Selective formylation and methylation of amines using carbon dioxide and hydrosilane catalyzed by alkali-Metal carbonates

Article abstract of DOI:10.1021/acscatal.6b01856

The formylation and methylation of amines with carbon dioxide and hydrosilanes are emerging yet important types of transformations for CO₂. Catalytic methods effective for both reactions with wide substrate scopes are rare because of the difficulty in controlling the selectivity. Herein, we report that simple and readily available inorganic bases alkali-metal carbonates, especially cesium carbonatecatalyze both the formylation and methylation reactions efficiently under mild conditions. The selectivity can be conveniently controlled by varying the reaction temperature and silane. A “cesium effect” on both reactions was observed by comparing the catalytic activity of various alkali-metal carbonates. Combined experimental and computational studies suggested the following reaction mechanism: (i) activation of Si?H by Cs₂CO₃, (ii) insertion of CO₂ into Si?H, (iii) formylation of amines by silyl formate, and (iv) reduction of formamides to methylamines.

Full text of DOI:10.1021/acscatal.6b01856

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Article
Selective Formylation and Methylation of Amines Using Carbon
Dioxide and Hydrosilane Catalyzed by Alkaline Metal Carbonates
Chi Fang, Chunlei Lu, Muhua Liu, Yiling Zhu, Yao Fu, and Bo-Lin Lin
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01856 • Publication Date (Web): 13 Oct 2016
Downloaded from http://pubs.acs.org on October 13, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
Selective Formylation and Methylation of Amines
Using Carbon Dioxide and Hydrosilane Catalyzed
by Alkaline Metal Carbonates
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Chi Fang,†,‡,§ Chunlei Lu,‡,ǁ,§ Muhua Liu,‡,ǁ Yiling Zhu,‡ Yao Fu,*,† and BoꢀLin Lin*,‡,ǁ
† Department of Chemistry, University of Science and Technology of China, Hefei 230026,
China
‡ School of Physical Science and Technology (SPST), ShanghaiTech University, Shanghai
201210, China
ǁ Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032,
China
ABSTRACT: The formylation and methylation of amines with carbon dioxide and hydrosilanes
are emerging yet important types of transformations for CO2. Catalytic methods effective for
both reactions with wide substrate scopes are rare because of the difficulty in controlling the
selectivity. Herein, we report that simple and readily available inorganic bases—alkaline metal
carbonates, especially cesium carbonate—catalyze both the formylation and methylation
reactions efficiently under mild conditions. The selectivity can be conveniently controlled by
1
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 21
1
2
3
4
5
6
7
8
9
varying the reaction temperature and silane. A “cesium effect” on both reactions was observed
by comparing the catalytic activity of various alkaline metal carbonates. Combined experimental
and computational studies suggested the following reaction mechanism: (i) an activation of Si‒H
by Cs2CO3, (ii) insertion of CO2 into Si‒H, (iii) formylation of amines by silyl formate, and (iv)
reduction of formamides to methylamines.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
KEYWORDS: CO2, hydrosilanes, amines, Cs2CO3, formylation, methylation
Introduction
Recent years have witnessed great advances in the activation of CO2 as a renewable, lowꢀ
cost C1 feedstock in the synthesis of valueꢀadded chemicals.1 However, to overcome the
thermodynamic and/or kinetic barriers in the activation, reductive transformations of CO2, e.g.,
hydrogenation of CO2,2,3 usually require relatively forceful conditions, such as high temperatures
and high pressures as well as stoichiometric amounts of basic additives.
Growing research attention has been devoted to the development of new catalytic
methodologies for the conversion of CO2 using hydrosilanes as the reductants. Compared with
dihydrogen, many hydrosilanes are more convenient to use in laboratory syntheses partially due
to safety reasons and their hydrogen‒silicon bonds are weaker and more polar than the hydrogenꢀ
hydrogen bond, which allows for milder reaction conditions.4 Furthermore, the formation of
strong Si‒O bonds in the products provides an extra thermodynamic driving force.5
Although many catalysts leading to the formation of various products, such as formate,
methanol, and methane, have been developed,3 few have been shown to catalyze efficiently the
2
ACS Paragon Plus Environment

