Gold-Catalyzed Reductive Transformation of Nitro Compounds Using Formic Acid: Mild, Efficient, and Versatile

Article abstract of DOI:10.1002/cssc.201500869

Developing new efficient catalytic systems to convert abundant and renewable feedstocks into valuable products in a compact, flexible, and target-specific manner is of high importance in modern synthetic chemistry. Here, we describe a versatile set of mild catalytic conditions utilizing a single gold-based solid catalyst that enables the direct and additive-free preparation of four distinct and important amine derivatives (amines, formamides, benzimidazoles, and dimethlyated amines) from readily available formic acid (FA) and nitro starting materials with high level of chemoselectivity. By controlling the stoichiometry of the employed FA, which has attracted considerable interest in the area of sustainable chemistry because of its potential as an entirely renewable hydrogen carrier and as a versatile C₁ source, a facile atom- and step-efficient transformation of nitro compounds can be realized in a modular fashion. Renewable formic acid as a flexible feedstock: A versatile heterogeneous gold-based catalytic system has been developed for the controlled, flexible, and target-specific reductive transformation of nitro compounds using stoichiometric equivalents of formic acid as a key starting material under mild and convenient conditions. The overall operational simplicity, high chemoselectivity, functional-group tolerance, and reusability of the catalyst make this approach an attractive and reliable tool for organic and process chemists.

Full text of DOI:10.1002/cssc.201500869

DOI: 10.1002/cssc.201500869
Communications
Gold-Catalyzed Reductive Transformation of Nitro
Compounds Using Formic Acid: Mild, Efficient, and
Versatile
[
a]
Lei Yu, Qi Zhang, Shu-Shuang Li, Jun Huang, Yong-Mei Liu, He-Yong He, and Yong Cao*
Developing new efficient catalytic systems to convert abun-
dant and renewable feedstocks into valuable products in
a compact, flexible, and target-specific manner is of high im-
portance in modern synthetic chemistry. Here, we describe
a versatile set of mild catalytic conditions utilizing a single
gold-based solid catalyst that enables the direct and additive-
free preparation of four distinct and important amine deriva-
tives (amines, formamides, benzimidazoles, and dimethlyated
amines) from readily available formic acid (FA) and nitro start-
ing materials with high level of chemoselectivity. By controlling
the stoichiometry of the employed FA, which has attracted
considerable interest in the area of sustainable chemistry be-
cause of its potential as an entirely renewable hydrogen carrier
is pertinent to point out that the use of H is not perfectly
2
atom-economical as it might seem owing to current industrial
production of H relying overwhelmingly on fossil fuels and
2
the fact that the associated emissions have led to a net in-
[
6]
crease in global CO levels.
2
There is considerable current interest in exploiting formic
acid (FA) as a promising molecule for hydrogen storage and
delivery, which has been advocated as a carbon-neutral energy
source to meet the ever-increasing demand for a sustainable
[
7]
and affordable energy supply. Of the most attractive features
of FA, apart from its accessibility as a major product from bio-
mass processing, is the possibility to establish an integrated
energy storage scheme for a dispatchable solar- and wind-
and as a versatile C source, a facile atom- and step-efficient
powered energy system based on a reversible FA–CO inter-
1
2
[
8]
transformation of nitro compounds can be realized in a modu-
lar fashion.
conversion. Given the fact that FA easily undergoes selective
dehydrogenation to yield H , FA can be envisioned as an ap-
2
[
9]
pealing terminal reductant. With regard to green organic syn-
thesis, this approach is particularly attractive in light of the ap-
parent and compelling advantage of using FA as a biorenewa-
Chemical reduction of unsaturated bonds of readily available
chemical feedstocks is one of the most fundamental transfor-
[
10]
ble C source for attaching CO, CHO, or methyl groups. In
1
[1]
mations in organic chemistry. In particular, the reductive
transformation of molecules containing nitro functional groups
is of special interest since the reduced products (amines and
related derivatives) are key intermediates or targets in the syn-
thesis of pharmaceuticals, dyes, agrochemicals, pigments, and
this regard, reductive transformation using FA may bring
about new opportunities for the construction of molecular
[
10b,c]
complexity.
