Hydroformylation of olefins and reductive carbonylation of aryl halides with syngas formed ex situ from dehydrogenative decarbonylation of hexane-1,6-diol

Article abstract of DOI:10.1039/c4ob01958j

A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then consumed in the other chamber in either a rhodium-catalysed hydroformylation of olefins or a palladium-catalysed reductive carbonylation of aryl halides. Hexane-1,6-diol was found to be the optimum alcohol for both reactions where moderate to excellent yields were obtained of the product aldehydes. A relatively low pressure of 1.5-2.4 bar was measured in the closed system during the two transformations.

Full text of DOI:10.1039/c4ob01958j

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Hydroformylation of olefins and reductive
carbonylation of aryl halides with syngas
formed ex situ from dehydrogenative
decarbonylation of hexane-1,6-diol†
Cite this: Org. Biomol. Chem., 2015,
13, 938
Stig Holden Christensen,‡ Esben P. K. Olsen,‡ Jascha Rosenbaum and
Robert Madsen*
A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of
carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated
in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then
consumed in the other chamber in either a rhodium-catalysed hydroformylation of olefins or a palladium-
catalysed reductive carbonylation of aryl halides. Hexane-1,6-diol was found to be the optimum alcohol
for both reactions where moderate to excellent yields were obtained of the product aldehydes. A relatively
low pressure of 1.5–2.4 bar was measured in the closed system during the two transformations.
Received 15th September 2014,
Accepted 12th November 2014
DOI: 10.1039/c4ob01958j
www.rsc.org/obc
reductive carbonylation of aryl halides where 9-methylfluo-
rene-9-carbonyl chloride served as the carbon monoxide source
Introduction
The mixture of carbon monoxide and molecular hydrogen (i.e. and potassium formate as the hydride source.7 However, it
syngas) is a very useful feedstock in chemistry and can be would be desirable to have a cheaper and more easily available
applied in a number of transformations such as the Fischer– syngas surrogate for use in this system.
Tropsch process,1 the hydroformylation of alkenes2 and the
We have recently combined the dehydrogenation of a
reductive carbonylation (formylation) of aryl halides.3 primary alcohol and the decarbonylation of the resulting alde-
However, for applications in organic chemistry the high tox- hyde into one transformation where carbon monoxide and
icity of carbon monoxide constitutes
a severe problem molecular hydrogen are produced in a 1 : 1 ratio together with
especially because a high pressure of syngas is often required. the one-carbon shorter alkane.8 This dehydrogenative decarbo-
As a result, there has been a significant interest in finding nylation is catalysed by 2.5% of [Ir(coe)2Cl]2, 5% of rac-BINAP
alternative ways to generate and deliver syngas to a reaction and 10% of LiCl in mesitylene saturated with water at reflux
mixture. This has led to the development of several syngas sur- (164 °C). The transformation has been applied to a variety of
rogates which are molecules that release syngas in situ.4 These primary alcohols and functional groups such as ethers, esters,
surrogates include formaldehyde, carbon dioxide and deriva- imides and aryl halides are stable under the reaction con-
tives of formic acid where the last two also require a reducing ditions while olefins are partially saturated.8 The mechanism
agent.4,5 However, the challenge is to combine the syngas- is believed to involve two separate catalytic cycles with the
releasing reaction with the syngas-consuming reaction in the same iridium(I)-BINAP species where the first removes mole-
same pot. An alternative strategy is to separate the two trans- cular hydrogen from the primary alcohol and the second
formations into two reaction vessels which are connected by a cleaves carbon monoxide from the resulting aldehyde.
tube allowing syngas to flow from one vessel to another. This
We envisioned that the dehydrogenative decarbonylation
two-chamber setup for ex situ generation of carbon monoxide from an alcohol could serve as the syngas-releasing reaction in
has been especially developed by the Skrydstrup group and one chamber with a hydroformylation or a reductive carbonyla-
applied in a number of carbonylation reactions6 including the tion as the syngas-consuming reaction in the other chamber.