Page 3 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
formylation and methylation of amines with CO2 and hydrosilanes. The latter two
transformations, featuring the formation of a new carbon‒nitrogen bond, have expanded the
scope of valueꢀadded products from CO2. The products, formamides and methylamines, are
important intermediates widely used in the domains of medicines, agrochemicals and dyes.6 In
particular, Nꢀmethylation of amines has been shown to increase significantly the cytotoxicity of
drug molecules.7
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Known catalysts that can catalyze both the formylation and methylation of amines
using CO2 and hydrosilanes. 15,17
Cantat and coꢀworkers8 described initially an organocatalyst that mediated the formylation
of amines with CO2 and hydrosilanes (FACH) in 2012. Subsequently, in 2013, Cantat et al.9a and
Beller et al.9b reported Znꢀbased and Ruꢀbased catalysts, respectively, for the methylation of
amines with CO2 and hydrosilanes (MACH). Since then, several organic bases10‒15 and transition
metal complexes16‒22 have emerged as effective catalysts for either the formylation or
methylation of various amines.23‒25 To date, however, only two examples have been shown to
catalyze both FACH and MACH, with limited substrate scopes for the latter, presumably
because of the difficulty in obtaining selective MACH in the presence of FACH in the same
3
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 21
1
2
system (Scheme 1).17 Identifying catalytic systems with distinctive selective conditions for the
3
4
5
6
two reactions appears to be a key challenge.
7
8
9
Herein, we report a new methodology using simple and readily available inorganic bases—
especially cesium carbonate—as efficient catalysts for the construction of C‒N bonds from CO2
and amines under mild conditions. Interestingly, remarkable selectivities for both FACH and
MACH have been achieved.26‒28 The substrate scope covers more than 20 different nitrogenous
substrates for both reactions with yields up to 99%. A remarkable “cesium effect” unprecedented
for the reduction of CO2 by hydrosilane was observed. Combined experimental and
computational studies provided insights into the reaction mechanisms. Notably, a related
“cesium effect” was also reported very recently in a carbonateꢀpromoted C‒H carboxylation
using CO2 under moltenꢀsalt conditions.29 Combined experimental and computational studies
provided insights into the reaction mechanisms.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Results and Discussion
We reasoned that effective catalysts for the hydrosilylation of aldehydes, ketones, or amides
are promising candidates to catalyze FACH because they all share the same key step—the
activation of a carbon‒oxygen double bond. Because Cui and coꢀworkers30 have shown that
cesium carbonate can effectively catalyze the hydrosilylation of aldehydes, ketones, and amides,
it appears reasonable to postulate that inorganic carbonates may also catalyze FACH. The initial
conditions were explored using Nꢀmethylaniline (1a) as the substrate and 1 equiv of PhSiH3
(relative to 1a) as the reductant. The reactions were performed with 5 mol % Cs2CO3 under 1 bar
of CO2 at RT for 12 h. As shown in Table 1 (Entries 1‒8), the best yield for Nꢀformanilide (2a,
94% GC yield; 90% isolated yield) was obtained when using acetonitrile as the solvent. In
4
ACS Paragon Plus Environment

Page 5 of 21
ACS Catalysis
1
2
contrast to the hydrosilylation of aldehydes, ketones, and amides,30a no reaction was detected
under the solventꢀfree condition. When we decreased the amount of PhSiH3 to 0.33 equiv (1
equiv of Si‒H corresponding to 1a), the yield of Nꢀformanilide reduced to 30% (Entry 9, Table
1). Notably, yields greater than 90% can still be obtained even after decreasing the catalyst
loading to 2.5 mol % or 1 mol % (Entries 10, 11, Table 1), although a further reduction of the
loading to 0.5 mol % gave a significantly lower yield (80%) (Entry 12, Table 1). The
performance of various hydrosilanes was probed next. The use of Ph2SiH2 as the reductant led to
a 24% yield of 2a (Entry 13, Table 1), while no reaction was observed when using 1,1,4,4ꢀ
tetramethyldisiloxane (TMDS), polymethylhydrosiloxane (PMHS), or triethylsilane (Et3SiH)
(Entries 14‒16, Table 1). Thus, PhSiH3 appeared to be the best reductant for the current reaction
and was used in further investigations.
3
4
5
6
7
8
9
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of reaction conditions for the Nꢀformylation of Nꢀmethylaniline using
CO2.a
H
N
O
N
Cs2CO3
+
hydrosilane
+
CO2
solvent, RT
12 h
1a
2a
Catalyst loading
Entry
Silane
Solvent
(%)
Yield (%)b
1
2
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
‒
5
5
<1
94(90)c
<1
CH3CN
CH2Cl2
EtOAc
1,4ꢀdioxane
THF
3
5
4
5
<1
5
5
<1
6
5
<1
7
DMEd
5
48
8
toluene
CH3CN
CH3CN
CH3CN
5
<1
e
9
5
30
10
11
2.5
1
91
90
5
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 21
1
2
3
4
5
6
7
8
9
12
13
14
15
16
PhSiH3
Ph2SiH2
TMDS
PMHS
Et3SiH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
0.5
5
80
24
<1
<1
<1
5
5
5
a Reaction conditions: 1a (0.5 mmol), hydrosilane (0.5 mmol or 3 equiv Si–H), Cs2CO3 (0.5‒5.0
mol %), solvent (1 mL), CO2 (1 bar), 12 h, RT. Yield was determined by H NMR
spectroscopy using ferrocene as the internal standard. c Isolated yield in the parentheses. d DME=
dimethoxyethane. e 0.17 mmol.
b
1
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The scope of amines was subsequently studied with 1 equiv PhSiH3 and 1 mol % of Cs2CO3
in acetonitrile under 1 bar of CO2 at RT for 12 h (Table 2). Most secondary amines were
successfully formylated with good to excellent yields (2a‒2n). Tolyl, aryl chloride, aryl bromide,
allyl, and cyano groups (2g‒2n) were well tolerated in the reaction, while only a moderate yield
was obtained with the sterically hindered diisopropylamine (2f). In addition to the secondary
amines, primary amines can also be selectively transformed to the monoformylated products
(2o‒2u). Both tertꢀbutylamine and aniline gave excellent yields (2o, 2p). A strong remote
substituent effect was observed for aniline and its derivatives. Compounds with electronꢀ
donating groups on the paraꢀposition showed much higher reactivity than those with electronꢀ
withdrawing groups (2q‒2t). It is noteworthy that Nꢀbenzylmethanediamine was selectively
converted to Nꢀ((benzylamino)methyl)formamide in good yield presumably owing to the
stronger basicity and smaller steric hindrance of the terminal alkylamine group (2u). Modest
formylating yields for phenylhydrazine compounds were observed (2v‒2x), indicating that the
present method is also applicable to nonamine nitrogenous compounds.
Table 2. Substrate scope for the Nꢀformylation of various amines with CO2.a
R1
R2
R1
or
HN
H
O
O
Cs2CO3 1 mol%
or R1NH +
N
R1
R2
CO2
2
N
PhSiH3, CH3CN, RT
1aꢀx
2aꢀx
6
ACS Paragon Plus Environment

