Palladacycles, Heck reactions

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

Although only a dozen known metal complexes were tested in this manner, proof of principle was demonstrated. The test revealed Wilkinson s catalyst to be the most active hydrosilylating agent, its use in this type of reaction being known. However, the study also led to the discovery that a palladacycle, [Pd (o-tolyl)2PC6H4 (OAc)]2, which is usually considered to be potent in Heck reactions, is also an excellent hydrosilylation catalyst.37,38 Control experiments showed that the relative order of catalyst activity is the same when conventional substrates are used in place of the dyes (8). 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

A key feature of PdCys as precursors of Pd(0) nanoparticles is that reduction of Pd(II) -> Pd(0) involving C-Pd bond cleavage is required. This accounts for both the high temperatures invariably required and the induction period in the absence of reductants. Rosner et al. have developed a detailed kinetic model of a Heck reaction catalyzed by dimeric palladacycles (Rosner et al. 2001 a,b). This model explains the experimental observations and is consistent with an active species... 

Gruber AS, Zim D, Ebeling G, Monteiro AL Dupont (2000) Sulfur-containing palladacycles as catalyst precursors for the Heck reaction. J Org Lett 2 1287-1290... 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

As detailed elsewhere, the fluorous palladacycle acetates and hahdes 7 and 8 were synthesized [38,39]. These feature three Rfg ponytails, and were poorly soluble in common organic solvents at room temperature, and insoluble in DMF. However, they were very soluble in DMF at higher temperatures. All were effective catalyst precursors for Heck reactions (100-140 °C), and precipitated (as the halides) upon cooling. However, a number of control experiments established that 7 and 8 served as steady-state sources of colloidal palladium nanoparticles, formed anew with each cycle imtil the palladacycles were exhausted. These, or low-valent Pd(0) species derived therefrom, were the true catalysts. 

Palladacycles, such as (80), derived from tri(l-naphthyl)phosphine, proved to be very active catalysts for Heck reactions to produce (81) (ArX = Phi, 4-MeCOC6H4Br,... 

A twofold intramolecular Heck reaction of the dibromobenzene derivative 19 has been used to construct the heptacyclic skeleton 20 of cephalostatin analogs. This reaction required a precise control of the reaction time and temperature. The conversion proceeded best with a catalytic amount of the palladacycle from tris(< -tolyl)phosphine and palladium acetate, and gave exclusively (in 80% yield) the heptacycle 20 with an unusual m-annelation of the two newly formed rings (Scheme 10). ... 

Benzofurans and dihydrobenzofurans have been prepared on polymeric supports by the palladium-mediated reaction of 2-iodophenols with dienes or alkynes (Entries 1 and 2, Table 15.9). This reaction is closely related to the synthesis of indoles from 2-iodoanilines, and probably proceeds via an intermediate palladacycle (Figure 15.3). Benzofuran and isobenzofuran derivatives have also been prepared on cross-linked polystyrene by intramolecular addition of aryl radicals to C=C double bonds and by intramolecular Heck reaction. 

Iyer, S. Ramesh, C. Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts for the Heck reaction. Tetrahedron Lett. 2000, 41, 8981-8984. 

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. 

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

Crabtree and coworkers used the disappearance of color to monitor the activity of 12 potential catalysts for hydrosilation reactions [6], The group used alkenes and imines with ferrocenyl and pyrimidyl substituents at either end as colored reactants. On hydrosilation the color is bleached, because conjugation between the electron donor and acceptor groups is reduced. The bleaching is easily observed by eye and can be recorded quantitatively by means of a digital camera (Figure 5.4.1). By use of this method, the known Wilkinson catalyst was identified in a proof-of-concept experiment. A palladacycle, [ Pd (o-tolylfi PQ H4 OAc 2, usually used in Heck reactions, was also found to be catalytically active. 

A = Bu4N or C16PBu3, MePPh3 or C3mim Scheme 2. Palladacycle catalyzed Heck reactions in ionic liquids. 

