Application of phase-vanishing method with CO gas evolution to carbonylation reactions

Article abstract of DOI:10.1016/j.jfluchem.2018.10.006

Although carbon monoxide (CO) is considered a practical source of the carbonyl functionality in various compounds, handling CO gas is difficult. The phase-vanishing (PV) method, using highly fluorinated solvents as the phase screen, was thus employed, in which CO was evolved for use in organic synthesis. An H-shaped reactor bearing two reaction chambers was employed. In the first chamber, CO was efficiently generated from sulfuric acid and ammonium formate under the PV conditions, and then consumed in the second chamber in a range of palladium-catalysed carbonylation reactions, affording the desired products. Use of this PV system allowed for easy and safe generation of hazardous CO gas, and its use thereof in organic synthesis.

Full text of DOI:10.1016/j.jfluchem.2018.10.006

Accepted Manuscript
Title: Application of Phase-Vanishing Method with CO Gas
Evolution to Carbonylation Reactions
Authors: Yusuke Adachi, Hiroshi Matsubara
PII:
S0022-1139(18)30342-7
DOI:
Reference:
https://doi.org/10.1016/j.jfluchem.2018.10.006
FLUOR 9231
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Revised date:
Accepted date:
28-8-2018
9-10-2018
9-10-2018
Please cite this article as: Adachi Y, Matsubara H, Application of Phase-Vanishing
Method with CO Gas Evolution to Carbonylation Reactions, Journal of Fluorine
Chemistry (2018), https://doi.org/10.1016/j.jfluchem.2018.10.006
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1
Application of Phase-Vanishing Method with CO Gas Evolution to Carbonylation
Reactions
Yusuke Adachi and Hiroshi Matsubara*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka
599-8531, Japan
Graphical abstract
Highlights




The phase-vanishing (PV) method with CO gas evolution was demonstrated.
CO gas was evolved easily and safely under the PV conditions.
The aminocarbonylation reaction was successfully performed using an H-shaped reactor.
Several other carbonylation reactions using palladium catalysts were also carried out.
Abstract
Although carbon monoxide (CO) is considered a practical source of the carbonyl functionality in
various compounds, handling CO gas is difficult. The phase-vanishing (PV) method, using highly
fluorinated solvents as the phase screen, was thus employed, in which CO was evolved for use in
organic synthesis. An H-shaped reactor bearing two reaction chambers was employed. In the first
chamber, CO was efficiently generated from sulfuric acid and ammonium formate under the PV
conditions, and then consumed in the second chamber in a range of palladium-catalysed carbonylation
reactions, affording the desired products. Use of this PV system allowed for easy and safe generation
of hazardous CO gas, and its use thereof in organic synthesis.

2
Keywords
Phase-vanishing method
Fluorous solvent
Carbon monoxide
Carbonylation reaction
Palladium catalyst
1. Introduction
Fluorous solvents (highly fluorinated compounds) have unique properties such as immiscibility
with commonly used organic solvents and water and higher densities than those of typical organic
solvents [1]. Utilising these features, a novel synthetic methodology known as the ‘phase-vanishing
(PV) method’ was developed by our research group [2]. The PV method involves a triphasic reaction
system, in which the fluorous medium acts as a liquid membrane, regulating the transport of reagents
from the lower (reagent) layer to the upper organic layer that contains the substrate (passive diffusion).
The PV system allows for the simple and easy control of heat evolution in exothermic reactions. The
experimental setup requires simple equipment such as a common test tube, eliminating the need for
cooling equipment and dropping funnels.
The PV method was initially utilised in our group for the bromination of alkenes, using molecular
bromine (Br2) as the brominating reagent in the bottom layer [3]. The methodology has since been
further exploited in our research group [4], as well as by others [5], in a range of reactions, e.g. the
Friedel-Crafts acylation using SnCl4, [4b], cyclopropanation using CH2I2 [4d], Grignard-type reaction
using CH3I or C2H5I [4e], and aldol condensation using TiCl4 [4f]. The PV bromination system has
also been used in combination with photoirradiation, which allows for the efficient generation of
hydrogen bromide (HBr) from Br2 in the top layer, followed by radical addition to 1-alkenes to afford
terminal bromides in good yields [6].
Recently, the PV method was employed in our research group to generate gaseous reagents, which
were subsequently utilised in organic synthesis [7]. Specifically, acetylene gas was generated in the
PV system and was used in three organic reactions, namely the Sonogashira coupling, Cu-catalysed
azide–alkyne cycloaddition, and aldehyde–alkyne–amine coupling, affording the desired products in
good yields [7a]. This method allows for the passive diffusion of water into the fluorous solvent,
leading to gradual evolution of acetylene gas from calcium carbide. Therefore, this method is
promising for reactions requiring acetylene gas because the simple setup avoids the use of high-
pressure apparatus, such as regulators and gas cylinders.
Taking inspiration from previous studies in which gaseous reagents were generated within the PV
system, we report herein the evolution of carbon monoxide (CO) by the PV method and utilisation of