Very recently, the same setup was used for generating syngas
at 210 °C from polyols in the hydroformylation of styrene, but
Department of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby,
the transformation was often accompanied by significant
Denmark. E-mail: rm@kemi.dtu.dk
†Electronic supplementary information (ESI) available: Two-chamber setup and
copies of 1H and 13C NMR spectra. See DOI: 10.1039/c4ob01958j
reduction to ethylbenzene as a side reaction.9 Accordingly, we
here describe our development of commercially available alco-
hols as precursors for carbon monoxide and molecular hydro-
‡These authors contributed equally to this work.
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gen in the synthesis of aldehydes from alkenes and aryl slightly lower yield of 92% since the reaction was accompanied
halides.
by 8% reduction to ethylbenzene (entry 5). This can be
explained by the higher stability and slower decarbonylation of
benzaldehyde as compared to aliphatic aldehydes.8,11 The
result is a higher initial H2 : CO ratio with benzyl alcohol than
with aliphatic alcohols and thus more reduction to ethylben-
zene is observed. Several α,ω-diols were also included in the
alcohol screening where hexane-1,6-diol and dodecane-1,12-
diol both gave ≥97% yield (entries 6 and 7). The branched
alcohol 2-methylpropane-1,3-diol reacted slowly and only gave
55% conversion of styrene (entry 8).
Besides simple alcohols, carbohydrates would also be a very
attractive syngas source since they can potentially undergo
complete degradation into carbon monoxide and molecular
hydrogen. Unfortunately, D-sorbitol and glycerol afforded very
little of the desired aldehydes and the reactions were
accompanied by significant reduction to ethylbenzene (entries
9 and 10). The gas development from the dehydrogenative de-
carbonylation of D-sorbitol and glycerol was measured in a sep-
arate flask and only about one equivalent was liberated. The
poor conversion could be due to the limited solubility of D-sor-
bitol and glycerol in mesitylene at 164 °C. Attempts were made
to improve the solubility by adding phenylboronic acid or
dibutyltin oxide as hydroxyl complexing agents, but these
experiments did not lead to additional syngas formation.
Therefore, hexane-1,6-diol was selected as the syngas source
for general use since it gives complete conversion in the hydro-
formylation and is easy to handle as a solid. It is a very cheap
substrate which is produced commercially by hydrogenation of
adipic acid. The only byproduct from the dehydrogenative de-
carbonylation is butane which evaporates after unsealing the
two-chamber reactor. The butane formation was confirmed by
1H NMR of the hydroformylation reaction immediately after
Results and discussion
The iridium-catalysed dehydrogenative decarbonylation of a
primary alcohol requires a temperature of at least 150 °C in
order to produce syngas at a reasonable rate.8 However, the
hydroformylation of olefins and the reductive carbonylation of
aryl halides are usually performed at significantly lower temp-
eratures. As a result, the two chambers in the reactor will have
to operate at different temperatures and the original design
from the Skrydstrup group was therefore slightly modified. A
longer connecting tube was employed between the two
chambers and a coldfinger was installed in the syngas-releas-
ing chamber to allow for the higher temperature and to
prevent mesitylene from diffusing into the syngas-consuming
chamber (see ESI†). In this way, the iridium-catalysed dehydro-
genative decarbonylation could be studied under the opti-
mised conditions with a variety of alcohols in the first
chamber. In the second chamber the hydroformylation of
styrene was selected for the first experiments and the complex
RhH(CO)(PPh3)3 was chosen as the catalyst since it has shown
high activity at both low temperature and pressure.10 During
the optimisation the hydroformylation was carried out in
benzene-d6 which allowed for quick determination of the
yields by 1H NMR spectroscopy.
First, simple primary alcohols were included as syngas
sources in the first chamber (Table 1). Pentan-1-ol, heptan-1-
ol, dodecan-1-ol and 2-phenylethanol all gave full conversion
of styrene and resulted in ≥97% yield of the two aldehyde pro-
ducts (entries 1–4). Benzyl alcohol, on the other hand, gave a
Table 1 Alcohols as syngas source for the hydroformylation reaction
Equiv. of
alcohol
Aldehyde
yielda (%)
Linear :
Ethylbenzene
yielda (%)
Entry
Alcohol
brancheda
1
2
3
4
5
6
7
8
9
Pentan-1-ol
Heptan-1-ol
2
2
2
2
2
1
1
1
98
100
97
100
92
100
97
55
5 : 3
5 : 4
5 : 4
1 : 1
5 : 4
5 : 4
5 : 4
2 : 1
7 : 3
7 : 3
2
0
3
0
8
0
3
0
13
6
Dodecan-1-ol
2-Phenylethanol
Benzyl alcohol
Hexane-1,6-diol
Dodecane-1,12-diol
2-Methylpropane-1,3-diol
D-Sorbitol
0.3
0.5
4
24
10
Glycerol
a Determined by 1H NMR.
