2A palladium-catalyzed α-arylation of amides is reported. Intermolecular arylation of N,N-dimethylamides and lactams occurs using aryl halides, silylamide base, and a palladium catalyst.
Intramolecular arylation of N-(2-halophenyl)amides occurs using alkoxide base and a palladium
catalyst. The palladium catalyst was formed in situ from Pd(dba)2 (dba = trans,trans-dibenzylidene
acetone) and BINAP (2,2‘-bis(diphenylphosphino)-1,1‘-binaphthalene). Although the intermolecular
arylation of amides is less general than that reported previously for ketones, unfunctionalized and
electron-rich aryl halides gave α-arylamides in 48−75% yield and N-methyl-α-phenylpyrrolidinone
in 49% yield. These reactions provided the highest yields yet reported for regioselective amide
arylations. Intramolecular amide arylation of 2-bromoanilides gave oxindoles in 52−82% yield.
Mono- and disubstituted acetanilides gave 1,3-di- and 1,3,3-trisubstituted oxindoles. The use of
dioxane, rather than THF, solvent was important for some of the amide arylations.