Pd-catalyzed N-arylation of secondary acyclic amides: catalyst development, scope, and computational study.
We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the "top ring" ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate.
Hicks
Jacqueline D
JD
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Hyde
Alan M
AM
Cuezva
Alberto Martinez
AM
Buchwald
Stephen L
SL
D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D002712:Chlorides / Q000737:chemistry*; D003198:Computer Simulation; D008024:Ligands; D010165:Palladium / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry
D000577:Amides; D002712:Chlorides; D008024:Ligands; D010720:Phosphines; D013449:Sulfonamides; D010165:Palladium; C044646:phosphine