerance that efficiently and reliably operates at low catalyst loadings with general applicable reaction protocols.
Dichloro-bis(aminophosphine) complexes of palladium were recently introduced as easy accessible, cheap and air stable but highly active C-C cross-coupling catalysts with excellent functional group tolerance30-34, of which dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) proved to be a highly efficient, reliable, and versatile Heck catalyst that efficiently operates at 100 &#176;C35. 1 was quantitatively prepared within only a few minutes by treatment of THF suspensions of [Pd(Cl)2(cod)] (cod = cycloocta-1,5-diene) with 1,1',1''-(phosphinetriyl)tripiperidine under air atmosphere at 25 &#176;C. 1,1',1''-(phosphinetriyl)tripiperidine, the respective ligand system was achieved in one step by the dropwise addition of an excess of piperidine to cooled diethyl ether solutions of PCl3. The substrate costs for the preparation of 1,1',1''-(phosphinetriyl)tripiperidine for 1 g of palladium precursor is less than 1&#8364; (estimated from catalogue prices of a chemical supplier) and hence, very cheap.
<img ALT="Figure 3" fo:content-width="6in" fo:src="/files/ftp_upload/51444/51444fig3highres.jpg" src="/files/ftp_upload/51444/51444fig3.jpg" /> 
Figure 3. Synthesis of dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1). <a HREF="https://www.jove.com/files/ftp_upload/51444/51444fig3highres.jpg" target="_blank">Click here to view larger image.</a>
Moreover, despite the simple and cheap synthesis of 1 and its excellent catalytic performance, the addition of aqueous hydrochloric acid (work-up conditions), lead to a rapid and complete catalyst degradation, accompanied by the formation of phosphonate, piperidinium salt, and insoluble palladium-containing decomposition products, which are easily separated from the coupling products. This is an often ignored, but very important issue to be considered (from ecologic and economic points of view) and is of particular importance for the preparation of pharmaceutically relevant compounds.

<table><tbody><tr><td>Phosphorous&amp;nbsp; trichloride</td><td>Sigma-Aldrich</td><td>157791</td><td>Reagent Plus, 99%</td></tr><tr><td>Piperidine</td><td>Sigma-Aldrich</td><td>104094</td><td>Reagent Plus, 99%</td></tr><tr><td>Dichloro(1,5-cyclooctadiene)palladium(II)</td><td>Sigma-Aldrich</td><td>275891</td><td>99%</td></tr><tr><td>Styrene</td><td>Sigma-Aldrich</td><td>S4972</td><td>Reagent Plus, contains 4-&lt;em&gt;tert&lt;/em&gt;-butylcatechol as stabilizer, &amp;ge;99%</td></tr><tr><td>1-Bromo-4-phenoxybenzene</td><td>Sigma-Aldrich</td><td>B65209</td><td>99%</td></tr><tr><td>Tetrabutylammonium bromide</td><td>Acros Organics</td><td>185680025</td><td>+99%</td></tr><tr><td>Potassium carbonate</td><td>Sigma-Aldrich</td><td>347825</td><td>Reagent grade, &amp;ge;98%, powder, -325 mesh</td></tr><tr><td>Silica gel</td><td>Merck</td><td>107734</td><td>Silica gel 60 (0.063-0.2 mm), for column chromatoraphy</td></tr><tr><td>Diethyl ether</td><td>Sigma-Aldrich</td><td>673811</td><td>Anhydrous, ACS reagent, &amp;ge;99.0%, contains BHT as inhibitor</td></tr><tr><td>Tetrahydrofuran (THF)</td><td>Sigma-Aldrich</td><td>186562</td><td>anhydrous, contains 250 ppm BHT as inhibitor, &amp;ge;99.9%</td></tr><tr><td>Pentane</td><td>Sigma-Aldrich</td><td>158941</td><td>reagent grade, 98%</td></tr><tr><td>N-Methyl-2-pyrrolidone (NMP)</td><td>Sigma-Aldrich</td><td>M79603</td><td>Reagent Plus, 99%</td></tr></tbody></table>

mizoroki-heck cross-coupling reactions catalyzed by dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium under mild reaction conditions

