Aryl halides, palladium-catalyzed Heck

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

Members of the she same compound class, arylethenylpurines, can also be prepared in a two step sequence. The cross-coupling of a halopurine with vinyl-tributylstannane leads to the formation of a vinylpurine, which in turn can undergo palladium catalyzed Heck reaction with a series of aryl halides (8.20.),28 The two step procedure is of particular interest, since the alternate approach, the Heck reaction of halopurines and arylethenes is of very limited scope. 

The palladium-catalyzed Heck reaction of a vinyl or aryl halide with an alkene... 

Direct (instead of stepwise) transition metal catalyzed dicarboration is achieved by a modification of the palladium-catalyzed Heck reaction 2 4-85,86 116 if the final dehydropal-ladation step is suppressed. This step usually occurs after alkene insertion into an aryl - or a vinyl-palladium bond formed from the corresponding halide or triflate. 

Heck couplings of aryl halides with alkenes in room temperature ionic liquids have been reported [44]. Dialkylimidazolium and n-hexylpyridinium hexafluoro-phosphate and tetrafluoroborate ionic liquids were used as solvents, Pd(OAc)2 and PdCl2 as catalysts, and an amine as base. Addition of ligands such as triphe-nylphosphine, tri-o-tolylphosphine, and triphenylarsine usually had a negative affect on product yield. Addition of cosolvents such as DMF was not necessary. Palladium-catalyzed Heck reactions involving aryl bromides have been performed... 

Cal, M. and Wang, P. (1998) Use of phase-transfer catalysis in palladium-catalyzed Heck carbonylation of aryl halides. Jiangxi Shifan Daxue Xuebao, Ziran Kexueban, 22, 231. ... 

Palladium-catalyzed Heck additions of aryl halides to vinyltrimethylsilane have been reported, however (a) Daves, G.D. Jr., and Hallberg, A. (1989) Chem. Rev., 89, 1433-1445 For examples utilizing henzendiazonium salts as... 

In 2011, a palladium-catalyzed Heck-type reaetion between allylic esters and aryl halides was developed by Deng, Li and their co-workers. When 2-iodoanilines and 2-iodophenol were applied as substrates with allyl aeetate, indole and benzofuran derivatives were selectively produced... 

As a Generator of Alkyl Radicals from Alkyl Halides in the Presence of Cobalt Catalysts. A conceptually novel use of Me3SiCH2MgCl recently emerged in cobalt-catalyzed Heck-type transformations. The palladium-catalyzed Heck reaction always etT5)loys aryl- or alkenyl halides. In eontrast, alkyl halides are not available for use as starting material, due to predominant 0-hydride elimination from the corresponding alkylpalladium... 

Cross Coupling. In cross-coupling reactions, an aryl, vinyl, or acyl halide or triflate undergoes a palladium-catalyzed Heck-type coupling to an aryl-, vinyl-, or alkyl-metal reagent (eq 14) to give a new carbon-carbon bond. ... 

It has been shown that ionic liquids in combination with high temperatures and prolonged reaction times are mandatory in the rrickel catalyzed Heck coupling of aryl bromides and butyl vinyl ether. See Sun L, Pei W, Shen C (2006) J Chem Res 388. For palladium catalyzed Heck reaction of aryl bromides in ionic liquids with added halides. See ref [51]... 

The ruthenium catalyzed reactions of aromatic ketones and alkenes or a,o)-dienes maybe related mechanistically to the palladium catalyzed Heck reaction of aryl halides with alkenes (77). Insertion of palladium into the C-X bond of the aryl halide leads to a reactive aryl palladium species which is the key intermediate in this reaction. The Heck reaction has also been applied to the synthesis of polymers (72-76). 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

Palladium catalyzed reaction of aryl halides and olefins provide a useful synthetic method for C-C bond formation reaction [171, 172], The commonly used catalyst is palladium acetate, although other palladium complexes have also been used. A sol-vent-free Heck reaction has been conducted in excellent yields using a household MW oven and palladium acetate as catalyst and triethylamine as base (Scheme 6.51) [173], A comparative study revealed that the longer reaction times and deployment of high pressures, typical of classical heating method, are avoided using this MW procedure. 

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,... 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

Intramolecular arylation of alkenes. The intramolecular palladium-catalyzed condensation of aryl halides with an alkene group (Heck arylation5) can actually proceed more readily than the original bimolecular version. These intramolecular cyclizations typically proceed in acetonitrile at room temperature, particularly when catalyzed by Ag2C03, which also inhibits isomerization of the double bond of the product. They can be used to obtain spiro, bridged, and fused systems. Even tetrasubstituted alkenes can participate, with formation of quaternary centers.6... 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

Heck in one of his first papers already demonstrated the feasibility of applying the palladium-catalyzed crosscoupling of aryl and alkenyl halides with alkenes repetitively on appropriate oligofunctional substrates. For example, twofold coupling of 1,4-diiodobenzene with styrene furnished 1,4-distyrylbenzene in 67% yield (Scheme 1). Since then, a large number of ortho-, meta-, and / r< -dihaloarenes and -heteroarenes have been subjected to twofold Heck reactions with various alkenes (Schemes 2-4). 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

The Heck reaction is a palladium-catalyzed C-C bond-forming procedure that joins benzylic, vinylic, and aryl halides or the corresponding triRates with alkenes or alkyncs. The result is an alkenyl-or aiyl-substituted alkene. The mechanism below is assumed to apply to the Heck reaction.18... 

The palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base is referred as the Heck Reaction . Recent developments in the catalysts and reaction conditions have resulted in a much broader range of donors and acceptors being amenable to the Heck Reaction. 

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