Metal-Free Catalytic Formylation of Amides Using CO2 under Ambient Conditions

Article abstract of DOI:10.1021/acscatal.8b04023

This study reports the metal-free formylation of amides using carbon dioxide under ambient conditions. An abnormal N-heterocyclic carbene (aNHC) acts as an efficient catalyst for the formylation of amides in the presence of hydrosilane at room temperature

Full text of DOI:10.1021/acscatal.8b04023

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Letter
Metal-Free Catalytic Formylation of Amides
Using CO2 under Ambient Conditions
Pradip Kumar Hota, Samaresh Chandra Sau, and Swadhin K. Mandal
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b04023 • Publication Date (Web): 20 Nov 2018
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ACS Catalysis
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Metal-Free Catalytic Formylation of Amides Using CO2 under
Ambient Conditions
Pradip K. Hota, Samaresh C. Sau and Swadhin K. Mandal*
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Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India
11-16
using CO2 and silane3,
as well as using CO2 and other
ABSTRACT: This study reports the metal-free formylation of
amides using carbon dioxide under ambient conditions. An
abnormal N-heterocyclic carbene (aNHC) acts as an efficient
catalyst for the formylation of amides in presence of hydrosilane
at room temperature. This methodology enables the formation of a
C–N bond and can be utilized in building up of core moieties of
two natural products having strong larvicidal activity such as
alatamide or lansiumamide A. A preliminary mechanistic picture
for this transformation has been proposed through isolation of
reaction by-product (confirmed by single crystal X-ray study) as
well as by characterizing intermediates with spectroscopy.
KEYWORDS: metal-free, amide, formylation, carbon dioxide,
reductive functionalization.
reducing agents.17-22 However; the catalytic formylation of amides
has never been reported.
a)
b)
OMe
O
H
O
N
H
H
H
Reductive functionalization
(diagonal transformation)
Alatamide
O
H
Ar
N
O
O
H
H
N
H
O
H2N NH2
CO2 functionalization
(formation of C-O, C-N, C-C,... bonds)
Lansiumamide A
Figure 1. a) CO2 recycling (“diagonal transformation”). b)
Example of drug molecules those can be synthesized applying this
“diagonal transformation” method.
Carbon dioxide is the most significant long-lived greenhouse
gas on this planet. The direct utilization of carbon dioxide (CO2)
as a sustainable C1 source for synthesis of value-added products
as well as fuels is not only of intrinsic value but also it decreases
the increasing levels of carbon dioxide in the atmosphere.1−2
Among two major ways to effectively utilize thermodynamically
stable and kinetically reluctant carbon dioxide: one is the
reduction to products such as methane, methanol, formic acid,
formaldehyde etc. and another is functionalization of CO2 (e.g.
urea, polycarbonates, cycliccarbonates etc.). But neither the
reduction nor the functionalization of CO2 can satisfy the
feedstock of fine petrochemicals synthesis. In this perspective,
simultaneous reduction and functionalization are required. This
reductive functionalization is well documented as “diagonal
transformation” by Cantat et al. (Figure 1a).3 The efficient
utilization of this fascinating “diagonal transformation” can lead
to the synthesis of versatile chemicals and energy-storage
materials, such as formamides, aminals, and methylamines.4−5
One such direction focuses the hydrosilylation of CO2. The major
advantages of hydrosilylation of CO2 are: a) addition of Si−H
bond to CO2 is energetically more favourable compared to
addition of H−H bond to CO2, b) hydrosilylation of CO2 can
progress in a stepwise manner to allow a series of products with
different carbon oxidation state, which includes silyl formates,
silyl acetals, methoxy silanes, and methane.6−7 Although there are
various reports on hydrosilylation of CO2, the reaction usually
suffers from the use of precious and rare metal based catalysts at
elevated temperature.8−9 As a part of our ongoing investigation to
develop an alternative metal-free approach for CO2 reduction
under ambient conditions,10 herein we report the first catalytic
hydrosilylation of CO2 towards formylation of amides to form a
new C−N bond at room temperature (Figure 1). It may be noted
that there are several reports in literature on formylation of amines
.Previous work:
Catalytic formylation of amine using silane:3,11
R1
R1
H
O
TM/Organocatalyst
CO2
Silane
(reducing agent)
N
N
H
(1)
R2
R2
This work:
Catalytic formylation of amide :

Stoichiometric
(reported earlier)
O
H
O
(2)
Ar
N
H
O
Ar
NH2
The first catalytic reaction
Silane
(reducing agent)
CO2

Scheme 1. Catalytic Formylation of Amine using Silane
(equation 1) and The Present Work Describes The First
Catalytic Formylation of Amide (equation 2).
