Reactivity palladacycles

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

It appears that a modified mechanism operates when tr .s-(o-tolyl)phosphine is used as the ligand,133 and this phosphine has been found to form a palladacycle. Much more stable than noncyclic Pd(0) complexes, this compound is also more reactive toward oxidative addition. As with the other mechanisms, various halide adducts or halide-bridged compounds may enter into the overall mechanism. 

Generally, monophosphine complexes can be generated by decomposition of suitable precursors, among which the most notable are palladacycles (Section 9.6.3.4.7). A spectacular example makes use of spontaneous disproportionation of a dimeric complex of Pd1 with very bulky ligands to give one of the most reactive catalytic systems known so far, which catalyzes the fast crosscoupling of arylboronic acids with aryl chlorides and hindered aryl bromides at room temperature (Equation (28)) 389... 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

Palladium(II) effects orthometalation of acetanilides to form the corresponding palladacycles [185]. De Vries, van Leeuwen, and coworkers exploited this reactivity to achieve regioselective oxidative coupling of acetaniUdes and n-butyl acrylate that proceeds efficiently with BQ as the stoichiometric oxidant (Eq. 46) [ 186], The use of TsOH as an additive and acetic acid as a cosolvent significantly improves the results. Inferior results are observed with hydrogen peroxide or copper(II) acetate as the stoichiometric oxidant, but efforts to use molecular oxygen were not described. 

Scheme 1. Palladacycles and their ring-size-dependent reactivity (general pictogram).

Scheme 6 Reactivity of palladacycle 68 in KTC coupling generating di- and tri-ortho-substituted biaryls...

In 2010, Kantchev and co-workers developed a series of palladacycle complexes of the formula [Pd(NHC)(palladacycle)] and evaluated their activity in Suzuki-Miyaura coupling. Complex 84 was found to be the most active pre-catalyst, efficiently forming a number of C—C bonds, including sp —sp, sp —sp, sp —sp, and sp —sp, in good-to-excellent yield (Scheme 19). The high reactivity of complex 84 in... 

In the mechanistic studies of the reactivity of (arylnorbomyl) palladacycles [39], Catellani observed the ort/zo-arylation of the PNP dimer to generate unsymmetrical homobiaryl products. This o/t/io-arylation was combined with the Mizoroki-Heck... 

While optimizing the reaction conditions, Lautens found that cyanation took place with many intermediates in the Catellani reaction sequence, as all non-palladacycle palladium(II) species in the sequence underwent cyanation (Scheme 29). Through optimization experiments, the target product could be obtained in good to excellent yields from either tethered or intermolecular alkyl bromides and iodides (Scheme 30). As alkyl chlorides are more widely commercially available, lower in cost, and more stable than the corresponding alkyl bromides or iodides, Lautens reported a method to incorporate alkyl chlorides as reaction partners. This study eventually led to the use of benzyl chlorides, a-chloroesters, and a-chloroamides as coupling partners, which were far too reactive as the analogous bromides or iodides. 

The search for more stable or more reactive catalysts has produced many new leads. One of the most promising is represented by the palladacycle (14), known as Hermann s catalyst. This can be used in Heck reactions at high temperatures (above 140 °C), which leads to high turnover numbers of up to 10 with electron-poor aryl bromides. 

We shall also see that the study of the reactivity of the intermediate pal-ladacycle first led us to find that R=aryl migrated to the norbornyl site of the palladacycle and not to the aryl site, as for R=alkyl, and incorporated the norbornane structure into a ring (Eq. 2) [6]. 

The palladium complex isomer resulting from aryl migration to the norbornyl site was clearly the less reactive for ring closure to hexahydromethanotriphenylene and it could be trapped by norbornene itself, according to Scheme 5 [44]. The formation of the two isomers was interpreted as resulting from a common intermediate which forms by oxidative addition of the aryl halide to the palladacycle, according to Eq. 38. 

The reason why certain bromides are more active than iodides in the attack to palladium(II) is probably connected to steric effects. We ascertained that at room temperature the order of reactivity of aryl iodides and bromides with palladium(O) and paUadiiun(II) is the same (I>Br), so the difference is hkely to lie in the easier accessibility of the reaction center of the palladacycle to suitably activated bromo derivatives than to o-alkyl-substituted aryl iodides, which are considerably bulkier. We ascertained that several groups are compatible as shown in Table 4, referring to the reaction of o-substituted aryl iodides, substituted aryl bromides, norbornene, methyl acrylate, K2CO3, and Pd(OAc)2 in the molar ratio 50 50 50 80 120 1. 

The reactions that have been illustrated should give an idea of the potential of a methodology which combines the criterion of multicomponent reactions with that of selectivity, usually difficult to reconcile. One key feature is the use of an olefin as a scaffold for the construction of a palladacycle that is able to direct aromatic functionalization selectively and can be easily removed at the end of the process. Another important feature is the use of different oxidation states of palladium to control reactivity. The combination of an inorganic catalyst (palladium) with an organic one (norbornene) leads to a variety of syntheses in one-pot reactions, which represent only the beginning of what may be expected to be a very fruitful development. Needless to say, any advancement in this area requires a thorough study of the reactivity of the organometallic species involved. 

It seems highly likely that all palladium-catalysed reactions that commence with an oxidative addition as the first step of the catalytic cycle proceed though a Pd(0) / Pd(ll) mechanism. Thus one needs to conclude that all palladacycles and pincers are converted to some form of Pd(0) in these reactions. In many cases this was shown to be in the form of palladium nanoparticles. However, with the more reactive iodoarenes it is possible that most of the catalyst is in the form of an anionic or neutral monomeric or dimeric palladium species. 

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