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been shown that the reductive carbonylation of aryl halides
can be performed at moderate pressure and temperature with
Pd(OAc)2 and cataCXium
A
(di-1-adamantyl-n-butylphos-
phine).12 These conditions were therefore selected for
chamber two where p-bromoanisole (1) was chosen as the sub-
strate for the exploratory experiments. The reaction was per-
formed in toluene where the conversion of 1 as well as the
yield of p-anisaldehyde (2) and anisole (3) were determined by
GC. In chamber one a number of different alcohols were sub-
jected to the dehydrogenative decarbonylation (Table 3). Only
high-boiling alcohols were investigated since an experiment
with ethanol gave small amounts of ethyl p-anisate due to
alcohol diffusion into the second chamber. The simple alco-
hols pentan-1-ol, heptan-1-ol and dodecan-1-ol gave decent
yields of the desired aldehyde, but it was not possible to
achieve full conversion of p-bromoanisole (entries 1–3). Com-
plete consumption was obtained with 2-(2-naphthyl)ethanol
and benzyl alcohol which both gave good yields of p-anisalde-
hyde (entries 4 and 5). Benzyl alcohol resulted in a larger
amount of anisole than 2-(2-naphthyl)ethanol which is pre-
sumably due to the increased stability of benzaldehyde result-
ing in a higher initial H2 : CO ratio. Several diols were also
investigated where poor results were obtained with 2-methyl-
and 2,2-dimethylpropane-1,3-diol (entries 6 and 7). The same
was observed with butane-1,4-diol and pentane-1,5-diol where
a low selectivity between 2 and 3 was also attained (entries 8
and 9). The latter is most likely caused by cyclisation of the
diols into five- and six-membered hemiacetals after the de-
hydrogenation which makes the decarbonylation more demand-
ing.13 Hexane-1,6-diol and dodecane-1,12-diol both gave
complete conversion and high yields of p-anisaldehyde
(entries 10–13). No improvement was observed by increasing
or decreasing the amount of hexane-1,6-diol. As a result,
hexane-1,6-diol was again selected for general use and the
scope of the transformation investigated on a variety of aryl
halides.
The isolated yield from the conversion of p-bromoanisole
was found to be 71% (Table 4, entry 1). A similar result was
obtained with the corresponding iodide although the trans-
formation required a longer reaction time (entry 2). The same
reaction time was necessary for 4-bromoveratrole which
afforded the aldehyde in 60% yield (entry 3). The reactions
with 2-bromonaphthalene and 4-bromobiphenyl were unevent-
ful and gave the aldehydes in 79 and 69% yield, respectively
(entries 4 and 5). Substrates with electron-withdrawing substi-
tuents, however, reacted poorly due to competing dehalogena-
tion (entries 6, 8 and 11). Some improvement could be
achieved by lowering the temperature and increasing the reac-
tion time (entries 7, 9 and 12). It has previously been observed
that the chemoselectivity usually improves at a lower tempera-
ture.12 An alternative strategy would be to increase the CO : H2
ratio by including a hydrogen scavenger in chamber one.
Norbornene, diphenylacetylene and benzophenone were inves-
tigated as scavengers in the reaction with p-bromochloro-
benzene and the best result was obtained with 0.3 equivalent
of diphenylacetylene as judged by GC. Under these modified
Fig. 1 Gas formation as a function of time.
Fig. 2 Pressure in two-chamber reactor during the hydroformylation of
styrene.
opening the system. The gas development during the dehydro-
genative decarbonylation was measured by reacting 0.5 mmol
of hexane-1,6-diol in a Schlenk tube connected to a burette
filled with water. A total gas volume of 48.6 mL was collected
which corresponds to approximately 2.0 mmol (Fig. 1).
