Tetracoordinate borates as catalysts for reductive formylation of amines with carbon dioxide

Article abstract of DOI:10.1039/d0gc01741h

We report sodium trihydroxyaryl borates as the first robust tetracoordinate organoboron catalysts for reductive functionalization of CO2. These catalysts, easily synthesized from condensing boronic acids with metal hydroxides, activate main group element-hydrogen (E-H) bonds efficiently. In contrast to BX3 type boranes, boronic acids and metal-BAr4 salts, under transition metal-free conditions, sodium trihydroxyaryl borates exhibit high reactivity of reductive N-formylation toward a variety of amines (106 examples), including those with functional groups such as ester, olefin, hydroxyl, cyano, nitro, halogen, MeS-, ether groups, etc. The over-performance to catalyze formylation of challenging pyridyl amines affords a promising alternative method to the use of traditional formylation reagents. Mechanistic investigation supports electrostatic interactions as the key for Si/B-H activation, enabling alkali metal borates as versatile catalysts for hydroborylation, hydrosilylation, and reductive formylation/methylation of CO2.

Full text of DOI:10.1039/d0gc01741h

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DOI: 10.1039/D0GC01741H
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ARTICLE
Tetracoordinate Borates as Catalysts for Reductive Formylation of
Amines with Carbon Dioxide
Xiaolin Jiang†,‡, Zijun Huang†,§, Mohamed Makha†, Chen-Xia Du‖, Dongmei Zhao*,‡, Fang Wang*,†,
Received 00th January 20xx,
Accepted 00th January 20xx
and Yuehui Li*,†
DOI: 10.1039/x0xx00000x
We report sodium trihydroxyaryl borates as the first robust tetracoordinate organoboron catalysts for reductive
functionalization of CO2. Easily synthesized from condensing boronic acids with metal hydroxides, these catalysts activate
main group element-hydrogen (E-H) bonds efficiently. In contrast to BX3 type boranes, boronic acids and metal-BAr4 salts,
under transition metal-free conditions, sodium trihydroxyaryl borates exhibit high reactivity of reductive N-formylation
toward a variety of amines (106 examples), including those with functional groups such as ester, olefin, hydroxyl, cyano,
nitro, halogen, MeS-, ether groups etc. The over-performance to catalyze formylation of challenging pyridyl amines affords
a promising alternative method to the use of traditional formylation reagents. Mechanistic investigation supports the
electrostatic interaction as the key for Si/B-H activation, enabling alkali metal borates as versatile catalyst for
hydroborylation, hydrosilylation, and reductive formylation/methylation of CO2.
www.rsc.org/
catalysts were shown to be active in the titled reaction,16 the
principle governing transition metal-free
catalysis mainly relies on acid-base interactions between the
Introduction
Boron-based catalysts such as BF3, HB(C6F5)2 (Piers borane),
B(C6F5)3, Corey-Bakshi-Shibata oxazaborolidine reduction
catalysts, boron nitrides, boronic acids and borinic acids etc are
widely used in organic synthesis and/or industrial applications.1-
4 In the procedures using boron-based catalysts and the related
borylation reactions, tetradentate borates are known as key
intermediates formed due to the Lewis acidity of boron atom
originated from the existence of empty 2p orbital.5-7 Here, these
borate intermediates are treated as active species assisting the
chemical reactions (Figure 1a).
catalyst and reductant. For instance, FLPs (Frustrated Lewis
Pairs) are used as efficient and successful catalysts to activate
small molecules including even dihydrogen.17-18 Therefore, the
presence of strong acids or bases tends to be the preferred
choice to activate main group element-H (E-H) bond. However,
these known systems often suffer from limited substrate scope
drawbacks, especially for the acidic or basic groups containing
substrates (e.g. phenolic, pyridyl amines).
a) CBS reduction intermediate
Ph
b) Design of anionic catalyst to active Si-H
H
H
CO2 reduction with functionalization for the preparation of
formamides and methylated amines represents one of the most
important ways to incorporate CO2 into organic molecules as C1
building block. Other than the use of transition metal catalysts,8-
Ph
O
H
O
N
Si
B
Ar
B
R
O
H
H
B
O
CH3
OH
H
H
Ph
12
non-covalent weak interactions such as Van der Waals,
This work
c)
R
: hydroxyarylborates for CO2 reduction (E = Si/B)
hydrogen and halogen bondings are widely involved weak
forces in organo-activation of chemical bonds.13-15 In this
respect, although quite many types of transition metal-free
CO2
O
OH
OR'
OH
B
M-OR'
B
M
OH
E
OH
-H
R
(Cat.)
H
X
Electrostatic activation of E-H
Broad substrate scope
Robust, modular catalyst
Recyclable catalyst
X = OR, NRR'
> 100 examples
(
)
† State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research
Institute of LICP, Center for Excellence in Molecular Synthesis, Lanzhou Institute of
Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P.R. China
‡ Key Laboratory of Structure-based Drug Design & Discovery of Ministry of
Education, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China
§ University of Chinese Academy of Sciences, Beijing 100049, P.R. China
‖ College of Chemistry and Molecular Engineering, Zhengzhou University,
Zhengzhou 450001, P.R. China
Figure 1. Metal hydroxyaryl borates for activation of E-H to selectively reduce CO2.
