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

Various substituted carboxylic acid 2-chloro- and 2-bromoanilides 1a-j reac t with triethylphosphite in the presence of anhydrous NiCl2 or NiBr2 to giv e o-acylamido-benzenephosphonic acid esters 2a-g and 2j. Yields depend stro ngly 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 phosphon ylation 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-be nzenephosphonic acid esters 2 with excess LiAlH4 is coupled with an intramo lecular cyclisation to the 1H-1,3-benzazaphospholes 6 whereas the N-tertiar y derivative 5 does not undergo cyclisation upon reduction. NMR data and th e crystal structure of 6d are reported. (C) 2001 Elsevier Science Ltd. All rights reserved.