The pressure during the hydroformylation of styrene was
measured continuously by attaching a manometer to the
second chamber. The initial pressure with hexane-1,6-diol was
about 1.5 bar which slowly rose to 2.4 bar during the reaction
(Fig. 2). Similar values were measured with pentan-1-ol and
dodecane-1,12-diol and in all cases a sudden increase in
pressure was observed after 15–25 h. This probably illustrates
the time at which the hydroformylation has gone to
completion.
The two aldehydes from the hydroformylation of styrene
were separated and isolated in a combined yield of 83%
(Table 2, entry 1). The optimised conditions were also applied
to a number of other alkenes to give aldehyde yields between
85 and 96% (entries 2–8). The ratio between the linear and the
branched aldehyde is in line with the previous experiments
with RhH(CO)(PPh3)3 at low temperature and pressure.10 These
results clearly illustrate that hexane-1,6-diol can be used as a
syngas source in the hydroformylation reaction.
We then switched to the reductive carbonylation reaction to
investigate whether a similar cheap alcohol could be employed
for syngas delivery in this transformation. It has previously
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Table 2 Hydroformylation of olefins with hexane-1,6-diol as the syngas source
Entry
1
R
Linear product
Yielda (%)
50
Branched product
Yielda (%)
33
H
2
3
4
Me
Cl
52
53
44
41
35
49
MeO
b
5
6
—
53
65
43
30
MeOOC
AcO
7
8
50
48
46
37
BnOCH2
a Isolated yield. b 2-Vinylnaphthalene was used as the substrate.
conditions a moderate yield was obtained with chloride and formed and the reductive carbonylation commences. Mechan-
tosylate as the para substituent (entries 10 and 13). Similar istic studies of the reaction have shown that palladium acetate
results were attained with acetate, benzoate, silyloxy and ben- is first converted into carbonyl and hydride complexes from
zyloxy in the para position (entries 14–17). These experiments which the catalytically active species is slowly released.14
again demonstrate that hexane-1,6-diol is a suitable source of
syngas in a formylation reaction.
The pressure during the reductive carbonylation of 2-bromo-
naphthalene (with 0.3 equiv. of diphenylacetylene) was
Conclusions
measured and found to be around 1.6 bar during the course of
the reaction (Fig. 3). The slight decrease in pressure after
about 8 h may indicate the time at which the active catalyst is
In summary, we have presented a new application of the
iridium-catalysed dehydrogenative decarbonylation of primary
alcohols where the transformation serves as a syngas-releasing
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Table 3 Alcohols as syngas source for the reductive carbonylation reaction
Equiv. of
alcohol
Conversion
Yield of
Yield of
Entry
Alcohol
of 1a (%)
2a (%)
3a (%)
1
2
3
4
5
6
7
8
Pentan-1-ol
Heptan-1-ol
Dodecan-1-ol
2-(2-Naphthyl)ethanol
Benzyl alcohol
2-Methylpropane-1,3-diol
2,2-Dimethylpropane-1,3-diol
Butane-1,4-diol
Pentane-1,5-diol
Hexane-1,6-diol
Hexane-1,6-diol
Hexane-1,6-diol
2
2
2
2
2
1
1
1
1
1
0.75
1.5
1
89
82
85
100
100
53
24
42
34
100
25
78
75
77
93
83
45
17
25
17
92
16
85
93
11
7
8
7
17
8
7
17
17
8
9
15
7
9
10
11
12
13
100
100
Dodecane-1,12-diol
a Determined by GC.
reaction in a closed two-chamber setup. Hexane-1,6-diol was separate oil baths, where the reaction in chamber 1 was stirred
found to be a convenient syngas surrogate from which the at 170 °C while the reaction in chamber 2 was stirred at rt.
gaseous mixture can be liberated continuously at low pressure. After 40 h the crude mixture in chamber 2 was purified directly
The transformation has been used for hydroformylation of by column chromatography (Et2O–pentane) to isolate first the
olefins and reductive carbonylation of aryl halides to afford a branched and then the linear aldehyde.
variety of aldehydes in moderate to excellent yields.