Electrostatic catalysis refers to substrate activation by catalyst
via electrostatic interactions.19-21 The strategy is late emerging
approach to activate B-H bond with the recent report by Hirao
and Kinjo et al on elegant reduction of ketone/aldehyde/CO2
using diazadiborinine compounds as pre-catalyst.22 However, to
the best of our knowledge, there is no previous report on the
use of metal borates for Si-H activation and reductive
Electronic Supplementary Information (ESI) available: Experimental details and
characterization of all compounds and copies of 1H and 13C NMR for the new
compounds. CCDC 1971981. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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PMHS (polymethylhydrosiloxane) at 100 oC for 12 h. fReaction cVairerwiedAroticulteaOtn1li0ne0
funcationalization of CO2, even though they contain multiple
functional sites such as acidic proton, basic oxygen atom, aryl
group possibly useful for catalysis. Our design strategy stem
from the use of aryl bronate base catalysts to activate Si-H
through electrostatic interactions, which in turn reacts with
acidic CO2 to form the silyl formate reagent required for N-
formylation (Figure 1b). Such electrostatic interaction induces
hydride transfer to affect hydrosilylation of CO2 and form silyl
formates. Herein, we demonstrate the use of transition metal-
free arylborates, well-known Suzuki coupling reagents, for an
efficient catalytic reduction of CO2 and selective N-
formylation/methylation of a broad scope of aromatic and
aliphatic amines (Figure 1c).
oC with THF (tetrahydrofuran) as solvent. gToluene as solvent.
DOI: 10.1039/D0GC01741H
Initial investigation of N-formylation of aniline with CO2 in the
presence of hydrosilanes was examined (Table 1). Surprisingly,
we find that boronic acids 3a-c were ineffective for N-
formylation even though aromatic boronic acids were used for
the hydrosilylation reduction of amides.34 Boronic acids bearing
pyridyl group were beneficial, albeit only low yields were
obtained (Table 1, entries 5 - 7). The exploration of other
aromatic heterocyclic boronic acids and borate esters were
unsuccessful (Table 1, entries 8 - 10). To our delight, when ionic
sodium trihydroxyphenyl borate 3j was used, moderate
reactivity could be achieved (Table 1, entry 11). Increasing the
o
temperature to 100 C led to higher yield of 88% while lower
Results and discussion
yields were obtained when using other types of silanes or
solvents (Table 1, entries 11 - 16). We believe that the
aggregation and shielding of hydridic silanes around the catalyst
induce hydride transfer to CO2. And, the choice of hydrophobic
diglyme as solvent is effective for the adsorption of CO2 in the
presence amines.35 Notably, such kind of catalyst working under
heating conditions in polar solvents implying special activation
mode different from the known σ-hole catalysis.36 Notably,
when 1.0 gram of N-methylaniline was used as substrate, the
desired product 2aa was obtained in 86% yield (1.1 gram) under
the optimized conditions.
Formates and formamides are ever present functionality in
many drug intermediates, fine chemicals and polymer materials
etc.23 From the multitude of methods for the preparation of
formamides, direct N-H formylation using CO2 in the presence
of reductants represents the most viable approach.24-27
Generally, selective formylation of primary amines is always
challenging because of possible formation of di-formylated or
methylated by-products, and moreover occurrence of serious
over-reduction or side-reactions of functional groups in
complex amine substrates. In our continuing interest on CO2
utilization and of using hydrosilane as reductant28-32 and boronic
acid as catalyst,33 we considered the use boron-contained
compounds as catalyst for the N-formylation of amines.
As shown in the work of Hall et al, aromatic borates (such as
sodium trihydroxyphenyl borate, phenoxy-dialkoxy borates)
were elegantly applied into base-free Pd-catalysed Suzuki
coupling reactions.37-38 Here, we stress that the use of such
compounds as catalysts for E-H bond activation have never
been reported nor discussed before this work.39 Metal borates
are known as core structure of natural products (e.g.
boromycin),40 Lewis acid catalysts,41-42 and boron “ate” complex
related reaction intermediates.43-44 However, borates are
unstable/reactive intermediates in these reactions.
Table 1. Discovery of the new borate catalysta
H
N
catalyst (10 mol %)
silane
O
N
+
CO2
60 oC, 12 h
- silanol
2aa
1aa
B(OH)2
B(OH)2
B(OH)3
B(OH)2
3b
N
B(OH)2
3a
N
3c
3d
3e
H
catalyst (20 mol %)
PhSiH3 (1equiv.)
B(OH)2
O
N
N
OH
S
O
B
+
CO2
OH
60 oC, 12 h
- silanol
B(OH)2
B
B(OC3H7)3
O
Na
OH
O
2aa
N
3f
1aa
N
3g
3h
3i
3j
OtBu
OEt
OMe
OH
OH
Entry
catalyst
Yield (%)b
Entry
catalyst
Yield (%)b
OH
OH
OH
B
B
B
B
Na
OH
Na
OH
Na
Na
OH
OH
1
-
0
9
3h
<3
a
3m
(34%)
a
a
3l
(68%)
OH
a
b
3k
(65%)
3j
(45%) ; (88%)
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
0
0
10
11
3i
3j
3j
3j
3j
3j
3j
<3
48
OH
OH
OPh
OH
OH
Me
OH
B
B
OH
OH
0
12c
13d
14e
15f
16g
68
OH
B
Na
Me
B
OH Na
Na
Na
Na
OH
9
88
Me
a
a
3q
(58%)
a
5
25
3p
(47%)
a
3o
(65%)
OH
3n
(60%)
0
20
OEt
OH
Et
OH
OH
CN
OMe
OH
OH
3g
<3
trace
Et
OH
OH
OH
B
B
B
B
Na
aReaction conditions: 1aa (0.2 mmol, 1 equiv.), catalyst (0.02 mmol, 10 mol %),
phenylsilane (0.2 mmol, 1equiv.), CO2 (0.25 MPa) in diglyme (diethylene glycol
dimethyl ether, 1 mL) at 60 oC for 12 h. bYields determined based on GC analysis
using n-hexadecane as internal standard. cReaction carried out at 100 oC.
Na
OH
OH
a
b
a
a
3u
(82%) ; (90%)
3t
(3%)
a
3s
(5%)
3r
(71%)
Figure 2. Screening of the sodium arylborates. aReaction conditions: 1aa (0.2 mmol, 1
equiv.), catalyst (0.04 mmol, 20 mol %), phenylsilane (0.2 mmol, 1 equiv.), CO2 (0.25 MPa)
dReaction carried out using 2 equiv. of phenylsilane at 100 oC. Using 5 equiv. of
e
2 | J. Name., 2012, 00, 1-3
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in diglyme at 60 oC for 12 h. bPhenylsilane (0.4 mmol, 2 equiv.) at 100 oC for 12 h. Yield
of 2aa shown in brackets was determined by GC analysis using n-hexadecane as internal
standard. The catalyst was prepared quantitatively from in situ reaction of aryl boronic
acids with the base.
