Heck reaction substituted alkenes

Halofurans and halobenzofurans readily participate in Heck reactions with alkenes, and it is possible to synthesize benzofurans via intramolecular Heck reactions of aryl vinyl ethers. The heteroaromatic behavior of furans enable them to undergo heteroaryl Heck reactions to provide substituted furans. 

It is interesting to note that the substitution pattern of nonactivated alkene functions also has only minor influence on the 5-endo- ng Mizoroki-Heck cyclization (Scheme 5.15). The Mizoroki-Heck reaction of alkene 71 without terminal substitution proceeded well and provided indanone 72 in 65% yield (71 72) [40]. Furthermore, terminal substitution is tolerated -configured 73 was cyclized in moderate yield (52%) (73 74) [31], while... 

Intramolecular reactions with alkenes. While the intermolecular reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and various cyclic compounds are prepared by the intramolecular Heck reaction. Particularly the... 

Heck reaction, palladium-catalyzed cross-coupling reactions between organohalides or triflates with olefins (72JOC2320), can take place inter- or intra-molecularly. It is a powerful carbon-carbon bond forming reaction for the preparation of alkenyl- and aryl-substituted alkenes in which only a catalytic amount of a palladium(O) complex is required. 

The regioselectivity of the addition of complex 4 to a substituted alkene is mainly influenced by steric factors. The substitution of hydrogen occurs preferentially at the carbon center which has the larger number of hydrogens. The 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. 

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

This method ensures the deposition of very reactive metal nanoparticles that require no activation steps before use. We shall review here the following examples of catalytic reactions that are of interest in line chemical synthesis (a) the hydrogenation of substituted arenes, (b) the selective hydrogenation of a, 3-unsaturated carbonyl compounds, (c) the arylation of alkenes with aryl halides (Heck reaction). The efficiency and selectivity of commercial catalysts and of differently prepared nanosized metal systems will be compared. 

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... 

In aqueous DMF, the reaction can be applied to the formation of C-C bonds in a solid-phase synthesis with resin-bound iodobenzoates (Eq. 6.33).80 The reaction proceeds smoothly and leads to moderate to high yield of product under mild conditions. The optimal conditions involve the use of 9 1 mixture of DMF-water. Parsons investigated the viability of the aqueous Heck reactions under superheated conditions.81 A series of aromatic halides were coupled with styrenes under these conditions. The reaction proceeded to approximately the same degree at 400°C as at 260°C. Some 1,2-substituted alkanes can be used as alkene equivalents for the high-temperature Heck-type reaction in water.82... 

Thus, Alami and coworkers [102] have shown that benzylhalides as 6/1-201 can react with 1-alkynes as 6/1-202 in the presence of Pd° and Cul in a Sonogashira reaction which is followed by a Heck and a second Sonogashira reaction to give tetra-substituted alkenes 6/1-203 in yields of 22 to 90% (Scheme 6/1.52). 

Intramolecular Heck reactions.6 Heck intramolecular coupling of alkenyl or aryl iodides substituted by 3-cycloalkenyl group is an attractive route to fused, spiro, and bridged polycyclic products. Coupling is achieved with a Pd-phosphine catalyst such as Pd[P(QH5),]4 in combination with a base, N(C2H5)3 or NaOAc. The coupling tends to produce a mixture of two isomeric alkenes, in which the newly formed bond is allylic or homoallylic to the ring juncture. 

Halogen atoms. The introduction of side-chains on 9-trifluoromethyl-paullone 409 can be accomplished applying a Stille coupling (Scheme 86, Section 5.2.1.1 (2005EJM655)). Similarly, a Heck reaction of iodo 409 with terminal alkenes under standard conditions affords 2-substituted paullones 413 exclusively as E-isomers. The reaction of terminal alkynes with 409 in the presence of cuprous iodide and a palladium catalyst in triethylamine furnishes the 2-alkynyl-paullones 412 (2000BMCL567). 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

Regio- and enantioselective Heck reactions of 2 3-dihydrofuran with aryl and alkenyl triflates in the presence of the chiral ligand (R)-BITIANP provides 2-substituted 23-dihydro-furans with complete regioselectivity, high enantioselectivity (86-96% ee) and good yields (76-93%) <99CC1811>. A catalytic oxyselenylation-deselenylation reaction of alkenes offers a stereoselective one-pot conversion of alkenes into 2 -dihydrofurans <99EF0797>. 

Arylation of alkenes catalyzed by palladium compounds is known as the Heck reaction [65]. While these reactions are very sensitive to steric effects, subtle electronic contributions to the regiochemical outcome may be assessed by comparing reactions of alkenes with similar substitution patterns. The arylating agents, being the nucleophilic arylpalladium species, tend to dictate the facility of their reaction with unsym-metrical, electron-deficient alkenes. 

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... 

Intramolecular versions of the Heck reaction are very useful for the construction of ring systems. The entropic advantage of having both coupling partners present in the same molecule increases the efficiency of the insertion reaction and leads to efficient reactions. Moreover the intramolecular version can be carried out on hindered substituted alkenes, whereas the intermolecular Heck reaction is largely restricted to monosubstituted alkenes. These reactions illustrate the syn stereochemistry of both the insertion reaction and the elimination. A number of multicyclic natural products have been synthesized using intramolecular Heck reactions to assemble the skeletons, and this has become a powerful synthetic tool for such compounds. 

Whereas the intermolecular Heck reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and many cyclic compounds can be prepared by the intramolecular Heck reaction [37]. The stereospecific synthesis of an A ring synthon of la-hydroxyvitamin D has been carried out. Cyclization of the (7T)-alkene 88 gives the (fT)-exo-diene 90, and the (Z)-alkene 91 affords the (Z)-exo-diene 92 [38]. These reactions are stereospecific, and can be understood by cis carbopalladation to form 89 and the. sun-elimination mechanism. 

Bauerle and coworkers [38] suggested and applied Pd-catalyzed cross-coupling reactions of 3 -bromocoumarin derivatives for the generation of coumarin libraries with a highly diverse substitution pattern. In the case of 3-bromocoumarin (18), the reaction conditions for combinatorial Heck vinylations with alkenes 19, Suzu-... 

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