2-Phenylpropanal. Rf 0.50 (Et2O–pentane 1 : 20). 1H NMR
(400 MHz, CDCl3): δ 9.69 (d, J = 1.2 Hz, 1H), 7.39 (t, J = 7.2 Hz,
2H), 7.31 (tt, J = 7.2, 1.2 Hz, 1H), 7.22 (dd, J = 7.2, 1.2 Hz, 2H),
3.64 (dq, J = 6.8, 1.2 Hz, 1H), 1.45 (d, J = 6.8 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 201.2, 137.8, 129.2, 128.4, 127.6, 53.1,
14.7. MS m/z 134 [M]+. NMR data are in accordance with litera-
ture values.16
Experimental section
General information
Gas chromatography was performed on
a
Shimadzu
3-Phenylpropanal. Rf 0.37 (Et2O–pentane 1 : 20). 1H NMR
(400 MHz, CDCl3): δ 9.83 (t, J = 1.2 Hz, 1H), 7.31 (tt, J = 6.8, 1.6
Hz, 2H), 7.25–7.18 (m, 3H), 2.97 (t, J = 7.6 Hz, 2H), 2.79 (dt, J =
7.6, 1.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 201.6, 140.4,
128.7, 128.4, 126.4, 45.4, 28.2. MS m/z 134 [M]+. NMR data are
in accordance with literature values.17
2-(4-Methylphenyl)propanal. Rf 0.48 (Et2O–pentane 1 : 20).
1H NMR (400 MHz, CDCl3): δ 9.68 (d, J = 1.2 Hz, 1H), 7.21 (d,
J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 3.61 (dq, J = 7.2, 1.2
Hz, 1H), 2.37 (s, 3H), 1.44 (d, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 201.3, 137.1, 134.7, 129.9, 128.3, 52.7,
21.1, 14.7. MS m/z 148 [M]+. NMR data are in accordance with
literature values.18
GCMS-QP2010S instrument fitted with an Equity 5, 30 m ×
0.25 mm × 0.25 μm column. Flash column chromatography
separations were performed on silica gel 60 (35–70 μm). NMR
spectra were recorded on a Bruker Ascend 400 spectrometer.
Chemical shifts were measured relative to the signals of
residual CHCl3 (δH 7.26 ppm) and CDCl3 (δC 77.16 ppm).
HRMS measurements were made using ESI with TOF
detection.
General procedure for hydroformylation
To chamber
1 was added hexane-1,6-diol (118.2 mg,
1.0 mmol), [Ir(cod)Cl]2 (16.8 mg, 0.025 mmol), rac-BINAP
(31.1 mg, 0.050 mmol), LiCl (4.2 mg, 0.10 mmol) and 2.0 mL
of mesitylene saturated with H2O (150 ppm). To chamber 2
3-(4-Methylphenyl)propanal. Rf 0.30 (Et2O–pentane 1 : 20).
1H NMR (400 MHz, CDCl3): δ 9.83 (t, J = 1.6 Hz, 1H), 7.14 (d,
J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 2.95 (t, J = 7.6 Hz, 2H),
2.77 (dt, J = 7.6, 1.6 Hz, 2H), 2.35 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 201.8, 137.3, 135.8, 129.3, 128.2, 45.4, 27.8, 21.0.
15
was added the olefin (1.0 mmol), RhH(CO)(PPh3)3 (23.0 mg,
0.025 mmol) and dry benzene (1.5 mL). The system was sealed
with a coldfinger over chamber 1 and a screw cap over
chamber 2. The two-chamber system was lowered into two
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Table 4 Reductive carbonylation of aryl halides with hexane-1,6-diol
as the syngas source
Entry
1
Substrate
Product
Yielda (%)
71
Fig. 3 Pressure in two-chamber reactor during reductive carbonylation
of 2-bromonaphthalene.
2b
73
60
MS m/z 148 [M]+. NMR data are in accordance with literature
values.18
3b
2-(4-Chlorophenyl)propanal. Rf 0.45 (Et2O–pentane 1 : 20).
1H NMR (400 MHz, CDCl3): δ 9.65 (d, J = 1.2 Hz, 1H), 7.34 (d,
J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 3.62 (dq, J = 7.2, 1.2 Hz,
1H), 1.43 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 200.6, 136.3, 133.6, 129.7, 129.3, 52.4, 14.7. MS m/z 168 [M]+.