For amine formylation, a well-established procedure is reported
using CO2 and H2.19−24 The reduction of CO2 using molecular
hydrogen in presence of an amine requires metal catalysts, high
temperature and pressure.21 For example, Ding et al. utilized
ruthenium-pincer-type complexes for N-formylation of various
amines with CO2 and H2.21 Beller et al. also exploited well-
defined iron phosphine complex for the reduction of CO2 to
formates in presence of an amine and H2.22 Recently, Kobayashi
and coworkers developed chelating bis(NHC)rhodium complex
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Page 2 of 6
(NHC stands for N-heterocyclic carbene) for the N-formylation of
best solvent delivering the highest isolated yield of 74% using 5
mol% of aNHC under an atmospheric CO2 pressure (entry 12,
Table 1) at 25 oC.
1
2
3
4
5
6
7
8
amine using silane as a reductant.11 Given the low-abundance,
high price and toxicity of heavier transition metals, there have
been a continuous urge for such catalytic N-formylation of amines
under metal-free conditions. Using silane as a reductant, Cantat et
al. first disclosed the metal-free version of this reaction, using a
nitrogen base (1,5,7-Triazabicyclo[4.4.0]dec-5-ene, TBD) as
catalyst (Scheme 1, equation 1).3 The major disadvantage of this
Having the optimal catalytic conditions in hand, the scope of the
reaction was evaluated for formylation of a variety of amides with
PhSiH3 as a reductant and aNHC as a metal-free catalyst under an
atmospheric pressure of CO2 (Scheme 2).
o
method was that it only worked at 100 C. Soon after, the same
Table 1. Metal-free Catalytic Formylation of Amide Under
Ambient Conditions Using CO2.a
group introduced NHC as an excellent metal-free catalyst in
converting amines and CO2 to formamides, in presence of
hydrosilanes at room temperature (Scheme 1, equation 1).23
Nonetheless, this so-called the “diagonal transformation” is
limited to only amines. To expand the horizon of the “diagonal
transformation”, herein we report the first catalytic formylation of
amides using CO2 under ambient and metal-free conditions
(Scheme 1, equation 2). Formylation of amides using CO2 is of
significant challenge when compared with amines. In contrast to
amines, amides are very weak bases. Amides (pKa ~ -0.5) are less
reactive towards nucleophilic attack because the nitrogen lone
pair is engaged in conjugation with the C=O of the amide. This is
not surprising because amines are more basic and can easily
capture the acidic CO2 thereby increasing the concentration of
CO2 in the reaction medium.24-25 In the current study, the first
catalytic formylation of amides using CO2 as a reagent has been
accomplished using aNHC (abnormal N-heterocyclic carbene) as
a catalyst. Because of aNHC’s strong proton affinity (pKa ~ 33),
it may interact with amide proton via hydrogen bonding
facilitating nucleophilic attack of amide to the electrophilic silicon
centre of silane (see Supporting Information, Scheme S2).