More recently, cationic intermediates have been observed in the Heck reactions of arene diazonium salts catalyzed by triolefinic macrocycle Pd(0) complexes [17,59], o-iodophenols and enoates to form new lactones [60], and o-iodophenols with olefins (the oxa-Heck reaction) [61 ]. In the first case ions were formed by oxidation of the analyte at the capillary, or by association of [NH4] or Na". In the two other cases ionization occurred through the more typical loss of a halide ligand. The oxa-Heck reaction provides a good example of how these experiments are typically performed and the type of information that can be obtained. The oxyarylations of olefins were performed in acetone, catalyzed by palladium, and required the presence of sodium carbonate as base. Samples from the reaction mixtures were diluted with acetonitrile and analyzed by ESI(+)-MS. Loss of iodide after oxidative addition of o-iodophenol to palladium afforded positively-charged intermediates. Species consistent with oxidative addition, such as [Pd(PPh3)2(C6H50)], and the formation of palladacycles of the type seen in Scheme 8 were observed. Based on this, a mechanism for the reaction was proposed (Scheme 8). 

Oxitne-derived palladacycles act as efficient catalysts for the Heck reaction [132], They could be isolated and are found to be thermally stable, not sensitive to air or moisture, and were readily prepared from inexpensive starting material. This was exemplified in the reaction catalyzed by 376 to prepare 377 from 3 and 375. 

Palladacycles prepared by the addition of furancarbothioamide to a methanol solution of Li2PdCl4 at room temperature are soluble in hexane, chloroform, and moderately soluble in polar solvents DMF and DMSO [187]. These palladacycles are thermally stable, not sensitive to air or moisture, and can be applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers... 

Scheme 2 Heck reaction with palladacycles as catalysts...

The increase of the catalyst turnover numbers is indeed one other major area where further improvements could be expected. Such improvements have recently been achieved for the standard Heck reaction by the use of high pressure conditions [86], the use of preformed palladacycles as catalysts [87], or by using a macrocyclic tetraphole as hgand [88].Dendritic diphosphine-palladium complexes as catalysts for Heck reactions have also been reported to possess superior stabihty compared to the monomeric parent compounds [89]. Transferring such iimovations to the AHR remains an important goal. 

Coupling. In the synthesis of ArCH=CH2 and ArCH=CHAr from ethylene hy the Heck-reaction hoth steps can he catalyzed by palladacycle 1. ... 

Heterocyclic analogues of BINAP, such a< 2,2, 5,5 -tetramethyl-4,4 -bis(dipheny Iphosph and tested in the Heck reaction. Incorporaut sulfinyl group to a double bond elicits enj intramolecular Heck reaction. Optically ai ides are produced from (/ )-l-f-butylsulfinylcy Palladacycle (109) and its analogues ind rearrangement of allylic imidates. - For a thioamides, it is convenient to allylate thi dine. This process involves a thio-Claisen n Enantioselective deprotonation of ketones slum bis[yV-benzyl-N-(a-phenethyl)]amide.-- tonation of enolates. ... 

Acceleration of the intramolecular coupling of phenol and aryl halide moieties that is effected with a fJC-palladacycle by a base is realized. o-AminophenyIdiphenylphosphine is a ligand that forms effective Pd complexes for the Heck reaction. ... 

Note that palladacycles typified by 2 are poisoned by 1,4-dienes, in contrast to other Pd(0) catalyst systems. Accordingly, the Heck reaction cannot employ these catalysts. On the other hand, 3 has a high thermal stability and broad scope of application (aryl couplings). Complex 4 is also a highly active catalyst for the Heck reaction (3 examples,... 

Other stable and efficient catalysts for the Heck reaction are pyrazole- and benzothia-zole-based palladacycles. They are capable of promoting Barbier-type reactions. Note that palladacycles derived from aromatic imines decompose to form metallic Pd as the active species. ... 

Sulfur-containing palladacycles such as 5, which are stable to air, water, and heat, show excellent utility in the phosphine-free Heck reaction (turnover number up to 1,850,000) and Suzuki couplings at room temperature. ... 

The search for more stable or more reactive catalysts has produced many new leads. One of the most promising is represented by the palladacycle (14), known as Hermann s catalyst. This can be used in Heck reactions at high temperatures (above 140 °C), which leads to high turnover numbers of up to 10 with electron-poor aryl bromides. 

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