NMR data are in accordance with literature values.16
3-(4-Chlorophenyl)propanal. Rf 0.24 (Et2O–pentane 1 : 20).
1H NMR (400 MHz, CDCl3): δ 9.78 (t, J = 1.6 Hz, 1H), 7.24 (d,
J = 8.8 Hz, 2H), 7.11 (d, J = 8.8 Hz, 2H), 2.91 (t, J = 7.2 Hz, 2H),
2.75 (dt, J = 7.2, 1.6 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 201.1, 138.9, 132.0, 129.7, 128.7, 45.1, 27.4. MS m/z 168 [M]+.
NMR data are in accordance with literature values.19
2-(4-Methoxyphenyl)propanal. Rf 0.49 (Et2O–pentane 1 : 10).
1H NMR (400 MHz, CDCl3): δ 9.65 (d, J = 1.6 Hz, 1H), 7.13 (d,
J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H), 3.58 (dq,
J = 7.2, 1.2 Hz, 1H), 1.41 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 201.3, 159.1, 129.7, 129.5, 114.6, 55.4, 52.2, 14.8. MS
m/z 164 [M]+. NMR data are in accordance with literature
values.16
4
5
79
69
6
20
35
7b,c
8
27
56
47
9b,c
10d,e
11
33
56
62
12c, f
13d,e
3-(4-Methoxyphenyl)propanal. Rf 0.35 (Et2O–pentane 1 : 10).
1H NMR (400 MHz, CDCl3): δ 9.81 (t, J = 1.6 Hz, 1H), 7.11 (d,
J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 2.91 (t, J =
7.6 Hz, 2H), 2.74 (dt, J = 7.6, 1.6 Hz, 2H). 13C NMR (100 MHz,
CDCl3): δ 201.9, 158.2, 132.4, 129.3, 114.1, 55.3, 45.6, 27.4. MS
m/z 164 [M]+. NMR data are in accordance with literature
values.20
14d,e
15d,e
16d,e
17d,e
49
54
44
65
2-(2-Naphthyl)propanal. Rf 0.46 (Et2O–pentane 1 : 20). 1H
NMR (400 MHz, CDCl3): δ 9.78 (d, J = 1.2 Hz, 1H), 7.90–7.82
(m, 3H), 7.70 (s, 1H), 7.56–7.49 (m, 2H), 7.34 (dd, J = 8.4, 1.6
Hz, 1H) 3.81 (dq, J = 6.8, 1.2 Hz, 1H), 1.57 (d, J = 6.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 201.0, 135.2, 133.7, 132.7, 128.9,
127.8, 127.2, 126.5, 126.3, 126.2, 53.1, 14.7. MS m/z 184 [M]+.
NMR data are in accordance with literature values.16
3-(2-Naphthyl)propanal. Rf 0.23 (Et2O–pentane 1 : 20).
1H NMR (400 MHz, CDCl3): δ 9.83 (t, J = 1.2 Hz, 1H), 7.88–7.80
a Isolated yield. b Reaction time 90 h. c Temperature 60 °C in chamber
2. d 0.3 Equiv. of diphenylacetylene added to chamber 1. e Reaction
time 64 h. f Reaction time 114 h.