Page 7 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a
Reaction conditions: substrate (0.5 mmol), PhSiH3 (1 equiv), Cs2CO3 (1 mol %), CO2 (1 bar),
b
1
CH3CN (1.0 mL), RT, 12 h; Isolated yields are shown. Yields were determined by H NMR
spectroscopy of the crude reaction mixture using ferrocene as the internal standard.
A remarkable size effect on the activity was observed after comparing the catalytic activity
of various alkaline metal carbonates for the FACH reaction of 1a and phenylsilane. For the
smallꢀsized alkaline metals—Li2CO3 or Na2CO3—no reaction was observed. As the size of the
cation increased, a modest yield of 2a was obtained for K2CO3, while Rb2CO3 further enhanced
the yield and Cs2CO3 gave the highest yield (Table 3). Such an activity trend is reminiscent of
the classical “cesium effect”31 and may be attributed to the increased solubility and/or
nucleophilicity of the carbonates due to the aggravating mismatch between the hard oxygen base
and the softening acid as the cation changes from Li+ to Cs+. To probe these two factors, 15ꢀ
Crownꢀ5 ether was added to the Na2CO3ꢀbased system and surprisingly, the yield of 2a was
increased to 21% (Entry 6, Table 3), suggesting that the solubility of the carbonates be an
important factor. In the carbonateꢀpromoted CꢀH carboxylation using CO2 under moltenꢀsalt
conditions,29 the higher reactivity of Cs2CO3 compared with K2CO3 was attributed to the lower
melting point of the cesium salt mixture during the reaction.
7
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 21
1
2
3
4
5
Table 3. The Nꢀformylation of Nꢀmethylaniline using CO2 catalyzed by various alkaline metal
carbonates.a
6
7
8
9
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Entry
Catalyst
Li2CO3
Yield of 2a (%)b
1
2
3
4
5
6
<1
<1
65
81
94
21
Na2CO3
K2CO3
Rb2CO3
Cs2CO3
Na2CO3/ 15ꢀCrownꢀ5 etherc
a Reaction conditions: 1a (0.5 mmol), PhSiH3 (0.5 mmol), catalyst (5.0 mol %), CH3CN (1 mL),
CO2 (1 bar), 12 h, RT. b Yields were determined by 1H NMR spectroscopy of the crude reaction
mixture using ferrocene as the internal standard. c 15ꢀCrownꢀ5 ether (10 mol %).
Further reduction of formamides to form methylamines was observed upon elevating the
reaction temperature. Using 5 mol % Cs2CO3 as the catalyst, the initial MACH reaction was
studied with 1a as the substrate and 2 equiv PhSiH3 as the reductant in acetonitrile.
Encouragingly, a 71% yield of Nꢀdimethylaniline (3a) was obtained after 24 h at 80 oC (Entry 1,
Table 4). Notably, a limited amount of CO2 (4 equiv) was used in the present MACH instead of
large excess amounts, i.e. constant pressures of CO2, used in previous examples.9,11,14,15,17,22
Other hydrosilanes were then screened (Entries 2ꢀ9, Table 4). Given the same number of Si‒H
bonds relative to 1a (6 equiv), Ph2SiH2 exhibited the highest yield of 3a (92%). In contrast, other
silanes, such as Ph3SiH and (EtO)3SiH, led to poor or no yields of 3a. As such, Ph2SiH2 was used
for further studies. The effects of temperature and stoichiometry of the starting materials were
o
examined next. The yield of 3a increased from 76% to 92% as the temperature rose from 50 C
o
o
to 80 C, while no further improvement of the yield was observed at 95 C (Entries 2, 10‒12,
Table 4). In additon, decreasing the equivalents of CO2 (Entries 2, 13, 14, Table 4) or Ph2SiH2
8
ACS Paragon Plus Environment

