Palladium-Catalyzed Cross-Coupling of Nitroarenes

Full text of DOI:10.1002/anie.201708940

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International Edition: DOI: 10.1002/anie.201708940
German Edition: DOI: 10.1002/ange.201708940
Cross-Coupling
Palladium-Catalyzed Cross-Coupling of Nitroarenes
Yang Yang*
aromatic substitution · copper · cross-coupling ·
palladium · sustainable chemistry
T
ransition-metal-catalyzed cross-coupling has widely been
recognized as an indispensable tool for the synthesis of highly
[1]
functionalized aromatic compounds. With the contributions
from numerous research groups over the past decades, a range
of carbon- and heteroatom-based nucleophiles can now be
utilized in the coupling process, allowing for the rapid
construction of CÀC, CÀN, CÀO, and other carbon–heter-
[1]
oatom bonds with excellent functional group compatibility.
These coupling reactions typically hinge on the use of aryl
halides as the electrophilic coupling partner. In an effort to
further expand the scope of aromatic electrophiles suitable
for cross-coupling, recent studies have focused on the
development of novel catalytic techniques to efficiently
transform phenol derivatives that are considered to be less
reactive. Despite these notable advances, it is still highly
desirable to engage other classes of widely available aromatic
electrophiles in this coupling process.
Scheme 1. Rhodium- and copper-catalyzed carbon–heteroatom bond
forming cross-coupling of nitroarenes. EWG=electron-withdrawing
group.
[2]
Nitroarenes constitute a class of easily accessible building
blocks that can be conveniently prepared from the parent
scope and electron-withdrawing groups are typically required
to ensure excellent yield of the coupled products. In contrast
to these CÀO/CÀS bond forming processes, transition metal-
catalyzed CÀC and CÀN bond forming cross-coupling of
[
3]
arenes via Friedel–Crafts nitration. In contrast to Friedel–
Crafts halogenation, the electrophilic nitration process gen-
erally furnishes nitroarene products with good site selectivity.
Furthermore, a number of commonly employed aryl halides
are synthesized from the corresponding nitroarenes by
reduction and subsequent Sandmeyer-type halogenation. In
this context, the direct use of nitroarenes as the electrophilic
coupling partner would substantially enhance the synthetic
utility of cross-coupling chemistry and circumvent many of
the problems originating from the need to prepare a stoichio-
metric quantity of aryl halides from the parent arene.
nitroarenes remained elusive. Moreover, because of the
inherent difficulty associated with the oxidative addition of
2
low valent transition metal catalysts into the C(sp )ÀNO
2
2
bond and the lack of alternative C(sp )ÀNO bond activation
2
mechanisms, the development of a general catalyst system for
the coupling of a diverse range of nitroarenes, particularly
electron-rich ones, remains a daunting challenge.
Compared to systems derived from other transition
metals, palladium-based catalysts are inarguably the most
widely used in cross-coupling processes. In stark contrast to
coupling reactions utilizing aryl halides and pseudohalides,
the palladium-catalyzed cross-coupling of nitroarenes was not
previously known. As a related process involving the oxida-
In 2011, Wu and co-workers described a rhodium-cata-
lyzed CÀO bond forming reaction starting from nitroarenes
[4a]
[
Scheme 1, Eq. (1)].
Later on, the same research group
developed an improved protocol for the conversion of
nitroarenes to diaryl ethers using copper catalyst
3
a
tive addition of palladium into activated C(sp )ÀNO bonds,
2
[
4b]
[
Eq. (2)]. Additionally, an analogous copper-catalyzed CÀ in 1982?, Hegedus and Tamura reported a palladium-cata-
[5]
S cross-coupling of nitroarenes was reported by Shinde et al.
lyzed allylic substitution of allylnitro compounds. In 2009,
Fors and Buchwald reported a palladium-catalyzed conver-
sion of aryl chlorides and triflates to nitroarenes using
a catalyst system derived from a bulky monodentate phos-
[
4c]
[
Eq. (3)].
Although these methods represent powerful
synthetic tools, they suffer from a relatively limited substrate
[6]
phine ligand, t-BuBrettPhos (Scheme 2, L1). In this process,
[*] Dr. Y. Yang
the ArÀNO bond forming reductive elimination from
2
Department of Chemistry, University of California, Berkeley
Berkeley, CA 94720 (USA)
II
(
L1)Pd (Ar)(NO ), which is the microscopically reverse
2
process of nitroarene oxidative addition, was facilitated by
the use of t-BuBrettPhos (L1). These results suggested the
utility of bulky biarylphosphine ligands in the catalytic
transformation of nitroarenes.
E-mail: yang89@berkeley.edu
The ORCID identification number for the author of this article can be
found under:
https://doi.org/10.1002/anie.201708940.
2
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under these reaction conditions, further highlighting the
synthetic utility of this coupling process.
Nakao and co-workers also developed an efficient CÀN
[7b]
cross-coupling process (Scheme 4). A range of nitroarenes
with diverse electronic properties represented excellent
substrates for this amination process. In addition to secondary
amines, primary amines can also be effectively converted
under these conditions. Interestingly, commonly used strong
bases such as NaOtBu were ineffective for this nitroarene
amination.
Scheme 2. Palladium-catalyzed nitration of aryl chlorides, triflates and
nonaflates. dba=trans,trans-dibenzylideneacetone, TDA=tris(3,6-
dioxaheptyl)amine.
Recently, the groundbreaking work from the group of
Nakao and Sakaki demonstrated that an array of nitroarenes
could be coupled with arylboronic acids to afford biaryl
[
7a]
products in excellent yields (Scheme 3). After an extensive
Scheme 4. Palladium-catalyzed CÀN cross-coupling of nitroarenes and
organoboron reagents: selected examples. [a] CPhos was used instead
of BrettPhos. [b] K PO ·nH O was used as the base and DMF was
3
4
2
used instead of n-heptane. [c] K PO ·nH O was used as the base and
3
4
2
dioxane was used instead of n-heptane.
To gain further insight into the reaction mechanism,
stoichiometric reactions using (cod)Pd(CH TMS) (cod = 1,5-
2
2
cyclooctadienyl, TMS = trimethylsilyl), L2 and the nitroarene
[
7a]
substrate were also performed (Scheme 5). Treatment of
cod)Pd(CH TMS) and L2 with 4a in THF at 608C afforded
(
2
2
0
complex 5a, demonstrating the oxidative addition of a Pd
center into an ArÀNO bond for the first time. On the other
2
hand, reacting (cod)Pd(CH TMS) and L2 with 4b in toluene
2
2
0
at room temperature furnished a nitroarene-bound Pd
Scheme 3. Palladium-catalyzed Suzuki–Miyaura cross-coupling of nitro-
arenes and organoboron reagents: selected examples. [a] From the
corresponding acetal after hydrolysis. [b] In the absence of 18-crown-6.
[
c] CsF was used in lieu of K PO . acac=acetylacetonate, Cy=cyclo-
3 4
hexyl.
optimization, the use of a palladium catalyst generated from
the biarylphosphine BrettPhos (L2) was found to be the key
to the successful implementation of this challenging trans-
formation. In addition, the use of K PO as the base in the
3
4
presence of 18-crown-6 and a trace amount of water proved
crucial for the success of this palladium-catalyzed cross-
coupling. Under the optimized reaction conditions, a diverse
range of nitroarenes underwent this Suzuki–Miyaura cou-
pling, affording biaryl compounds in excellent yields (1a–1d).
Heterocyclic substrates such as a pyridine (1e) and a quinoline
(
1 f) were also compatible with this protocol. Furthermore,
0
electron-rich (1g), electron-deficient (1h), and sterically
hindered boronic acids (1i) were readily accommodated
Scheme 5. Stoichiometric studies: oxidative addition of Pd into the
ArÀNO bond. C gray, N blue, O red, P orange, Pd green.
2
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1
0
complex 5b. P NMR studies indicated that this Pd inter- Conflict of interest
mediate is likely the catalyst resting state. Combined with
other mechanistic and computational evidence, it was sug-
gested that this nitroarene cross-coupling proceeds through
a classic oxidative addition/transmetalation/reductive elimi-
nation mechanism, with the oxidative addition being the rate-
determining step.
The authors declare no conflict of interest.
[
1] a) A. de Meijere, F. Diederich in Metal-Catalyzed Cross—Cou-
pling Reactions, 2nd ed., Wiley-VCH, Weinheim, 2004; b) N.
Miyaura, Cross-Coupling Reactions—A Practical Guide, Spring-
er, Berlin, 2002.
In conclusion, the elegant work of Nakao and Sakaki on
the cross-coupling of nitroarenes demonstrates invaluable
advancements to the field of cross-coupling. In particular, the
0
identification of a Pd species capable of undergoing facile
[
2] a) B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A.-M.
Resmerita, N. K. Garg, V. Percec, Chem. Rev. 2011, 111, 1346;
b) M. Tobisu, N. Chatani, Acc. Chem. Res. 2015, 48, 1717; c) B. Su,
Z.-C. Cao, Z.-J. Shi, Acc. Chem. Res. 2015, 48, 886.
oxidative addition into the ArÀNO2 bond represents an
important addition to the organometallic chemistry of
palladium. Furthermore, this work sets the stage for the
development of a new class of cross-coupling reactions
utilizing broadly available nitroarene substrates, thereby
providing an exciting opportunity for accessing value-added
coupling products from inexpensive and easily available
starting materials. Further efforts to lower the catalyst loading
and the reaction temperature will make these nitroarene
cross-coupling reactions a powerful tool for the formation of
CÀC and CÀheteroatom bonds.
[
[
3] G. Booth, Nitro Compounds, Aromatic; Ullmannꢀs Encyclopedia
of Industrial Chemistry, Wiley-VCH, New York, 2012.
4] a) X. Zheng, J. Ding, J. Chen, W. Gao, M. Liu, H. Wu, Org. Lett.
2011, 13, 1726; b) J. Zhang, J. Chen, M. Liu, X, Zheng, J. Ding, H.
Wu, Green Chem. 2012, 14, 912; c) S. S. Bahekar, A. P. Sarkate,
V. M. Wadhai, P. S. Wakte, D. B. Shinde, Catal. Commun. 2013, 41,
123.
[5] R. Tamura, L. S. Hegedus, J. Am. Chem. Soc. 1982, 104, 3727.
[6] B. P. Fors, S. L. Buchwald, J. Am. Chem. Soc. 2009, 131, 12898.
[7] a) M. R. Yadav, M. Nagaoka, M. Kashihara, R.-L. Zhong, T.
Miyazaki, S. Sakaki, Y. Nakao, J. Am. Chem. Soc. 2017, 139, 9423;
b) F. Inoue, M. Kashihara, M. R. Yadav, Y. Nakao, Angew. Chem.
Int. Ed. 2017, 56, 13307 – 13309; Angew. Chem. 2017, 129, 13492 –
Acknowledgements
13494.
I thank the Miller Institute for Basic Research in Science for
a research fellowship.
Manuscript received: August 30, 2017
Version of record online: && &&
,
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Highlights
Cross-Coupling
Y. Yang*
Pd at the crossroads: The palladium-
catalyzed cross-coupling of nitroarenes
has eluded chemists for decades.
&&&& — &&&&
Recently, the first palladium-catalyzed
Suzuki–Miyaura and Buchwald–Hartwig
cross-couplings of nitroarenes were
reported. Mechanistically, this process
involves the challenging oxidative addi-
Palladium-Catalyzed Cross-Coupling of
Nitroarenes
0
tion of LPd into the ArÀNO bond. This
2
process features a broad substrate scope
with respect to both the nitroarene and
the nucleophilic coupling partners.
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