Suzuki phosphine-free catalysts

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

However, efforts were also directed to the development of phosphine-free catalysts. For example, the ligand-free Pd(OAc)2 promoted Suzuki reaction in water was reported using microwave heating. In this way, a low palladium loading (0.4 mol.%) was required and the cross coupling proceeded quickly (5-10 min reaction time), using boronic acids and aryl iodides, bromides and chlorides. 

Rostamnia S, Xin H. Pd(OAc)2 SBA-15/PrEn nanoreactor a highly active, reusable and selective phosphine-free catalyst for Suzuki-Miyaura cross-coupling reaction in aqueous media. Appl Organometal Chem 2013 27 348-52. 

Indoleboronic acid 96 was employed by Neel to prepare bis(indolyl)maleimides such as 109 [119]. However, since the standard Suzuki conditions failed (triflate 108 apparently decomposing under the reaction conditions), the use of a phosphine-free Pd catalyst [120] and cesium fluoride [121] was necessary and gave 109 in an acceptable yield of 55%. 

Greater durability of the colloidal Pd/C catalysts was also observed in this case. The catalytic activity was found to have declined much less than a conventionally manufactured Pd/C catalyst after recycling both catalysts 25 times under similar conditions. Obviously, the lipophilic (Oct)4NCl surfactant layer prevents the colloid particles from coagulating and being poisoned in the alkaline aqueous reaction medium. Shape-selective hydrocarbon oxidation catalysts have been described, where active Pt colloid particles are present exclusively in the pores of ultramicroscopic tungsten heteropoly compounds [162], Phosphine-free Suzuki and Heck reactions involving iodo-, bromo-or activated chloroatoms were performed catalytically with ammonium salt- or poly(vinylpyrroli-done)-stabilized palladium or palladium nickel colloids (Equation 3.9) [162, 163],... 

In a modified version of the Suzuki reaction arylboronates or boranes are utilized instead of arylboronic acid. Under the action of phosphine-free palladium catalysts NaBPh4 and tra(l-naphtyl)borane were found suitable phenyl-sources for arylation of haloaromatics in fully or partially aqueous solutions at 20-80 °C with good to excellent yields (Scheme 6.12) [32-34]. Aryl halides can be replaced by water-soluble diaryliodonium salts, At2IX (X = HSO4, BF4, CF3COO) in the presence of a base both Ar groups take part in the coupling [35]. 

Palladacycles [17] have been established as important class of catalysts, an unusual phosphine-free sulfur containing catalyst was introduced by Zim [18] et al. A phosphinite based palladacycle [19] proved to be very efficient in Suzuki coupling reactions. An N,P-Ligand type was synthesized by Kocovsky [20] et al. Tridentate pincer ligands [21] have been proved use-fill in the Heck reaction. Recent developments regarding Heck (22] and Suzuki [23] reactions have been reviewed by Fu and Littke. A new catalyst especially suitable for Heck couplings has been introduced by Beller [24] et al. 

Pd(PtBu3)2 does not appear to be the active catalyst in the Suzuki coupling process under Fu s conditions, since the reaction of 3-chloropyridine with 2-tolylboronic acid proceeds sluggishly at room temperature. However, the addition of phosphine-free Pd2(dba)3 to the Pd(PtBu3)2 leads to a marked increase in the rate of cross-coupling (Eq. (80)). 

A different example of triphasic catalysis for the Heck, Stille and Suzuki reactions relied on a three-phase microemulsion/sol-gel transport system. Gelation of an z-octyl(triethoxy)silane, tetramethoxysilane and Pd(OAc)2 mixture in a H2O/CH2CI2 system led to a hydrophobicitized sol-gel matrix that entrapped a phosphine-free Pd(ii) precatalyst. The immobilized precatalyst was added to a preformed microemulsion obtained by mixing the hydrophobic components of a cross coupling reaction with water, sodium dodecyl sulfate and a co-surfactant, typically zz-propanol or butanol. This immobilized palladium catalyst was leach proof and easily recyclable. 

The cross-coupling reactions of various aryl halides and triflates with vinyl- or arylboronic acids and esters (Suzuki cross-coupling reaction) was also carried out in water in the presence of tetrabutylammonium bromide and a base such as Na2C03, using a phosphine-free palladium catalyst to give biaryl derivatives [Eq. 18)1 [108,109]. More recently, Casalnuovo [101] and Gen t [102,110] have performed this reaction using water-soluble palladium catalysts PdCla (tppms)2 and Pd(OAc)2/tppts in water/acetonitrile. 

Palladium on charcoal, in the presence of a phosphine, can be used as the catalyst in Sonogashira and Suzuki reactions," but a phosphine-free method, shown below, is effective with a wide range of heterocyclic partners." ... 

Polyurea-encapsulated palladium catalysts promote the phosphine-free Mizoroki-Heck reaction, which results in a high yield of cinnamates 46 (Scheme 86). The catalyst, which is easily recovered by filtration, is also applicable to the Suzuki-Miyaura and Stifle coupling reactions. 

Another useful variation of the phosphine-free Suzuki reaction uses a heterogeneous system with neat water as solvent and tetrabutylammonium chloride as promoter and phase-transfer catalyst (Scheme 42). Aryl bromides were shown to give higher yields than aryl iodides, because of inhibition of phase-transfer by the hberated iodide ion. ... 

It should be noted that cross-coupling in the presence of phosphine complexes of palladium usually requires high amounts of catalyst, with initial loadings of 25-30 mol% not being uncommon. An entirely new approach to the Suzuki reaction is phosphine-free palladium catalysis. The use of palladium catalysts without the addition of phosphine ligands for cross-coupling with organoboron compounds in aqueous media opened a new chapter in the story of this powerful synthetic method. This approach allows catalyst efficiency to be dramatically increased, and the reaction to be performed under milder conditions. 

Shylesh, S., Wang, L. and Thiel, W.R. (2010) Palladium(II)-phosphine complexes supported on magnetic nanoparticles filtration-free, recyclable catalysts for Suzuki-Miyaura crosscoupling reactions. Advanced Synthesis and Catalysis, 352 (2-3), 425-432. 

Much research has been carried out on the Ugand-free palladium-catalysed Suzuki reaction. Already in 1989, Beletskaya reported a Ugand-free Suzuki reaction in water, between iodobenzoates and phenylboronic acid using Pd(OAc)2 as catalyst [81]. Later, Novak took up the quest to develop a highly active catalyst for the Suzuki reaction and since he noted that this reaction suffers from phosphine inhibition he decided to test three Ugand-free palladium catalyst precursors Pd(OAc)2, [(Ti -CsHsjPd PdCl]2, and Pd2(dba)3.QH6 [82]. All three catalysts performed well in the Suzuki reaction between 4-nitro-iodobenzene and phenylboronic acid. In the reaction with 4-nitro-bromobenzene the first and last catalyst were clearly superior with yields of 96-98% (Scheme 10.7). Novak suggests that... 

Alkylboronic acids, which are often less reactive in Suzuki reactions than aryl-boronic acids, are suitable substrates for this catalyst, with turnover numbers (TONs) as high as 9700 being achieved with this system. In addition, Fu was able to demonstrate that the air-stable and crystalline tetrafluoroborate salt, P(t-Bu)3HBp4 was equally efficient as the low-melting and air-sensitive free phosphine P(t-Bu)3 [29],... 

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