Page 9 of 21
ACS Catalysis
1
2
3
4
5
6
(Entries 2, 15ꢀ16, Table 4) lowered the yields of 3a significantly. A “cesium effect” similar to
that observed in the FACH (supra infra) was also observed in the MACH (Table S1).
7
8
9
Table 4. Optimization of reaction conditions for the Nꢀmethylation of Nꢀmethylaniline using
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CO2. a
Temp
(oC)
Equiv
(CO2)
Equiv
(silane)
Yieldb
(%)
Entry
Silane
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
80
80
80
80
80
80
80
80
80
50
65
95
80
80
80
80
80
PhSiH3
Ph2SiH2
Ph3SiH
Et3SiH
PMHS
4
4
4
4
4
4
4
4
4
4
4
4
1
2
4
4
4
2
3
6
6
2
6
3
6
6
3
3
3
3
3
2.5
2
71
92
<1
<1
7
8
1
2
1
76
86
90
20
60
76
57
25
Me(EtO)2SiH
(Me2SiH)2O
(EtO)3SiH
Me(Me3SiO)2SiH
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
1.5
a
Reaction conditions: 1a (0.5 mmol), hydrosilane (6 equiv Si‒H), Cs2CO3 (5 mol %), CH3CN
(1.6 mL). b Yield was determined by GC using anisole as the internal standard.
Most of secondary monoaromatic amines can be successfully methylated and the
corresponding methylated products were obtained with excellent yields (3a‒3l, Table 5), while
only a poor yield was observed for diphenylamine (3m, Table 5). In contrast to secondary
monoaromatic amines, dimethylation was observed for primary aromatic amines with much
lower reactivity (3n‒3r, Table 5) presumably due to the lower basicity. Such low reactivity is
consistent with the lack of their monomethylation products, likely intermediates that are more
basic and thus consumed faster than the starting materials. Interestingly, selective
9
ACS Paragon Plus Environment

ACS Catalysis
Page 10 of 21
1
2
3
4
5
6
7
8
9
monomethylation can be achieved with excellent yields for primary substrates with strong
basicity and large steric hindrance (3s, 3t, Table 5). To examine the potential application of the
present methodology, we next evaluated the Nꢀmethylation of a drug molecule—Cinacalcet. An
excellent isolated yield (92%) was obtained for the reaction (Scheme 2).
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The methylation may occur via three possible pathways (Scheme 3). A) An acidꢀbase
reaction between CO2 and an amine forms a carbamate salt, followed by a dehydration to
generate a urea. Reduction of the urea then leads to the methylation product.32 B) FACH occurs
first to generate a formamide, followed by deoxygenative reduction to produce the corresponding
methylamine. C) CO2 may initially be hydrosilylated to generate a methoxide intermediate. The
resultant methyl group might be attacked nucleophilically by an amine to furnish the
methylamine.
Table 5. Substrate scope for Nꢀmethylation of various amines with CO2.a
10
ACS Paragon Plus Environment

Page 11 of 21
ACS Catalysis
1
2
a
3
4
5
6
7
8
Reaction conditions: substrate (0.25‒0.5 mmol), Ph2SiH2 (3.0‒6.0 equiv), Cs2CO3 (5‒10
mol %), CO2 (4 equiv), CH3CN (1.6 mL), 80 C, 24ꢀ72 h; Yield was determined by 1H NMR
spectroscopy of the crude reaction mixture using ferrocene as the internal standard. Isolated
yields in parentheses.
o
9
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. The Nꢀmethylation of Cinacalcet using CO2.
Because virtually no reaction was observed for N,N'ꢀdiphenylꢀN,N'ꢀdimethylurea under the
optimized conditions of MACH (Scheme S1), path A was ruled out. Path B was supported by the
further reduction of 2a to 3a (Scheme S2, Figs S1‒S3) upon heating the product mixture of the
formylation reaction of 1a with an exogenous amount of silane. Although a significant amount of
silyl methoxides was formed in Cs2CO3ꢀcatalyzed hydrosilylation of CO2 in the absence of
amine, subsequent addition of amine did not convert the methoxide to the methylation product
(Scheme S3, Figs S4‒S7), disfavoring path C. These observations suggest that path B should be
the most likely path for the present MACH reaction.
Recent experimental evidence12,13,18‒20,33‒35 suggested that FACH might involve two steps:
(i) hydrosilylation of CO2 to form silyl formates and (ii) formylation of amines with the formates
to yield formamides (Scheme S4). Consistent with this mechanistic proposal, we found that
Cs2CO3 catalyzed the reaction of PhSiH3 and CO2 to form silyl formates, which yielded 2a upon
addition of 1a (Figs S8‒S12). Step (i) could occur with or without the transfer of hydrogen from
Si‒H to Cs+ (Fig. S13). Our DFT calculations suggested that the formation of a precomplex
between PhSiH3 and Cs2CO3 to activate the Si‒H bond before the insertion of CO2 is a more
favorable pathway (Fig. 1, Fig. S14).36 But since Cs(OCOH), a hypothetical intermediate in the
11
ACS Paragon Plus Environment

