Alkenes palladium-catalyzed reaction with aryl halides

Catellani and Lautens have independently reported unique palladium/ norbornene-catalyzed reactions of aryl halides, which mechanistically involve a reversible alkene insertion/p-carbon elimination process [11]. For example, iodobenzene reacted with 1-iodobutane and methyl acrylate to form the multiply-alkylated benzene 29 (Scheme 7.9) [12]. The following mechanism is proposed oxidative addition of phenyl iodide onto palladium generates phenylpalladium(ll) iodide. A double bond of norbornene inserts into the C-Pd bond to form an alkylpalladium species, which cleaves a C-H bond nearby to form the palladacycle 25. -Butyl iodide then reacts with 25 to form the Pd(IV) intermediate 26, which undergoes reductive elimination. Repetition of the cyclometalation/alkylation process leads to the formation of 27. Then, P-carbon elimination affords the arylpalladium species 28 together with norbornene. Subsequently, a Heck-type reaction takes place with methyl acrylate, giving rise to 29. 

Palladium-catalyzed reaction of alkyne 47 with a variety of aryl and vinyl halides afforded alkenes 48 in good yield. Cyclization to quinolines 49 was performed by treating 4 8 with TsOH in EtOH <96T(52)10225>. 

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 first Pd-catalyzed carboamination and carboetherification reactions of y-amino or y-hydroxy alkenes with aryl halides were described by Wolfe in 2004 [ 100]. As shown below, treatment of these substrates with aryl or heteroaryl bromides in the presence of NaOfBu and a palladium catalyst provides substituted tetrahydrofuran or pyrrolidine products. 

Heck reaction the palladium-catalyzed reaction of an aryl or vinyl halide with an alkene to give an arylated or vinylated alkene... 

Shortly thereafter, a more general palladium-catalyzed carbonylative Heck reaction of aryl halides was able to be developed by our group [34]. For the first time, various aromatic and aliphatic alkenes were used successfully in this system, and good yields of the corresponding a,jS-unsaturated ketones were obtained (41-90 %). Starting from easily available aryl iodides and bromides, interesting building blocks were obtained under mild conditions (Scheme 7.15). With respect to the reaction mechanism, the aryl palladium complex and acyl palladium complex were characterized by X-ray, and the mechanism was studied step by step. The results fit well with DFT calculations. 

Before 1970, the reactions of aryl halides (ArX) with nucleophiles were restricted to electron-deficient aryl halides via S Ar mechanisms. The reactivity of aryl hahdes in S Ar reactions decreases in the order ArF>ArCl>ArBr ArI [1]. The range of reactive nucleophiles was narrow, and reactions of alkenes or alkynes were not known. The discovery in 1968 of oxidative additions of palladium(O) (Fitton [2a]) and then nickel(O) (Kochi [2b]) with aryl hahdes (ArI>ArBr>ArCl) that generate ArM XL (M=Pd, Ni) paved the way to new palladium- and nickel-catalyzed reactions of aryl hahdes with C-nucleophiles, leading to the formation of C—C bonds. Palladium- or nickel-catalyzed cross-couphng reactions are described herein, following the historical order of discovery. 

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). 

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 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... 

Cross-coupling reactions of alkenylsilicates 114 with aryl or vinyl halides or triflates are catalyzed by a palladium complex to give the corresponding alkenes (equation 92)173. 

Palladium/silver-catalyzed Heck reactions have usually involved vinyl or aryl halides and alkenes, but these reaction conditions were also extended to allenes. Indeed, Zenner and Larock65 showed that simple alkyl allenes readily reacted with aryl and vinyl iodide derivatives in the presence of palladium acetate or chloride and silver phosphate. Moreover, the reaction could be rendered asymmetric using chiral ligands the best one was a bisoxazolidine derivative (Scheme 10.37). 

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