Ligand-free catalysts Heck reaction

Pal and collaborators designed a ligand- and phase-transfer-catalyst-free intramolecular Heck reaction which they applied to the synthesis of 1,3-disubstituted pyrrolo[2,3-f)]quinoxalines 158, some of which were... 

Palladium-catalyzed carbon-carbon cross-coupling reactions are among the best studied reactions in recent decades since their discovery [102, 127-130], These processes involve molecular Pd complexes, and also palladium salts and ligand-free approaches, where palladium(O) species act as catalytically active species [131-135]. For example, the Heck reaction with aryl iodides or bromides is promoted by a plethora of Pd(II) and Pd(0) sources [128, 130], At least in the case of ligand-free palladium sources, the involvement of soluble Pd NPs as a reservoir for catalytically active species seems very plausible [136-138], Noteworthy, it is generally accepted that the true catalyst in the reactions catalyzed by Pd(0) NPs is probably molecular zerovalent species detached from the NP surface that enter the main catalytic cycle and subsequently agglomerate as N Ps or even as bulk metal. 

Therefore, a good catalyst leads to weak fluorescence in the Heck product (15). A relatively small library of 96 known phosphines was tested in the palladium-catalyzed Heck coupling. Several sterically hindered ligands led to high catalyst activity. Fluorescence tags have also been used in the combinatorial search for metal-free catalysts in other types of reaction.42,43... 

The Mizoroki-Heck reaction in liquid imidazolium salts as the solvent is a special case of an in situ system Under the reaction conditions NHC complexes of palladium are formed as the active catalyst from the solvent and the ligand-free palladium precursor. In general, ionic liquids are novel reaction media for homogeneous catalysis. They allow easy separation of product and catalyst after the reaction. ... 

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. 

Because aryl phosphines are not only costly but can also act as aryl sources themselves, giving rise to unwanted byproducts, there has been steady interest in extending ligand-free Heck reactions to aryl bromides and aryl chlorides. Reetz and de Vries recently found that these can be performed with high efficiency using stabilized colloidal Pd catalysts [21]. If the palladium is kept at a low concentration between 0.01 and 0.1 mol%, precipitation of the Pd(0) is avoided and the colloids serve as a reservoir for the catalytically active species (Scheme 5). This economically attractive method has been successfully applied on an industrial scale by DSM [22]. 

Another particularly attractive substrate class for industrial Heck reactions are the arenediazonium salts, because of to their ready availability from anilines. Matsuda et al. found that for these highly reactive compounds, ligand-free Pd(dba)2 suffices as catalyst [32], Even palladium catalysts on solid supports are highly effective [33], The diazotization of an aniline 25 and its olefination can be performed separately, or in one pot (Scheme 12). 

A practical ligand-free palladium-catalyzed intramolecular reductive Heck cyclization was developed by Liu et al. <07TL2307>. The authors found that water was an essential component of the reaction mixture. Using a series of aryl halide intermediates this cyclization resulted in the desired 1,2,3,4-tetrahydroisoquinolines in high yields. Cook and co-workers found that InCU was an efficient catalyst for an intramolecular Friedel-Crafts cyclization of Ar-(4-bromobut-2-enyl)-A-(bcnzyl)-4-methylbcnzcncsulfonamidc to form the desired 3-substituted tetrahydroisoquinolines <07OL1311>. 

Phosphine free catalysts and halogen-free reactions are known for the Heck reaction. Improvements on the palladium catalyst system are constantly being reported, including polymer-supported catalysts." °° The influence of the ligand has been examined." Efforts have been made to produce a homogeneous catalyst for the Heck reaction." The Heck reaction can be done in aq. media," ° in perfluori-nated solvents," in polyethylene glycol," ° in neat tricaprylmethylammonium... 

Aryl bromides as well as aryl chlorides show increased reactivity in the Mizo-roki-Heck vinylation (eq. (3)) with various olefins when the reaction is performed in molten ammonium or phosphonium salts [28] (see also Section 3.1.6). Many common catalysts, including ligand-free Pd salts, show a substantial inerease in activity and thermal stability. 

In 1984, Jeffery discovered that under ligand-free conditions, Pd-catalyzed vinylation of organic halides proceeds at or near room temperature, whereas normal Heck reactions require higher temperatuies [64]. Jeffery s hgand-free conditions have been broadly applied to a variety of Heck arylations that were not feasible using more standard reaction conditions. For example, efforts to use classical Heck-reaction conditions for the conversion of Al-allyl-Al-benzyl(3-bromoquinoxalin-2-yl)amine (64) to l-benzyl-3-methylpyrrolo[2,3-/ ]quinoxaline (65), resulted in slow reactions and low yields [65], which may be attributed to the poisoning of the palladium catalyst via complexation to the aminoquinoxalines. In contrast, the Jeffery conditions afforded the desired product in 83% yield. The enhanced reactivity and yield under Jeffery s ligand-free conditions may be due to the coordination/solvation of the palladium intermediates by bromide ions present in the reaction mixture, which presumably prevents the precipitation of Pd(0). 

The reaction between aryl or alkenyl halides or arenediazonium salts and al-kenes catalyzed by palladium complexes, the so-called Heck reaction, has been performed in aqueous media. Arylation of styrene or acryHc acid derivatives occurred in high yields in the presence of a free-ligand palladium complex as catalyst and a base (Na2C03 or K2CO3) [96-98] and, eventually, a quaternary ammonium salt [Eq. (14)] [99,100]. 

A special focus of modem research in Pd-catalyzed Heck-coupling reactions is to investigate the ligand-free reaction in ionic liquids using Pd(OAc)2, PdQz or Pd/C as catalyst precursors [210]. In these examples the role of the ionic liquid is as either solvent, ligand or both. Of special interest for these studies is the regioselectivity of the Heck products when electron-rich olefins, such as acyclic enol ethers, silanes, and enol amides are applied as substrates. Possible products are the branched olefin (a. Scheme 5.3-24) and the linear olefin (P, Scheme 5.3-24). 

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