Heck reaction vinylic substitution

Apart these cases, many other reactions have been investigated, including carbo-nylations, Heck reactions, vinyl substitutions, and hydrosylation. In general, based on available data, it is difficult to establish whether these studies could extend beyond the laboratory scale. However, as Eric Beckman has stressed, when reviewing the use of supercritical or near-critical carbon dioxide in green chemical syntheses [26], the role of these studies in demonstrating the extreme versatility of... 

A related Heck reaction of substituted o-bromoacetanilides with styrenes followed by selenium-induced cyclization of the resulting o-styiylacetanilides gives 2-arylindoles [378], Substituted o-bromonitrobenzenes react with ethyl vinyl ether under the influence of Pd(OAc)2 to give the corresponding o-ethoxyethenylnitrobenzenes. Zinc reduction then yields indoles [379]. The one-step Pd-catalyzed conversion of o-bromoanilines to indoles 302 with enamines (or with A/-vinyl-2-pyrrolidone) has been reported [380]. 

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... 

The Heck reaction consists in the Pd(0)-catalysed coupling of alkenes with an aryl or alkenyl halide or triflate in the presence of a base to form a substituted alkene (Scheme 7.1). The reaction is performed in the presence of an organopalladium catalyst. The halide or triflate is an aryl or a vinyl compound and the alkene contains at least one proton. 

Another important type of reactivity of palladium, namely oxidative addition to Pd(0), is the foundation for several methods of forming carbon-carbon bonds. Aryl126 and alkenyl127 halides react with alkenes in the presence of catalytic amounts of palladium to give net substitution of the halide by the alkenyl group. The reaction, known as the Heck reaction,128 is quite general and has been observed for simple alkenes, aryl-substituted alkenes, and substituted alkenes such as acrylate esters, vinyl ethers, and A-vinylamides.129... 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

Both inter- and intramolecular Heck reactions of indoles have been pursued and these will be considered in turn. Appropriately, Heck and co-workers were the first to use Pd-catalyzed vinyl substitution reactions with haloindoles [239]. Thus, l-acetyl-3-bromoindole (217) gave a 50% yield of 3-indolylacrylate 218. A similar reaction with 5-bromoindole yielded ( )-methyl 3-(5-indolyl)acrylate (53% yield), but 3-bromoindole gave no identifiable product. 

The research group of Cacchi made extensive use of these tandem cyclization-Heck reactions to prepare a wide variety of indoles [311-314], For example, vinyl triflates react with o-aminophenylacetylene to afford an array of 2-substituted indoles in excellent yield, e.g., 356 to 357 [312], and a similar reaction of 358 with aryl iodides leads to an excellent synthesis of 3-arylindoles 359 [313],... 

When the Heck vinylic arylation reaction is carried out with an olefin which is either a gas or a low boiling liquid, it must be run in a pressure vessel. Depending upon the product desired, the olefin is usually present in an excess concentration in order to insure formation of vinyl substituted products. In the case of the reaction of ethylene with 2 the stoichiometry of the reactants is critical (Fig. 5). If 4-bromobenzocyclobutene 2 is present in higher concentrations than ethylene, a different monomer, l,2-di(4-benzocyclobutenyl)-ethylene 11 is obtained. 

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... 

This review attempts to provide an overview of microwave-promoted metal-catalyzed transformations of aryl and vinyl halides (or pseudo halides), providing a personal selection of both pioneering and very recently published work. Covered areas include carbonylative transformations, Heck and Sono-gashira reactions, nucleophilic substitutions and cross-couplings. Because of the diversity of the microwave systems used, the reader should consult the original references for detailed descriptions of settings and instrumentation. 

The inter- and intramolecular Heck reactions provide other routes to substituted pyridines . Although electron-deficient 2-bromopyridines are resistant to substitution under Heck conditions, the aminopyridine 142 affords a high yield of the adduct 143 (Equation 68) <1998T6311>. The intermolecular Heck reaction of a 3-pyridyltriflate with ethyl acrylate is accelerated by LiCl <1999SL804>. An efficient Heck vinylation of 3-substituted-2-bromo-6-methylpyridines with methyl acrylate has been developed <2005T4569>. 

The Heck reaction is the palladium-catalyzed coupling of an aryl or vinyl halide with an alkene to give a new C—C bond at the less substituted end of the alkene, usually with trans stereochemistry. 

The palladium-catalysed addition of aryl, vinyl, or substituted vinyl groups to organic halides or triflates, the Heck reaction, is one of the most synthetically useful palladium-catalysed reactions. The method is very efficient, and carries out a transformation that is difficult by more traditional techniques. The mechanism involves the oxidative addition of the halide, insertion of the olefin, and elimination of the product by a p-hydride elimination process. A base then regenerates the palladi-um(0) catalyst. The whole process is a catalytic cycle. 

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