Earlier, calculation also shows that the energies of two highest
occupied molecular orbitals (HOMO and HOMO-1) of aNHC are
–4.403 eV and –4.879 eV, respectively. These molecular orbitals
are much higher in energy than those of the isomeric NHC (–
5.000 and –5.279 eV, respectively), which indicates that aNHCs
are more nucleophilic than normal NHCs.26
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O
O
H
5 mol% aNHC
NH2
N
H
O
CO2
hydrosilane
solvent, RT, time
1 atm
1a
2a
iPr
Ph
Dipp
N
Dipp
N
N
N
iPr
Ph
N
N
Dipp
iPr
N
Dipp
N
iPr
s-IPr
IPr
DBU
aNHC
Entry Hydrosilane
Catalyst
(5 mol%)
Solvent
Time
(h)
Yield
(%)
1
PhSiH3
-
-
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
12
12
12
24
24
24
24
12
24
24
24
-
2
aNHC
DBU
-
3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PMHS
PMHS
Butylsilane
-
4
Pyridine
Et3N
-
5
-
6
PPh3
-
7
PPh2Cl
aNHC
IPr
-
8
31
10
14
53
74
69
-
For our initial investigation, the catalytic formylation of
benzamide (1a) using CO2 in the presence of a hydrosilane was
chosen as a model reaction for optimization (Table 1). No product
formation was realized without either catalyst or phenylsilane
(entries 1 and 2, Table 1). Alternatively, the catalytic activity was
tested using a nitrogen base, 1,8-diazabicycloundec-7-ene (DBU)
(entry 3, Table 1), pyridine (entry 4, Table 1) and triethylamine
(entry 5, Table 1) in presence of phenylsilane in tetrahydrofuran
(THF), which did not result formation of the product. We have
also attempted this reaction using triphenylphosphine or
chlorodiphenylphosphine as a catalyst; but no product was
obtained after reaction (entries 6 and 7, Table 1). Next, we
delightfully established that an aNHC in the presence of a silane
(PhSiH3) can afford the desired formylated product in 31% yield
within 12 h (entry 8, Table 1) which was increased to 53% yield
by elongating the reaction time in THF for 24 h (entry 11, Table
1). Using the normal NHC such as IPr and s-IPr (see Table 1 for
drawing) bearing diisopropylphenyl group on the nitrogen atoms
exhibit a decreased reactivity (10 % and 14% yield under identical
conditions, entries 9 and 10, Table 1) which clearly establishes
our assumption on superior catalytic activity using more
nucleophilic aNHC as a catalyst. When the reaction was carried
out in acetonitrile (CH3CN) solvent, the yield further increased to
74 % (entry 12, Table 1). Next, the reaction was tested in a highly
polar solvent such as dimethyl sulfoxide (DMSO) resulting in
69% yield of the desired product (entry 13, Table 1). Next, the
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11
12
13
14
15
16
s-IPr
aNHC
aNHC
aNHC
aNHC
aNHC
aNHC
CH3CN 24
DMSO
DMSO
24
24
CH3CN 24
DMSO 24
-
3
aAll reactions were conducted with amide (0.5 mmol),
phenylsiane (1 mmol), CO2 (1 atm) and dry solvent (1 mL).
Isolated yields were given based on 1a.
Here we focused on a various commercially available amides
bearing electron donating as well as electron withdrawing
substituent including heterocycles. The reaction afforded the
formylated product in good to very good isolated yield.
Formylation of amides, having electron donating methyl group at
the benzene ring is efficient and afforded the formyl derivative 2b
(70%), 2g (72%), 2k (80%) and 2p (69%) in very good isolated
yield. Methoxy group at the aromatic ring also delivered the
formylated product, 2c (78%) and 2i (81%). Under the reaction
conditions, substrate with electron withdrawing group such as
NO2 at the aromatic ring afforded 2d and 2j in 51% and 53%,
respectively. Similarly, functionalization of N−H bonds of
chlorobenzamide (2e, 2l, and 2m) was successfully performed in
good isolated yield (>60%). Substrate containing thiophene (2n)
performance
of
other
hydrosilanes
was
tested.