3
the gas in organic synthesis. CO is considered a practical source of the carbonyl moiety in various
compounds, including aldehydes, ketones, carboxylic acids, and their derivatives [8]. However, it is
well known that the handling of CO gas is difficult as it is colourless, odourless, inflammable, and
toxic. To avoid direct use of dangerous CO gas, many alternative methods have been developed in
which CO gas is generated in situ from CO precursors [9], such as aldehydes, formates, formamides,
and metal carbonyls. However, these methods often require complex reaction systems and are
difficult to control because substrates, catalysts, and other additives are mixed with the reagent in the
same reaction vessel. On the other hand, Skrydstrup and co-workers have recently developed an ‘ex-
situ’ carbonylation methodology using a two-chamber reactor (COware), where CO gas is generated
from CO precursors in the first chamber, and the generated gas is consumed in the second chamber
during carbonylation reactions [10][12]. While complicated reaction system can be avoided using
this methodology, it still requires intricate CO precursors [13]. Thus, we applied the PV method to
carbonylation reactions, involving CO gas generation from common reagents like sulfuric acid and
ammonium formate. Although there are many reactions involving CO gas that are well established,
we chose to explore this methodology using palladium-catalysed carbonylation reactions since these
reactions usually proceed well under mild conditions.
2. Results and discussion
The Heck aminocarbonylation of iodobenzenes [12] was chosen as the model reaction. The concept
of the PV system with CO gas evolution using a test tube is shown in Fig. 1. Concentrated sulfuric
acid ( = 1.84 g.cm-3) was used as the reagent phase (bottom layer), while 1,4-dioxane ( = 1.03
g.cm-3) was employed as the organic phase (top layer). Perfluoropolyether (Galden HT-135,  = 1.72
g.cm-3) [14] was used as the fluorous phase, to which ammonium formate ( = 1.28 g.cm-3) [15] was
successfully added. 4-iodoanisole (1a), n-hexylamine (2a), base (triethylamine), ligand (PPh3), and
palladium catalyst (Pd(dba)2) were added to the top layer, and the test tube was degassed using a
syringe. The bottom layer was gently stirred at 45 °C, taking care not to mix the layers. Although the
bottom layer disappeared after 24 h, no desired product was obtained. We had envisaged that sulfuric
acid would react with ammonium formate that floated at the interface between the fluorous and
organic phases to generate CO, which would then be utilised in the carbonylation of iodobenzene in
the presence of palladium catalyst. However, due to the poor results, it was speculated that most of
the acid immediately reacted with the amines in the organic phase, and thus, an insufficient amount
of CO gas was evolved using this setup. To circumvent this problem, an H-shaped two-chamber
reactor [16] resembling the COware system (Fig. 2) was subsequently employed as this would prevent
mixing of the sulfuric acid with amines in the organic phase (Fig. 3). To this end, sulfuric acid (0.8
mL, 15.0 mmol) and Galden HT-135 (1.5 mL) were placed in chamber 1 of the reactor, resulting in