H
catalyst (20 mol %)
PhSiH3 (1equiv.)
O
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N
N
DOI: 10.1039/D0GC01741H
+
CO2
60 oC, 12 h
- silanol
2aa
1aa
Hence, we embarked into a systematic study probing the
catalytic activity of various borates to verify the reliability of
catalysis by borates, and ultimately further discover more
efficient catalysts. As shown in Figure 2, a variety of sodium
aromatic borates were conveniently prepared by in-situ mixing
aromatic boronic acids with NaOH or sodium alkoxides.45-46 It is
interesting that different reactivity was observed depending on
the counter base used. Specifically, when using MeONa, EtONa,
tBuONa or PhONa as the base (catalyst 3k-3n), the yields
ranging from 34 to 68% were obtained, with catalyst 3l from
EtONa giving better reactivity. Meanwhile, ortho-substitution
by alkyl groups on aryl ring influenced the reactivity significantly
with methyl substitution to form 3o giving the highest yield of
the desired product of 65%. Meta or para-substitution with
methyl group decreased the reactivity (47 - 58% yields).
catalyst
Entry
1
2aa
yield (
)
OH
Et
OH
B
Na
71%
OH
3r
Et OH
B
NR
2
OH
3
4
5
NaOH
BF3
Trace
NR
B(C6F5)3
NR
Finally, when catalyst 3u was used, the highest yield of 82% was
achieved. When lowering catalyst loading (10 mol%) under
elevated temperature, higher yields were obtained for both 3j
and 3u. Notably, in principle, unlimited number of metal
aromatic borates type compounds could be obtained by
combining different aromatic boronic acids with metal
hydroxide/alkoxides. To the best of our knowledge, metal
borates have never been used for catalytic reduction reactions.
We also compared the reactivity of other types of boron-
contained compounds. As shown in Table 2, only the use of
borate 3r led to high reactivity under similar conditions. Even
the use of strong base NaOH or strong Lewis acids such as BF3
or B(C6F5)3 resulted in poor reactivity for the desired reaction,
with significant amounts of aniline starting material recovered.
Substrate-catalyst activation via weak interactions could be
tested by NMR techniques. Therefore, 1H NMR measurement of
mixtures of CO2, PhSiH3 or N-Me aniline, individually with 3j
were performed (See the SI). Initially, when 3j was added to
PhSiH3, chemical shift changes of Si-H of PhSiH3 and C-H on
phenyl ring of 3j were not observed (Si-H at 4.03 ppm for
PhSiH3). Control experiments suggested that borates could be
stabilized by silane molecules. Specifically, without silane, CO2
reacts with borate salt 3j to form free phenyl boronic acid and
NaHCO3. In contrast, with PhSiH3, no decomposition of 3j
occurred in the presence of CO2. This result suggests the
occurrence of weak interactions (not able to be detected in 1H
NMR time scale) between silane and borate catalysts offering a
protective shield to the borate catalyst from decomposition by
CO2. In this respect, silane might be activated via the
stabilization of borate catalyst with the formation of the
energized favored intermediate. Regarding the role of alkali
metal cation (i.e. Na+), no influence on reactivity was observed
in the reaction of N-Me aniline with 3j in the presence of other
alkali metals CsCl, LiCl or KCl. Hence, we envision that the borate
anion plays the key role in the activation of Si-H bond.
NaBPh4
NaBH4
6
7
Trace
16%
Reaction conditions: 1aa (0.2 mmol, 1 equiv.), catalyst (0.04 mmol, 20 mol %),
phenylsilane (0.2 mmol, 1 equiv.), CO2 (0.25 MPa) in diglyme (1 mL) at 60 oC for 12
h. Yields determined by GC analysis using n-hexadecane as internal standard.
Moreover, in 1H NMR experiments B-H formation was
undetected unlike with the recent development of alkali metal
hydridotriphenylborate catalysts for the hydroboration of CO2
via B-H and B-OR interconversion.7 Therefore, we advance the
involvement of weak interactions seemingly weaker than
classical hydrogen bonding. Meanwhile, it is interesting to note
that in the Pd-catalysed Suzuki coupling reaction of acyl
chlorides or aryl iodides with sodium trihydroxyphenylborate,
the presence of PhSiH3 strongly suppressed the C-C coupling
reaction. This result implies that the interaction between silanes
and borates influence the original coupling reaction (Figure S1,
see the SI).