Poly(methylhydrosiloxane) (PMHS) and butylsilane did not result
in the product formation with appreciable yield (entries 14−16,
Table 1). Form this study, it was established that acetonitrile is the
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ACS Catalysis
exhibited moderate reactivity and converted to formylated product
CO2 (Scheme S1, 76%, Supporting Information). This result
supports that aNHC-CO2 adduct is a pre-catalyst for this reaction.
To gain further insight into the reaction mechanism, we
performed the reaction between aNHC-CO2 adduct and
triphenylsilane in 1:1 ratio in acetonitrile medium in absence of
CO2. The reaction was monitored by 1H and 13C NMR
spectroscopy. It was found that silane was completely consumed
1
2
3
4
5
6
7
8
in 57% yield. Substrate bearing electron donating as well as
electron withdrawing group was also tolerated for the reaction
(2o, 68%). aNHC is also able to promote the formylation of
benzamide having electron withdrawing fluorine substituent 2q
(56%), 2r (51%), 2s (49%). Given the same reaction conditions,
functionaization of N-H bonds in aliphatic amides (2t-2v, 31% to
74%) derivatives was successfully performed in modest to good
conversions. Using our synthetic procedure, starting precursors
1
within 12 h. The H NMR spectrum of the reaction mixture in
CDCl3, revealed a singlet at δ = 8.71 ppm, which was assigned to
–CHO hydrogen arising from a formoxysilane intermediate 3
(Scheme 3) as reported in previous literature.29 This was further
confirmed by 13C NMR spectrum of the reaction mixture. In the
13C NMR spectrum recorded in CDCl3, a peak appeared at δ 168.1
ppm confirming the C=O of formoxysilane intermediate when
compared with previous report (Supporting Information).29-31 The
formation of formoxysilane can be envisaged by considering an
intermediate A (Scheme 3) through a concerted attack by aNHC-
CO2 adduct to silane, which triggers a hydride transfer generating
the free aNHC. Such a concerted attack by NHC-CO2 adduct
with silane was proposed earlier by Zhang, Ying and co-workers
during CO2 reduction into methanol using silane and NHC.29
(2a and 2f) of two natural products having a strong larvicidal
27
activity such as alatamide and lansiumamide A
were also
9
synthesized in 74% and 77% yield, respectively (Scheme 2 and
Figure 1b) and the detailed synthesis of these molecules from 2a
and 2f are reported in literature.28 During the isolation of 2f,
cinnamonitrile was identified as a minor (9%) side product.
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O
H
O
5 mol% aNHC
PhSiH3
CO2
R
N
O
R
NH2
CH3CN, 24 h
RT
H
1 atm.
1
2
O
H
O
H
O
H
O
H
N
O
N
H
O
N
H
O
N
O
Furthermore,
the catalytic reaction under the optimized
H
H
OMe
conditions resulted in the formation of a white solid as a by-
O2N
1
product which was characterized as Ph3SiOSiPh3 by H, 13C, 29Si
2a (74%)
2b (70%)
2c (78%)
2d (51%)
NMR spectroscopy (29Si in CDCl3, δ = -18.6 ppm, Supporting
Information, Figure S49) and the molecular structure of
Ph3SiOSiPh3 was established by single crystal X-ray study
(Supporting Information, Figure S50).32 To further investigate the
reaction mechanism, another stoichiometric reaction was carried
out in absence of CO2 using the aNHC-CO2 adduct, phenylsilane
and benzamide in 1:2:1 ratio in a screw cap NMR tube in CD3CN
solvent. The reaction was monitored by 1H and 13C NMR
spectroscopy. During the course of this stoichiometric experiment,
O
H
O
H
O
H
O
H
N
O
N
O
N
O
N
O
H
H
H
H
Cl
Br
2f (77%)
2g (72%)
2e (63%)
2h (64%)
O
H
O
H
O
H
O
H
N
O
N
O
N
O
N
O
H
H
H
H
NO2
OMe
2j (53%)
2i (81%)
2k (80%)
2l (69%)
Cl
1
a gas was evolved; upon H NMR spectroscopic analysis it was
identified as dihydrogen (δ = 4.57 ppm33 in CD3CN solvent;
Supporting Information, Figure S5). On the basis of above
observations and based on previous reports on formylation
mechanism, a plausible catalytic cycle is proposed in Scheme 3.
