Ortho-metallation palladium catalysts

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules with biological relevance. The ability to prepare haloarenes selectively by an ortho-metallation halogenation sequence allows for the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metallation to form aryl halides that were subsequently reacted with anilines to prepare diarylamines (Eq. 34)) [156]. Frost and Mendon a have reported an iterative strategy to prepare (by palladium-catalyzed chemistry) amides and sulfonamides that may act as peptidomimetics. Diarylamine units are constructed using the DPPF-ligated palladium catalysts, and the products are then acylated or sulfo-nated with 4-bromo benzoyl or arylsulfonyl chlorides [157]. 

The L -iodane PhI(OAc)2 has been used extensively, most notably by Sanford, to oxygenate the C-H bonds of arenes and even alkanes in the presence of palladium catalysts." Interestingly, this reaction was likely mediated by a binuclear complex featuring two Pd(III) atoms joined by a palladium-palladium (Pd-Pd) bond however, this complex can disproportionate into a Pd(IV)-Pd(II) complex without a formal Pd-Pd bond, and this intricate interplay is often controlled by the presence and nature of hypervalent iodine oxidants." We discovered that this reaction manifold could be extended to include the amination of arene substrates heating 2-phenylindole 51 in the presence of the -iodane 49 and palladium acetate provided the ortho-aminated product 52 in a 19% yield however, switching the metal from palladium acetate... 

As carboxylic acid additives increased the efficiency of palladium catalysts in direct arylations through a cooperative deprotonation/metallation mechanism (see Chapter 11) [45], their application to ruthenium catalysis was tested. Thus, it was found that a ruthenium complex modified with carboxylic acid MesC02H (96) displayed a broad scope and allowed for the efficient directed arylation of triazoles, pyridines, pyrazoles or oxazolines [44, 46). With respect to the electrophile, aryl bromides, chlorides and tosylates, including ortho-substituted derivatives, were found to be viable substrates. It should be noted here that these direct arylations could be performed at a lower reaction temperatures of 80 °C (Scheme 9.34). 

These reactions are typically promoted by metal catalysts. While ortho-directing groups have promoted the formation of ortho-substituted arenes using palladium catalysts [68], ruthenium complexes have been shown to generate the meta-substituted aryl sulfone using the same ortho-directing group [67]... 

The ruthenium-, rhodium-, and palladium-catalyzed C-C bond formations involving C-H activation have been reviewed from the reaction types and mechanistic point of view.135-138 The activation of aromatic carbonyl compounds by transition metal catalyst undergoes ortho-alkylation through the carbometallation of unsaturated partner. This method offers an elegant way to activate C-H bond as a nucleophilic partner. The rhodium catalyst 112 has been used for the alkylation of benzophenone by vinyltrimethylsilane, affording the monoalkylated product 110 in 88% yield (Scheme 34). The formation of the dialkylated product is also observed in some cases. The ruthenium catalyst 113 has shown efficiency for such alkylation reactions, and n-methylacetophenone is transformed to the ortho-disubstituted acetophenone 111 in 97% yield without over-alkylation at the methyl substituent. 

In substrates where a halogen is located ortho to nitrogen, ring closure to benzimidazoles can be achieved by palladium(0)-catalysed or copper-catalysed sequences similar formation of benzothiazoles from orf/20-haloarylamine-thioamides, does not require a metal catalyst. ... 

This reaction was first reported by Mori and Ban in 1976. It is a synthesis of indole derivatives by an intramolecular Heck Reaction of o-halo-fV-aUylanilines catalyzed by a low-valent metal complex and is known as the Mori-Ban indole synthesis. In this reaction, the low-valent metal can be nickel or palladium, but the ortho halogen must be bromine or iodine. Often the o-iodo-fV-allylaniline is more reactive than corresponding o-bromo substrate. In addition, it has been found that the catalyst can be deactivated under the reaction conditions, thus aperiodic provision of fresh catalyst normally gives higher overall yields than that using the same total amount of catalyst at once. ... 

The intramolecular hydroarylation of alkynes is a useful method for the synthesis of fused arenes. For example, biphenyl derivatives, bearing an alkyne unit at the ortho position, were converted into substituted phenanthrene derivatives in the presence of various jc-electrophihc transition metal catalysts such as platinum, palladium, gold, gaUium, indium, iron, and so on (Scheme 21.48) [54]. 

The use of transition metal catalysts to effect alkylations, alkenylations, arylations, and acylations in pyridines has been reviewed, and there has been a computational study of the ortho-alkylation of pyridine by scandium-catalysed reactions with alkenes. DFT calculations indicate that the stability of the developing metal-aryl bonds may be important in determining regioselectivity in palladium-acetate-catalysed carbon-hydrogen substitution in heteroarenes. ... 

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