Heck reaction Anionic cycle

In an oxidative addition, Pd(0) complex 22 with BINAP as a ligand accepts alkenyl triflate It. The resulting Pd complex 23 is cationic, since the triflate anion is bound only loosely to the palladium and dissociates from the complex.1 Syn insertion of one of the two enantiotopic double bonds of the cyclopentadienc into the alkenyl-Pd bond of complex 23 leads firs to q -allyl-Pd complex 24. This is in rapid equilibrium with t 3-allyl-Pd complex 25. Neither 24 nor 25 contains a p-H atom in a yn relationship to palladium. Moreover, internal rotation is impossible in the con form a-tionaily fixed ring system. For this reason there is no possibility of a subsequent p-hydride elimination that would once again release the palladium catalyst. In a normal Heck reaction (see discussion) the catalytic cycle would be broken at this point. 

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. ... 

In this context, a functionalized ionic liquid, 1-(2-hydroxyethyl)-3-methyl imidazolium tetrafluoroborate [hemim][BF4], is reported as an efficient and recyclable reaction medium for the palladium catalyzed Heck reaction. The olefination of iodoarenes and bromoarenes with olefins generates the corresponding products in good to excellent yields under phosphine-ffee reaction conditions. After separation of the product, fresh starting materials are charged into the recovered ionic liquid which entraps the palladium catalyst. The reactions still proceed quantitatively for six cycles, without significant loss of catalytic activity. " The effect of both the cation and the anion on the chemical yield is shown in Figure 28. 

Quite a few groups have performed additional research trying to answer the question as to whether the Heck reaction takes place on the surface of the clusters or if it occurs entirely or partially in solution. De Vries and coworkers applied electrospray MS (negative mode) on the Heck reaction of aryl iodides with butyl acrylate. They uncovered a number of monomeric anionic species which led them to propose the catalytic cycle depicted in Scheme 10.6 [57, 58]. 

Two hypothetical mechanisms have been proposed to explain the Heck reaction on the basis of Pd(II)/Pd(IV) cycles (Scheme 2.12). As discussed in Section 2.2.1, oxidative addition of aryl halides to Pd(II) precursors is both kinetically and thermodynamically difficult. The Pd(II)/Pd(IV) mechanism proposed by Shaw for the Heck reaction (Scheme 2.1) tried to elude this problem by postulating the intermediacy of anionic Pd(II) complexes with increased nucleophilicity, but it is not evident how this mechanism could be adapted to complexes containing PCP or related pincer ligands. With this problem in mind, Jensen [93] made an alternative proposal (Scheme 2.12a), which starts with the oxidative addition ofa C-H bond of the olefin to the Pd(II) pincer complex to afford a Pd(IV) vinyl-hydride intermediate. This idea was inspired by a similar reaction observed with an isostructural Ir(I) PCP complex, but such C-H bond activations are unusual in palladium chemistry. A theoretical analysis by Freeh [63] raled out such possibility, leading instead to the alternative Pd(II)/Pd(IV) cycle depicted in Scheme 2.12b. A key element... 

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]. 

In further experiments, preformed TBAX-stabilized Pd-colloids were shown to interact with iodobenzene in a stoichiometric reaction with formation of Ph-PdX species, possibly in an ionic form as indicated by UVA is and NMR analysis. De Vries made the claim, (based on TEM, MS, EXAFS, filtration studies and Finke inhibition tests) that in standard Mizoroki-Heck reactions at high temperatures (>120 °C), the palladium catalyst is rapidly reduced to Pd(0) which tends to form soluble colloids. The atylating agent continuously attacks the palladium atoms at the rim of the nanoparticles leading to the formation of soluble anionic complexes, completion of a Mizoroki-Heck cycle in solution. 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

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-... 

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