As the first step, the aNHC by virtue of its strong nucleophilic
nature activates the thermodynamically stable CO2 to form
abnormal NHC-carboxylate (aNHC-CO2), which has been
reported also previously.28, 29 In the next step, the carboxyl moiety
of abnormal NHC-carboxylate attacks the Lewis acidic silane and
promotes hydride transfer to form formoxysilanes 3. Next, the
amide (1a) may undergo activation by reaction with another
molecule of silane in presence of aNHC catalyst followed by
formyl transfer reaction with release of a hydrogen molecule
leading to the formation of the desired product 2a (characterized
X-ray study) and Ph3SiOSiPh3 as a by-product (also characterized
by X-ray study). The dehydrogenation step is supported by the
aNHC (see Supporting Information, Scheme S2), which facilitates
formation of a silane-amide adduct as proposed earlier for amine
methylation with borane.34 It was also noted that for amine
activation by 9-borabicyclo(3.3.1)nonane (9-BBN) followed by
formyl transfer reaction with liberation of hydrogen gas during
metal-free catalysis of amine formylation leading to amine
methylation.34
O
H
O
H
O
H
O
H
N
O
N
O
N
O
N
O
H
H
H
H
S
Br
Cl
2m (65%)
2n (57%)
O
2p (69%)
H
2o (68%)
O
H
O
H
H
O
F
N
O
N
O
N
H
O
N
O
H
H
H
F
CF3
2t (55%)b
2s (49%)
2q (56%)
2r (51%)
O
H
O
O
H
N
N
O
H
H
2v (31)b
2u (74%)b
Scheme 2. Metal-free Formylation of Amides Using CO2.a
aAll reactions were conducted with amide (0.5 mmol),
phenylsilane (1 mmol), CO2 (1 atm.), dry CH3CN (1 mL). Isolated
yields are given in parentheses. NMR conversions were given
based on corresponding substrate.
b
Further to build up the mechanistic understanding of this
transformation, several control experiments were performed as
depicted in the Supporting Information. To delineate the potential
role of the aNHC, reaction between the aNHC and CO2 was
performed following previous method.26 In a typical reaction,
aNHC was dissolved in tetrahydrofuran (THF) in a 25 mL
Schlenk flask and CO2 was introduced at low temperature to
afford a white solid (aNHC-CO2 adduct) after removal of solvent.
In the 13C NMR spectrum of the reaction mixture in CDCl3
solvent, a peak at δ 158.8 ppm,26 was assigned to C=O of aNHC-
CO2 adduct. This isolated aNHC-CO2 adduct was further used as
catalyst in the formylation of amide which afforded the
corresponding desired product in very good yield under 1 atm. of
In the present work, we have developed the first catalytic
formylation of amide. We demonstrated that an aNHC can act as
an efficient catalyst under ambient conditions using CO2 as a
reagent. This catalytic transformation enables formylation of
various substrates, including heterocycle containing amide. This
catalytic reaction directly produces core moiety of two
biologically active molecules via formation of new C−N bond at
room temperature. A series of stoichiometric reactions helped us
to delineate the mechanistic picture for this fascinating
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transformation. The isolation of the reaction by-product and its
1
2
characterization through single crystal X-ray study also
complimented our understanding of the catalytic pathway.
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ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Author
*swadhin.mandal@iiserkol.ac.in
9
Notes
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The authors declare no competing financial interests.