4
two layers, to which ammonium formate (7.0 mmol) was added. A solution of 4-iodoanisole (1a, 0.5
mmol), n-hexylamine (2a, 1.1 mmol), triethylamine (1.2 mmol), PPh3 (0.05 mmol), and Pd(dba)2
(0.025 mmol) in 1,4-dioxane (2 mL) was placed in chamber 2 of the reactor (Fig. 4A). The reactor
was degassed using a syringe, and the contents of the two reaction chambers were gently stirred at
45 °C, taking care not to mix the layers in chamber 1. Continuous CO gas evolution was observed in
chamber 1, and after 24 h, ammonium formate had vanished to afford two layers in chamber 1 (Fig.
4B). The reaction mixture in chamber 2, which had turned dark reddish yellow, was purified directly
by column chromatography on silica gel (hexane/ethyl acetate = 10/0 – 8/2) to afford the desired
product N-hexyl-4-methoxybenzamide (3a) in 83% yield (Table 1, Entry 1). Optimisation studies
showed that halving the amount of ammonium formate to 3.5 mmol (7 equiv.) drastically lowered the
product yield (Entry 2). However, reducing Galden HT-135 to 1.0 mL, even whilst using the same
amount of ammonium formate (3.5 mmol), improved the yield (Entry 3). In contrast, increasing the
amount of the formate to 6.0 or 7.0 mmol (12 or 14 equiv., respectively) obviously increased the
product yield (Entries 4 and 5). Based on these results, the optimal reaction conditions were
established as 1.5 mL Galden HT-135 and 7.0 mmol (14 equiv.) ammonium formate (entry 5).
b
a
l
l
o
o
n
Substrate
CO
Organic solvent
HCO2NH4
Galden HT-135
H2SO4
stirrer bar
Fig. 1. Concept of PV method with CO gas evolution using a test tube.
12.5
11.7
92.5
26.0
55.0
Fig. 2. H-shaped reactor (in mm) for the PV method. Centre neck of the reactor is usually fitted with a rubber
stopper.

5
b
a
l
l
o
o
n
Chamber 1
Chamber 2
CO
HCO2NH4
Galden HT-135
Substrate
H2SO4
Organic Solv.
stirrer bar
Fig. 3. Concept of PV method with CO gas evolution using an H-shaped reactor.
Fig. 4. PV aminocarbonylation of 4-iodoanisole with n-hexylamine in the presence of palladium catalyst.
Arrows pointing to the left chamber indicate the phase interface. (A) A triphasic system: sulfuric acid, Galden
HT-135, and ammonium formate (from the bottom). (B) After 24 h, the ammonium formate layer disappeared,
affording two phases, Galden HT-135 and aqueous sulfuric acid phases (from the bottom). The right chamber
(reaction chamber) changed colour form light yellow to dark reddish yellow.
Table 1 Optimisation of reaction conditions for aminocarbonylation of 4-iodoanisole using PV
method with CO evolutiona
O
C
Chamber 1
HCO2NH4, H2SO4
Galden HT-135
I
N
4
+
H
H2N
4
Chamber 2
Pd(dba)2, PPh3, TEA
1,4-dioxane, 45 °C, 24 h
MeO
MeO
1a
2a
3a
Entrya
Galden HT-135 (ml)
HCO2NH4 (equiv.)
Yield (%)b
1
2
1.5
1.5
14
7
83c
7

6
3
4
5
1.0
1.0
1.0
7
39
74
12
14
98 (96)c
aReaction conditions: Chamber 1: H2SO4 (0.8 mL), 45 °C; Chamber 2: 1a (0.5 mmol), 2a (1.0 mmol), Pd(dba)2
(5.0 mol%), PPh3 (10 mol%), TEA (1.2 mmol), 1,4-dioxane (2 mL). bDetermined by GC. cIsolated yield.
Having established the optimal conditions, the substrate scope was explored using a variety of
haloarenes and amines. As shown in Table 2, iodoarenes possessing electron-donating or electron-
withdrawing groups successfully underwent aminocarbonylation to afford the N-hexylbenzamide
derivatives in good yield (Table 2, Entries 1–5). In contrast, the reaction was unsuccessful with the
bromoarene (Entry 6), and changing the phosphine ligand from PPh3 to PCy3 did not improve the
yield of the product (Entry 7).
Skrydstrup et al. conducted most of their aminocarbonylation reactions with CO at 80 °C [12]. The
PV system cannot be controlled at temperatures as high as 80 °C because the diffusion rate of sulfuric
acid would be so high at such temperatures that CO evolution would be uncontrolled. Thus, PV
aminocarbonylation was not investigated at higher temperatures.
In the investigation of the substrate scope of the amine, primary and cyclic amines afforded the
corresponding benzamides in good yields (Table 3, Entries 1, 2, 4 and 5), while an acyclic secondary
amine gave the desired product in lower yields (Entry 3).
Table 2 Aminocarbonylation of haloarenes using PV method with CO evolutiona
Entry
Aryl halide 1
Yield (%)b
1
2
3
4
5
R1 = H
1b
1c
1a
1d
1e
94
86
I
R1 = Me
R1 = OMe
R1 = Br
R1 = CN
R1
96 (98)c
75
92
Br
6
1f
< 1 (3)c
MeO