Despite the prospects for contributions to
both flexibility and step economy of such types of transforma-
tions, progress in this area, especially expanding the scope of
the FA–nitro reaction, has been largely limited to nitro-to-
[
2,3]
polymers.
Despite many known methods, there are unceas-
[
11]
ing efforts to develop new clean, facile, cost-effective, green,
and chemoselective procedures that eliminate the use of large
excess of expensive and perilous stoichiometric reducing
amine transformations.
Moreover, the reported reactions
[
11a–d]
generally necessitate the use of FA in large excess,
adversely affects the overall atom efficiency.
which
[
4]
agents. In this respect, H gas is arguably one of the most
Heterogeneous Au catalysis has recently emerged as an im-
portant and powerful tool for clean and resource-efficient
2
popular and attractive means to effect reduction, thereby lead-
ing to a number of catalytic hydrogenation procedures amena-
[
12]
chemical synthesis. In particular, various supported Au cata-
lysts have been reported to show distinct reactivity, activity,
and selectivity in a number of industrially important process-
[5]
ble to reduce nitro compounds. However, application of
these processes is constrained by the need for specialized
equipment, limited functional group tolerance, and potential
[
13]
es, complementing and expanding the existing areas of tra-
ditional platinum-group metal (PGM) catalysis. As part of our
continuing exploration into new reaction chemistry by sup-
safety issues regarding H handling. Even more importantly, it
2
[
14]
ported Au nanoparticles (NPs), we recently discovered the
outstanding catalytic ability of Au NPs for FA activation, where-
in we found that subnanomeric gold NPs (ca. 0.8 nm) finely
dispersed on ZrO can promote efficient and selective H gen-
+
+
[
a] L. Yu, Q. Zhang, S.-S. Li, Dr. J. Huang, Dr. Y.-M. Liu, Dr. H.-Y. He,
Prof. Dr. Y. Cao
Department of Chemistry
Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials
Fudan University
Handan Road 220, Shanghai 200433 (P.R. China)
Fax: (+86)21-65643774
E-mail: yongcao@fudan.edu.cn
2
2
eration from FA dehydrogenation under ambient condition-
[14a]
s.
Realizing the advantages of adopting the Au-based re-
duction protocols and also utilizing the excellent catalytic ac-
[
12–14]
+
tivity of supported Au toward FA activation,
we became
[
] These authors contributed equally to this work.
intrigued by the catalytic utility of the Au–FA protocol to de-
velop innovative catalytic processes that enable direct and ad-
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201500869.
ChemSusChem 2015, 8, 3029 – 3035
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Communications
ditive-free transformation of nitro compounds under mild and
clean conditions. Herein, we report an efficient, versatile, and
scalable approach to the target-specific transformation of nitro
compounds employing FA as the hydrogen source using
a single supported Au catalyst system under mild and atom-ef-
ficient conditions.
1.8 nm) compared to the Au/ZrO –NCs material (0.8 nm), re-
2
sulted in dramatic improvements, thus providing a boosted
conversion of 1a and a moderate yield (30%) of 2a (entry 2).
While an attempt to further optmize the process parameters
failed to give higher yields of 2a (Table S1, entries 1 and 2),
even by prolonging the reaction time or elevating the reaction
temperature, careful analysis of the gas phase reaction mix-
tures at the end of a typical reaction employing the Au/ZrO2
catalyst showed a CO -to-H ratio of ca. 1.8, demonstrating that
Initial experiments were aimed at evaluating the feasibility
of Au-catalyzed nitro-to-amine reduction using only a stoichio-
metric amount of FA under base-free conditions. As a prelimi-
nary test, the reductive conversion of nitrobenzene (1a) was
carried out, where 3.0 equivalents of FA were used as a hydro-
2
2
about 51% of the consumed FA was decomposed to H (see
2
Section 2.1 in the Supporting Information).
