Dearomative Aminocarbonylation of Arenes via Bifunctional Coordination to Chromium

Abstract

Amides are ubiquitous in physical and life sciences. Given the significant abundance of arenes, dearomative aminocarbonylation of arenes would lead to a large and underexplored chemical space for amide discovery. However, such reactions are challenging due to the high degree of resonance stabilization and selectivity issues. Herein, we disclose an unprecedented dearomative trifluoromethylative aminocarbonylation of arenes via bifunctional coordination to chromium, providing a modular platform for the construction of amides possessing trifluoromethyl (CF 3 ) groups and three-dimensional rings. Its versatility further enabled a switchable difluoromethylation or trifluoromethylation aminocarbonylation of arene CÀ H bonds. A possible mechanism was proposed based on control experiments. Finally, the synthetic utility was well demonstrated by diverse applications in the total synthesis of CF 3 -functionalized amide-type drugs, including praziquantel, nateglinide, maraviroc and alloyohimbane.

Reactivity umpolung (reversal) of ligands in transition metal complexes

“…1, 17 vs exo addition of carbanions to [Mn(η 6 -arene)(CO) 3 ] + ( 86 ) or Cr(η 6 -arene)(CO) 3 87 . 104…”