Heck olefinations

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

Under microwave heating, the Heck olefinations were achieved in 30-60 min, as opposed to 10-40 h by conventional heating. The recyclable heterogeneous LDH-Pd(0) catalytic system circumvents the need to use expensive and air-sensitive basic phosphines as ligands in the palladium-catalyzed coupling of chloroarenes. This novel Mg-Al layered double-hydroxide (LDH) support in the catalytic system stabilizes the nanopalladium particles and also supplies adequate electron density to the anchored palladium(O) species and facilitates the oxidative addition of the deactivated electron-rich chloroarenes. 

An efficient synthesis of functionalized carbazoles was developed by the palladium-catalyzed annulation of a variety of internal alkynes. This reaction involves arylpalladation of the alkyne, followed by intramolecular Heck olefination, and double bond isomerization. The iodoindole 588 reacts with the alkyne 589 in the presence of a catalytic amount of palladium(O) to give substituted carbazoles 590. In this reaction two new C-C bonds are formed in a single step. Higher reaction temperatures were necessary due to the low reactivity of the iodoindole (566) (Scheme 5.29). 

These fundamental steps of the catalytic cycle have been confirmed by stoichiometric reactions starting from isolated stable complexes, and by DFT calculations [11], Although many aspects of the Heck olefination can be rationalized by this textbook mechanism , it provides no explanation of the pronounced influence that counter-ions of Pd(II) pre-catalysts or added salts have on catalytic activity [12], This led Amatore and Jutand to propose a slightly different reaction mechanism [13]. They revealed that the preformation of the catalytically active species from Pd(II) salts does not lead to neutral Pd(0)L2 species a instead, three-coordinate anionic Pd(0)-complexes g are formed (Scheme 3, top). They also observed that on the addition of aryl iodides la to such an intermediate g, a new species forms quantitatively within seconds and the solution remains free of iodide and acetate anions. It may then take several minutes before the expected stable, four-... 

These cationic conditions are also used for intermolecular Heck olefinations in which the chiral centers are generated via double-bond migration. The synthesis of 2-aryl-2,3-dihydrofurans 17 is a good example (Scheme 9) [26]. 

Scheme 11. Heck olefination of deactivated aryl chlorides.

In a process developed by Myers et al., aromatic carboxylic acids were directly employed as substrates for Heck olefinations, albeit in the presence of a large excess of silver carbonate [38]. This base both facilitates the decarboxylation step and acts as an oxidant, generating arylpalladium(II) intermediates. In related processes, arylphosphonic [39] and arylboronic acids [40] were used as aryl sources in the presence of an oxidant. 

Heck olefination of a diazonium salt is a key step in the industrial synthesis of sodium 2-(3,3,3-trifluoropropyl)benzenesulfonate, en route to Novartis sulfonylurea herbicide Prosulfuron (Scheme 15) [46]. Pd(dba)2 (0.5-1.5 mol%, prepared in situ from PdCl2), is used as catalyst. After completion of the arylation step, charcoal is added, thus directly providing a heterogeneous catalyst for the subsequent hydrogenation step and enabling easy removal of the now supported catalyst by filtration. 

Heck Olefination of Aryl Bromides According to Spencer Synthesis of Ethyl 4-Cyanocinnamate[18]... 

Heck Olefination of Aryl Chlorides According to Fu Synthesis of ( )-3-(2-Methyl-phenyl)-2-methylacrylic Acid Methyl Ester [49]... 

Table 6.2 Heck olefination of chlorobenzene with styrene in [(C4)4N]Br to afford 1,2-diphenyl ethene. -1...

Application of phosphinated silica-supported metal complexes, e. g., in hydroformylation [69], cyclooligomerization [75], and Heck olefination [76] reactions, did not reveal any surprising effects. 

Chapters 8 and 11 emphasized that there are relatively few instances of insertion of a C=C bond into an M-C bond, with Z-N polymerization serving as the most significant example. Perhaps the migratory C=C insertion most useful to synthesis chemists is the Heck reaction, which is also known as Heck olefination.89... 

The first report of C-C bond formation by C=C insertion, which we now call Heck olefination, was reported by Mizoroki in Japan in 1971 about a year before Heck s first paper appeared. Some refer to the Heck reaction as the Mizoroki-Heck reaction, but Mizoroki unfortunately died shortly after his original work was published. Since Heck and his co-workers vigorously pursued research on the mechanism and scope of this transformation after 1972, Heck s name is the only one usually attached to the process. T. Mizoroki, K. Mori, and A. Ozaki, Bull. Chem. Soc. Jpn., 1971, 44, 581 and R. F. Heck and J. P. Nolley, Jr., J. Org. Chem., 1972, 37, 2320. 

The rate of reaction and regioselectivity of Heck olefination are sensitive to steric hindrance about the C=C bond of the vinylic partner. For simple aryl halides reacting with alkenes, the rate of reaction as a function of alkene substitution varies95 according to... 

Although Pd(0) is the active oxidation state for catalysis and some procedures use Pd(0) catalysts such as Pd(PPh3)4 or [Pd2dba3], typical Heck olefination procedures utilize Pd(II) salts (such as PdCl2, Pd(OAc)2, or Na2PdCl4) and a reducing... 

Equations 12.45103 and 12.46104 show two examples of intramolecular Heck olefination. In the first case, under Jeffrey s ligandless conditions, the Pd catalyst also acts to isomerize a C=C bond to give a final product that has the C=N bond in conjugation with the aromatic ring. The second example demonstrates how the Heck reaction can cause alkynes as well as alkenes to undergo 1,2-insertion. The transformation is also a nice application of tandem Pd-catalyzed reactions to create a rather complex ring system. 

The variety of carbon fragments that can join and the general tolerance of the reaction conditions to functional groups already present on these fragments lead to countless possibilities for rapid construction of complex molecules, especially biologically active compounds. One key difference between cross-coupling reactions and the Tsuji-Trost allylation or Heck olefination is the occurrence of a transmetalation step during the catalytic cycle. 

As with Heck olefination or Pd-catalyzed CO insertion, almost any organic bromide or iodide (without hydrogens attached to an. v/P-hybridizcd (3 carbon,... 

The transformation shown on the next page has been described as a Heck olefination followed by nucleophilic attack by the enolate on the rf-allyl-Pd... 

The cyclization shown below is another example of Heck olefination however, because a quaternary center forms that makes -elimination impossible, a reducing agent (HC02 ) was also required to reduce Pd(II) to Pd(0).219 Propose a catalytic cycle for the reaction. How does HCG2 act as a reducing agent ... 

The first detailed study of alkyl to aryl palladium migrations, reported in 2004, involved homobenzylic to phenyl migration (Table 5) [58], The process was demonstrated using aryl iodides tethered to an olefin. An additional hap, either intramolecular arylation or intermolecular Heck olefination, was used to hap the migrated palladium. The reaction gives high yields of the desired polycyclic products. 

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