gen source, with the Au/ZrO –NCs (NC=nanoclusters;
Given the recognized critical role of the support for render-
ing the catalytic properties of supported Au, we turned our at-
tention to Au deposited on various other support materials for
converting 1a to 2a. It turns out that the integration of Au
2
1
mol%) catalyst in toluene at 608C. Unfortunately, this experi-
ment afforded only modest yield (ca. 10%) of aniline (2a), with
appreciable amounts of formanilide (3a) as a sole by-product
resulting from the direct reductive formylation of 1a (Table 1,
and TiO was essential for this particular transformation. Grati-
2
fyingly, the use of high surface area rutile TiO as the support
2
yielded the highest activity to give a quantitative formation of
the desired 2a in 40 min at 608C (Table 1, entry 4). Note that
Au/rutile successfully promoted the reduction reaction even at
room temperature (Table 1, entry 9), conditions under which
other supported metals, such as Pd, Pt, Ir and Ru, are com-
pletely inefficient (Table 1, entries 10–13). Remarkably, the reac-
tion was equally efficacious even upon decreasing the Au load-
ing to 0.01 mol% (Table 1, entry 14). Thus, in a gram-scale reac-
tion of 1a (tenfold scale up) for 5 h, 99% yield of 2a was ob-
tained (Figure S1). In this case, no traces of hydroxylamine
[
a]
Table 1. Reduction of nitrobenzene to aniline under various conditions.
Entry
Catalyst
T
Solvent
Conversion
[%]
Selectivity
[%]
[
8C]
1
2
3
4
5
6
7
8
Au/ZrO
Au/ZrO
2
–NCs
60
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
ethanol
cyclohexane
THF
15
43
68
>99
16
47
71
72
>99
>99
>99
78
76
85
>99
–
2
60
60
60
60
60
60
60
25
25
25
25
25
90
120
60
60
60
60
60
60
70
40
Au/TiO
2
Au/rutile
Au/anatase
(
<1%), an unwanted potentially explosive by-product that
usually formed in appreciable levels with traditional protocols
Au/Al
Au/CeO
Au/SiO
2
O
3
[
4,5]
2
40
6
under mild conditions,
are observed during the reaction.
2
Furthermore, the recovered Au/rutile can also be reused at
least five times while still maintaining the high conversion
value on this scale (Figure S1). At an even a lower loading of
0.001 mol% of Au, a high conversion of 97% was still achieva-
ble, although a longer reaction time at elevated temperature is
required (Table 1, entry 15). This correponds to a turnover
[
b]
9
1
Au/rutile
Pd/rutile
Ru/rutile
Pt/rutile
Ir/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
Au/rutile
>99
n.r.
n.r.
n.r.
n.r.
>99
97
78
73
69
23
[
b]
b]
0
[
1
1
–
–
–
[
b]
b]
c]
1
1
1
1
1
1
1
1
2
2
2
2
2
3
4
5
6
7
8
9
0
1
2
3
[
[
[
>99
>99
91
99
86
d]
4
number (TON) close to 9.7”10 , which is, to the best of our
knowledge, the highest value ever recorded in FA-mediated
catalytic reduction of nitroaromatics.
1,4-dioxane
water
water
toluene
toluene
87
By filtering off the Au/rutile catalyst after conducting the
nitro-to-amine reduction for 10 min, we observed no further
conversion during the next 30 min under the same conditions
(Scheme S1), indicating that the heterogeneous reaction in-
volves minimal catalyst leaching and that mechanisms entail-
ing homogeneous reactions are not likely operating. Additional
investigation under FA-limited conditions revealed that lower
amounts of FA (1 or 2 equivalents) lead to incomplete reduc-
tion (Table S2), albeit 2a was still the sole product during the
whole reaction process. Furthermore, it was found that the
choice of solvent has a profound influence on the reaction
outcome (Table 1, entries 16–20). In contrast to previously re-
[
[
[
[
e]
>99
>99
>99
>99
>99
>99
>99
>99
f]
g]
h]
[
(
a] 1a (1 mmol), FA (3 mmol), catalyst (1 mol% metal), solvent (5 mL), N
1 bar), 40 min; GC analysis using n-decane as an internal standard; n.r.=
no reaction. [b] 12 h. [c] 1a (2 mmol), FA (6 mmol), Au (0.01 mol%), 4 h.