ACS Catalysis
Page 12 of 21
1
2
3
4
5
6
7
8
9
catalytic cycle of the CsH pathway (path 3, Fig. S14), was also an active catalyst, albeit with a
relatively lower activity than Cs2CO3 (Scheme S5), the CsH pathway cannot be firmly excluded.
In addition, DFT calculations also indicated that different cations show little influence on the
energy barriers (K2CO3 vs Cs2CO3, Fig. S15), so the influence of the cations on the
nucleophilicity of the oxygen atom can be ruled out as an important factor controlling the
catalytic activity, further supporting that the “cesium effect” may result from the increased
solubility of its carbonate salt. Interestingly, the calculated energy barrier drops 2.5 kcal/mol
when the solvent is changed to THF (Fig. S15), which ostensibly contradicts to the experimental
observation that MeCN is a better solvent. This again indicates that the solubility factor
dominates when it comes to the activity of cesium salts.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Potential pathways for the methylation of amines with CO2 and silane catalyzed by
Cs2CO3.
12
ACS Paragon Plus Environment

Page 13 of 21
ACS Catalysis
1
2
3
4
5
6
21.3
TS-1
12.0
Si-1+CO2
7
8
9
Si-3+Cs2CO3
0.0
Cs2CO3+PhSiH3+CO2
Si-2
-4.8
-3.3
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. The reaction freeꢀenergy profile (in kcal/mol) for the computationally favorable
pathway forming silyl formate and the optimized structures of the silyl species along with key
bond lengths (in Å).
Conclusion
Collectively, we have found that cesium carbonate, albeit simple, is a remarkably efficient
catalyst for the formylation/methylation of amines with CO2 and silane to produce
formamides/methylamines under mild conditions. Upon changing the reaction temperature and
the relative amount of silanes, the formylation/methylation selectivity can be controlled
conveniently. The excellent yield for the methylation of a drug molecule, Cinacalcet, using the
present methodology demonstrates its potential application in syntheses of complex molecules.
An interesting “cesium effect” on the catalytic activity of alkaline metal carbonates was observed
for both formylation and methylation. Further explorations of such an effect on related reductive
transformations of CO2 is ongoing.
ASSOCIATED CONTENT
Supporting Information. Experimental details, spectra, and computational data. This material is
available free of charge via the Internet at http://pubs.acs.org.
13
ACS Paragon Plus Environment

ACS Catalysis
Page 14 of 21
1
2
3
4
AUTHOR INFORMATION
5
6
7
Corresponding Author
8
9
*Email: linbl@shanghaitech.edu.cn
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
fuyao@ustc.edu.cn
Author Contributions
§C.F. and C.L. (coꢀfirst author) contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The financial support by National Science Foundation of China (NSFC U1532125).
REFERENCES
(1) (a) New And Future Developments In Catalysis; Suib, S. L., Ed.; Elsevier: Oxford, 2013;
Vol. 4. (b) Sakakura, T.; Choi, J. C.; Yasuda, H. Chem. Rev. 2007, 107, 2365ꢀ2387. (c)
D’Alessandro, D. M.; Smit, B.; Long, J. R. Angew. Chem., Int. Ed. 2010, 49, 6058ꢀ6082. (d)
Riduan, S. N.; Zhang, Y. Dalton trans. 2010, 39, 3347ꢀ3357. (e) Cokoja, M.; Bruckmeier, C.;
Rieger, B.; Herrmann, W. A.; Kuhn, F. E. Angew. Chem., Int. Ed. 2011, 50, 8510ꢀ8537. (f)
Huang, K.; Sun, C. L.; Shi, Z. J. Chem. Soc. Rev. 2011, 40, 2435ꢀ2452. (g) Appel, A. M.;
Bercaw, J. E.; Bocarsly, A. B.; Dobbek, H.; DuBois, D. L.; Dupuis, M.; Ferry, J. G.; Fujita, E.;
Hille, R.; Kenis, P. J.; Kerfeld, C. A.; Morris, R. H.; Peden, C. H.; Portis, A. R.; Ragsdale, S. W.;
(2) Rauchfuss, T. B.; Reek, J. N.; Seefeldt, L. C.; Thauer, R. K.; Waldrop, G. L. Chem. Rev.
2013, 113, 6621ꢀ6658. (h) Aresta, M.; Dibenedetto, A.; Angelini, A. Chem. Rev. 2014, 114,
14
ACS Paragon Plus Environment

