Oxidative addition palladacycles

Keywords Annulation reaction Oxidative addition Palladacycle Palladium(IV)... 

The use of well-defined complexes has been widespread in this reaction, despite intriguing studies by Beller and others that have shown that in situ catalytic systems often give better yields in comparison to isolated carbene-Pd(O) complexes [147-149]. Since the mechanism consists of an oxidative addition on a Pd(0)-monocarbene species, efforts in catalyst synthesis have been directed towards Pd(ll)-monocarbene complexes with other labile groups that can be easily released leading to the formation of Pd(0). This is the case for dimers of the type [Pd( j,-C1)C1(NHC)]2, a family of pre-catalysts effective under aerobic conditions [150], the [Pd(acac)Cl(NHC)] complexes [151] and related palladacycles [152-154],... 

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. 

Phosphites P(OR)3 are much weaker ligands for Pd, and are not capable of supporting Pd° species in solution for the reactions where oxidative addition is rate-limiting therefore they are very rarely used in cross-coupling reactions. Phosphite-derived palladacycles, however, are among the most effective precatalysts (Section 9.6.3.4.8). 

It has been found that A-tosyl aziridines undergo oxidative addition to palladium complexes to form azapalladacyclobutanes <06JA15415>. Reaction of aziridine 95 with Pd2(dba)3 and 1,10-phenanthroline provides the palladacycle 96 in 45% isolated yield. This compound is an air stable solid. Treatment the palladacycle 96 with catalytic Cul is believed to open the palladacycle to form a copper intermediate, which cyclizes to cyclopentyl alkylpalladium intermediate 97. Loss of Cul then provides the product palladacycle 97 as an air stable solid. Several different aziridines were examined in this reaction. Only a limited set of olefin substituted aziridines provided the azapalladacyclobutanes (e.g. 96). 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

The intramolecular arylation of sp3 C-H bonds is observed in the reaction of l-/ r/-butyl-2-iodobenzene under palladium catalysis (Equation (71)) 94 94a 94b The oxidative addition of Arl to Pd(0) gives an ArPdl species, which undergoes the electrophilic substitution at the tert-butyl group to afford the palladacycle. To this palladacycle, another molecule of Arl oxidatively adds, giving the Pd(iv) complex. 

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. 

Another example of transient formation of a palladacycle is the Pd-mediated ortho-alkylation and ipso-vinylation of aryl iodides depicted in Scheme 8.23. In this multicomponent reaction the ability of norbomene to undergo reversible arylation and palladacycle formation is exploited. This reaction also illustrates that aryl halides undergo oxidative addition to Pd faster than do alkyl halides, and that aryl-alkyl bond-formation by reductive elimination also proceeds faster than alkyl-alkyl bond-formation. The large excess of alkyl iodide used in these reactions prevents the formation of biaryls. Benzocyclobutenes can also be formed in this reaction, in particular when the alkyl group on the aryl iodide is sterically demanding or when a secondary alkyl iodide is used [161]. 

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

The C-H activation step could, in principle, occur either by oxidative addition of the C-H bond - pathway (a) - or by electrophilic displacement - pathway (b). The oxidative addition pathway would proceed via the formation of a palla-dium(IV) species. Although such intermediates have been postulated in some coupling reactions catalyzed by palladacycles, as yet no conclusive experimental evidence has been presented [14], It is perhaps more likely that C-H activation results from electrophilic displacement of the ortho proton [15]. 

C-H transformation is achieved by cyclometallation by use of a unique catalytic system which involves the in-situ formation of a palladacycle [1]. Our work in this field takes advantage of the stability toward /3-hydrogen elimination of as,exo-aryl-norbomylpalladium complexes formed by a sequence of oxidative addition of an aryl halide to palladium(O) and stereoselective insertion of norbornene into the... 

Scheme 1. Palladacycle formation through a sequence of oxidative addition, insertion, and electrophilic aromatic substitution. L= phosphorous or nitrogen ligands, solvent, or coordinating species.

Palladacycle 5 reacts in various ways depending on ligands and reaction conditions. In particular it readily undergoes oxidative addition of alkyl halides to form a palladium(IV) complex 6, which has been isolated and characterized with stabilizing nitrogen ligands such as phenanthroline. This palladium(IV) metallacycle... 