2
[
[
d] 1a (10 mmol), FA (30 mmol), Au (0.001 mol%), 25 h. [e] 30 min.
f] 30 min, under air. [g] 15 min. [h] 3.5 h.
entry 1). It was hypothesized that the extremely high activity
[
11b]
of the subnanometric Au/ZrO –NCs catalyst toward FA activa-
ported activities using Fe-based complexes,
less polar or-
2
tion favors rapid H gas release as a result of unproductive FA
ganic solvents appear to be more suitable and the highest effi-
ciency is obtained in toluene. Interestingly, the use of neat
water as a solvent can lead to an even higher reduction effi-
ciency (Table 1, entry 20). Of yet further interest is that this cat-
alytic system can also afford quantitative formation of 2a in air
2
decomposition, thus preventing the desired conversion of 1a
into 2a. In agreement with this reasoning, the use of Au/ZrO2,
which is less reactive toward FA decomposition as a catalyst
and which possesses a larger average Au particle size (ca.
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(
Table 1, entry 21), thus offering distinct practical advantages
(Table 2, entries 2g–2j). In the transformation of chloronitroar-
omatics as well as methylnitrobenzene, the higher reaction
rate found for p-substituted nitrobenzene compared to the
corresponding o- or m-substituted counterparts can be attrib-
uted to the steric effects. Moreover, a number of other reduci-
ble functional groups are also tolerated, including ester,
ketone, alkene, nitrile (Table 2, entries 2k–2n), and phenyl
(Table 2, entry 2p) functionality. In these transformations, the
significant chemoselectivity for the specific reduction of the
nitro group in the reactant is most likely due to the higher re-
activity of the nitro group than that of the other reducible
groups over the Au/rutile–FA system. This assumption is
strongly supported by the intermolecular competitive reduc-
tion of nitrobenzene and other unsaturated substrates, such as
acetophenone, benzonitrile, and styrene (Table S3). Especially
noteworthy is that 6-aminoquinoline, possessing value as im-
portant intermediate for dyes, could be also successfully ob-
tained from 6-nitroquinoline with excellent yield, indicating
the heterocyclic ring was compatible in this reaction
over existing methods to establish a more convenient and in-
dustrially viable amine production process. To the best of our
knowledge, a simple heterogeneous catalytic system that does
not have ligands and additives and is highly efficient for reduc-
tion of nitro compounds by chemically equivalent amounts of
FA in neat water has not been reported to date.
To investigate the scope and limits of this FA-mediated nitro
reduction process, we next tested various structurally diverse
functionalized nitro compounds. Remarkable amine selectivi-
ties were observed by applying a variety of nitro aromatics
with both electron-withdrawing and electron-donating groups
(
Table 2, entries 2b–2p). Note that reduction of halogen-sub-
stituted nitroaromatics, such as fluoro- or chlorobenzenes, pro-
ceeded smoothly and selectively, affording the corresponding
anilines in excellent yields with no observable dehalogenation
Table 2. Reduction of nitro compounds to corresponding amines with
(
entry 2q). As more challenging examples, reduction proceed-
[a,b]
FA.
ed almost quantitatively with non-activated aliphatic nitro
compounds by employing this Au/rutile–FA system, resulting
in complete consumption of the reactants accompanied by ex-
cellent selectivity (Table 2, entries 2r–2u).
