DPPF ligand amination reactions

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

Numerous groups have used the BINAP/Pd- and DPPF/Pd-based reaction protocols for the arylation of cyclic secondary amines. Independently, Ward and Farina [31] as well as Willoughby and Chapman [32] disclosed that the palladium-catalyzed arylation reaction could be effected on resin-bound amines, Eq. (7). Both groups reported that while the (o-tol)3P-based catalysts were often inferior to the BINAP-based system, using DPPF as ligand often resulted in comparable yields and reaction rates. They also observed that BINAP-derived catalysts usually yielded smaller amounts of reduced arene by-products. 

The Buchwald-Hartwig amination reaction can facilitate the synthesis of nitrogen-containing heterocycles. For instance, Buchwald demonstrated that the amination reaction could be used to prepare N-arylhydrazones from hydrazones and aryl halides. Acid-catalyzed condensation of the hydrazone with a ketone then yielded the desired indoles.Hartwig described a similar arylhydrazone formation with DPPF as a ligand and CS2CO3 as a base."... 

The formation of alkoxo intermediates may be occurring when monophosphines are used, but the stability of the amine complexes favors the deprotonation of coordinated amine. Instead, the alkoxo complexes may be important in catalytic systems involving chelating ligands [51]. Indeed, the DPPF complex [Pd(DPPF)(p-Bu C6H4)(0-f-Bu) reacted with diphenyl amine, aniline, or piperidine, as shown in Eq. (48), to give the product of amine arylation in high yields in each case [51]. Since, no alkali metal is present in this stoichiometric reaction, the palladium amide is formed by a mechanism that cannot involve external deprotonation by alkali metal base. 

Lipshutz has reported nickel on carbon catalysts for the amination of aryl chlorides [173]. The reactions were conducted with added DPPF as the ligand. The scope of the process is similar to that seen with homogeneous nickel species. Secondary amines provide good yields with electron-poor or electron-rich aryl chlorides, and anilines are suitable for coupling with a range of aryl chlorides. 

Recently, the arylation of several specific primary amines have been studied because of the potential biological relevance of the products or products further downstream in a synthetic sequence. For example, cyclopropylamine was shown to be a viable substrate for the coupling under standard conditions [203]. Reactions of 7-azabicyclo[2.2.1]heptane have also been conducted [204] under relatively standard conditions, but with bis(imidazol-2-ylidene) as ligand. Complexes of this ligand and DPPF showed similar catalytic activities, which proved to be superior to those of most bis(phosphine)s. ortfio-Halo anilines were also studied, in this case to provide access to carbolines after use of the halogen as a means of effecting cycliza-tions by an electrophilic or reductive C-C bond formation with the other N-aryl group [205]. 

Presumably, the use of a bidentate ligand such as ( )-BINAP or DPPF results in the occupation of a vacant coordination site, preventing -hydride elimination of the Pd (II) amide intermediate [53]. Dissociation of the imine and C-H bond reductive elimination results in formation of the reduced aryl bromide. If this -hydride elimination is rapid relative to reductive elimination and reversible, then significant erosion of the enantiomeric excess of optically active a-substituted amines maybe observed during the reaction (Scheme 3). 

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