Heck reactions proposed cycles

A tandem palladium-catalysed ort/io-alkylation/intramolecular Heck reaction coupling sequence was used effectively to access in fair yields the tetrahydro 1-benzoxepines 67 from the iodoaryl precursor 66 and the appropriate alkyl bromide. The norbornene plays a relay role in the proposed reaction cycle <06JOC4937>... 

Figure 1.11 Proposed catalytic cycle for the Heck reaction, showing a the various catalytic intermediates and bthe black box version. Some Pd catalysts exhibitTONs and TOFsofover 100 000 in this reaction.

Figure 2.3 Proposed catalytic cycle for the Heck reaction between an alkene and an aryl halide in the presence of a homogeneous palladium complex.

A general catalytic cycle proposed for Heck reaction is shown in Fig. 7.17. While all the steps in the catalytic cycle have precedents, the proposed reaction mechanism lacks direct evidence. The basic assumption is that under the reaction conditions, the precatalyst is converted to 7.64, a coordinatively unsaturated species with palladium in the zero oxidation state. Oxidative addition of ArX, followed by alkene coordination, leads to the formation of 7.65 and 7.66, respectively. Alkene insertion into the Pd-C bond followed by /3-H abstraction gives 7.67 and 7.68, respectively. Reductive elimination of HX, facilitated by the presence of base B, regenerates 7.64 and completes the catalytic cycle. The C-C coupled product is formed in the 7.67 to 7.68 conversion step. 

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. ... 

The key step in the catalytic cycle with regard to enantioselectivity is clearly B), association of the alkene 2 and insertion of it into the Pd-R bond. As with the Heck reaction itself, the mechanism for this process remains a matter for conjecture, with the overall rationale currently in favor having been proposed in 1991 by Ozawa and Hayashi [18] and independently by Cabri [19] (although the cationic pathway via 8 and 9 had been proposed as early as 1990 [20]). Its development and subsequent evolution has recently been reviewed by the latter author [ 12]. 

Scheme 37 Proposed catalytic cycle for Pd(II) catalyzed oxidative Heck reaction...

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... 

Scheme 10.10 Generally proposed catalytic cycle of the Heck reaction catalyzed by palladium pincer complexes involving Pd intermediates and cationic styrene complexes as resting state.

A catalytic cycle is proposed for Mizoroki-Heck reactions involving a P,C-palladacycle precursor based on the fact that a monoligated Pd(0) complex is formed from P,C-palladacycle precursors (see above). The structure of the Pd(0) complex 10 is close to thatof Pd° P(o-Tol)3 generated from Pd° P(o-Tol)3 2 as the minor but active species in oxidative additions of aryl bromides, as reported by Hartwig and Paul [62a]. The oxidative addition gives the dimeric complex [ArPd(/u.-Br) P(c>-Tol)3 ]2 in equilibrium with the former T-shaped complex ArPdBr P(c -Tol)3 prone to react with a nucleophile [62b,c]. Such a mechanism must be vahd for the Pd(0) complexes 10 or 13 generated in situ from the... 

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]. 

A detailed discussion of the current understanding of the mechanism of the Mizoroki-Heck reaction can be found in earUer chapters of this book and in several excellent reviews [7]. Two mechanistic pathways, typically termed neutral and cationic, have been proposed to account for the differences in reactivity and enantioselectivity observed in asymmetric Mizoroki-Heck cycUzations of unsaturated trillates and halides. These pathways differ in the degree of positive charge and the number of available coordination sites assignable to the palladium(II) intermediates of the catalytic cycle. Because catalytic asymmetric Mizoroki-Heck cyclizations are typically carried out with bidentate Ugands, these pathways will be illustrated with a chelating diphosphine Ugand. 

It was shown that palladacydes 1 [3c, 24] prepared from palladium] I) acetate and tris(o-tolyl)- or trimesitylphosphine are excellent catalysts for the Heck coupHng of triflates and halides including certain aryl chlorides. In some of these cases, a possible involvement of oxidation states +II and +IV in the catalytic cycle has been considered [25]. Similarly, other palladacydes such as 3 [26e,h] or 6 [27] have been used in the Heck reactions (Figure 8.1) [24, 26, 28]. It has been proposed that, at least for NC palladacydes, the reaction proceeds through the classical phosphine-free Pd(0)/Pd(II) catalytic cycle and that the active catalysts are actually slowly formed palladium clusters [29]. Besides classical palladacydes, complexes with pincer-type ligands such as 2 [30] have become very popular in palladium catalysis [31]. 

Scheme 3.12 The catalytic cycle proposed by Matsuda and coworkers for the Heck reaction with arene diazonium salts.

Another of the standard palladium-catalyzed C—C bond formations is the Mizoroki-Heck reaction. This reaction is based on the palladium-catalyzed coupling of olefins with aryl or vinyl halides under basic conditions [21]. The catalytic cycle that is typically proposed for this reaction is outlined in Scheme 7.7. The first step of the reaction postulated in the mechanism is an oxidative addition of R -X to a Pd(0) complex. The next step is the insertion of the alkene to the Pd complex II. In order for this to be possible, an uncharged ligand has to break away giving a neutral Pd(II) complex that will be coordinated by the olefin. The insertion of the alkene into the Pd— bond results in the C C bond-forming step to give BO. Rotation around the C—C bond and 3-hydride elimination yields the new substituted olefin and intermediate 131. Regeneration of the active catalytic species occurs by the addition of a base. 

Scheme 7.14 Proposed catalytic cycle for the oxidative Heck reaction shown in Scheme 7.13.

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