Synthesis of Unsymmetrical Diaryl Acetamides, Benzofurans, Benzophenones, and Xanthenes by Transition-Metal-Free Oxidative Cross-Coupling of sp3and sp2C-H Bonds.
A chemo- and regioselective intermolecular sp3C-H and sp2C-H coupling reaction for C-C bond formation is described to access unsymmetrical diaryl acetamides under TM-free conditions from sec- and tert-arylacetamides and nitroarenes using tert-butoxide base in DMSO at room temperature. The coupling partners with sensitive functionalities such as chloro, bromo, hydroxy, and cyano were also amenable to the developed reaction. Synthesized α-(2/4-nitroaryl) phenylacetamides have been transformed into biologically important benzofurans, xanthenes, diaryl indoles, and unsymmetrical benzophenones by novel routes without applying a transition metal. Overall, an economical, yet efficient, strategy has been devised to access unsymmetrical diarylacetamides with the possibility of their further elaboration into a variety of biologically important heterocycles. Mechanistic understanding suggests that the reaction proceeds by a nucleophilic addition of a phenylacetamide carbanion, which is generated in the presence of tert-butoxide base, to the para or ortho (if para is substituted) position of nitrobenzene. The formed α-(4-nitrocyclohexa-2,4-dien-1-yl) phenylacetamide anion intermediate oxidized by a basic solution of DMSO or atmospheric oxygen led to the desired sp3C-H and sp2C-H coupled α-(2/4-nitroaryl) phenylacetamides.
Department of Chemistry, Indian Institute of Science Education and Research (IISER) , Bhopal, MP 462 066, India.
Vandana
V
Rathore
Department of Chemistry, Indian Institute of Science Education and Research (IISER) , Bhopal, MP 462 066, India.
Moh
M
Sattar
Department of Chemistry, Indian Institute of Science Education and Research (IISER) , Bhopal, MP 462 066, India.
Raushan
R
Kumar
Department of Chemistry, Indian Institute of Science Education and Research (IISER) , Bhopal, MP 462 066, India.
Sangit
S
Kumar