10.1002/anie.202001824
Angewandte Chemie International Edition
COMMUNICATION
the benzyl radical, and single-electron reduction of the acyl
triazolium provides the azolium radical while regenerating the
ground-state photocatalyst (IrIII). Loss of the NHC and radical-
radical combination affords the desired ketone (Scheme 3B). The
recent mechanistic studies of Breslow intermediates and acyl
azoliums reported by Bertrand and Martin suggest that definitive
evidence of radical intermediates in thermal NHC-catalyzed
processes does not exist.[46] In contrast, this NHC-mediated
reaction is conducted under photochemical conditions. Moreover,
the observed enantioselectivity (vide supra) provides additional
evidence that an NHC-bound radical species is most likely
involved in this process.
Northwestern University for assistance with purification. We also
thank Joshua Zhu and Ada Kwong (NU) for assistance with cyclic
voltammetry experiments and HRMS, respectively.
Keywords: N-heterocyclic carbene
•
acyl azolium
•
photochemistry • ketone • radical coupling
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In summary, we have developed a reductive single-electron
alkylation of acyl azoliums to form ketones from carboxylic acids.
Activation of readily available carboxylic acids with CDI followed
by addition of the NHC catalyst produces the acyl azolium
intermediate in situ. This combined NHC and photoredox
catalysis enabled a one-electron reduction of the acyl azolium,
and subsequent radical-radical combination allowed for the facile
construction of a C–C bond to furnish a ketone. The utility of this
method in synthesis was showcased in the direct, one-step late-
stage functionalization of pharmaceutical compounds. Importantly,
preliminary results using a chiral NHC demonstrated that
enantioselectivity is possible using this process, thus highlighting
the potential advantage of using acyl azolium radicals in acyl
radical transformations.
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We thank Northwestern University and the National Institute of
General Medical Sciences (GM073072 and GM131431) for
support of this work. The authors thank Purav Vagadia of the
Center for Molecular Innovation and Drug Discovery at
5
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