.
Angewandte
Communications
Photoredox Catalysis
Photoredox-Catalyzed Reductive Coupling of Aldehydes, Ketones, and
Imines with Visible Light
Masaki Nakajima, Eleonora Fava, Sebastian Loescher, Zhen Jiang, and Magnus Rueping*
Abstract: Ketyl radical and amino radical anions, valuable
lung to the corresponding ketyl radical anion strongly ender-
gonic. To overcome this barrier, nature, in part, takes
advantage of two-center/three-electron bonding.[9,10] In con-
trast to a stepwise mechanism, wherein an electron and
proton are transferred sequentially, the formation of ener-
getic intermediates is avoided, resulting in a lower activation
barrier. Owing to the low oxidation potential, tertiary amines
À
reactive intermediates for C C bond-forming reactions, are
=
=
accessible through a C O/C NR umpolung. However, their
utilization in catalysis remains largely underdeveloped owing
to the high reduction potential of carbonyl compounds and
imines. In the context of photoredox catalysis, tertiary amines
are commonly employed as sacrificial co-reducing agents.
Herein, an additional role of the amine is proposed, in which it
is essential for the organocatalytic substrate activation. The
combination of photoredox catalysis and carbonyl/imine
activation enables the reductive coupling of aldehydes, ketones,
and imines under mild reaction conditions.
A
are commonly employed as cost-efficient reductive
quenchers in photoredox chemistry, being further converted
to the amino radical cation B (Scheme 1).[11] Based on
À
T
he development of atom- and step-economical C C bond-
forming reactions is a subject of considerable importance in
the field of organic chemistry. In this regard, the discovery of
less-conventional intermediates is highly desirable and poten-
tially opens the door for new unexplored reactivities. In the
recent past, the arena of photoredox catalysis has gained
renewed attention through numerous discoveries of non-
classical transformations.[1,2] The reactions are generally
classified according to the four different types of operative
reactive intermediates: neutral radicals, radical anions, and
radical cations, as well as ions resulting from the previous
species through further single-electron transfer (SET).[1j]
Despite the impressive progress in this field, we realized
that the photoredox chemistry of ketyl radicals remains still
underdeveloped. While Yoon[3] and Fensterbank[4] have
pioneered the concept of the conjugated ketyl system for
the reductive cyclization of enones and reductive epoxide/
aziridine opening, respectively, methods based on the direct
utilization of ketyls are restricted to a handful of reports.[5] In
1983 Pac et al. reported the first photoredox-catalyzed
reduction of benzaldehydes to the corresponding alcohols.[5a]
The reductive dimerization of benzaldehyde was subse-
quently described by Yanagida[6] and co-workers employing
poly(p-phenylene) as an effective photocatalyst. However,
these methods are generally limited to few specific aldehydes
and, moreover, not applicable to ketones.[7] This deficit is
attributed to the large discrepancy in reduction potential
between ketones (acetophenone: E1/2red = À2.48 V vs. Fc)[8]
and established photoredox catalysts, rendering the umpo-
Scheme 1. Postulated catalytic cycle for the photoredox-catalyzed pina-
col coupling of aldehydes and ketones.
literature reports, we assumed that an attractive interaction
=
between the Lewis acidic species B and the weakly basic C O
bond[10] in terms of a two-center/three-electron bond (D)
would render the activation process less endergonic. Alter-
natively, the a-ammonium radical C, resulting from B via
=
a [1,2]-H shift, could engage in the C O activation as
a hydrogen-bond donor.[12] If such a scenario is feasible,
a dual role of amines in photoredox catalysis could be
established, namely, in substrate activation in addition to
serving as a simple sacrificial electron/hydrogen donor.
In considering the limitations associated with the photo-
redox-catalyzed pinacol coupling, and in order to probe our
hypothesis, we selected the photoreduction of benzaldehyde
as our initial subject of investigation.[13] Generally, this
transformation allows direct access to diols, which are
important structural motifs in natural products,[14] pharmaco-
logically active compounds, ligands, and auxiliaries.[15]
Unfortunately, due to the reductive nature, classical protocols
operate with the usage of more than stoichiometric amounts
[*] Dr. M. Nakajima, M. Sc. E. Fava, B. Sc. S. Loescher, M. Sc. Z. Jiang,
Prof. Dr. M. Rueping
Institute of Organic Chemistry, RWTH Aachen
Landoltweg 1, 52068 Aachen (Germany)
E-mail: Magnus.Rueping@rwth-aachen.de
Supporting information for this article is available on the WWW
8828
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 8828 –8832