Arylation of Primary Arylamines

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]. 

Two recent reports have detailed the palladium-catalyzed formation of diaryl-amines to prepare nucleosides of damaged DNA. Sigurdsson et al. reported the formation of a precursor to an interstrand cross-link by the reaction in Eq. (35) [158]. Lakshman reported the reaction of bromonucleosides with amines shown in Eq. (36) as a route to the DNA adducts of carcinogenic aminobiphenyls [159]. In this case, a number of reaction conditions were attempted and those using potassium phosphate and the P,N ligand 13 were effective for the transformation, albeit with high catalyst loads. 

---