To further understand the mechanism, density functional
theory (DFT) calculations on the interaction of silanes with
borates were examined. It is suggested that the weak attraction
between borate catalysts and hydrosilanes is through Si-H…H-O,
Si-H…H-C and Si…O interactions, I and II as illustrated in Figure
3. The stabilized energy is at the level of 4-5 kcal mol-1 belonging
to the energy strength of electrostatic interaction. Besides, the
electrostatic potential map illustrated in Figure 4 also suggest
that the negatively charged hydride of phenylsilane interacts
with the positively charged hydrogen atoms connected by
oxygen atoms and carbon atoms in sodium aryl borates. This is
also consistent with the results of NMR experiments that
interactions weaker than hydrogen bonding could exist and
were undetectable in 1H NMR time scale. Besides, as mentioned
above, the presence of methyl group at ortho-position to the
boron (catalyst 3o) or methoxy group on boron atom (catalyst
Table 2. Comparison of different acids or bases with 3r
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3k) increased the reaction efficiency significantly. From the DFT with electron-withdrawing aromatic amines substituents like F,
View Article Online
DOI: 10.1039/D0GC01741H
study, it is clear that the CH3 moiety interact with hydride of Cl, Br, I, CF3, 3,5-di-F, 3,5-di-Cl and NO2 to afford the desired
silane. The Si-H…H-O and Si-H…H-C distances are shortened in compounds (2g - j, 2p - r) in 70 - 88% yields. To our surprise, the
comparison with those in I and II. Moreover, the binding reaction gave the desired compounds 2z in 77% yields using
energies are -7.6, -5.7, and -6.2 kcal mol-1 for I-MeO, II-MeO, allylamine without affecting the double bond which is often
and I-Me, while they are -5.6 and -4.0 kcal mol-1 for I and II, sensitive to reductants. Fortunately, this method was also
respectively (Table S5). These results demonstrate that the successful in the N-formylation of amines which contain
interactions between PhSiH3 and sodium aromatic borates are piperidyl (2s, 81% yield), oxygen heterocyclic (2t, 84%), ester (2v,
effectively strengthened by the introduction of methoxy group 82%), trifluoromethoxy (2y, 80%) and naphthalene derivatives
on boron atom or ortho-methyl substitution to boron, being showing good to excellent reactivity (2w - x, 85 - 90% yields)
beneficial for the activation of Si-H bonds for the key CO2
reduction step. The present results rationalize the experiment
findings.
Pathway A
O
O
R2NH
PhSiH3
SiH2Ph
CO2
H
O
[PhB(OH)3]-
- silanol
H
NR2
Pathway B
R2NH
R2N
O
O
PhSiH3, [PhB(OH)3]-
- silanol, - R2NH
R2NH2
H
O
NR2
H
H
O
-
HO
+
O
C
H
O
B
O
HO
+
H
H
H
H
B
O
-
Si
Ph
R2N
O
X = H, silyl group
CO2 or carbamate
inducible charges
Si-H activation for C-H formation
Figure 4. Proposed Reaction Mechanism
Figure 3. DFT-Calculated Interaction Modes. (A) Optimized complex structures of
sodium aryl borates (3j, 3k, 3o) with phenylsilane at the M06-2X-D3/6-311G(d, p)
level of theory in solvent. Values in parenthesis denote the binding energies (in
kcal mol-1) calculated at DSD-PBEP86/def2-TZVPP level in solvent. Bond lengths
are in Å. (B) Electrostatic potential map for the catalyst-silane interaction.
In light of the success with aromatic primary amine derivatives,
we extended the scope to aromatic secondary amine substrates,
as also presented in Table 3. To our delight, the reactions also
underwent smooth conversion to afford the expected N-
formylated product. Similarly to aromatic primary amines,
aromatic secondary amines also exhibit functional group
tolerance and display good to excellent reactivity. The reaction
underwent smooth conversion regardless of electron-
withdrawing and donating substituents affording the desired
compounds in good to excellent yields (2ab - ac, 2ae - ai, 73% -
91%). Conversely, we find that the product conversion is slightly
lowered with ortho position substituted substrate, presumably
due to steric hindrance 2ad (68% yield).
From experimental results and theoretical studies, we propose
that the ionic borate moiety of sodium phenyl trihydroxy borate
could interact with hydrosilane selectively via electrostatic
interactions (Figure 3). This is a key step for CO2 reduction to
give silyl formate intermediates, which further undergo additive
substitution reaction with amine substrates to give the desired
formamide product (Pathway A). Besides, the formation of
carbamate intermediates followed by reduction to give the
formamide product is also possible (Pathway B). The use of
borates to promote the activation of Si-H or B-H bond is unique.
In addition, it is suggested that the non-coordinating nature of
tetrahedral borate makes them suitable for tasks that involve
ion-pairing with sensitive organometallic complexes or reactive
cationic intermediates.
Heterocyclic secondary amines were also amenable to this
transformation and converted to the corresponding
carboxamide products in good to excellent yields (2aj - al, 73 -
95%). For alkylated secondary amines, we found that the
length and branching of the carbon chain of the alkyl
substituent on the N atom has influence on the yield. For
instance, amine substrates with sterically hindered isopropyl
or t-butyl substituents afford desired products with lower
yields, while side reaction methylation products increase (2an -
aq, 53 - 73%). Acceptable yields were obtained when
secondary amine substrates (substituted N-methylanilines)
bearing electron withdrawing substituent (2ar - as, 47 - 70%).
Notably, the presence of nitro group often inhibits N-
formylation Using CO2 in previous reports. Substituted amines
(anilines) with either electron donating or electron
With the optimized reaction conditions in hands, investigation
of substrate scope was performed. Firstly, different aromatic
aniline substrates were tested (Table 3). It was found that good
to excellent reactivity and selectivity for the desired N-
formylation reaction was achieved for most aromatic primary
o
amines at 60 C, with occasionally aromatic primary amines
requiring 100 oC. Electron donating aromatic amines such as Me,
Et, iPr, tBu, di-Me, MeS and OMe derivatives afforded the
desired compounds (2b - f, 2k - o, 2u) in 80 - 86% yields
respectively. The reaction also underwent smooth conversion
4 | J. Name., 2012, 00, 1-3
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Table 3. N-Formylation of aromatic aminesa
withdrawing groups afforded the desired products in moderate
to good yields (2ba, 83%; 2au - 2az, 68 - 89%). Secondary alkenyl
View Article Online
DOI: 10.1039/D0GC01741H
R2
N
H
OH
N
3j
10 mol%
silane
OH
R2
O
B
R1
+ CO2
amines allylphenylamine was also transformed to the
corresponding formylated products in lower moderate yield
(2at, 44%). Secondary amines bearing bulky substituents
regarded incompatible for such transformation also afforded
the desired products in moderate yields (2bc - be, 40 - 58%).