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website. Experiment details, spectral data,
1
copies of
H, 13C and 29Si NMR spectra, and X-ray
crystallographic data for 2a (CIF)
ACKNOWLEDGMENT
We thank the SERB (DST), India (Grant No. EMR/2017/000772).
PKH thanks IISER Kolkata for a research fellowship. SCS thanks
Invictus Oncology, Delhi for research scientist position. PKH
thanks Shiv Pal, IISER-Pune and Gonela Vijaykumar, IISER-
Kolkata for their help in single crystal X-ray study. Authors also
thank the NMR and X-ray facilities of IISER-Kolkata.
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1
2
R
R
a)
3
4
5
6
7
8
9
CO2 (1 atm)
iPr
R
Si
R
O
Si
R
R
O
H
iPr
Ph
iPr
Ph
N
N
N
O
3a
H
1H, 13C, 29Si, X-ray, R = Ph
(aNHC)
2a
(1H NMR data)
H2
iPr
1H, 13C, X-ray data
(See below)
R
R
O
H
R3SiH
Si
R
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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60
iPr
Ph
O
O
iPr
Ph
3
N
N
NH2
O
1H and 13C NMR data,
R = Ph
iPr
(aNHC-CO2)
1H and 13C NMR data
1a
O
iPr
b)
O
iPr
Ph
iPr
Ph
N
N
N
H
O
O
iPr
H
Si
R
R
Si
R
O
R
R
R
iPr
A
Scheme 3. a) Proposed Reaction Pathway on Catalytic Formylation of Amide. b) Molecular View of 2a Determined by X-
ray Crystallography.
(11) Nguyen, T. V. Q.; Yoo, W. –J.; Kobayashi, S. Effective Formylation
REFERENCES
of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by
(1) Aresta, M. Ed. Carbon Dioxide as Chemical Feedstock; Wiley-
VCH: Weinheim, 2010, 414 pp.
(2) Sakakura, T.; Choi, J. C.; Yasuda, H. Transformation of Carbon
Dioxide. Chem. Rev. 2007, 107, 2365–2387.
(3) Das Neves Gomes, C.; Jacquet, O.; Villiers, C.; Thuery, P.;
Ephritikhine, M.; Cantat, T. A Diagonal Approach to Chemical
Recycling of Carbon Dioxide: Organocatalytic Transformation for
the Reductive Functionalization of CO2. Angew. Chem., Int. Ed.
2012, 51, 187−190.
(4) Meyer, K. D.; Saletore, Y.; Zumbo, P.; Elemento, O.; Mason, C. E.;
Jaffrey, S. R. Comprehensive Analysis of mRNA Methylation
Reveals Enrichment in 30 UTRs and Near Stop Codons. Cell 2012,
149, 1635−1646.
(5) Hiersemann, M.; Katritzky, A. R. Functions Bearing Two Nitrogens.
Comprehensive Organic Functional Group Transformations II,
Elsevier, Oxford, 2005.
(6) Fernández-Alvarez, F. J.; Aitani, A. M.; Oro, L. Homogeneous
Catalytic Reduction of CO2 with Hydrosilanes. Catal. Sci. Technol.
2014, 4, 611–624.
(7) Bontemps, S. Boron-mediated Activation of Carbon Dioxide. Coord.
Chem. Rev. 2016, 308, 117–130.
(8) Park, S.; Bézier, D.; Brookhart, M. An Efficient Iridium Catalyst for
Reduction of Carbon Dioxide to Methane with Trialkylsilanes. J.
Am. Chem. Soc. 2012, 134, 11404–11407.
Chelating bis(tzNHC) Rhodium Complexes. Angew. Chem. Int. Ed.
2015, 54, 9209–9212.
(12) Liu, X. -F.; Li, X. –Ya.; Qiao, C.; He, L. -N. Transition-Metal-Free
Catalysis for the Reductive Functionalization of CO2 with Amines.