Dichloro-bis(aminophosphine) complexes of palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family of easy accessible, very cheap, and air stable, but highly active and universally applicable C-C cross-coupling catalysts with an excellent functional group tolerance. Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1), the least stable complex within this series towards protons; e.g. in the form of water, allows an eased nanoparticle formation and hence, proved to be the most active Heck catalyst within this series at 100 &#176;C and is a very rare example of an effective and versatile catalyst system that efficiently operates under mild reaction conditions. Rapid and complete catalyst degradation under work-up conditions into phosphonates, piperidinium salts and other, palladium-containing decomposition products assure an easy separation of the coupling products from catalyst and ligands. The facile, cheap, and rapid synthesis of 1,1',1"-(phosphinetriyl)tripiperidine and 1 respectively, the simple and convenient use as well as its excellent catalytic performance in the Heck reaction at 100 &#176;C make 1 to one of the most attractive and greenest Heck catalysts available.
We provide here the visualized protocols for the ligand and catalyst syntheses as well as the reaction protocol for Heck reactions performed at 10 mmol scale at 100 &#176;C and show that this catalyst is suitable for its use in organic syntheses.

The above described reaction protocol was successfully applied with styrene (a), 1-ethenyl-3-nitrobenzene (b), 1-chloro-3-ethenylbenzene (c), 1-ethenyl-4-methoxybenzene (d) and 4-ethenylpyridine (e) as well as N,N-dimethylacrylamide (f), 4-acryloylmorpholine (g), and butyl acrylate (h) as coupling partners. Table 1 shows a selection of recently prepared cross-coupling products and gives an impression about the scope of this protocol.35 The coupling products are cleanly formed (Figure 4) and typically obtained in excellent yields within reasonable reaction times. The E-isomer of the arylated olefins is often exclusively formed.
<img alt="Figure 4" fo:content-width="6in" fo:src="/files/ftp_upload/51444/51444fig4highres.jpg" src="/files/ftp_upload/51444/51444fig4.jpg" /> 
Figure 4.&#160;Gas chromatograms recorded from reaction mixtures of the Heck reaction of ethyl 4-bromobenzoate and styrene at 100 &#176;C in DMF in the presence of ~10 mol% of tetrabutylammonium bromide and 0.05 mol% of catalyst, showing the time-dependent product formation. Note that the reaction time is slightly prolonged when compared to the data given in Table 1. This is due to periodical sampling. <a href="https://www.jove.com/files/ftp_upload/51444/51444fig4highres.jpg" target="_blank">Click here to view larger image.</a>
Accordingly, 1 is a cheap, easy accessible and green, stable and hence, convenient but highly reactive Heck catalyst with high functional group tolerance, which efficiently and reliably operates at low catalyst loadings (0.05 mol%) with an easy adaptable and robust reaction protocol.
<img alt="Table 1" fo:content-width="6in" src="/files/ftp_upload/51444/51444table1highres.jpg" width="500" /> 
Table 1. Heck cross-coupling products derived by reactions between aryl bromides and different olefins, catalyzed by 1. Reaction conditions: 1.0 mmol aryl bromide, 1.5 mmol olefin, 2.0 mmol K2CO3, 2.5 ml NMP, tetrabutylammonium bromide (10 mol%), catalyst (0.05 mol%) added in solution (THF), reaction performed at 100 &#176;C under N2 atmosphere. The conversions and product ratios (trans/gem/cis) are determined by GC/MS and are based on aryl bromide. Isolated yields are given in brackets. [a] DMF was used as solvent. <a href="https://www.jove.com/files/ftp_upload/51444/51444table1highres.jpg" target="_blank">Click here to view larger image.</a>
Palladium nanoparticles are the catalytically active form of 1 in the Heck reaction. Hence, increasing amounts of catalyst do not improve but can lower the catalyst&#8217;s performance due to formation of inactive palladium black.
Tetrabutylammonium bromide is known to stabilize nanoparticles and was (in contrast to the Heck reactions performed at 140 &#176;C) found to be essential as additive for the reliable conversion of the substrates into the cross-coupling products with 1 at 100 &#176;C35.
Best results were achieved with DMF when electronically activated or nonactivated aryl bromides were applied to give a2, a5, a6, a7, a13, a17, a18, b1, and h4, for example (Table 1). NMP, however, was found to be the solvent of choice when electronically deactivated and sterically hindered or heterocyclic aryl bromides were coupled with alkenes. Examples include the preparation of a9, a12, a14, c3, d3, d4,e2, e3, f2, f4, g3, g4, h5, and h6 (Table 1).

Watch this Scientific Journal Video about Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions at JoVE.com

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) is an easy accessible, cheap, and air stable, but highly active Heck catalyst with an excellent functional group tolerance that efficiently operates under mild reaction conditions to give the coupling products in very high yields.

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

Dichloro-bis(aminophosphine) complexes of palladium with the general formula of [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family ...

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25.3K Views.  University of Zürich. Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) is an easy accessible, cheap, and air stable, but highly active Heck catalyst with an excellent functional group tolerance that efficiently operates under mild reaction conditions to give the coupling products in very high yields.