Page 15 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
1709ꢀ1742. (i) Yeung, C. S.; Dong, V. M. Top. Catal. 2014, 57, 1342ꢀ1350. (j) Maeda, C.;
Miyazaki, Y.; Ema, T. Catal. Sci. Technol. 2014, 4, 1482ꢀ1497. (k) Liu, Q.; Wu, L.; Jackstell, R.;
Beller, M. Nat. Commun. 2015, 6, 5933ꢀ5948.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3) Selected recent examples and references for hydrogenation of CO2: (a) Huff, C. A.;
Sanford, M. S. J. Am. Chem. Soc. 2011, 133, 18122ꢀ18125. (b) Grabow, L. C.; Mavrikakis, M.
ACS Catal. 2011, 1, 365ꢀ384. (c) Wesselbaum, S.; Stein, T. V.; Klankermayer, J.; Leitner, W.
Angew. Chem., Int. Ed. 2012, 51, 7499ꢀ7502. (d) Ziebart, C.; Federsel, C.; Anbarasan, P.;
Jackstell, R.; Baumann, W.; Spannenberg, A.; Beller, M. J. Am. Chem. Soc. 2012, 134, 20701ꢀ
20704. (e) Moret, S.; Dyson, P. J.; Laurenczy, G. Nat. Commun. 2014, 5, 4017ꢀ4024. (f) Yadav,
M.; Linehan, J. C.; Karkamkar, A. J.; van der Eide, E.; Heldebrant, D. J. Inorg. Chem. 2014, 53,
9849ꢀ9854. (g) Rezayee, N. M.; Huff, C. A.; Sanford, M. S. J. Am. Chem. Soc. 2015, 137, 1028ꢀ
1031. (h) Wesselbaum, S.; Moha, V.; Meuresch, M.; Brosinski, S.; Thenert, K. M.; Kothe, J.;
Stein, T.; Englert, U.; Hölscher, M.; Klankermayer, J.; Leitner, W. Chem. Sci. 2015, 6, 693ꢀ704.
(4) Selected examples and references for hydrosilylation of CO2: (a) Koinuma, H.;
Kawakami, F.; Kato, H.; Hirai, H. J. C. S. Chem. Comm. 1981, 231ꢀ214. (b) Eisenschmid, T. C.;
Elsenberg, R. Oganometallics 1989, 8, 1822ꢀ1824. (c) Matsuo, T.; Kawaguchi, H. J. Am. Chem.
Soc. 2006, 128, 12362ꢀ12363. (d) Deglmann, P.; Ember, E.; Hofmann, P.; Pitter, S.; Walter, O.;
Chem. Eur. J. 2007, 13, 2864ꢀ2879. (e) Berkefeld, A.; Piers, W. E.; Parvez, M. J. Am. Chem. Soc.
2010, 132, 10660ꢀ10661. (f) Lalrempuia, R.; Iglesias, M.; Polo, V.; Sanz Miguel, P. J.;
FernándezꢀAlvarez, F. J.; PérezꢀTorrente, J. J.; Oro, L. A. Angew. Chem., Int. Ed. 2012, 51,
12824ꢀ12827. (g) Park, S.; Bézier, D.; Brookhart, M. J. Am. Chem. Soc. 2012, 134, 11404ꢀ11407.
(h) Schäfer, A.; Saak, W.; Haase, D.; Müller, T. Angew. Chem., Int. Ed. 2012, 51, 2981ꢀ2984. (i)
Khandelwal, M.; Wehmschulte, R. J. Angew. Chem., Int. Ed. 2012, 51, 7323ꢀ7326. (j) Motokura,
15
ACS Paragon Plus Environment

ACS Catalysis
Page 16 of 21
1
2
3
4
5
6
7
8
9
K.; Kashiwame, D.; Miyaji, A.; Baba, T. Org. Lett. 2012, 14, 2642ꢀ2645. (k) Zhang, L.; Hou, Z.
Chem. Sci. 2013, 4, 3395ꢀ3403. (l) Zhang, L.; Cheng, J.; Hou, Z. Chem. Commun. 2013, 49,
4782ꢀ4784. (m) Motokura, K.; Kashiwame, D.; Takahashi, N.; Miyaji, A.; Baba, T. Chem. Eur. J.
2013, 19, 10030ꢀ10037. (n) Berkefeld, A.; Piers, W. E.; Parvez, M.; Castro, L.; Maron, L.;
Eisenstein, O. Chem. Sci. 2013, 4, 2152ꢀ2162. (o) LeBlanc, F. A.; Piers, W. E.; Parvez, M.
Angew. Chem., Int. Ed. 2014, 53, 789ꢀ792. (p) Scheuermann, M. L.; Semproni, S. P.; Pappas, I.;
Chirik, P. J. Inorg. Chem. 2014, 53, 9463ꢀ9465. (q) Courtemanche, M. A.; Legare, M. A.;
Rochette, E.; Fontaine, F. G. Chem. Commun. 2015, 51, 6858ꢀ6861. (r) Tani, Y.; Kuga, K.;
Fujihara, T.; Terao, J.; Tsuji, Y. Chem. Commun. 2015, 51, 13020ꢀ13023. (s) Jaseer, E. A.;
Akhtar, M. N.; Osman, M.; AlꢀShammari, A.; Oladipo, H. B.; Garcés, K.; FernándezꢀAlvarez, F.
J.; AlꢀKhattaf, S.; Oro, L. A. Catal. Sci. Technol. 2015, 5, 274ꢀ279. (t) Chakraborty, S.;ꢀAcc.
Chem. Res. 2015, 48, 306ꢀ316.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4) (a) Tlili, A.; Blondiaux, E.; Frogneux, X.; Cantat, T. Green Chem. 2015, 17, 157ꢀ168. (b)
Liu, M.; Qin, T.; Zhang, Q.; Fang, C.; Fu, Y.; Lin, B.ꢀL. Sci. China Chem. 2015, 58, 1524ꢀ1531.
(5) FernándezꢀAlvarez, F. J.; Aitani, A. M.; Oro, L. A. Catal. Sci. Technol. 2014, 4, 611ꢀ624.
(6) (a) Grant, H. G.; Summers, L. A. Aust. J. Chem. 1980, 33, 613ꢀ617. (b) Kobayashi, K.;
Nagato, S.; Kawakita, M.; Morikawa, O.; Konishi, H. Chem. Lett. 1995, 24, 575ꢀ576. (c) Chen,
B. C.; Bednarz, M. S.; Zhao, R.; Sundeen, J. E.; Chen, P.; Shen, Z.; Skoumbourdis, A. P.;
Barrish, J. C. Tetrahedron Lett. 2000, 41, 5453ꢀ5456. (d) Ail, M. F.; El Ali, B. M.; Speight, J. G.
In Handbook of Industrial Chemistry ‒ Organic Chemicals; McGrawꢀHill Education: New York
2005.
(7) Barreiro, E. J.; Kϋmmerle, A. E.; Fraga, C. A. M. Chem. Rev. 2011, 111, 5215ꢀ5246.
16
ACS Paragon Plus Environment

Page 17 of 21
ACS Catalysis
1
2
3
4
5
6
(8) Das Neves Gomes, C.; Jacquet, O.; Villiers, C.; Thuéry, P.; Ephritikhine, M.; Cantat, T.
Angew. Chem., Int. Ed. 2012, 51, 187ꢀ190.
7
8
9
(9) (a) Jacquet, O.; Frogneux, X.; Das Neves Gomes, C.; Cantat, T. Chem. Sci. 2013, 4, 2127ꢀ
2131. (b) Li, Y.; Fang, X.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2013, 52, 9568ꢀ9571.
(10) Jacquet, O.; Das Neves Gomes, C.; Ephritikhi ne, M.; Cantat, T. J. Am. Chem. Soc. 2012,
134, 2934ꢀ2937.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(11) Das, S.; Bobbink, F. D.; Laurenczy, G.; Dyson, P. J. Angew. Chem., Int. Ed. 2014, 53,
12876ꢀ12879.
(12) Chong, C. C.; Kinjo, R. Angew. Chem., Int. Ed. 2015, 54, 12116ꢀ12120.
(13) Hao, L.; Zhao, Y.; Yu, B.; Yang, Z.; Zhang, H.; Han, B.; Gao, X.; Liu, Z. ACS Catal.
2015, 5, 4989ꢀ4993.
(14) Yang, Z.; Yu, B.; Zhang, H.; Zhao, Y.; Ji, G.; Ma, Z.; Gao, X.; Liu, Z. Green Chem. 2015,
17, 4189ꢀ4193.
(15) Das, S.; Bobbink, F. D.; Bulut, S.; Sou dani, M.; Dyson, P. J. Chem. Commun. 2016, 52,
2497ꢀ2500.
(16) Motokura, K.; Takahashi, N.; Kashiwame, D.; Yamaguchi, S.; Miyaji, A.; Baba, T.; Catal.
Sci. Technol. 2013, 3, 2392ꢀ2396.
(17) Frogneux, X.; Jacquet, O.; Cantat, T. Catal. Sci. Technol. 2014, 4, 1529ꢀ1533.
(18) Nguyen, T. V.; Yoo, W. J.; Kobayashi, S. Angew. Chem., Int. Ed. 2015, 54, 9209ꢀ9212.
(19) Itagaki, S.; Yamaguchi, K.; Mizuno, N. J. Mol. Catal. A. 2013, 366, 347ꢀ352.
(20) GonzálezꢀSebastián, L.; FloresꢀAlamo, M.; Garcıa, J. J.; Organometallics 2013, 32, 7186ꢀ
́
7194.
17
ACS Paragon Plus Environment

ACS Catalysis
Page 18 of 21
1
2
3
4
5
6
(21) Motokura, K.; Takahashi, N.; Miyaji, A.; Sakamoto, Y.; Yamaguchi, S.; Baba, T.
Tetrahedron 2014, 70, 6951ꢀ6956.
7
8
9
(22) Santoro, O.; Lazreg, F.; Minenkov, Y.; Cavallo, L.; Cazin, C. S. Dalton Trans. 2015, 44,
18138ꢀ18144.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(23) Selected recent references for the formylation and methylation of amines with CO2 and
H2: (a) Baffert, M.; Maishal, T. K.; Mathey, L.; Copéret, C.; Thieuleux, C. ChemSusChem 2011,
4, 1762ꢀ1765. (b) Bi, Q. Y.; Lin, J. D.; Liu, Y. M.; Xie, S. H.; He, H. Y.; Cao. Y. Chem.
Commun. 2014, 50, 9138ꢀ9140. (c) Cui, X.; Zhang, Y.; Deng, Y.; Shi, F. Chem. Commun. 2014,
50, 189ꢀ191. (d) Zhang, L.; Han, Z.; Zhao, X.; Wang, Z.; Ding, K. Angew. Chem., Int. Ed. 2015,
54, 6186ꢀ6189. (e) Li, Y.; Sorribes, I.; Yan, T.; Junge, K.; Beller, M. Angew. Chem., Int. Ed.
2013, 52, 12156ꢀ12160. (f) Beydoun, K.; Stein, T.; Klankermayer, J.; Leitner, W. Angew. Chem.,
Int. Ed. 2013, 52, 9554ꢀ9557. (g) Cui, X.; Zhang, Y.; Deng Y.; Shi F. Chem. Commun. 2014, 50,
13521ꢀ13524. (h) Cui, X.; Dai, X.; Zhang, Y.; Deng, Y.; Shi, F. Chem. Sci. 2014, 5, 649ꢀ655. (i)
Kon, K.; Siddiki, S. M. A. H.; Onodera, W.; Shimizu, K. Chem. Eur. J. 2014, 20, 6264ꢀ6267.
(24) References for the formylation and methylation of amines with CO2 and borane: (a)
Shintani, R.; Nozaki, K. Organometallics 2013, 32, 2459ꢀ2462. (b) Blondiaux, E.; Pouessel, J.;
Cantat, T. Angew. Chem., Int. Ed. 2014, 53, 12186ꢀ12190. (c) Chen, W. ꢀC.; Shen, J. ꢀS.; Jurca,
T.; Peng, C. ꢀJ.; Lin,Y. ꢀH.; Wang, Y. ꢀP.; Shih, W. ꢀC.; Yap, G. P. A.; Ong, T. ꢀG. Angew.
Chem., Int. Ed. 2015, 54, 15207ꢀ15212.
(25) Selected recent examples for amine methylations using other C1 sources: (a) Fu, M.ꢀC.;
Shang, R.; Cheng, W.ꢀM.; Fu, Y. Angew. Chem., Int. Ed. 2015, 54, 9042ꢀ9046. (b) Atkinson, B.
N.; Williams, J. M. J. ChemCatChem 2014, 6, 1860ꢀ1862.
18
ACS Paragon Plus Environment

Page 19 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
(26) A “catalystꢀfree” methodology for FACH was reported very recently, in which the organic
solvent, DMSO, might act as the actual catalyst. No MACH reactivity was reported for the
DMSO system: Lv, H.; Xing, Q.; Yue, C.; Lei, Z.; Li, F. Chem. Commun. 2016, 52, 6545ꢀ6548.
(27) During the preparation of this manuscript, a related FACH using alkaline metal carbonates
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
was reported. The reaction conditions (30 atm CO2 and 100 C) are much harsher than the
present one (1 atm CO2 and RT). The use of a polar solvent (CH3CN) instead of a nonpolar
solvent (THF) appears to be the key allowing for the distinctive reaction conditions for FACH
and MACH: Bhanage, B.; Nale, D. Synlett 2016, 27, 1413ꢀ1417.
(28) FACH of two amines using CsF as the catalyst was reported by Baba and coworkers:
Motokura, K.; Naijo, M.; Yamaguchi, S.; Miyaji, A.; Baba, T. Chem. Lett. 2015, 44, 1217ꢀ1219.
(29) Banerjee, A.; Dick, G. R.; Yoshino, T.; Kanan, M. W. Nature 2016, 531, 215ꢀ219.
(30) (a) Xie, W.; Zhao, M.; Cui, C. Organometallics 2013, 32, 7440ꢀ7444. (b) Zhao, M.; Xie,
W.; Cui, C.; Chem. Eur. J. 2014, 20, 9259ꢀ9262.
(31) (a) Dijkstra, G.; Kruizinga, W. H.; Kellogg, K. M. J. Org. Chem. 1987, 52, 4230ꢀ4234. (b)
Ostrowicki, A.; Vogtle, F. In Topics In Current Chemistry; Weber, E., Vogtle, F., Eds.; Springerꢀ
Verlag: Heidelberg, 1992; Vol. 161, p 37ꢀ67. (c) Galli, C. Org. Prep. Proced. Int. 1992, 24, 285ꢀ
304. (d) Blum, Z. Acta Chem. Scand. 1989, 43, 248ꢀ250. (e) Salvatore, R. N.; Nagle, A. S.; Jung,
K. W. J. Org. Chem. 2002, 67, 674ꢀ683.
(32) An analogous path was proposed for the methylation of amines using CO2 and hydrogen
given the observation of urea as an intermediate in reference 9b.
(33) Julián, A.; Polo, V.; Jaseer, E. A.; FernándezꢀAlvarez, F. J.; Oro, L. A. ChemCatChem
2015, 7, 3895ꢀ3902.
19
ACS Paragon Plus Environment

ACS Catalysis
Page 20 of 21
1
2
3
4
(34) GonzálezꢀSebastián, L.; FloresꢀAlamo, M.; García, J. J. Organometallics 2015, 34, 763ꢀ
5
6
769.
7
8
9
(35) Jin, G.; Werncke, C. G.; Escudie, Y.; SaboꢀEtienne, S.; Bontemps, S. J. Am. Chem. Soc.
2015, 137, 9563ꢀ9566.
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(36) It should be noted that DFT calculations are well known to overestimate reaction barriers
and the calculated numbers reported in this work is used for qualitative purpose.
20
ACS Paragon Plus Environment

Page 21 of 21
ACS Catalysis
1
2
3
4
5
6
7
8
9
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
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
For Table of Contents Only
21
ACS Paragon Plus Environment