Anionic pathways Heck reaction

A key feature of the cationic mechanism is that removal (or dissociation) of an anionic ligand from the palladium coordination sphere allows alkene complexation to occur while maintaining coordination of both phosphines of a bisphosphine ligand. That both phosphines can be accommodated in a square-planar four-coordinate intermediate during the insertion step has provided a simple rationalization for the higher enantioselectivities often observed for the cationic pathway. Concrete information on the enantioselective step of asymmetric Heck reactions proceeding by the cationic pathway has not been reported to date. It is likely to be either coordination of the alkene to generate 20.S or the insertion step (20.5 —> 20.6, Scheme 8G.20). 

Under standard reaction conditions, the mechanism of the Heck reaction is more complicated than the textbook pathway shown in Scheme 5. The active catalyst responsible for oxidative addition of the ArX substrate is an anionic Pd species, either I PdCl or L2Pd(OAc), depending on the starting palladium compound, where L is triphenylphosphine. Reduction of the starting palladium salt to a Pd species is carried out by the phosphine. A mechanism that is consistent with spectroscopic and electrochemical data is given in Scheme 13. 

The mechanism of the Heck reaction is not fully understood and the exact mechanistic pathway appears to vary subtly with changing reaction conditions. The scheme shows a simplified sequence of events beginning with the generation of the active Pd catalyst. The rate-determining step is the oxidative addition of Pd into the C-X bond. To account for various experimental observations, refined and more detailed catalytic cycles passing through anionic, cationic or neutral active species have been proposed. ... 

Research into the mechanism of the Heck reaction continues and the understanding of the reaction is increasing. Recent research has revealed that in some intramolecular cases another mechanism is observed. Cationic intermediate 68 can be accessed by associative displacement via the pentacoordinate intermediate 70, leading to high enantioselectivity from a reaction that might be thought to proceed via a neutral pathway. Other studies have also identified key roles for pentacoordinate intermediates as well as anionic complexes.f ... 

Much of the recent hteiature on the mechanism of the enantioselective intramolecular Mizoroki-Heck reaction has focused on the anionic mechanism, o-iodoanilide substrates, pathways involving neutral pentacoordinate palladium intermediates and the influence of additives. The new examples and mechanistic findings indicate that the potential may exist to control the stereoselectivity of the intramolecular Mizoroki-Heck reaction through pathways other than the cationic mechanism. However, further research is needed to obtain the level of effectiveness of the traditional cationic pathway. 

A catalytic cycle arising from the common precatalyst mixture of Pd(OAc)2 and PPhs, termed the anionic pathway, has recently been proposed [ 14]. This pathway involves anionic palladinm(O) and palladium(II) intermediates in which the acetate anion is coordinated with palladinm in the catalytically active species persisting after oxidative addition. The anionic pathway has not been invoked or thoroughly explored for enantioselective intramolecular Mizoroki-Heck reactions. However, it may become more significant based on recent studies with Pd(OAc)2 and bidentate phosphine ligands for which the palladium(n) species is only formed in the presence of added acetate ion [15]. 

The mechanism for the Heck reaction is shown in Scheme 4.63. The first step involves the oxidative addition of an aryl or vinyl halide, R -X, to a palladium(O) species. This species normally contains an auxiliary donor, L, where L is often a phosphine. This may be preceded by a reduction of the metal if a palladium(II) salt is employed initially. Thereafter, two different pathways are possible depending on which group dissociates to provide a vacant coordination site for the incoming alkene. If a neutral ligand (such as a phosphine) detaches and the halide is retained, the active species immediately prior to the C-C coupling step is the neutral complex III-90. Conversely, if the anionic ligand (such as a halide) dissociates, the active species is the cationic complex III-91. 

An important development in Heck chemistry arose from the recognition that a-palladium(II) intermediates can be exploited for transformations other than y3-hydride elimination [50]. Examples of potential reaction pathways include insertion of a second olefin (path A), anion capture (path B), or carbonylation (path C) (Scheme 6-22). Due to the... 

The first example of an enantioselective intramolecular cascade Mizoroki-Heck-cyanation sequence was recently reported which included the reaction of amide 104 (Scheme 12.24) [33], The cyanide source employed was potassium ferro(II)cyanide, which has been utilized for the palladium-catalysed cyanation of aryl halides. The proposed reaction pathway for the Mizoroki-Heck-cyanation involves capture of a a-alkylpalladium intermediate. Previous examples of enantioselective Mizoroki-Heck cyclization-anion capture most often involve trapping of the 7r-allylpalladium complexes in group-selective reactions. Reaction conditions were surveyed for the Mizoroki-Heck cyanation sequence. It was found that Pd(dba)2 afforded better enantioselectivities than Pd(OAc)2 with Ag3P04 as the additive. Using PMP under neutral conditions led to racemic product. To improve the enantioselectivity, several bidentate ligands were screened, and the ligand DIFLUORPHOS 54a was found to give the best enantioselectivity. 

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