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Synfacts 2023; 19(06): 0565
DOI: 10.1055/s-0042-1752500
Metals in Synthesis

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

Contributor(s):
Mark Lautens
,
Xavier Abel-Snape
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.
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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.


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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.


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Publication History

Article published online:
11 May 2023

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