Metal insertion Heck reaction

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

Transition metal catalyzed insertion reactions offer a variety of alternate approaches for the preparation of heterocyclic rings, of which Heck reactions were utilised extensively to prepare rings with more than 6 atoms. At the end of this Chapter some examples of the use of insertion reactions in the formation of the carbacyclic part of condensed heterocyclic systems will also be presented. 

Another method for activating the versatile alkenyl halide moiety was the oxidative addition of a late transition metal species, which would then facilitate insertion of the C13-C14 double bond. The Rawal,7h Bonjosch,7e and Mori7b syntheses of 1 all employed a Pd-mediated intramolecular Heck reaction to build the F ring of the molecule.71 Our system, in as much as it contained additional unsaturation, was somewhat different from those in the literature and thus had the potential for displaying new chemistry. For example, in Rawal s approach (Scheme... 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

In the insertion step of the Heck reaction (see Scheme 3-1), a new metal carbon bond is formed which, in principle, can undergo any of the typical reactions of an-M—C bond (Scheme 3-13), if the S-hydride elimination is not too fast. When the -hydride elimination is totally suppressed, the palladium species can undergo a number of reactions with the formation of new C—C bonds. With an appropriate choice of... 

As described above in Section 1.4, intramolecular Heck-reactions proceed via. vy -al kene insertion into Pd—C bonds of intermediate (Ar)Pd(X) complexes. Although alkene insertions into late-transition metal—carbon bonds are common and well precedented, the analogous yn-insertion of alkenes into palladi um-heteroatom bonds of (R,N)Pd(X) complexes are quite rare. However, the known examples of these transformations (het-eroatom-Heck reactions) provide useful routes into an array of nitrogen heterocycles. 

Prior chapters have covered the use of transition metals in asymmetric hydrogenations ( 6.2 and 7.1), hydroborations ( 7.3), hydrosilylations and hydro-cyanations ( 6.3, 6.4, 7.4 and 7.5), cyclopropanations ( 7.19), aldol reactions ( 6.11), allylations of carbanions ( 5.3.2), and some sigmatropic rearrangements ( 10.3). This chapter covers other reactions catalyzed by transition metal complexes including coupling of organometallic reagents with vinyl, aryl or allyl derivatives, Heck reactions allylamine isomerizations, some allylation reactions, car-bene insertions into C-H bonds and Pauson-Khand reactions. 

Direct (instead of stepwise) transition metal catalyzed dicarboration is achieved by a modification of the palladium-catalyzed Heck reaction 2 4-85,86 116 if the final dehydropal-ladation step is suppressed. This step usually occurs after alkene insertion into an aryl - or a vinyl-palladium bond formed from the corresponding halide or triflate. 

As with other transition metal-catalyzed reactions (Ziegler-Natta polymerization of alkenes, olefin metathesis), the mechanism of the Heck reaction is complicated. In brief, the species that reacts with the aryl halide is I Pd, where L is a ligand such as tiiphenylphosphine. By a process known as oxidative addition, palladium inserts into the carbon-halogen bond of the aryl halide. 

The solution to this synthesis problem goes back to the work of Reiner Sust-mann, who successfully carried out the formal, nickel(0)-mediated addition of alkyl or aryd halides to electron-deficient alkenes, like acrylate esters or acrylonitrile. [101] Sub-stoichiometric amounts of nickel(ll) chloride hexahydrate (15-20 mole %) are reduced with zinc in presence of pyridine to nickel(O), which forms together with pyridine a complex with the alkene. Oxidative addition of the alkyl halide leads to an alkyl-nickel species, the carbon-metal bond of which undergoes an alkene insertion. Hydrolysis gives ultimately the product. Heck reaction products are not observed. 

Evidence for the intermediacy of a-arylpalladium acetate complexes c was provided by the isolation of their trinuclear dialkyl sulfide adducts [11]. The two following steps, insertion of the alkene 4 and )8-hydride elimination, correspond to the classical Mizoroki-Heck reaction pathway. The resulting palladium(0) species, which is likely to be stabilized in the form of a hydridopalladium carboxylate e, is then reoxidized by molecular oxygen to the initial palladium(II) acetate (a) under liberation of water. The precise mechanism of this reoxidation is not yet fully understood, but it seems that, at elevated oxygen pressures, it is not rate-determining even in the absence of promoters. Mechanistic studies by Jacobs and coworkers [10] indicate that the beneficial effect of adding transition metal salts, originally intended to facilitate this oxidation step, in fact arises from an acceleration... 

The insertion of olefins into metal-alkyl linkages is the cornerstone of the preparation of polyolefins and a-olefins, and the insertions of olefins into metal-aryl bonds is one step of a common class of palladium-catalyzed coupling reactions (the Mizoroki-Heck reaction). The insertions of olefins into early-metal-alkyl bonds is part of the so-called Cos-see mechanism of Ziegler-Natta olefin polymerization and of Cramer s mechanism for olefin dimerization. The following sections present examples of these insertion reactions and information on the mechanisms of this type of C-C bond formation. 

In the Heck reaction (Fig. 3, pp. 76 and 343), an organopalladium (II) complex inserts an olefin and eliminates "Pd-H", resulting in an overall vinylic alkylation. The thermal catalytic mixture is identical to the one used for sonochemical activation. The mechanism is not completely clarified electrochemistry has, however, recently brought new information. The sonochemical version of the Heck reaction allows obtaining the product in 6 h at 50°C instead of 24 h at 80 C for the purely thermal one.i The process could be rationalized either at substitution step 1 by interfacial effects or in step 2, where an anionic transition metal complex attacks the substrate. 

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