Video: Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

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

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

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

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

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 ...

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from ...

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.

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.

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

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

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

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

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

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

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) is an important intermediate of Upatinib. To date, the steady industrial production of this intermediate compound (ACT051-3) has not been reported. In this study, we described the specific synthesis method and process of the compound ACT051-3 in terms of laboratory synthesis, pilot scale-up, and industrial production. During the exploration of the process route for ACT051-3, many appropriate adjustments and improvements were made to the reaction conditions, finally leading to the successful development of the optimal industrial production process for ACT051-3. The reaction time was nearly doubled by changing the state of the potassium carbonate involved in the reaction, which greatly improved the reaction efficiency. Additionally, by introducing N,N-diisopropylethylamine (DIPEA) to the reaction, the amount of the expensive catalyst Pd(OAc)2 was reduced 2.5-fold, significantly lowering production costs, confirming the feasibility of this process route and the industrial production of ACT051-3, and satisfying market demand for this important intermediate.

Here, we present a protocol for the scaled-up synthesis of the intermediate tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) of Upatinib.

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl ...

Synthesis of Low-Valent MOFs from Multitopic Phosphine Linkers

Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers

Metal-organic frameworks (MOFs) are the subject of intense research focus due to their potential applications in gas storage and separation, biomedicine, energy, and catalysis. Recently, low-valent MOFs (LVMOFs) have been explored for their potential use as heterogeneous catalysts, and multitopic phosphine linkers have been shown to be a useful building block for the formation of LVMOFs. However, the synthesis of LVMOFs using phosphine linkers requires conditions that are distinct from those in the majority of the MOF synthetic literature, including the exclusion of air and water and the use of unconventional modulators and solvents, making it somewhat more challenging to access these materials. This work serves as a general tutorial for the synthesis of LVMOFs with phosphine linkers, including information on the following: 1) the judicious choice of the metal precursor, modulator, and solvent; 2) the experimental procedures, air-free techniques, and required equipment; 3) the proper storage and handling of the resultant LVMOFs; and 4) useful characterization methods for these materials. The intention of this report is to lower the barrier to this new subfield of MOF research and facilitate advancements toward novel catalytic materials.

Author Spotlight: Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers  

Here, we describe a protocol for the synthesis of low-valent metal-organic frameworks (LVMOFs) from low-valent metals and multitopic phosphine linkers under air-free conditions. The resulting materials have potential applications as heterogeneous catalyst mimics of low-valent metal-based homogeneous catalysts.

Metal-organic frameworks (MOFs) are the subject of intense research focus due to their potential applications in gas storage and separation, biomedicine, ...

Introduction to Catalysis

Source: Laboratory of Dr. Ryan Richards &#8212; Colorado School of Mines
Catalysis is among the most important fields of modern technology and presently accounts for approximately 35% of the gross domestic product (GDP) and sustenance of approximately 33% of the global population through fertilizers produced via the Haber process.1 Catalysts are systems that facilitate chemical reactions by lowering the activation energy and influencing the selectivity. Catalysis will be a central technology in addressing the energy and environmental challenges of modern times.

Catalysis: Homogeneous and Heterogeneous Catalysts

Source: Laboratory of Dr. Ryan Richards &#8212; Colorado School of Mines
Catalysis is among the most important fields of modern technology and presently ...

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Palladium-Catalyzed Cross Coupling

Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate the concept of a palladium-catalyzed cross coupling. The set-up of a typical Pd-catalyzed cross coupling reaction will be illustrated. Pd-catalyzed cross coupling reactions have had a profound effect on how synthetic chemists create molecules. These reactions have enabled chemists to construct bonds in new and more efficient ways. Such reactions have found widespread applications in the fine chemical and pharmaceutical industries. Pd-catalyzed cross coupling reactions add another tool to the chemist&#39;s toolbox for constructing carbon-carbon bonds, which are central to organic chemistry. The combination of the importance of making carbon-carbon bonds and the impact of Pd-catalyzed cross coupling have resulted in these reactions being the subject of the 2010 Nobel Prize in Chemistry. Ei-ichi Negishi, one of the recipients of the 2010 Nobel Prize in chemistry, explained in his Nobel lecture that one of his motivations for developing this chemistry was to develop &#34;widely applicable straightforward Lego-like methods for hooking up two different organic groups&#34;.

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions

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Chapters in this video

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

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphos^Ph Complexes

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

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

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

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers

Introduction to Catalysis

Palladium-Catalyzed Cross Coupling