Lastly, when substrate is an ortho-diamine, the corresponding
benzimidazole or benzothiazole compounds were formed in
moderate yields (2bf, 46%; 2bg, 55%; 2bh, 52%). Here, it is
important to note that under elevated temperature the catalyst
remained stable after the reaction showing the robustness of
the borate catalyst in this catalytic system. With respect to the
concept of green chemistry, the development of reusable
heterogeneous catalysts is highly attractive.47 In our system, the
catalyst recycling test shows that the catalytic activity is still
high after two times of reuse with the yields of the desired
product as 88%, 75%, 70% respectively.
Na
R1
OH
diglyme, 12 h
60-100 o
C
1
3j
2
H
H
H
H
O
H
O
O
N
N
N
O
R
N
O
N
R
, R = H,
(83%)a 2k
, R = CH3, (81%)
a
a
a
2a
2b
2c
2d
2e
a
2m
(80%)
2o
2n
(82%)
(83%)
O
, R = CH3, (86%)a 2l
,
R = OMe, (84%)a
a,d
, R = C2H5, (84%)
, R = iPr, (81%)a,d
, R = tBu, (80%)a
H
N
F
H
O
O2N
N
R = OMe, (85%)a
2f
,
(84%)a
(83%)a
(79%)a
(88%)a,d
2g
2h
, R = F,
, R = Cl,
R = Br,
R = I,
F
a
2p
a
(67%)
2i
,
2q
(76%)
CCDC (1971981)
2j
,
H
H
H
N
O
N
O
Cl
H
N
N
O
HN
O
O
O
N
O
Cl
S
Table 4. N-Formylation of aliphatic aminesa
a
a
a
a
a,d
2r
2s
2t
(84%)
(75%)
(81%)
2w
2u
(85%)
(85%)
H
OH
3j
10 mol%
silane
H
N
O
H
N
N
OH
H
O
R
N
O
O
R
NHR1
B
O
N
+
CO2
Na
OH
diglyme, 60 o
12 h
C
R1
O
2
1
3j
F3CO
O
a,d
a,d
a
a
2v
(82%)
2x
2y
2z
(77%)
(90%)
(80%)
2bj
,
X = CH2, (78%)a
HN
O
O
2bk
, X = O,
(77%)a
(74%)a
O
O
R
N
2bl
,
X = NH,
N
X
O
O
N
N
N
O
, X = NCH3, (80%)a
N
2bm
2bn
,
X = NCHO, (58%)a
F3C
(88%)b
b,c
R
a
2bq
(93%)
a
2bi
(81%)
2bo
NCHO
, (56%)
,
X =
2aa
,
R = H,
2amb
b
b,d
O
2ai
2ak
, R = Bn, 88%
R = Et, 73%
O
(73%)
(84%)
N
, R = H, (86%)b,c
2bt
, R = CH3, (81%)b
2bx, R = OH, (92%)b
2ab
,
,
R = p-CH3, (91%)b
R = m-CH3, (79%)b
R = o-CH3, (68%)b
R = OMe, (87%)b
2ac
2anb
2aob
N
2bv
,
,
O
N
N
O
O
NC
CN
2ad
,
,
R = iPr, 67%
R
, R =
,
(77%)b
(84%)b
N
b
b,c
2by
2ca
CN
CF
2ae
2af
2bp
(75%)
2bs
(92%)
2apb,d
, R = tBu, 53%
R = nBu, 72%
(80%)b
(82%)b,d
(78%)b
, R =
,
,
2ag
2ah
R = F,
3
2aqb
,
, R = Cl,
O
NC
N
O
N
b
O
b,d
N
O
2aj
(95%)
N
2al
2at
(73%)
O
,
R = Br,
N
H
H
Cl
N
O
Br
N
O
N
O
b
b
b
b
2br
2bu
2bw
2bz
(87%)
(90%)
(72%)
(75%)
N
O
, R1 = H,
R2 = Et, (85%)b
, R1 = CH3, R2 = Et, (50%)b
2cc
H
O2N
N
Br
2au
O
2cd
2ce
b
N
R2
b,d
b,d
b
O
(76%)
2ar
2as
(70%)
(47%)
(44%)
, R1 = H,
R1 = H,
, R1 = H,
R2 = Bn, (87%)b,c
R2 = iPr, (78%)b
R2 = tBu, (41%)b
R1
2cf
,
b
H
2cb
(80%)
H
N
O
N
H
N
2cg
O
O
N
O
O
( )
nN
H
N
O
O
F3C
H
O
N
N
O
O2N
Me
H
Cl
b
b
2ax
2ay
(72%)
(78%)
b,d
b
, n = 1, (88%)b,c
2av
2aw
(68%)
(89%)
O
2cj
n = 3, (72%)b
n = 4, (61%)b
b
b
2ck
b,c
,
2ch
(82%)
2ci
(85%)
2cm
2cn
(R-94%)
(S-96%)
O
iPr
H
N
N
O
b,c
H
2cl
,
O
N
N
aReaction conditions: 1 (0.2 mmol, 1 equiv.), catalyst (0.02 mmol, 10 mol %), phenylsilane
(0.3 mmol, 1.5 equiv.), CO2 (0.25 MPa) in diglyme (1 mL) at 60 oC for 12 h. b.Phenylsilane
(0.2 mmol, 1 equiv.). cYields refer to isolated yield. Other yields determined based on GC
analysis using n-hexadecane as internal standard.
OMe
iPr
b
b,d
b
b,d
2az
2ba
2bb
2be
(70%)
O
(79%)
O
(88%)
(51%)
N
N
c
N
N
N
N
N
S
H
We further investigated a wide range of aliphatic amines (Table
4). Reactions with both aliphatic and benzylic primary and
secondary amines afforded the corresponding formylated
products in good to excellent yields, including substrates with
bulky tBu group substitution. Notably, functional groups such as
ether, nitrile, cyclopropyl, halogen, phenol and trifluoromethyl
groups were well tolerated. Cyclohexamine, benzylamine,
aminopropylbenzene and aminobutylbenzene were converted
successfully to N-formylated derivatives in good to excellent
c
c
b
b
2bf
2bh
(52%)
(46%)
2bg
(55%)
2bc
2bd
(58%)
(40%)
aReaction conditions: 1 (0.2 mmol, 1 equiv.), catalyst (0.02 mmol, 10 mol %), phenylsilane
(0.4 mmol, 2 equiv.), CO2 (0.25 MPa) in diglyme (1 mL) at 60 oC for 12 h. bPhenylsilane
(0.4 mmol, 2 equiv.) at 100 oC for 12 h. cPhenylsilane (0.4 mmol, 2 equiv.) at 100 oC for
24 h. dYields determined based on GC analysis using n-hexadecane as internal standard.
