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ChemComm
DOI: 10.1039/C9CC05055H
COMMUNICATION
Pd/NHC-Catalyzed Cross-Coupling Reactions of Nitroarenes
Received 00th January 20xx,
Accepted 00th January 20xx
Myuto Kashihara,a Rong-Lin Zhong,b Kazuhiko Semba,a Shigeyoshi Sakaki b and Yoshiaki Nakao*a
DOI: 10.1039/x0xx00000x
N-heterocyclic carbene (NHC) ligands effective for the cross- reactions opened a novel aspect in chemistry of nitroarenes,
coupling of nitroarenes were identified. A rational design of the there still remained serious issues from a practical point of view
NHC ligand structures enabled significant reduction of catalyst such as high loadings of precious Pd (>5 mol%) and expensive
loadings compared with the previous system employing BrettPhos Buchwald-type ligands6 (10–20 mol%). Phosphine ligands could
as a phosphine ligand. Experimental and theoretical studies to also be deactivated through oxidation by the NO2 group.
compare these ligands gave some insgihts into high activity of the
newly developed NHC ligands.
To deviate from phosphine ligands, we turned our attention
to the use of NHC ligands.8 In 2005, the groups of Lassaletta and
Glorius independently reported the use of imidazo[1,5-
a]pyridinylidenes,9a,b which appeared to be a hybrid form of the
Buchwald-type ligands and NHC ligands (Scheme 1).
Subsequently, some derivatives were investigated and
published.9c–9k Despite being structural mimics of the Buchwald-
type ligands, they have rarely been applied to metal-catalysed
reactions. We conceived the use of imidazo[1,5-
a]pyridinylidene bearing an Ar group at the C5 position as a
supporting ligand in the cross-coupling reactions of nitroarenes.
NHC ligands generally possess higher electron-donicity and
tolerance toward oxidation than phosphine ligands. We
expected that the NHC ligands could facilitate the rate-
determining oxidative addition of Ar–NO2 bond and elongate a
catalyst lifetime by preventing the ligand oxidation.
Denitrative transformations of nitroarenes are advantageous in
synthetic chemistry because they serve as an important class of
chemical feedstocks readily available from simple nitration of
aromatic compounds.1 In addition, well-established
functionalisations of nitroarenes including SNAr/SEAr/VNS
and/or C–H functionalisation2,3 to afford multi-substituted
nitroarenes in
transformations highly attractive to access
a
site-selective manner make the
variety of
a
substituted arenes. Conventionally, the replacement of the NO2
group with various functional groups could be achieved in 3
steps including reduction, diazotization, and Sandmeyer/cross-
coupling reactions. Direct transformations of nitro groups have
been therefore of high demand to upgrade the synthetic utility
of nitroarenes. Some examples of such single-step
transformations of Ar–NO2 bonds have been reported but
lacked generality in terms of scope of nitroarenes.4 The
difficulty in the use of nitroarenes for cross-coupling reactions
is partly derived from reduction of the NO2 group by low-valent
metal catalysts.5 Nevertheless, we previously reported that the
combination of palladium as a metal center and BrettPhos6a as
a supporting ligand enabled the unprecedented oxidative
addition of Ar–NO2 bonds to palladium(0) to enable the Suzuki–
Miyaura coupling,7a Buchwald–Hartwig amination,7b and
reductive denitration of nitroarenes.7c Although these coupling
Scheme 1. Design of imidazo[1,5-a]pyridinylidene ligands for
the cross-coupling of nitroarenes.
We examined the Suzuki–Miyaura coupling of 4-nitroanisole
(1a) and phenylboronic acid (2a) in the presence of 1.0 mol%
Pd(acac)2 and 2.0 mol% L19i (eq 1). In contrast to the use of
BrettPhos, which resulted in only 6% of the desired product 3a,
the use of L1 drastically improved the yield of 3a to 60%.
Motivated by the preliminary result, we screened various
imidazo[1,5-a]pyridinylidenes as ligands in the reaction of 1a
a. Department of Material Chemistry, Graduate School of Engineering, Kyoto
University, Nishikyo-ku, Kyoto 615-8510, Japan.
b. Fukui Institute for Fundamental Chemistry, Kyoto University, Sakyo-ku, Kyoto,
606-8130, Japan.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
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