Product
Yield
%]
Time
[h]
Product
Yield
[%]
Time
[h]
[
The outstanding catalytic activity for FA-mediated nitro re-
duction at above-mentioned conditions over Au/rutile clearly
reflects the fast surface kinetics towards the desired transfor-
mation, presumably due to an unusual and extraordinary
metal–support synergy enabling a facile surface-mediated
highly specific reduction of 1a to 2a. By investigating the
physicochemical properties of the Au/rutile catalyst, the follow-
ing information was obtained. From the X-ray absorption near
edge structure (XANES) results, it can be seen that there is
only the metallic Au species present in the Au/rutile catalyst
>
>
99
99
0.67
2
>99
>99
2.0
1.5
>
>
99
99
1.5
1.0
>99
>99
1.5
2.5
[
15]
(Figure S2).
Inductively coupled plasma–atomic emission
spectroscopy (ICP–AES) data revealed that there were no Au
species in the solution after the reaction, demonstrating the
>
99
2.5
2.0
>99
>99
2.5
2.5
[16]
absence of Au leaching during the whole reaction. The X-ray
diffraction (XRD) analysis showed that both the fresh and used
Au/rutile catalysts had the similar crystal phase and there were
no clear diffraction features for the Au species in these two
samples, suggesting that the Au particle sizes were quite small
(Figure S3). Transmission electron microscopy (TEM) was fur-
ther used to confirm that the average diameters of Au particles
were about 2.2 nm in the fresh and used Au/rutile catalysts,
demonstrating that no Au NP aggregation occurred during the
reaction (Figure S4). These results account for the remarkable
durability of the Au/rutile catalyst in the recycling tests.
9
8
>
>
>
>
99
99
99
99
1.0
1.5
1.0
2.0
2.0
>99
>99
>99
>99
4.0
4.0
4.0
4.0
To better understand the superior activity and selectivity, we
conducted several experiments to gain mechanistic insight
into the present Au/rutile-FA nitro reduction system. We con-
firmed in separate experiments that sole FA decomposition did
not occur to any practical degree in the absence of nitroben-
zene and only traces of aniline (4%) were detected when the
9
7
[
(
a] Substrate (1 mmol), FA (3 mmol), Au (1 mol%), toluene (5 mL), N
1 bar), 608C. [b] Yields determined using n-decane as an internal stan-
2
reaction was carried out with H under otherwise identical con-
2
ditions (Table S4). These results indicate that the present Au/
rutile-mediated nitro reduction catalysis is entirely a transfer
dard.
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hydrogenation process, excluding the possibility of direct hy-
These results indicated that the high adsorption affinity of the
rutile support may play an important role in favoring a higher
concentration of 1a and FA on the surface of Au/rutile, which
appears to be the key factor for achieving high activity in the
FA-induced nitro reduction. To shed more light on the mecha-
nism behind this surface-mediated reaction, a further study of
the reactions under 1 bar of H2 with DCOOD or D2 with
HCOOH (Table S7) was carried out. It is revealed that the pro-
tons of the resulting amines come solely from FA. All these re-
drogenation by H generated from FA decomposition. In addi-
2
tion, variation of the hydrogen source revealed that FA is most
effective (Table S5, entries 1–3). Compared to all other tested
formates, FA is unique in terms of functioning as a stoichiomet-
ric reductant without the formation of any by-products under
the present conditions. Hence, the addition of a base, for ex-
ample, NEt , which is usually required for transfer hydrogena-
3
[
11c]
tion,
is not necessary.
To gain more insight into the Au/rutile-catalyzed nitro reduc-
tion, the dependency of reaction rates in the FA-mediated re-
duction of 1a was investigated. The initial rates (R ) were line-
0
Table 4. Reductive N-formylation of nitro compounds to the corresponding
formamides with FA.
arly proportional to the amount of Au/rutile and independent
of the concentration of 1a (Figure S7). From deuterium-label-
ing studies using DCOOD, we observed a relatively large kinet-
ic isotope effect (KIE) of 5.25. A KIE of 4.67 was observed using
DCOOH, and a KIE of 1.13 was observed using HCOOD
[a]
[b]
[b]
Product
Yield
%]
Time Product
[h]
Yield
[%]
Time
[h]
[
(
Table 3). These results suggest that the CÀH bond breaking of
chemisorbed FA is the rate-limiting step of the present reduc-
>
99 (96) 2.0
99 (95) 3.5
97 (92) 3.0
>99 (94) 3.0
>99 (95) 3.0
Table 3. Reduction of nitrobenzene to aniline with D-substituted FA over
[a]
the Au/rutile catalyst.
