Catalytic Cycle for the Heck Reaction

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. 

There are two main uncertainties associated with this general mechanism. First, there are a number of C-C coupling reactions where there is no direct evidence for the reduction of the Pd(II) precatalyst into a zero-valent palladium species. Second, like the hydrosilylation system, a number of these reactions may involve colloidal palladium. Also, the general catalytic cycle needs to be substantially modified to rationalize the successful use of 7.63 as a precatalyst. 

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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.

Fig. 2.1 Catalytic cycle for the Heck reaction (ligands omitted for clarity).

Alk)Ties and 2-substituted 1-alkenes can readily undergo sy -carbopalladation but cannot readily undergo p-dehydropalladation to complete the catalytic cycle for the Heck reaction. However, the carbopalladation process itself is living, and it is fundamentally iterative. For termination of the living, carbopalladation to devise synthetically useful catalytic processes, termination via (a) )8-dehydropalladation (eq 39),... 

OUTLINE OF THE CATALYTIC CYCLE FOR THE HECK COUPLING REACTION... 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

For the first time, therefore, several cationic intermediates of the oxidative addition step of the Heck reaction involving arene diazonium salts were detected and characterized by ESI-MS(/MS). A dynamic, time-dependent process with ligand equilibria between several ionic intermediates was observed for the oxidative addition step. The most reactive intermediate for olefin addition (the ion of m/z 488 in Figure 3.5) was also detected and characterized, and this species predominates after mixing the arene diazonium salt and [Pd2(dba)3] dba after about 90 min. Therefore, a novel protocol for the Heck reaction with a delay of 90 min for olefin addition was established for maximum yield. A detailed catalytic cycle for the Heck... 

The general catalytic cycle for the Heck-Matsuda reaction using acyclic olefins starts with the oxidative addition of the Pd(0) catalyst A to the aryldiazonium salt and sequential elimination of nitrogen to produce the cationic palladium species C. This intermediate is very electrophilic and it promptly... 

SCHEME 3 General catalytic cycle for the Heck-Matsuda reaction. 

Scheme 6.5 Catalytic cycle for the Mizoroki-Heck reaction...

Many of the coupling reactions require a base such as OAc" or NEt3 in addition to the palladium. In the Heck reaction, for example, the base is used to effect elimination of hydrogen halide from an intermediate palladium complex, thus regenerating the palladium for use in further catalytic cycles. In the Suzuki reaction, on the other hand, the base binds to the boron atom of the boronic acid which activates the carbon-carbon bond for further reaction. 

The transformation that has come to be known as the Heck reaction is broadly defined as the palladium(O)-mediated coupling of an aryl or vinyl halide or triflate with an alkene. The basic mechanism for the Heck reaction of aryl halides or trifiates (as outlined in more detail in the Key Chemistry), involves initial oxidative addition of the chiral palladium(O) catalyst to afford a a-arylpalladium(II) complex. Coordination of an alkene and subsequent carbon-carbon bond formation by syn insertion provide a a-alkylpalladium(II) intermediate, which readily undergoes P-hydride elimination to release the alkene product. Finally, the hydridopalladium(II) complex has to be converted into the active palladium(O) catalyst to complete the catalytic cycle. 

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 ... 

Apart from intuitions based on experimental observations and support from computational work, the arguments in favor of Pd(II)/Pd(IV) mechanisms in the Heck reactions catalyzed by Pd pincer complexes are scarce. On the contrary, there is conclusive evidence indicating that in many cases the actual catalytic species results from the decomposition of pincer complexes [62, 76, 77, 97,100, 101, 103]. This conclusion can probably be extended to all systems that achieve exceptionally high TON numbers, such as 2 and 3, since the rate of the processes based on Pd(II)/Pd(IV) cycles would be always Hmited by the low reactivity of Pd(II) toward aryl halides. The observed influence of pincer ligands on the catalytic activity or the ability to catalyze difficult couplings (e.g., with aryl chlorides) can be rationalized on the basis of their ability to regulate the production of the actual catalytic species [11, 12, 96]. This, however, does not prevent the possibility that, in some specific cases, pincer complexes could act as true molecular catalysts for the Heck reaction or other closely related processes. In recent years, a couple of examples have been provided that demonstrate this possibility, as discussed below. 

The most common Mizoroki-Heck reaction mechanism is called the neutral mechanism, because its intermediates are uncharged. The catalytic cycle for the neutral manifold of the intramolecular Mizoroki-Heck reaction of alkenyl and aryl halides is shown in Scheme... 

Some of the latest developments in terms of substrates for the Heck reactions are nitrophenyl benzoates [55], acyl benzoates (mixed anhydrides) [236], and substituted benzoic acids [53]. For the last two, the leaving groups are carbon dioxide and carbon monoxide, respectively. A variety of alkenes have been coupled with these substrates. While esters and anhydrides presumably react in a catalytic cycle like that of the classical Heck reaction [237], arenecarboxylic acids, when treated with an equimolar amount of a silver salt as reoxidant, appear to undergo a nonclassical Heck reaction as demonstrated by the coupling with 2-cyclohexenone to give a 3-arylcyclohexenone. 

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