Organopalladium Heck reaction

The Heck reaction is considered to be the best method for carbon-carbon bond formation by substitution of an olefinic proton. In general, yields are good to very good. Sterically demanding substituents, however, may reduce the reactivity of the alkene. Polar solvents, such as methanol, acetonitrile, N,N-dimethylformamide or hexamethylphosphoric triamide, are often used. Reaction temperatures range from 50 to 160 °C. There are various other important palladium-catalyzed reactions known where organopalladium complexes are employed however, these reactions must not be confused with the Heck reaction. 

Arylation and Alkylation of Alkenes by Organopalladium Compounds The Heck Reaction... 

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. 

A domino process, which has been encountered with increasing frequency during the past few years, is the combination of a Heck reaction with a C-H-activation. This type of transformation takes place if the intermediate organopalladium compound cannot react in the usual manner, and an aryl-H-bond is in close vicinity. C-H-activation can also occur if the arylhalide is used in excess. 

In the last decade, organopalladium-catalysist C-C bond formation has become one of the most efficient approaches to synthesize organic molecules. The Heck reaction, in particnlar, is widely used as an important method to build biologically active compounds in synthetic chemistry and the pharmaceutical industry. 

Organopalladium(II) intermediates formed by oxidative addition of sp2 and sp3 organic halides and related compounds to Pd(0) species undergo a variety of synthetically useful reactions (e.g., Heck reaction) (191). For example, Pd complexes catalyze substitutive C—C bond formation between olefins and organic halides by the mechanism shown in Scheme 80 (192). The initially formed organo-Pd(II) intermediate adds across the C—C bond, and subsequent /3-elimination of Pd(II) hydride affords the final product. Other organic compounds that have electronegative... 

Polystyrene-bound secondary aliphatic amines and /V-alkyl amino acids can be ally-lated by treatment with a diene and an aryl iodide or bromide in the presence of palla-dium(II) acetate (Entry 14, Table 10.3). As the diene, 1,3-, 1,4-, and 1,5-dienes can be used, and, besides aryl halides, heteroaryl bromides have also been successfully used [63], This remarkable reaction is likely to proceed via the formation of an aryl palladium complex, with subsequent insertion of an alkene into the C-Pd bond. The resulting organopalladium compound does not undergo ( -elimination (as in the Heck reaction), but isomerizes to an allyl palladium complex, which reacts with the amine to give the observed allyl amines. 

The Heck reaction involves the coupling of an organopalladium species formed by oxidative addition to an alkene followed by /S-hydride elimination. The product is an alkene in which a vinyl hydrogen on the original alkene is replaced by die organic group on palladium. Thus aryl and alkenyl halides can be coupled to alkenes. 

If the initial organopalladium complex is formed in the presence of an alkene, transfer of the organyl group to the alkene can occur (Heck reaction, Scheme 8.7) [5, 78], Electron-deficient and electron-rich alkenes and even some arenes [79] can be used. In the last step of this process a Pd-hydrido complex is formed by /3-hydride elimination, leading to the formation of the C-C double bond. In the presence of bases the hydrido complex eliminates HX, regenerating the catalytically active Pd(0) complex (Scheme 8.7). 

Although this chapter focuses its attention on cyclic carbopalladation reactions other than the cyclic Heck reaction, it might be useful to discuss here the following variants of the cyclic Heck reaction. For the vast topic of the cyclic Heck reaction including those variants discussed below, the reader are referred to the following chapters of the Handbook of Organopalladium Chemistry for Organic Synthesis [40]. 

Shibasaki M, Miyazaki F (2002) Asymmetric Heck Reactions. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1283... 

With the variety of transformations that can be promoted by organopalladium reagents, it is unfortunate that palladium is such a rare metal. Biochemical processes might be much more exotic if palladium had been more abundant in the earth s crust at the origin of life (although selenium, which is an essential trace nutrient, is only approximately five times as concentrated as palladium in the earth s crust). The discovery of high turnover number catalysts has allowed several palladium-catalyzed reactions to be used in fine chemical and pharmaceutical synthesis. Naproxen (29) can be made using a Heck reaction. Ibuprofen s (30) synthesis... 

Aryl bromides and iodides undergo a series of aryl coupling reactions mediated by organometallic derivatives. An example is the Heck reaction in which an organopalladium iodide complex is formed and coupled with an alkene (Scheme 4.12). 

The Suzuki reaction is the first of two reactions that utilize a palladium catalyst and proceed by way of an intermediate organopalladium compound. The second is the Heck reaction (Section 26.3). 

Larhed, M., Hallberg, A. The Heck reaction (alkene substitution via carbopalladation-dehydropalladation) and related carbopalladation reactions, in Handbook of Organopalladium Chemistry for Organic Synthesis (eds. Negishi, E.-i.,De Meijere, A.), 1,1133-1178 (Wiley-... 

For intramolecular Heck reactions, Ihe migratory insertion of the initial organopalladium... 

---