7
7d
(2)c
aReaction conditions: Chamber 1: HCO2NH4 (7.0 mmol), H2SO4 (0.8 mL), Galden HT-135 (1.0 mL), 45 °C;
Chamber 2: 1 (0.5 mmol), 2a (1.0 mmol), Pd(dba)2 (5.0 mol%), PPh3 (10 mol%),TEA (1.0 mmol), 1,4-dioxane
(2 mL), 45 °C, 24 h. bIsolated yield. cDetermined by GC. dUsing PCy3 (10 mol%).
Table 3 Aminocarbonylation of 4-iodoanisole with various amines using PV method with CO
evolutiona
Entry
Amine 2
R3 = C12H25
R3 = Bn
Yield (%)b
1
2
3
R2 = H
2g
2h
2i
82
81
41
R2 = H
R2 = n-Bu
R3 = n-Bu
4
5
2j
71
98
N
H
O
2k
N
H
aReaction conditions: Chamber 1: HCO2NH4 (7.0 mmol), H2SO4 (0.8 mL), Galden HT-135 (1.0 mL), 45 °C;
Chamber 2: 1a (0.5 mmol), 2 (1.0 mmol), Pd(dba)2 (5.0 mol%), PPh3 (10 mol%), TEA (1.0 mmol), 1,4-dioxane
(2 mL), 45 °C, 24 h. bIsolated yield.
Next, the carbonylative Sonogashira coupling using the PV method with CO gas evolution in the
H-shaped reactor was investigated. Results of the optimisation studies are summarised in Table 4.
Firstly, the optimised reaction conditions in the literature [17] were applied to the coupling of
iodobenzene (4a) with phenylacetylene (5a) using the PV system. Unfortunately, the desired
carbonylative product 6a was obtained in only small amounts, while the Sonogashira coupling
product, diphenylacetylene (7a), was formed in high yield (Entry 1). The use of PEG-400 resulted in
similar (or inferior) results to that obtained using PEG-2000 (Entries 2–4). In contrast, changing the
reaction solvent from PEG to THF dramatically improved the yield of the desired product (Entry 5).
On the basis of their Henry’s constants, less polar solvents should dissolve more CO [18]; hence, the
carbonylation product was formed predominantly in THF.

8
Table 4
Optimisation of reaction conditions for carbonylative Sonogashira coupling of
iodobenzene with phenylacetylene using PV method with CO evolutiona
Chamber 1
HCO2NH4, H2SO4
Galden HT-135, 45 ºC
O
I
C
+
+
Chamber 2
Pd(PPh3)2Cl2, TEA,
Solvent, 25 °C, 24 h
4a
5a
6a
7a
Yield (%)b
Entry
Solvent
6a
7
7a
93
57
47
PEG-2000 / H2O
(1 / 1)
1
2
3
PEG-400
PEG-400 / H2O
(1 / 1)
2
5
PEG-400 / H2O
(3 / 2)
4
5
3
97
3
THF
92
aReaction conditions: Chamber 1: HCO2NH4 (7.0 mmol), H2SO4 (0.8 mL), Galden HT-135 (1.0 mL), 45 °C;
Chamber 2: 4a (1.0 mmol), 5a (1.2 mmol), PdCl2(PPh3)2 (5.0 mol%), TEA (2.5 mmol), Solvent (2 mL), 25 °C,
24 h. bDetermined by GC.
With the optimised conditions in hand, the substrate scope of the PV carbonylative Sonogashira
coupling using various iodoarenes and acetylenes was investigated. As shown in Table 5, iodoarenes
with an electron-donating group gave the corresponding ynones 6a–6c in high yields (90–94%), while
those with a strong electron-withdrawing group (CN) afforded the desired product 6e in a
significantly lower yield (37%). Phenylacetylenes with an electron-withdrawing or electron-donating
group (F or CH3) afforded ynones 6f and 6g in good yields (90% and 87%, respectively), whereas
phenylacetylene with a strong electron-withdrawing group (CF3) furnished ynone 6h in a moderate
yield (52%). An aliphatic acetylene provided the desired product 6i in a good yield (89%).
Table 5 Carbonylative Sonogashira coupling using PV method with CO evolutiona
Chamber 1
HCO2NH4, H2SO4
Galden HT-135, 45 ºC
O
I
C
+
Chamber 2
Pd(PPh3)2Cl2, TEA,
THF, 25 °C, 24 h
R4
R4
R5
R5
4
5
6

9
O
C
O
C
O
C
Me
NC
MeO
6a (92%)b
6b (94%)
6c (93%)
O
O
C
O
C
C
Br
Me
6d (85%)
6e (37%)
6f (90%)
O
O
C
C
O
C
Br
CF3
5
F
6g (87%)
6h (52%)
6i (89%)
aReaction conditions: Chamber 1: HCO2NH4 (7.0 mmol), H2SO4 (0.8 mL), Galden HT-135 (1.0 mL), 45 °C;
Chamber 2: 4 (1.0 mmol), 5 (1.2 mmol), PdCl2(PPh3)2 (5.0 mol%), TEA (2.5 mmol), THF (2 mL), 25 °C, 24
h. bDetermined by GC.
Several other carbonylation reactions were conducted using the H-shaped reactor under the PV
conditions (Scheme 1). Although various reaction conditions were attempted as listed in Tables S1
in the Supplementary data, carbonylative Suzuki coupling [19] of iodobenzene (4a) with
phenylboronic acid (8) afforded the desired product, benzophenone (9), in 30% yield. The poor yield
was attributed to the formation of the direct Suzuki coupling product, biphenyl (10), which was
consistently formed (Eq. 1). These results indicate that the direct Suzuki coupling proceeds faster
than the carbonylative coupling reaction under the PV conditions. Methoxycarbonylation of
diphenylacetylene 11 in the presence of copper chloride and palladium catalyst [20] gave the desired
product 12a in a moderate yield (Eq. 2), while the carbonylation of diphenyl ether (13), catalysed by
palladium acetate [21], afforded the xanthone (14) in a good yield (Eq. 3).

10
Scheme 1 Several carbonylation reactions with palladium catalyst
3. Conclusion
Although the PV method with CO gas evolution was unsuccessful when attempted in a simple test
tube, use of an H-type reactor under PV conditions allowed for the efficient generation of CO gas
from sulfuric acid and ammonium formate, and subsequent use thereof in aminocarbonylation and
carbonylative Sonogashira reactions, affording the desired products in good yields. Several other
palladium-catalysed carbonylation reactions were also carried out successfully under these conditions,
affording the desired products in moderate to high yields. However, a drawback of this approach with
respect to the carbonylative Suzuki coupling, was the formation of biphenyl derivatives due to direct
coupling. Thus, there is scope for future work, as it is envisaged that a pressurized CO atmosphere
under PV conditions will preferentially drive the carbonylative reaction. Indeed, studies towards
improvement of the PV reactors for use under a pressurized atmosphere are currently underway and
will be presented in a future paper.
Overall, the PV system, in which highly fluorinated solvents are employed as a key component of
the system, was modified such that dangerous CO gas could be evolved easily and safely from
common reagents (ammonium formate and sulfuric acid), and used in a variety of organic
transformations to yield carbonyl compounds. The PV method described herein, which employs an
H-shaped reactor, can be extended to other gaseous reagents. Further applications of this method will
be reported in due course.

11
4. Experimental
4.1. Typical procedure for the aminocarbonylation of iodoanisole in the presence of palladium
catalyst using the PV method with CO gas evolution (Table 1, entry 5)
An H-shaped reactor with two reaction chambers was purged with argon. A stirring bar (1.0 mm× 0.4 mm)
was then located in each chamber of the reactor. Sulfuric acid (0.8 mL, 1.47 g, 15.0 mmol) was placed at the
bottom of one chamber (chamber 1) of the reactor, and Galden HT-135 (1.0 mL) was slowly added to chamber
1 using a syringe. Subsequently, ammonium formate (442 mg, 7.0 mmol) was added, which formed a third
layer in chamber 1. A solution of 4-iodoanisole (1a, 117.0 mg, 0.5 mmol), Pd(dba)2 (14.3 mg, 5 mol%), and
PPh3 (13.4 mg, 10 mol%) in dioxane (2 mL) was placed in the other chamber (chamber 2) of the reactor. Then,
n-hexylamine (2a, 108.1 mg, 1.1 mmol) and triethylamine (121.1 mg, 1.2 mmol) were added to chamber 2.
Rubber septa were fitted to the reactor, and a needle equipped with a balloon was then pricked into the septum
of chamber 2. The air in the reactor was withdrawn using a syringe until the balloon was completely flattened.
The reactor was heated in an oil bath at 45 °C for 24 h under slow stirring, with care taken not to mix the layers
in chamber 1, then allowed to cool to 25 °C. The mixture in chamber 2 was then transferred to a column
charged with silica gel and purified by chromatography. Elution with hexane/ethyl acetate (10/08/2) afforded
1
the desired product, N-n-hexyl-4-methoxybenzamide (3a, 113.4 mg, 96%) as a pale yellow solid [12]. H-
NMR (400 MHz, CDCl3): δ 7.72 (2H, d, J = 8.7 Hz, ArH), 6.92 (2H, d, J = 8.7 Hz, ArH), 6.02 (1H, bs, NH),
3.85 (3H, s, OCH3), 3.46-3.41 (2H, m, NCH2), 1.60 (2H, quint, J = 7.2 Hz, Alkyl), 1.41-1.26 (6H, m, Alkyl),
13
0.89 (3H, t, J = 6.9 Hz, CH2CH3); C-NMR (100 MHz, CDCl3): δ 167.17, 162.05, 128.74, 127.22, 113.72,
55.44, 40.16, 31.61, 29.78, 26.78, 22.65, 14.10.
4.2. Typical procedure for the carbonylative Sonogashira coupling of iodoanisole with
phenylacetylene in the presence of palladium catalyst using the PV method with CO gas evolution
(Table 5, 6c)
An H-shaped reactor with two reaction chambers was purged with argon. A stirring bar (1.0 mm× 0.4 mm)
was then located in each chamber of the reactor. Sulfuric acid (0.8 mL, 1.47 g, 15.0 mmol) was placed at the
bottom of one chamber (chamber 1) of the reactor, and Galden HT-135 (1.0 mL) was slowly added to chamber
1 using a syringe. Subsequently, ammonium formate (442 mg, 7.0 mmol) was added, which formed a third
layer in chamber 1. A solution of 4-iodoanisole (234.1 mg, 1.0 mmol), phenylacetylene (124.8 mg, 1.2 mmol),
PdCl2(PPh3)2 (34.9 mg, 5 mol%), and triethylamine (251.3 mg, 2.5 mmol) in THF (2 mL), was placed in the
other chamber (chamber 2) of the reactor. Rubber septa were fitted to the reactor, and a needle equipped with
a balloon was then pricked into the septum of chamber 2. The air in the reactor was withdrawn using a syringe
until the balloon was completely flattened. Chamber 1 of the reactor was heated in an oil bath at 45 °C under
slow stirring, with care taken not to mix the layers, while chamber 2 was stirred at 25 °C. After 24 h, the

12
mixture in chamber 2 were transferred to an Erlenmeyer flask containing water using ether. The organic layer
was separated, and the aqueous layer was extracted with ether. The combined organic layers were washed with
brine then dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica-gel column
chromatography using hexane/chloroform (1/1) as the eluent to afford desired product, 1-(4-methoxyphenyl)-
3-phenyl-2-propyn-1-one (6c, 220.0 mg, 93%) as a brown solid [22]. 1H-NMR (400 MHz, CDCl3): δ 8.20 (2H,
d, J = 9.2 Hz, ArH), 7.69-7.67 (2H, m, ArH), 7.50-7.40 (3H, m, ArH), 6.99 (2H, d, J = 9.2 Hz, ArH), 3.91 (3H,
s, -OCH3); 13C-NMR (100 MHz, CDCl3): δ 176.74, 164.56, 133.04, 132.06, 130.69, 130.34, 128.73, 120.39,
113.96, 92.40, 86.99, 55.68.
Acknowledgements
This study was partially supported by JSPS KAKENHI Grant Number JP16K05755.
Appendix A. Supplementary data
Supplementary data associated with this article can be found in the online version at
http://dx.doi.org/10.1016/j.jfluchem.2018.xx.xxx. An alternative to the H-shaped reactor (Fig. S1),
Table S1, Experimental detail, and NMR data of the products.
Notes and References
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Rec. 8 (2008) 351–363;
(b) J. Iskra, Lett. Org. Chem. 3 (2006) 170–175;
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1167–1169;
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(c) Md.T. Rahman, N. Kamata, H. Matsubara, I. Ryu, Synlett (2005) 2664–2666;
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(e) H. Matsubara, Y. Niwa, R. Matake, Synlett (2015) 1276–1280;
(f) Y. Adachi, K. Kuniyoshi, H. Matsubara, J. Fluorine Chem. 197 (2017) 100–105.
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(g) K. Ma, S. Li, R.G. Weiss, Org. Lett. 10 (2008) 4155–4158;
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[6] H. Matsubara, M. Tsukida, D. Ishihara, K. Kuniyoshi, I. Ryu, Synlett (2010) 2014–2018.
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[8] For reviews of application of carbon monoxide to organic synthesis, see: (a) L. Kollár, Modern Carbonylation
Methods; Wiley-VCH: Weinheim, 2008;
(b) M. Beller, Catalytic Carbonylation Reaction; Springer-Verlag: Berlin, 2006;
(c) T. Fukuyama, S. Maetani, I. Ryu, Comprehensive Organic Synthesis (2nd Edition) Ed. P. Knochel, G.A.
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(b) T. Morimoto, M. Fujioka, K. Fuji, K. Tsutsumi, K. Kakiuchi, Pure Appl. Chem. 2008, 80, 1079–1087;
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[10] For a review of COware, see: S.D Friis, A.T. Lindhardt, T. Skrydstrup, Acc. Chem. Res. 49 (2016) 594–605.
[11] For some recent work using COware, see: (a) H. Yin, J.J. Kumke, K. Domino, T. Skrydstrup, Troels, ACS
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(b) S.Y. Chow, L.R. Odell, J. Org. Chem. 82 (2017) 2515–2522;
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[12] P. Hermange, A.T. Lindhardt, R.H. Taaning, K. Bjerglund, D. Lupp, T. Skrydstrup J. Am. Chem. Soc. 133
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[13] Ryu et al. performed ex-situ carbonylation using the COware with CO generated from sulfuric acid and formic
acid. In this reaction, formic acid was added dropwise to sulfuric acid in the first chamber of the COware
using a syringe. For details, see Reference 11i.
[14] Galden HT-135 is a polyether-type perfluorinated solvent (Fig. 5), which is commercially available from
Solvay Solexis Inc. This solvent has several advantages over typical fluorous solvents, such as FC-72
(perfluorohexanes). For example, Galden HT-135 is less expensive and has a higher boiling point, which
minimises solvent loss.
Fig. 5. Structure of Galden.®
[15] Formic acid ( = 1.22 g cm-3) was not used in the reaction, because formic acid is highly miscible in 1,4-
dioxane and amines in the organic layer, and was readily reacted with the amines before the sulfuric acid
reacted with formic acid to generate CO gas.
[16] A reviewer proposed an alternative to the H-shaped reactor (Fig. S1). See the Supplementary data.
[17] H. Zhao, M. Cheng, J. Zhang M. Cai, Green Chem. 16 (2014) 2515–2522.
[18] The Henry’s constants of CO in toluene and methanol are 1189 and 2285 bar, respectively (C.A. Ohlin, P.J.
Dyson, G. Laurenczy, Chem. Commun. (2004) 1070–1071).
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[21] H. Zhang, R. Shi, P. Gan, C. Liu, A. Ding, Q. Wang, A. Lei, Angew. Chem. Int. Ed. 51 (2012) 5204–5207.
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