>
[
b]
Entry
FA
Reaction rate
KIE
–
À1 AuÀ1
[
mmolmin
g
]
1
2
3
4
HCOOH
HCOOD
DCOOH
DCOOD
42
37
9
1.13
4.67
5.25
>99 (95) 3.0
8
[
(
[
a] Nitrobenzene (1 mmol), FA (3 mmol), Au (1 mol%), toluene (5 mL), N
2
1 bar), 608C; GC analysis using n-decane as an internal standard.
b] KIE=rate(entry 1)/rate(entry n); n=2–4.
>
>
99 (96) 2.0
99 (94) 4.0
>99 (95) 3.0
>99 (96) 4.0
tion, which is in agreement with previous reports clarifying the
dehydrogenative activation of FA over supported Au catalyst-
[14a]
s.
Relevant mechanistic information is further obtained
upon studying the reaction of hydroxylamine and nitroso-,
azoxy-, and azobenzenes (Table S6), respectively, which indi-
cates that the formation of 2a in the presence of the Au/rutile
catalyst preferentially takes place through the direct “nitro-ni-
troso-hydroxylamine” route (Scheme S2). An interesting obser-
vation that can be made upon inspection of Table S6 is that
the product distribution turns out to be very complex when
the reduction of intermediate hydroxylamine and nitroso was
carried out under otherwise identical conditi ons described in
Table 2, although the reduction of these two intermediates oc-
curred with much higher rates than that for 1a. This observa-
tion, together with the fact that only unreacted 1a and the
product amine were identified as transient species in solution
during the entire course of the reaction, underscores the inher-
ent surface-driven nature of the present FA-mediated nitro re-
duction. To elucidate the role of the support in the catalytic
process, Fourier transform infrared (FTIR) studies of the adsorp-
tion ability of various supports for 1a and FA were carried out.
The adsorption abilities of supports exhibited good correlation
with the catalytic activities of supported Au NPs (Figure S8).
9
7 (93) 3.0
>99 (95) 4.0
>
99 (96) 2.0
>99 (94) 4.0
>99 (94) 8.0
>99 (95) 8.0
>99 (95) 8.0
>99 (94) 3.0
>99 (96) 2.0
>
99 (95) 4.0
[a] Substrate (1 mmol), FA (4 mmol), Au (1 mol%), toluene (5 mL), N
08C. [b] Yields determined using n-decane as an internal standard; data in
parentheses indicate isolated yields.
2
(1 bar),
7
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sults further confirm that the reaction proceeds via a Lang-
muir–Hinshelwood kinetic model in which chemisorption of
both reactants (i.e., FA and nitrobenzene) occurred prior to
their interconversion.
structural delivery of products, and excellent functional-group
tolerance.
The high versatility of the Au-FA system for selective nitro
transformation encouraged us to explore the feasibility of
direct one-pot N-methylation of nitroaromatics to produce me-
thylated amines, an important class of bioactive compounds
Having demonstrated the synthetic utility of the Au–FA-
mediated nitro-to-amine process, we sought to evaluate the
feasibility of establishing a tandem direct transformation of
nitro compounds to formamides, an important class of inter-
mediates widely used in the construction of pharmaceutically
[
19]
widely found in many pharmaceuticals, using FA as a conven-
ient and straightforward C source. Traditional methods for N-
1
methylation make use of toxic formaldehyde or aggressive re-
[10c,17]
valuable compounds.