Other yields refer to isolated yields.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Journal Name
yields (2bi, 81%; 2cj - cl, 61 - 88%). Cyclic heterocyclic amines derivatives in excellent yields (2cu - cy, 75 - 95V%ie)w. AArtlicsloe,Ontlhinee
aza-cyclohexane, oxazine and piperazines afforded the desired reaction of thiophenemethylamine orDOfuI:r1a0r.1y0lm39e/Dth0yGlCa0m17in41eHs
products in moderate to good yields (2bj - bo, 56 - 80%). Di- afforded the desired products in good yields (2cz - db, 62 - 85%).
alkylated amine substrates, N-butyl amine, di-isopropylamine,
imidazole (2 equiv.)
DMF, 60 oC, 48 h
imidazole (2 equiv.)
DMF, 60 oC, 48 h
N,N,N-trimethyl diaminoethane and bis(2-cyanoethyl)amine
were transformed in excellent yields (2bp - bs, 75 - 93%). N-
Methyl benzylamine and derivatives bearing electron-
withdrawing or electron-donating groups were also amenable
to this transformation in good yields (2bt - cd, 72 - 92%). It is
interesting to note that aminomethyl phenol 2bx undergoes
chemoselective N-formylation smoothly. N-Substituted
benzylamines with various alkyl groups (ethyl, isopropyl, butyl
and benzyl) gave the corresponding N-formylated products in
moderate yields with bulky t-butyl one at the lower end of the
range (2cc, 2ce - cg, 41 - 87%). Reactions of chiral substrates (S)-
and (R)-2-Pyrrolidinemethyl-methyl ether (2cn, 2cm)
proceeded smoothly with the chiral properties maintained in
the product.
n.d.
n.d.
n.d.
n.d.
HCOOH
80 oC, 8 h
HCOOH
80 oC, 8 h
25%
HN
NH2
O
O
HCOONH4
HCOONH4
4%
CH3CN, reflux, 12 h
CH3CN, reflux, 12 h
N
2t
HCOOEt
HCOOEt
3co
trace
48%
reflux, 12 h
reflux, 12 h
3j
, PhSiH3
3j
, PhSiH3
92%
84%
DGDE, 60 o
C
DGDE, 60 o
C
(this work, Table 5)
(this work, Table 3)
Figure 5. Comparison results of borate-catalysis approach with non-catalytic
methods
A) Reduction of CO2
O
Pyridine based derivatives represent key motifs in drug and fine
chemicals including ligands for catalysis. It is noteworthy to
mention that the presence of pyridyl group is always
problematic in catalytic transformations. Satisfyingly, we found
that heterocyclic substrates such as substituted aminopyridine
and derivatives could be transformed to the desired product in
good to excellent yields (2co - ct, 48% - 92%; Table 5). Notably,
the Meyers formylating agent 2cq was produced in 58% yield.48a
These results implied that a new mechanism pathway is
involved to have basic pyridine group well tolerated.
3j
(10 mol %)
- silanol
SiPhH2
CO2
PhSiH3
+
H
O
formate
60 oC, 12 h
99% yield
B) N-methylation of aromatic amines
CH3
3j
H
N
(10 mol %)
N
R
PhSiH3 (2.0 equiv.)
R
+
CO2
R
120 oC, diglyme, 12 h
1
3
(yield)
3a
3b,
3c,
3d
3e
, R = tBu
R = iPr,
R = Ph,
, R = cyclohexyl, 76%
, R = naphthyl, 84%
87%
79%
82%
Table 5. Application to the synthesis of heteroaromatic formamidesa
C) HBpin as the reductant
H
N
OH
OH
O
3j
(10 mol %)
silane
H
B
O
O
O
N
3j
(10 mol %)
Na
OH
N
+
CO2
+
N
H B
R1 R1
+
R1 R1
CO2
60 oC, diglyme, 8 h
- borate
60 - 100 oC,12 h
3j
1aa
2
1
2aa
HBpin
(1 equiv.)
2aa
O
catalyst
NaOH
yield (%,
16
)
N
O
N
N
N
O
N
N
H
O
N
N
b
a
a,c
a,c
PhB(OH)2
NR
2co
2cp
2cq
2cr
(92%)
(62%)
(58%)
(60%)
Cl
PhB(OH)3Na
40
H
N
H
HN
O
O
O
N
N
Figure 6. Further applications on reduction, N-methylation and activation of
N
N
O
N
N
H
hydroborane.
a
a
a,c
a
2cs
2ct
2cu
2cv
(52%)
(48%)
(88%)
(79%)
To further demonstrate the usefulness of this new method, the
N-formylation of valuable pyridyl amines48b 3co and primary
amine 2t were carried out using the known non-catalytic
methods49 to demonstrate the applicability of this work (Figure
5). Notably, the presence of pyridyl group is often problematic
to the transition metal catalysed reactions that proceed via the
formation of metal-H species. Most of non-catalytic methods
tested were unsuccessful and only trace amounts of product
was observed using ethyl formate for the formylation of 3co
(Figure 5). Also for the reaction of 2t, poorer yields were
obtained compared to the approach this work based on borate
3j and PhSiH3. The generality of this approach is unprecedented
as shown above for substrate scope tolerance. Interestingly, in
spite of the presence of basic pyridyl group or acidic phenolic
O
N
O
O
N
N
N
N
O
N
N
O
b
b
b
2cw
S
2cx
2cy
(75%)
(94%)
(95%)
H
N
O
N
N
O
O
O
O
b,c
b
b
2cz
2da
2db
(62%)
(85%)
(80%)
aReaction conditions: 1 (0.2 mmol, 1 equiv.), catalyst (0.02 mmol, 10 mol %), phenylsilane
(0.3 mmol, 1.5 equiv.), CO2 (0.25 MPa) in diglyme (1 mL) at 60 oC for 12 h. b.Phenylsilane
(0.2 mmol, 1 equiv.). cYields refer to isolated yield. Other yields determined based on GC
analysis using n-hexadecane as internal standard.
