Ligands hydrophilic phosphine

Nishimura, M. Ueda, M. Miyaura, N. Palladium-catalyzed biaryl-coupling reaction of arylboronic adds in water using hydrophilic phosphine ligands. Tetrahedron 2002, 58, 5779-5787. 

Structures 15-23 are hydrophilic phosphine ligands bearing carboxylic groups. In contrast to their alkali-metal salts, the free acids show only moderate solubilities in water. The ligands 15-17 a have been obtained by standard preparative methods... 

The participation of hydrophilic phosphine ligand is not necessary. The reaction can be catalyzed by water-insoluble complex PdCl2(PPh3)2 in the presence of a stoichiometric amount of inorganic base K2CO3 and a substoichiometric amount of BU3N, which apparently performs the role of phase-transfer agent (Scheme Alternatively, the reac-... 

The reduction of allylic halides or acetates, as well as benzyl halides, can be achieved by the Pd-catalyzed reaction with formate ions in the biphasic system of toluene-water or heptane-water in the presence of hydrophilic phosphine ligands TPPMS, sodium 3-(diphenylphosphino)benzoate, and PEG-modilied trialkylphosphine. The process is accelerated by the addition of PEGJ ... 

Aqueous phosphine-assisted methods use hydrophilic phosphine ligands in aqueous organic solvents. The processes are very mild and selective but use high loads of catalysts and are not recyclable. This protocol is targeted at sophisticated organic synthesis, often involving hydrophilic biomolecules, where economic issues are not of primary importance. 

The application of aqueous mono- and biphasic techniques, both in the presence of hydrophilic phosphine ligands, and in phosphine-less mode, was investigated in detail, and turned out to be quite successful. 

Phase-separation techniques are particularly useful for hydroformylation. Olefin hydroformylation is the process in which the application of the phase-separation technique and hydrophilic phosphine ligands was first realized on an industrial scale. Rhone-Poulenc and RuhrChemie claim to have manufactured an average 300000 tons of butyric aldehyde per year by biphasic... 

The hydroformylation of propene in a biphasic system using rhodium complex with TPPTS ligand can be thought of as a perfect implementation of the ideal phase-separation technique. All new hydrophilic phosphine ligands are usually first tried in hydroformylation, with two primary goals (i) to improve selectivity with respect to the ratio of normal to branched products and (ii) to enhance productivity of the biphasic system. The latter goal depends on an intrinsic limitation of the biphasic system, in that the reaction takes place in the aqueous layer and the rate (turnovers per unit time) is limited by the sparse solubility of olefins in water and by mass transfer of olefin across the very small interfacial boundary between the organic and aqueous layers. 

Several examples of poly- and oligomerization of acetylenes are also quite typical. Water-soluble rhodium complexes with hydrophilic phosphine ligands catalyze the polymerization of arylacetylenes into stereoregular cis-oriented poly(arylacetylenes), which can further be selectively depolymerized on heating to provide a convenient method for the preparation of triaryl-benzenes [194]. Different types of product formed by regioselective di- and trimerization can be obtained by the reaction of such catalysts with other kinds of terminal acetylenes [195]. 

Vergara E, Casini A, Sorrentino F et al (2010) Anticancer therapeutics that target selenoenzymes synthesis, characterization, in vitro cytotoxicity, and thioredoxin reductase inhibition of a series of gold(l) complexes containing hydrophilic phosphine ligands. Chem Med Chem 5 96-102... 

When water-miscible ionic liquids are used as solvents, and when the products are partly or totally soluble in these ionic liquids, the addition of polar solvents, such as water, in a separation step after the reaction can make the ionic liquid more hydrophilic and facilitate the separation of the products from the ionic liquid/water mixture (Table 5.3-2, case e). This concept has been developed by Union Carbide for the hydroformylation of higher alkenes catalyzed by Rh-sulfonated phosphine ligand in the N-methylpyrrolidone (NMP)/water system. Thanks to the presence of NMP, the reaction is performed in one homogeneous phase. After the reaction. 

At the same time, Schmidtchen et al. compared cationic phosphine ligands containing the hydrophilic guanidinium (4.3, 4.4) and the anionic phosphine ligand TPPTS for this palladium-catalyzed coupling reaction. They found that the cationic ligands were effective for the coupling reaction but less efficient than TPPTS 43... 

In two recent communications this group has used formaldehyde as the CO source in aqueous media and has introduced chiral ligands in the rhodium complex reaching high yields and enantioselectivities. A hydrophilic phosphine (TPPTS) and a surfactant (SDS) are also added to enable the reaction (Scheme 38) [142,143]. 

In this section catalysts containing monophosphines for aqueous-phase catalysis will be presented, the influence of ligand variation on catalyst activity being emphasized. Syntheses of hydrophilic monodentate phosphine ligands will be discussed very briefly. Reference to catalysts containing other ligands (see Sections 3.2.2 to 3.2.6) is made only where appropriate. 

More recently, the application scope of thermoregulated phase-separable transition metal complex with nonionic phosphine ligand has been expanded from hy-droformylation to hydrogenation, and the central metal varied from Rh to Ru. The first experimental study is the hydrogenation of styrene catalyzed by thermoregulated phase-separable Ru3(CO)12/PETPP complex catalyst. Under the conditions of Ph2 = 2.0 MPa, T=90°C, catalyst/substrate (mol/mol) = 1/1000, 3 hours, the Ru3(CO)12/PETPP complex catalyst exhibited good activity (Table 5). Compared with other catalysts, Ru3(CO)12/PETPP complex showed the same catalytic activity compared to the lipophilic Ru3(CO)9(TPP)3, while the hydrophilic Ru3(CO)9-(TPPTS)3 and Ru3(CO)9(TPPMS)3 are less active (Table 6). 

Bombesin was derivatized at the C terminus with bidentate chelators (Smith et al. 2003 a, b). The labeled peptide fully retained the biological activity and was stable in vitro and in vivo. Since the bidentate coordination is not optimal with respect to stability (pharmacokinetics), the coordination sphere of the metal tricarbonyl core has been saturated with a highly hydrophilic phosphine. This additional coordination is an example of the 2-Hl approach mentioned in the previous section. The mixed-ligand approach resulted in significantly higher hydrophilicity of the radioconjugates and an improved biodistribution labeled with Tc-99m and also with Re-188 (Smith et al. 2003). 

Another pyrrolidone-based phosphine has been incorporated into amphiphilic, water-soluble diblock co-polymers based on 2-oxazalone derivatives (Scheme 61). The synthesis involved the initial preparation of a diblock co-polymer precursor with ester functionalities in the side chain. This was achieved by sequential polymerization of 2-methyl-2-oxazoline to form the hydrophilic block that provides water solubility, and subsequently a mixture of ester-functionalized oxazoline 147 and 2-nonyl-2-oxazoline, the latter increasing the hydrophobicity of the second polymer block. Having made the backbone, the ester functionalities were converted into carboxylic acids giving polymer 148, which was then reacted with the phosphine ligand to give the desired supported material, 149. This was used in asymmetric hydrogenation reactions with success. 

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