This envisioned transformation of
agents such as methyl iodide and dimethyl sulfate as the C
1
[
20]
nitro compounds to formamides requires the presence of at
least 4 equivs. of FA. It should be emphasized that there have
been no reports of this particular transformation, despite the
anticipated advantages of such a clean renewable process. We
were pleased to find that a wide diversity of formamides can
be achieved by performing a direct reductive nitro formylation
using Au/rutile with only 4 equivs. of FA (Table 4, entries 3b–
source. Several recent reports describe the use of abundant-
ly available CO as the benign C1 feedstock for N-methyla-
2
[
21]
tion. However, due to the inherent thermodynamic stability
[
21a]
of CO , strong reducing agent such as organosilanes
or
2
drastic reaction conditions (commonly >1508C and overall
[
21b,c]
pressure higher than 80 bar)
are generally required. There
was, therefore, a strong incentive for the development of new
efficient N-methylation methods relying on the use of more
sustainable reagents. Preliminary attempts to carry out the
direct nitro N-methylation with 1a in the presence of excess
FA (20–40 equivs.), however, resulted in a complex mixture of
mono- and dimethyl anilines, formamides, and other inter-
mediate products, with selectivity to methylated aniline prod-
ucts generally lower than 52% (Table S8, entry 3). The larger
production of oxygenated products such as formamides, in the
range 36–48%, over methylated anilines pointed to a lack of
hydrogen in the reaction system. Thus, aiming to facilitate the
N-methylation reaction, we turned to introducing additional H2
gas. Our expectation was realized by applying a required
3
t). As with the case with nitro-to-amine conversion, this un-
precedented one-pot protocol is tolerant to significant func-
tional group variations on the aromatic ring. Moreover, excel-
lent levels of direct reductive N-formylation are accomplished
using various structurally diverse non-activated aliphatic nitro
compounds. The utility and effectiveness of this one-pot re-
ductive formylation procedure is further exemplified in the
straightforward and efficient tandem synthesis of a diversity of
benzimidazoles, which are prevalent in natural products and
pharmaceutical agents and are important synthetic targets for
[18]
drug discovery and development, using various substituted
o-dinitroarenes and again only 7 equivs. of FA as the starting
materials (Table 5). Compared to previous known procedures,
the Au-catalyzed one-pot reductive N-formylation process es-
tablished here is notable for its expediency, the atom-efficient
utilization of renewable feedstocks, mild reaction conditions,
amount of 40 bar H (Table S8, entry 6), and we were able to
2
acess several synthetically interesting functionalized dimethyla-
nilines in excellent yields (Table 6) using this newly established
[
22]
reductive methylation procedure. These results are, to the
[a]
[a]
Table 5. Synthesis of benzimidazoles with o-dinitrobenzenes and FA.
2
Table 6. Synthesis of dimethlyated amines from nitroarenes with FA/H .
[
b]
[b]
[b]
[b]
Product
Yield
%]
Product
Yield
[%]
Product
Yield
[%]
Product
Yield
[%]
[
>
99 (97)
99 (96)
>99 (94)
>99 (96)
>99 (95)
>99 (96)
>99 (94)
>99 (95)
>99 (94)
>
>
>
>
>
99 (95)
99 (95)
99 (94)
99 (95)
99 (95)
97 (93)
>
>99 (95)
[
(
a] Substrate (1 mmol), FA (7 mmol), Au (1 mol%), toluene (5 mL), N
1 bar), 708C, 6 h. [b] Yields determined using n-decane as an internal
2
[
(
a] Substrate (0.25 mmol), FA (10 mmol), Au (4 mol%), toluene (5 mL), H
40 bar), 1408C, 3 h. [b] Yields determined using n-decane as an internal
2
standard; data in parentheses indicate isolated yields.
standard; data in parentheses indicate isolated yields.
ChemSusChem 2015, 8, 3029 – 3035
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
best of our knowledge, unprecedented examples of the con-
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[
1
Financial support from the National Natural Science Foundation
of China (21273044, 21473035), Research Fund for the Doctoral
Program of Higher Education (20120071110011) and Science &
Technology Commission of Shanghai Municipality (08DZ22705-00
and 12ZR1401500) is greatly appreciated.
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Received: June 26, 2015
1
Published online on July 29, 2015
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim