Ir-Catalyzed Regio- and Enantioselective Synthesis of β-Heteroaryl Amides via Site-Selective C–H Activation

Key words

iridium catalysis - site-selectivity - regioselectivity - heteroaryl amides - directing group

Significance

The Li group reports the iridium-catalyzed addition of substituted furans and thiophenes to internal alkenes in a highly regio- and ­enantioselective fashion. This atom-economical methodology featuring a C–H metalation provides access to valuable chiral amides bearing a tertiary benzylic center, which were subjected to subsequent transformations.

Comment

DFT calculations were performed to explain the site-, regio- and enantioselectivity of the reaction. The enamide moiety acts as a directing group, guiding the C–H addition onto the more electron-rich position of the olefin. This reactivity is contrary to the more established regioselectivity of hydro(hetero)arylation processes. KIE studies revealed C–H bond cleavage constitutes the turnover-limiting step.

Publication History

Article published online:
11 May 2023