The mechanism of the indenone synthesis (Scheme 3) seems to involve (1) oxidative addition of the aryl iodide to Pd(0) (2) arylpalladium coordination to the alkyne and subsequent insertion of the alkyne to form a vinylpalladium intermediate (8), (3) then either the vinylic palladium intermediate adds to the carbonyl group and subsequently undergoes a /3-hydride elimination (path A) or the alde-hydic C-H bond may oxidatively add to the palladium to produce an organopalla-dium(IV) intermediate (six-membered ring palladacycle) which subsequently undergoes rapid reductive elimination of the indenone and palladium (path B). The actual mode of ring closure of the vinylic palladium intermediate to the inde-... 

The palladacycle 29 is either prone to reductive elimination, furnishing the minor by-product 26, or to an oxidative addition of an alkyl iodide, giving rise to an octahedral Pd(IV) species 30. Reductive elimination places the alkyl substituent in the ortho position and another CH activation furnishes the palladacycle 31. Again, an octahedral Pd(IV) intermediate 32 is obtained after an oxidative addition of an alkyl iodide. As before, reductive elimination occurs and gives an alkyl-Pd intermediate 33 that sets the stage for a jd-elimination and expulsion of norbornene. Now, the resulting ortho, ortho double alkylated aryl Pd intermediate 34 reacts with the terminal olefin and finally concludes the sequence with a Heck vinylation to give the final product 27. 

More recently, cationic intermediates have been observed in the Heck reactions of arene diazonium salts catalyzed by triolefinic macrocycle Pd(0) complexes [17,59], o-iodophenols and enoates to form new lactones [60], and o-iodophenols with olefins (the oxa-Heck reaction) [61 ]. In the first case ions were formed by oxidation of the analyte at the capillary, or by association of [NH4] or Na". In the two other cases ionization occurred through the more typical loss of a halide ligand. The oxa-Heck reaction provides a good example of how these experiments are typically performed and the type of information that can be obtained. The oxyarylations of olefins were performed in acetone, catalyzed by palladium, and required the presence of sodium carbonate as base. Samples from the reaction mixtures were diluted with acetonitrile and analyzed by ESI(+)-MS. Loss of iodide after oxidative addition of o-iodophenol to palladium afforded positively-charged intermediates. Species consistent with oxidative addition, such as [Pd(PPh3)2(C6H50)], and the formation of palladacycles of the type seen in Scheme 8 were observed. Based on this, a mechanism for the reaction was proposed (Scheme 8). 

These reactions are considered to involve insertion of the unsaturated compounds to arylpalladium species followed by the formation of palladacycle intermediates. Oxidative addition of another halide molecule to them leads to the products. In the reaction with norbornene [105 -108] and diphenylacety-lene [109],the corresponding 3 1 and4 1 products and 3 1 product,respectively, are also formed under somewhat different conditions. The mechanisms to account for the formation of these unusual products involving multiple C-H cleavage steps have been proposed. It is noted that, in contrast to Eq. (49), treatment of aryl bromides with aliphatic internal alkynes gives allene derivatives (Eq.50) [110]. 

Only palladium- and platinum-containing heterocycles were described between 1995 and 2006. Mateo et a/, reported that iodoaryl stannane 70 reacts with Pd(PPh3)4 to afford palladacycle 71, as a result of an intramolecular Pd/Sn transmetallation of the intermediate oxidative addition arylpalladium(ll) complex (Equation 10) <1996CEJ1596>. 

NMR spectroscopy. Complex 22 was formed selectively by oxidative addition of allyl bromide to palladium(II) palladacycle 21. This structure is believed to result from cis oxidative addition of allyl bromide to palladacycle 21. 

The stereochemistry of oxidative addition to the palladium(II) palladacycle was studied by Lautens using an enantioenriched secondary alkyl halide (Scheme 9) [32], From alkyl halide 23, product 24 was obtained, showing a net inversion of stereochemistry [33-35], Previous work by Stille showed that reductive elimination from palladium(IV) occurs with retention of stereochemistry [36], suggesting that oxidative addition occurs with an inversion of stereochemistry. This corresponds with the generally accepted SN2 mechanism for the reaction of palladium(O) with alkyl halides [37, 38],... 

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