Synlett 2018, 29, 548-555.
(13) Song, Q. -W.; Zhou, Z. –H.; He, L. –N. Efficient, Selective and
Sustainable Catalysis of Carbon Dioxide. Green Chem., 2017, 19,
3707−3728.
(14) Tlili, A.; Blondiaux, E.; Frogneux, X.; Cantat, T. Reductive
Functionalization of CO2 with Amines: An Entry to Formamide,
Formamidine and Methylamine Derivatives. Green Chem., 2015, 17,
157−168.
(15) Klankermayer, J.; Wesselbaum, S.; Beydoun, K.; Leitner, W.
Selective Catalytic Synthesis Using the Combination of Carbon
Dioxide and Hydrogen: Catalytic Chess at the Interface of Energy
and Chemistry. Angew. Chem. Int. Ed. 2016, 55, 7296–7343.
(16) Li, Y.; Cui, X.; Dong, K.; Junge, K.; Beller, M. Utilization of CO2 as
a C1 Building Block for Catalytic Methylation Reactions. ACS
Catal. 2017, 7, 1077−1086.
(17) Frogneux, X.; Jacquet O.; Cantat, T. Iron-catalyzed Hydrosilylation
of CO2: CO2 Conversion to Formamides and Methylamines. Catal.
Sci. Technol. 2014, 4, 1529–1533.
(18) Motokura, K.; Takahashi, N.; Kashiwame, D.; Yamaguchi, S.;
Miyaji, A.; Baba, T. Copper-diphosphine Complex Catalysts for N-
formylation of Amines Under 1 atm of Carbon Dioxide with
Polymethylhydrosiloxane. Catal. Sci. Technol. 2013, 3, 2392–2396.
(19) Jessop, P. G.; Hsiao, Y.; Ikariya, T.; Noyori, R. Catalytic Production
of Dimethylformamide from Supercritical Carbon Dioxide. J. Am.
Chem. Soc. 1994, 116, 8851–8852.
(9) Jiang, Y.; Blacque, O.; Fox, T.; Berke, H. Catalytic CO2 Activation
Assisted by Rhenium Hydride/B(C6F5)3 Frustrated Lewis Pairs-
Metal Hydrides Functioning as FLP Bases. J. Am. Chem. Soc. 2013,
135, 7751–7760.
(10) Sau, S. C.; Bhattacharjee, R.; Vardhanapu, P. K.; Vijaykumar, G.;
Datta, A.; Mandal, S. K. Metal-Free Reduction of CO2 to
Methoxyborane under Ambient Conditions through Borondiformate
Formation. Angew. Chem. Int. Ed. 2016, 55, 15147–15151.
(20) Liu, H.; Mei, Q.; Xu, Q.; Song, J.; Liu, H.; Han, B. Synthesis of
Formamides Containing Unsaturated Groups by N-formylation of
Amines Using CO2 with H2. Green Chem. 2017, 19, 196–201.
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Page 6 of 6
(21) Zhang, L.; Han, Z.; Zhao, X.; Wang, Z.; Ding, K. Highly Efficient
(30) Rauch, M.; Parkin, G. Zinc and Magnesium Catalysts for the
Hydrosilylation of Carbon Dioxide. J. Am. Chem. Soc. 2017, 139,
18162−18165.
Ruthenium-Catalyzed N-Formylation of Amines with H2 and CO2.
Angew. Chem. Int. Ed. 2015, 54, 6186–6189.
1
2
3
4
5
6
7
8
9
(22) Federsel, C.; Boddien, A.; Jackstell, R.; Jennerjahn, R.; Dyson, P. J.;
Scopelliti, R.; Laurenczy, G.; Beller, M. A Well-Defined Iron
Catalyst for the Reduction of Bicarbonates and Carbon Dioxide to
Formates, Alkyl Formates, and Formamides. Angew. Chem. Int. Ed.
2010, 49, 9777–9780.