Moreover, we successfully transformed more complex
structures such quinolinamine and pyridinemethanamine
6 | J. Name., 2012, 00, 1-3
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group good reactivity was maintained. This is in a striking
contrast to the known base-acid interaction strategy.
Notes and references
View Article Online
DOI: 10.1039/D0GC01741H
1
2
3
4
5
6
R. Deloux and M. Srebnik, Chem. Rev., 1993, 93, 763-784.
P. Eisenberger and C. M. Crudden, Dalton Trans., 2017, 46, 4874-4887.
J. W. B. Fyfe and A. J. B. Watson, Chem, 2017, 3, 31-55.
D. G. Hall, Chem. Soc. Rev., 2019, 48, 3475-3496.
E. J. Corey and C. J. Helal, Angew. Chem. Int. Ed., 1998, 37, 1986-2012.
J. H. Docherty, J. Peng, A. P. Dominey and S. P. Thomas, Nat. Chem.,
2017, 9, 595-600.
The control experiment for the reduction of CO2 in the absence
of amines gave the silyl formate product in high yield (99%;
Figure 6A). Under slightly higher temperatures, the reductive N-
methylation using CO2 was also achieved with good reactivity
(76 - 87 yields; Figure 6B). To further prove the activation of
main group element-hydrogen bond using ionic borates, the
catalytic formylation of amines using hydroborane was
performed. Using HBpin as the reductant, the formylation of N-
Me aniline proceeded smoothly giving the desired product in 89%
yield. Similarly, when using phenyl boronic acid or NaOH as the
catalyst, much lower reactivity was observed (Figure 6C).
7
8
9
D. Mukherjee, H. Osseili, T. P. Spaniol and J. Okuda, J. Am. Chem. Soc.,
2016, 138, 10790-10793 and the literatures cited in.
C. D. N. Gomes, O. Jacquet, C. Villiers, P. Thuéry, M. Ephritikhine and
T. Cantat, Angew. Chem. Int. Ed., 2012, 51, 187-190.
L. Zhang, Z. Han, X. Zhao, Z. Wang and K. Ding, Angew. Chem. Int. Ed.,
2015, 54, 6186-6189.
10 T. V. Nguyen, W. J. Yoo and S. Kobayashi, Angew. Chem. Int. Ed., 2015,
54, 9209-9212.
11 X. Frogneux, O. Jacquet and T. Cantat, Catal. Sci. Technol., 2014, 4,
1529-1533.
12 H. Liu, Q. Mei, Q. Xu, J. Song, H. Liu and B. Han, Green Chem., 2017,
19, 196-201.
13 (a) J. P. Guthrie, Chem. Biol., 1996, 3, 163-170; (b) A. G. Doyle and E.
N. Jacobsen, Chem. Rev., 2007, 107, 5713-5743; (c) H. Konishi, T. Y.
Lam, J. P. Malerich and S. P. Nolan, Org. Lett., 2010, 12, 2028-2031.
14 (a) F. Niu, L. Zhang, S.-Z. Luo and W.-G. Song, Chem. Commun., 2010,
46, 1109-1111; (b) P. Nagorny and Z. Sun, Beilstein J. Org. Chem., 2016,
12, 2834-2848.
15 (a) S. Li, G. Li, W. Meng and H. Du, J. Am. Chem. Soc., 2016, 138, 12956-
12962; (b) W. Wang, H. Zhu, S. Liu, Z. Zhao, L. Zhang, J. Hao and Y.
Wang, J. Am. Chem. Soc., 2019, 141, 9175-9179.
16 (16) X.-F. Liu, X.-Y. Li, C. Qiao, H.-C. Fu and L.-N. He, Angew. Chem. Int.
Ed., 2017, 56, 7425-7429 and the literatures cited in.
17 X. Ren and H. Du, J. Am. Chem. Soc., 2016, 138, 810-813.
18 D. W. Stephan, J. Am. Chem. Soc., 2015, 137, 10018-10032.
19 S. Scheiner, Noncovalent Forces, Springer, 2015.
20 A. Barrozo, F. Duarte, P. Bauer, A. T. P. Carvalho and S. C. L. Kamerlin,
J. Am. Chem. Soc., 2015, 137, 9061-9076.
Conclusions
This work developed a general methodology of a transition
metal-free pathway based on alkali metal arylborate
electrostatic catalysts for hydroborylation, hydrosilylation, and
reductive
formylation/methylation
of
CO2.
Sodium
trihydroxyphenylborate was found to be superior catalyst in the
activation of main group element-hydrogen bond. This method
of N-formylation is broad in scope applicable to both aromatic
and aliphatic amine substrates (total 106 examples), especially
the unexplored pyridyl amine substrates. Notably, this is the
first example of using hydroxyborate for catalytic reductions of
carbon dioxide for N-formylation/methylation reactions.
Experimental data and DFT calculations show the action of
catalysts is presumably through the dual activation of Si and H
atoms in hydrosilane as proposed in the mechanism.
21 A. Warshel, P. K. Sharma, M. Kato, Y. Xiang, H. Liu and M. H. M. Olsson,
Chem. Rev., 2006, 106, 3210-3235.
22 D. Wu, R. Wang, Y. Li, R. Ganguly, H. Hirao and R. Kinjo, Chem, 2017,
3, 134-151.