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(m, 3H), 7.65 (s, 1H), 7.56–7.45 (m, 2H), 7.35 (dd, J = 8.4, 1.6 General procedure for reductive carbonylation
Hz, 1H), 3.12 (t, J = 7.6 Hz, 2H), 2.83 (dt, J = 7.6, 1.2 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 201.5, 137.9, 133.6, 132.1, 128.2, In
a
two-chamber system, hexane-1,6-diol (118 mg,
127.6, 127.5, 126.9, 126.4, 126.1, 125.5, 45.1, 28.2. MS m/z 184 1.00 mmol), [Ir(cod)Cl]2 (16.8 mg, 0.025 mmol), rac-BINAP
[M]+. NMR data are in accordance with literature values.21
(31.0 mg, 0.050 mmol), LiCl (4.2 mg, 0.10 mmol) and mesity-
Methyl 4-(1-oxopropan-2-yl)benzoate. Rf 0.32 (Et2O–pentane lene (2.0 mL, saturated with H2O) were added to chamber
1 : 5). 1H NMR (400 MHz, CDCl3): δ 9.68 (d, J = 1.2 Hz, 1H), 1. To chamber 2 were added the aryl halide (1.00 mmol), Pd
8.03 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 3.91 (s, 3H), (OAc)2 (11.2 mg, 0.050 mmol), cataCXium A (19.7 mg,
3.70 (dq, J = 7.2, 1.2 Hz, 1H), 1.46 (d, J = 7.2 Hz, 3H). 13C NMR 0.055 mmol), TMEDA (0.30 mL, 2.00 mmol) and dry toluene
(100 MHz, CDCl3): δ 200.3, 166.8, 143.0, 130.4, 129.6, 128.5, (2.0 mL). The two-chamber system was flushed with argon.
53.0, 52.3, 14.7. MS m/z 192 [M]+. NMR data are in accordance The system was sealed with a coldfinger over chamber 1 and a
with literature values.16
screw cap over chamber 2. Chamber 1 was heated to 170 °C
Methyl 4-(3-oxopropyl)benzoate. Rf 0.19 (Et2O–pentane while chamber 2 was heated to 80 °C. After 40 h, the system
1 : 5). 1H NMR (400 MHz, CDCl3): δ 9.78 (t, J = 1.2 Hz, 1H), 7.93 was allowed to reach rt and the pressure was released upon
(d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H), 2.97 (t, opening of the system. The suspension in chamber 2 was fil-
J = 7.2 Hz, 2H), 2.78 (dt, J = 7.2, 1.2 Hz, 2H). 13C NMR tered through a silica plug and the filter cake was rinsed with
(100 MHz, CDCl3): δ 200.9, 166.9, 145.9, 129.9, 128.4, 128.3, EtOAc. The filtrate was concentrated and purified by column
52.1, 44.8, 28.0. MS m/z 192 [M]+. NMR data are in accordance chromatography (Et2O–pentane) to afford the aldehyde
with literature values.22
4-(1-Oxopropan-2-yl)phenyl acetate. Rf 0.40 (Et2O–pentane
product.
4-Anisaldehyde (2). Rf 0.25 (Et2O–pentane 1 : 6). 1H NMR
1 : 3). 1H NMR (400 MHz, CDCl3): δ 9.65 (d, J = 1.2 Hz, 1H), (400 MHz, CDCl3): δ 9.88 (s, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.00
7.21 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.63 (dq, J = (d, J = 8.7 Hz, 2H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
7.2, 1.2 Hz, 1H), 2.28 (s, 3H), 1.42 (d, J = 7.2 Hz, 3H). 13C NMR 191.0, 164.7, 132.1, 130.1, 114.4, 55.7. MS m/z 136 [M]+. NMR
(100 MHz, CDCl3): δ 200.8, 169.5, 150.1, 135.3, 129.4, 122.3, data are in accordance with literature values.5a
52.4, 21.1, 14.7. MS m/z 192 [M]+. H NMR data are in accord-
3,4-Dimethoxybenzaldehyde. Rf 0.28 (Et2O–pentane 1 : 2).
1H NMR (400 MHz, CDCl3): δ 9.80 (s, 1H), 7.41 (dd, J = 8.2, 1.8
1
ance with literature values.23
4-(3-Oxopropyl)phenyl acetate. Rf 0.22 (Et2O–pentane 1 : 3). Hz, 1H), 7.36 (d, J = 1.8 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 3.92
1H NMR (400 MHz, CDCl3): δ 9.76 (t, J = 1.2 Hz, 1H), 7.17 (d, (s, 3H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 190.9,
J = 8.4 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 2.91 (t, J = 7.6 Hz, 2H), 154.5, 149.6, 130.1, 126.9, 110.4, 108.9, 56.2, 56.0. MS m/z 166
2.73 (dt, J = 7.6, 1.2 Hz, 2H), 2.25 (s, 3H). 13C NMR (100 MHz, [M]+. NMR data are in accordance with literature values.5a
CDCl3): δ 201.3, 169.5, 149.0, 137.9, 129.2, 121.6, 45.1, 27.4,
Naphthalene-2-carbaldehyde. Rf 0.28 (Et2O–pentane 1 : 20).
