Oxidative Addition to Palladium O

The species actually undergoing oxidative addition of iodobenzene has been shown by Amatore and Jutand [11] to involve palladium(O) anionic complexes such as [Pd°(PPh3)20Ac] . The process is represented by Eq. 5. 

When no phosphinic ligand is present the solvent or norbornene can act as ligand [12]. As to the rate of oxidative addition, the series PhI PhBr PhCl [13] has been confirmed. To obtain reactions at mild temperatures aryl iodides have usually been used. 

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The aforementioned reaction is an example where even quinolinyl chloride is a good substrate for the oxidative addition to palladium(O) if the chlorine atom is at the activated position (a or 5). 

Tn most organic syntheses involving palladium, palladium-carbon sigma bonds are involved at some stage in the reaction pathway (J). Two important types of reactions which take place in organo-palladium syntheses are oxidative additions to palladium(O) and addition of palladium (II) complexes across olefins as well as the respective reverse (elimination) reactions. In both these reactions, carbon-palladium sigma bonds are made and broken ... 

Extensive mechanistic studies have been conducted on the oxidative addition of aryl halides to Pd(0) complexes ligated by PPh3 in different media and with different additives175, 176. However, palladium complexes containing these ligands are not active catalysts for amination. Instead, one must consider the addition of aryl halides to palladium complexes bound by ligands relevant to amination. Studies of the mechanism of oxidative addition to palladium(O) complexes of P(tol-o)3, DPPF, BINAP, Q-phos, P(Bu-f)3 and an /V-heterocyclic carbene ligand have been reported. 

The animation of aryl chlorides is desirable due to their prevalence and lower costs as compared to aryl bromides and iodides. Aryl chlorides are less prone to oxidative addition to palladium(O) and therefore require more activating ligands. An early example of ArCl amination was reported by M. Beller and co-workers.52 They found a palladacycle derived from Pd(OAc)2 and (o-tol)3P, for example, trawj-di(p-acetato)-bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II). This catalyst allows for the amination of electron deficient aryl chlorides (13) with piperidine in the presence of catalytic LiBr and KO/-Bu as the stoichiometric base. The high temperature required (135 °C) also gives rise to a minor amount of the meta aminated product 15, likely due to aryne formation. It is unclear from this example whether a true oxidative addition to the aryl chloride is occurring, or whether the para product 14 also results from aryne formation, as a 1 1 mixture of products 14 and 15 also results without palladacycle present. 

An intermediate formed after oxidative addition to palladium(O) was isolated by Echavarren et al. [5]. Thus, when 2-iodo- or 2-bromophenyloxymethylstannanes were treated with Pd(dba)dppf (dba, diben2ylideneacetone dppf, l,T-bis(diphenyl-phosphino)ferrocene), an isolable arylpaUadium(II) intermediate was formed by oxidative addition of the haloarene to a palladium(O) species. If (Ph3P)4Pd or Pd(dba)dppe (dppe, l,2-bis(diphenylphosphino)ethane) was used, transmetallation... 

The need for an accurate balance of the reagents clearly emerges in the second variant of the alkylation-alkenylation process leading to o,o -unsynuneIilcaIly disubstituted alkenylarenes (Eq. 2 of Scheme 1). In this case it is necessary to start from an ortho-monoaUcylated aryl iodide and to increase the reaction tanperature to 55 C. After oxidative addition to palladium(O) and norbomene insertion, there is a strong tendency, also favored by the increased temperature, to close a benzocyclobutene ring because of the steric effect exerted by the ortho-alkyl substituent, and only a significant excess of the added alkyl halide can curtail this termination reaction. 

All substrates mentioned in the previous chapter easily undergo palladium-catalyzed aminocarbonylation also. It should be mentioned that even allylic carbonates instead of halides could be converted into carboxamides by this method, as it vas demonstrated during the total synthesis of antillatoxin [94]. The use of aryl chlorides is somewhat restricted owing to the low reactivity ofthese type of substrates in oxidative addition to palladium(O), as well as the competitive amination observed, for example, in the reaction of 1-chloroisoquinoline [95]. Functionalization of a great number of pharmaceutically important skeletons, for example, steroids [96-99], tropenes [100], benzodiazepines [101], indoles [102], benzo[c[quinolizine derivatives [103], and quinolones [104], have been carried out. 

Oxidative addition to palladium(O) complexes containing bidentate hgands are obtained from unsaturated 14 valence electron bisphospine complexes. The bent conformation adopted by such complexes leaves the paUadium(0) more reactive than the L2Pd(0) complexes obtained from monodentate phosphines with smaller cone angles, displaying a more linear geometry (Scheme 1.8) [2, 41]. 

Haloalkynes react with terminal alkynes in the presence of a palladium catalyst might give unsymmetrical diynes, as demonstrated by Wityak and co-workers. " However, under different conditions, 1-haloalkynes undergo rapid oxidative addition to palladium(O) to give palladium alkynyl complexes that in turn react with a second equivalent to yield diynes. ... 

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