Zhao W,
Li B.-J.
*
Tsinghua University, Beijing and Nankai University, Tianjin, P. R. of China
Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition
of Heteroaromatic C–H Bonds to Acyclic Internal Alkenes.
J. Am. Chem. Soc. 2023;
145: 6861-6870
DOI:
10.1021/jacs.3c00095
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.
