Synthesis of 1H-1,3-benzazaphospholes: substituent influence and mechanistical aspects

Various substituted carboxylic acid 2-chloro- and 2-bromoanilides 1a–j react with triethylphosphite in the presence of anhydrous NiCl2 or NiBr2 to give o-acylamido-benzenephosphonic acid esters 2a–g and 2j. Yields depend strongly on the substituents. 2-Fluoro-4,6-dibromoacetanilide 1g reacts only at 6-position, indicating an o-directed process. Based on substituent effects, we infer a mechanism via Ni(0) intermediates that insert into the carbon–halogen bond. The N-tertiary 2-bromoformanilide 4 does not undergo phosphonylation to 5 in the presence of the Ni-catalyst but reacts in the presence of Pd-catalysts. The subsequent reduction of the N-secondary o-acylamido-benzenephosphonic acid esters 2 with excess LiAlH4 is coupled with an intramolecular cyclisation to the 1H-1,3-benzazaphospholes 6 whereas the N-tertiary derivative 5 does not undergo cyclisation upon reduction. NMR data and the crystal structure of 6d are reported.