posted on 2020-11-30, 06:05authored byKai Lang, Chaoqun Li, Isaac Kim, X. Peter Zhang
Racemization is considered to be
an intrinsic stereochemical feature
of free radical chemistry as can be seen in traditional radical halogenation
reactions of optically active tertiary C–H bonds. If the facile
process of radical racemization could be effectively combined with
an ensuing step of bond formation in an enantioselective fashion,
then it would give rise to deracemizative functionalization of racemic
tertiary C–H bonds for stereoselective construction of chiral
molecules bearing quaternary stereocenters. As a demonstration of
this unique potential in radical chemistry, we herein report that
metalloradical catalysis can be successfully applied to devise Co(II)-based
catalytic system for enantioconvergent radical amination of racemic
tertiary C(sp3)–H bonds. The key to the success
of the radical process is the development of Co(II)-based metalloradical
catalyst with fitting steric, electronic, and chiral environments
of the D2-symmetric chiral amidoporphyrin
as the supporting ligand. The existence of optimal reaction temperature
is recognized as an important factor in the realization of the enantioconvergent
radical process. Supported by an optimized chiral ligand, the Co(II)-based
metalloradical system can effectively catalyze the enantioconvergent
1,6-amination of racemic tertiary C(sp3)–H bonds
at the optimal temperature, affording chiral α-tertiary amines
in excellent yields with high enantiocontrol of the newly created
quaternary stereocenters. Systematic studies, including experiments
utilizing optically active deuterium-labeled C–H substrates
as a model system, shed light on the underlying mechanistic details
of this new catalytic process for enantioconvergent radical C–H
amination. The remarkable power to create quaternary stereocenters
bearing multiple functionalities from ubiquitous C–H bonds,
as showcased with stereoselective construction of bicyclic N-heterocycles, opens the door for future synthetic applications
of this new radical technology.