Heck reaction alkene vinylation

S)-N-methyl-2-vinyloxymethylpyrrolidine have also been used as an alkene partner in Heck reactions on vinyl triflates under microwave irradiation [91]. 

Whether the reaction is inter- or intramolecular, the Heck reaction generates vinyl(hetero)arenes or dienes from an alkene and a (hetero)aryl or alkenyl halide [130]. This reaction has great versatility and is applicable to a wide range of aryl and alkene species. Mechanistically, the Heck reaction varies from that depicted in Fig. 4.3. While the oxidative addition of the halogen species occurs, the transmetalation step is replaced by the coordination of the alkene. This is followed by a migratory insertion which essentially substitutes for the cross-coupling step. The product is released not by a reductive elimination, but by a 3-hydride elimination sequence (Fig. 4.5). 

PdCE-catalyzed addition reaction of allyl chloride to alkynes is explained by chloropalladation of a triple bond, followed by insertion of the double bond of allyl chloride to generate 43. No jr-allyl complex is formed from allyl chloride and PdCl2. The final step is elimination of /3-Cl to afford 1-chloro-1,4-diene 44 with regeneration of Pd(ll) [37]. As another example, the Pd(0)-catalyzed Heck reaction of vinyl acetate affords stilbene in this reaction, the primary product is /3-phenylvinyl acetate (45), which reacts again with iodobenzene, and the last step is elimination of /S-OAc to give stilbene. At the same time, Pd(II) is generated, which is reduced to Pd(0) in situ [38]. However, elimination of /3-heteroatoms is not always faster than that of j8-H. For example, the Heck reaction of allyl alcohol with iodobenzene proceeds by preferential elimination of /3-H from the insertion product 46 to afford aldehyde 47, and no elimination of /3-OH from the same carbon occurs to give the alkene 48 [39,40]. 

The best procedures for 3-vinylation or 3-arylation of the indole ring involve palladium intermediates. Vinylations can be done by Heck reactions starting with 3-halo or 3-sulfonyloxyindoles. Under the standard conditions the active catalyst is a Pd(0) species which reacts with the indole by oxidative addition. A major con.sideration is the stability of the 3-halo or 3-sulfonyloxyindoles and usually an EW substituent is required on nitrogen. The range of alkenes which have been used successfully is quite broad and includes examples with both ER and EW substituents. Examples are given in Table 11.3. An alkene which has received special attention is methyl a-acetamidoacrylate which is useful for introduction of the tryptophan side-chain. This reaction will be discussed further in Chapter 13. 

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 consecutive reaction of vinyl halides and alkenes with activated methylene systems [42] in the presence of a palladium catalyst and phase-transfer catalyst results from the addition of the methylene carbanion with the initially formed Heck product (Scheme 6.31) an intramolecular version of the reaction leads to the formation of bicycloalk-l-enes (Scheme 6.31) [42], The analogous combined coupling reaction of iodoarenes and activated methylene compounds with non-conjugated dienes under similar conditions forms the monoalkene (Scheme 6.31) [43]. 

Vinylation or arylation of alkenes with the aid of a palladium catalysts is known as the Heck reaction. The reaction is thought to proceed through the oxidative addition of an organic halide, RX onto a zero-valent [PdL2] species followed by coordination of the olefin, migratory insertion of R, reductive elimination of the coupled product and dehydrohalogenation of the intermediate [HPdXL2] (Scheme 6.1). 

The Heck reaction yields the final product through a p-hydride elimination whereas hydroarylation or hydrovinylation generates the final product via a reductive elimination. Nonetheless, both reactions share a common first step, that is, addition of an aryl or a vinyl palladium species to an alkene, and thus are briefly discussed here. Norbornene 595 is the most studied alkene to evaluate an the... 

Heck-, Suzuki- and Stille-type Couplings - The Heck reaction, palladium-catalysed coupling of aryl or vinyl halides with alkenes or alkynes, is an extremely useful synthetic method. Only recently have Heck reactions been performed in aqueous media, probably due to the perception that water must be carefully... 

Support-bound triazenes, which can be prepared from resin-bound secondary aliphatic amines and aromatic diazonium salts [455], undergo cleavage upon treatment with acids, leading to regeneration of the aromatic diazonium salts. In cross-linked polystyrene, these decompose to yield nitrogen and, preferentially, radical-derived products. If the acidolysis of polystyrene-bound triazenes is conducted in the presence of hydrogen-atom donors (e.g. THF), unsubstituted arenes can be obtained (Entries 8 and 9, Table 3.47). In the presence of alkenes or alkynes and Pd(OAc)2, the initially formed diazonium salts undergo Heck reaction to yield vinylated or alkynylated arenes (Entry 10, Table 3.47). Similarly, unsubstituted arenes can be obtained by oxida-... 

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... 

Although the coupling of aiyl halides with alkenes (commonly referred to as the Heck reaction) was first reported more than 25 years ago [ 1 ], only in the past decade has its enormous synthetic potential been realized [2], Within that time, the reaction has been extended to many substrates, including vinyl iodides and bromides and enol triflates. Moreover, the intramolecular variant has become one of the more important reactions for the formation of carbon-carbon bonds and has emerged as a premier method for the construction of quaternary carbon centers. The ability of intramolecular Heck reactions to reliably fashion carbon-carbon bonds in polyfunctional molecules has led to wide application of this reaction at the strategy level for the synthesis of complex natural products [2g],... 

The neutral pathway differs from the cationic pathway in the absence of a vacant coordination site in the square-planar four-coordinate palladium(II) intermediate prior to alkene coordination. The key question is then how does alkene coordination take place. Early studies pointed out that Heck reactions of aryl or vinyl halides promoted by (bisphosphine)palladium complexes could be sluggish, and this sluggishness was attributed to a reluctance of one of the phosphines of the... 

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. 

The Heck-type reaction of vinylic bromides with alkenes in the presence of nucleophiles such as stabilized enolates or secondary amines (morpholine or piperidine) are efficient three-component reactions that were developed in the late 1970s... 

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. 

Representative examples of Heck reactions are depicted in Scheme 8.8. Terminal alkenes react faster than internal alkenes, and the formation of mixtures of products resulting from further arylation or vinylation of the initial product is therefore only observed when a large excess of halide and long reaction times are employed. Electron-poor alkenes usually react more rapidly than electron-rich alkenes, and the new C-C bond is usually formed at the most electron-deficient carbon atom. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

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