(23) Jacquet, O.; Gomes, C. D. N.; Ephritikhine, M.; Cantat, T. Recycling
of Carbon and Silicon Wastes: Room Temperature Formylation of
N−H Bonds Using Carbon Dioxide and Polymethylhydrosiloxane. J.
Am. Chem. Soc. 2012, 134, 2934−2937.
(24) Inagaki, F.; Matsumoto, C.; Iwata, T.; Mukai, C. CO2-Selective
Absorbents in Air: Reverse Lipid Bilayer Structure Forming Neutral
Carbamic Acid in Water without Hydration. J. Am. Chem. Soc. 2017,
139, 4639−4642.
(25) Kar, S.; Sen, R.; Goeppert, A.; Prakash, G. K. S. Integrative CO2
Capture and Hydrogenation to Methanol with Reusable Catalyst and
Amine: Toward a Carbon Neutral Methanol Economy. J. Am. Chem.
Soc. 2018, 140, 1580−1583.
(31) Liu, X. –F.; Li, X. –Y.; Qiao, C.; Fu, H. –C.; He, L. –N. Betaine
Catalysis for Hierarchical Reduction of CO2 with Amines and
Hydrosilane To Form Formamides, Aminals, and Methylamines.
Angew. Chem. Int. Ed. 2017, 56, 7425–7429.
(32) Percino, J.; Pacheco, Jos´e A.; Soriano-Moro, G.; Cer´on,
Margarita.; Castro, M. E.; Chapela, V. M.; Bonilla-Cruz, J.; Lara-
Ceniceros, T. E.; Flores-Guerrero, Mildred.; Saldivar-Guerra,
Enrique. Synthesis, Characterization and Theoretical Calculations of
Model Compounds of Silanols Catalyzed by TEMPO to Elucidate
the Presence of Si–O–Si and Si–O–N bonds. RSC Adv. 2015, 5,
79829–79844.
(33) Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.;
Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I. NMR
Chemical Shifts of Trace Impurities: Common Laboratory Solvents,
Organics, and Gases in Deuterated Solvents Relevant to the
Organometallic Chemist. Organometallics 2010, 29, 2176–2179.
(34) Blondiaux, E.; Pouessel, J.; Cantat, T. Carbon Dioxide Reduction to
Methylamines under Metal-Free Conditions. Angew. Chem. Int. Ed.
2014, 53, 12186–12190.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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48
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50
51
52
53
54
55
56
57
58
59
60
(26) Aldeco-Perez, E.; Rosenthal, A. J.; Donnadieu, B.; Parameswaran,
P.; Frenking, G.; Bertrand, G. Isolation of a C5-Deprotonated
Imidazolium, a Crystalline “Abnormal” N-Heterocyclic Carbene.
Science, 2009, 326, 556–559.
(27) Han, Y.; Li, L.-c.; Hao, W.-b.; Tang, M.; Wan, S.-q. Larvicidal
Activity of Lansiumamide
B from the Seeds of Clausena
lansium Against Aedes Albopictus (Diptera: Culicidae). Parasitol
Res. 2013, 112, 511–516.
(28) Pasqua, A. E.; Ferrari, F. D.; Crawford, J. J.; Marquez, R. Total
Synthesis of Lansiumamides A and B and Alatamide. Tetrahedron
Letters 2014, 55, 6042–6043.
(29) Riduan, S. N.; Zhang, Y.; Ying, J. Y. Conversion of Carbon Dioxide
into Methanol with Silanes over N-Heterocyclic Carbene Catalysts.
Angew. Chem. Int. Ed. 2009, 48, 3322–3325.
Metal-Free Catalytic Formylation of Amides Using CO2 under Ambient Conditions.
Pradip K. Hota, Samaresh C. Sau and Swadhin K. Mandal*
This study reports the first metal-free catalytic formylation of amides using an abnormal NHC as catalyst under an
atmospheric pressure of CO2 at room temperature.
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