23 T. M. E. Dine, D. Evans, J. Rouden and J. Blanchet, Chem. Eur. J., 2016,
22, 5894-5898
24 O. Jacquet, C. D. N. Gomes, M. Ephritikhine and T. Cantat, J. Am. Chem.
Soc., 2012, 134, 2934-2937.
25 L. Hao, Y. Zhao, B. Yu, Z. Yang, H. Zhang, B. Han, X. Gao and Z. Liu, ACS
Catal., 2015, 5, 4989-4993.
26 H. Lv, Q. Xing, C. Yue, Z. Lei and F. Li, Chem. Commun., 2016, 52, 6545-
6548.
27 (a) W.-D. Li, D.-Y. Zhu, G. Li, J. Chen and J.-B. Xia, Adv. Syn. Catal., 2019,
361, 5098-5104; (b) B. Dong, L. Wang, S. Zhao, R. Ge, X. Song, Y. Wang
and Y. Gao, Chem. Commun., 2016, 52, 7082-7085.
28 Z. Huang, X. Jiang, S. Zhou, P. Yang, C.-X. Du and Y. Li, ChemSusChem,
2019, 12, 3054-3059.
Experimental
General procedure for reductive formylation of amines with
CO2: To a 4 mL sealing tube in a nitrogen-filled glovebox, the
substrate (0.2 mmol), 3j and phenylsilane were added followed
by addition of solvent diglyme (1 mL). Then the tube was sealed,
taken out of the glovebox and placed into the autoclave. The
autoclave was sealed and purged three times with CO2 gas, then
pressurized to 2.5 atm. At last, the autoclave was heated at 60
- 100 °C for 12 h with stirring. After the reaction finished, the
autoclave was cooled to room temperature and the pressure
was carefully released. The yield was determined by GC analysis
or the product was purified by silica gel giving the isolated yield.
29 H. Wang, Y. Dong, C. Zheng, C. A. Sandoval, M. Makha, Y. Li, Chem,
2018, 4, 2883-2893.
30 Y. Li, X. Fang and K. Junge, M. Beller, Angew. Chem. Int. Ed., 2013, 52,
9568-9571.
31 Y. Li, L-Q. Lu, S. Das, S. Pisiewicz, K. Junge and M. Beller, J. Am. Chem.
Soc., 2012, 134, 18325-18329.
Conflicts of interest
There are no conflicts to declare.
32 Y. Li, S. Das, S. Zhou, K. Junge and M. Beller, J. Am. Chem. Soc., 2012,
134, 9727-9732.
Acknowledgements
The authors acknowledge financial support of this work by the
NSFC (21633013, 91745104) and the NSF of Jiangsu Province
(BK20180248).
33 Y. Li, J. A. M. de La Torre, K. Grabow, U. Bentrup, K. Junge, S. Zhou, A.
Brückner and M. Beller, Angew. Chem. Int. Ed., 2013, 52, 11577-11580.
34 K. Revunova and G. I. Nikonov, Dalton Trans., 2015, 44, 840-866.
35 A. V. Rayer, P. D. Mobley, M. Soukri, T. R. Gohndrone, J. Tanthana, J.
Zhou and M. Lail, Chem. Eng. J., 2018, 348, 514-525.
This journal is © The Royal Society of Chemistry 20xx
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36 W. Wang, H. Zhu, S. Liu, Z. Zhao, L. Zhang, J. Hao and Y. Wang, J. Am.
Chem. Soc., 2019, 141, 9175-9179.
View Article Online
DOI: 10.1039/D0GC01741H
37 M. Paladino, M. Boghi and D. G. Hall, Eur. J. Org. Chem. 2019, 2019,
6566-6570.
38 (a) A. Modak, J. Mondal, M. Sasidharan and A. Bhaumik, Green Chem.,
2011, 13, 1317-1331. (b) M. Odachowski, A. Bonet, S. Essafi, P. Conti-
Ramsden, J. N. Harvey, D. Leonori and V. K. Aggarwal, J. Am. Chem.
Soc., 2016, 138, 9521-9532.
39 Sodium arylborates could also be conveniently prepared in situ by the
reaction of boroxines with NaOH in aqueous solution, see the related
important progress: K. Aelvoet, A. S. Batsanov, A. J. Blatch, C.
Grosjean, L. G. F. Patrick, C. A. Smethurst and A. Whiting, Angew.
Chem. Int. Ed., 2008, 47, 768-770.
40 J. D. White, M. A. Avery, S. C. Choudhry, O. Prakash Dhingra, B. D. Gray,
M. Kang, S. Kuo and A. J. Whittle, J. Am. Chem. Soc., 1989, 111, 790-
792.
41 C.-C. Chang, B.-S. Liao and S.-T. Liu, Synlett, 2007, 283-287.
42 M. Uyanik, D. Nakashima and K. Ishihara, Angew. Chem. Int. Ed., 2012,
51, 9093-9096.
43 K. Yang, F. Zhang, T. Fang, G. Zhang and Q. Song, Angew. Chem. Int.
Ed., 2019, 58, 13421-13426.
44 Z. He, Y. Hu, C. Xia and C. Liu, Org. Biomol. Chem., 2019, 17, 6099-
6113.
45 C. L. Fields, Termochim. Acta., 1974, 8, 239-248.
46 A. N. Cammidge, V. H. M. Goddard, H. Gopee, N. L. Harrison, D. L.
Hughes, C. J. Schubert, B. M. Sutton, G. L. Watts and A. J. Whitehead,
Org. Lett., 2006, 8, 4071-4074.
47 H. Lv, W. Wang and F. Li, Chem. Eur. J., 2018, 24, 16588-16594.
48 (a) D. Comins and A. I. Meyers, Synthesis, 1978, 403-404; (b) C. W. Jr.
Holyoke, PCT Appl. No. 2018208595 (2018).
49 C. J. Gerack and L. McElwee-White, Molecules, 2014, 19, 7689-7713.
8 | J. Name., 2012, 00, 1-3
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