Angewandte
Communications
Chemie
Carbenes
Polyhalides as Efficient and Mild Oxidants for Oxidative Carbene
Organocatalysis by Radical Processes
Xingxing Wu, Yuexia Zhang, Yuhuang Wang, Jie Ke, Martin Jeret, Rambabu N. Reddi,
Song Yang, Bao-An Song,* and Yonggui Robin Chi*
Abstract: Simple and inexpensive polyhalides (CCl4 and
C2Cl6) have been found to be effective and versatile oxidants
in removing electrons from Breslow intermediates under N-
heterocyclic carbene (NHC) catalysis. This oxidative reaction
involves multiple single-electron-transfer (SET) processes and
several radical intermediates. The a, b, and g-carbon atoms of
aldehydes and enals could be readily functionalized. Given the
low cost of the oxidants and the broad applicability of the
reactions, this study is expected to greatly enhance the
feasibility of oxidative NHC catalysis for large-scale applica-
tions. Also this new SET radical process with polyhalides as
single-electron oxidants will open a new avenue in the
development of NHC-catalyzed radical reactions.
O
xidation is nearly an unavoidable process in chemical
synthesis. In the thiamine pyrophosphate (TPP; Vitamin B1)
mediated reactions in the biological systems, pyruvate
ferredoxin oxidoreductase (PFOR) is believed to enable
two single-electron-transfer (SET) processes which oxidize
the Breslow intermediate to an acyl azolium intermediate for
further transformations.[1] In synthetic chemistry with N-
heterocyclic carbenes (NHCs) as organic catalysts, oxidation
of NHC/aldehyde-derived Breslow intermediates to the
corresponding acyl azoliums has led to development of
numerous useful reactions (Figure 1a).[2] To date, dipheno-
quinone (DQ), pioneered by Studer and co-workers,[3a,b] has
become a most popular oxidant in NHC catalysis.[3] This
quinone oxidant likely behaves as an electron pair acceptor
which converts the Breslow intermediate into an acyl azolium
intermediate.[3b] Despite the amazing success, some of the
drawbacks in using the DQ oxidant include relatively high
cost and inconvenience in separating the stoichiometric
amount of reduced DQ adduct (hydroquinone) from the
Figure 1. Representative oxidants used in oxidative NHC catalysis and
our proposed oxidative pathway using simple polyhalides as oxidants.
SET=single-electron transfer.
reaction mixture (Figure 1b). Other common oxidants have
also been reported, such as nitrobenzene,[4] N-oxyl radical
(e.g., TEMPO),[5] azabenzene,[6] MnO2,[7] riboflavin, phena-
zine,[8] a catalytic transition metal (TM) in combination with
O2 as a terminal oxidant[9] or atmospheric O2,[10] NFSI,[11] and
electrochemistry.[12] However, these oxidants are found to
have fewer applications because of the various limitations.
For example, while O2 (and air) is in principle an excellent
choice as oxidant, its application in NHC catalysis is mostly
limited to the conversion of aldehydes into the corresponding
carboxylic acids and esters.[9,10] When O2 was used as the
oxidant for functionalization of the a, b, or g-carbon of
aldehydes, they are unproductively consumed to form simple
carboxylic acids or esters as the side products.[10e]
Our group is interested in the oxidation of Breslow
intermediates, through an SET process, for the development
of new activation modes and reactions.[13] In 2013, we
reported that a,b-unsaturated nitroalkenes could oxidize
aldehydes into the corresponding esters by an SET proc-
ess.[13a] Indeed, the nitro groups (NO2) in several different
reagents could behave as SET oxidants in a number of
reactions, as independently disclosed by the group of Rovis[14]
and our own group.[13] Very recently, we found that nitro-
benzyl bromide could oxidize aldehydes into esters.[13c] This
[*] X. Wu, Y. Zhang, Y. Wang, J. Ke, M. Jeret, R. N. Reddi,
Prof. Dr. Y. R. Chi
Division of Chemistry & Biological Chemistry
School of Physical & Mathematical Sciences
Nanyang Technological University
Singapore 637371 (Singapore)
E-mail: robinchi@ntu.edu.sg
Prof. Dr. S. Yang, Prof. Dr. B.-A. Song, Prof. Dr. Y. R. Chi
Laboratory Breeding Base of Green Pesticide and Agricultural
Bioengineering, Key Laboratory of Green Pesticide and Agricultural
Bioengineering
Ministry of Education, Guizhou University
Huaxi District, Guiyang 550025 (China)
E-mail: basong@gzu.edu.cn
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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