Nakafuku KM,
Zhang Z,
Wappes EA,
Stateman LM,
Chen AD,
Nagib DA.
*
The Ohio State University, Columbus, USA
Enantioselective Radical C–H Amination for the Synthesis of β-Amino Alcohols.
Nat. Chem. 2020;
12: 697-704
Key words
copper catalysis - enantioselectivity - photochemistry
Significance
The authors report a chemo-, regio- and enantioselective copper-catalyzed intramolecular
C–H amination for the synthesis of amino alcohols from achiral oximes derived from
readily available alcohols. A variety of oxazoline products containing diverse functional
groups were produced in moderate to excellent yield, and the utility of the process
was demonstrated by cleavage of the heterocycle under acidic conditions to give the
unprotected amino alcohol.
Comment
Extensive mechanistic studies were performed to elucidate the reaction mechanism;
in particular, the nature of the 1,5-hydrogen atom transfer (HAT) and the role of
the photocatalyst. A large, primary kinetic isotope effect was observed through a
competition experiment; suggesting the HAT is the product-determining step. Stern–Volmer
quenching studies indicated the acceptor of the triplet energy from the photocatalyst
was the Cu-coordinated imidate intermediate.