21.0. MS m/z 192 [M]+. NMR data for this compound are not 1H NMR (400 MHz, CDCl3): δ 10.17 (s, 1H), 8.35 (s, 1H),
known in the literature and HRMS data could not be obtained 8.07–7.86 (m, 4H), 7.68–7.56 (m, 2H). 13C NMR (100 MHz,
which is likely due to the instability of aliphatic aldehydes. CDCl3): δ 192.4, 136.6, 134.7, 134.3, 132.8, 129.68, 129.27,
Instead, the crude aldehyde mixture was reduced with NaBH4 129.3, 128.2, 127.2, 122.9. MS m/z 156 [M]+. NMR data are in
(20 mg, 0.53 mmol) in THF at 0 °C. The obtained alcohol had accordance with literature values.5a
the following NMR data where the 1H NMR values are in
Biphenyl-4-carbaldehyde. Rf 0.30 (Et2O–pentane 1 : 20). 1H
accordance with literature data.24 1H NMR (400 MHz, CDCl3): δ NMR (400 MHz, CDCl3): δ 10.06 (s, 1H), 7.96 (d, J = 8.2 Hz,
7.20 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 3.68 (t, J = 6.4 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.67–7.62 (m, 2H), 7.52–7.39 (m,
Hz, 2H), 2.70, (t, J = 7.6 Hz, 2H), 2.29 (s, 3H), 1.92–1.82 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 192.0, 147.3, 139.8, 135.3,
2H), 1.37 (bs, 1H). 13C NMR (100 MHz, CDCl3): δ 169.8, 148.9, 130.4, 129.1, 128.6, 127.8, 127.5. MS m/z 182 [M]+. NMR data
139.5, 129.5, 121.5, 62.3, 34.2, 31.5, 21.3.
2-(4-(Benzyloxymethyl)phenyl)propanal. Rf
are in accordance with literature values.5a
0.41
(Et2O–
Ethyl 4-formylbenzoate. Rf 0.20 (Et2O–pentane 1 : 15). 1H
pentane 1 : 5). 1H NMR (400 MHz, CDCl3): δ 9.65 (d, J = 1.6 Hz, NMR (400 MHz, CDCl3): δ 10.09 (s, 1H), 8.19 (d, J = 8.0 Hz,
1H), 7.40–7.15 (m, 9H), 4.56 (s, 2H), 4.54 (s, 2H), 3.61 (dq, J = 2H), 7.94 (d, J = 8.1 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 1.41 (t, J =
7.2, 1.6 Hz, 1H), 1.42 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 191.8, 165.7, 139.2,
CDCl3): δ 201.0, 138.2, 137.8, 137.1, 128.5, 128.5, 128.4, 127.8, 135.6, 130.3, 129.6, 61.7, 14.4. MS m/z 178 [M]+. NMR data are
127.7, 72.3, 71.7, 52.8, 14.7. MS m/z 254 [M]+. HRMS: m/z calcd in accordance with literature values.5d
for C17H18O2 277.1204 [M + Na]+, found 277.1203.
3-(4-(Benzyloxymethyl)phenyl)propanal. Rf 0.22
4-Chlorobenzaldehyde. Rf 0.26 (Et2O–pentane 1 : 30). 1H
(Et2O– NMR (400 MHz, CDCl3): δ 9.99 (s, 1H), 7.88–7.73 (m, 2H),
pentane 1 : 5). H NMR (400 MHz, CDCl3): δ 9.75 (t, J = 1.2 Hz, 7.57–7.45 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 191.0, 141.1,
1H), 7.37–7.11 (m, 9H), 4.52 (s, 2H), 4.49 (s, 2H), 2.91 (t, J = 7.6 134.9, 131.1, 129.6. MS m/z 140 [M]+. NMR data are in accord-
Hz, 2H), 2.71 (dt, J = 7.6, 1.2 Hz, 2H). 13C NMR (100 MHz, ance with literature values.5a
1
CDCl3): δ 201.5, 139.8, 138.3, 136.3, 128.4, 128.3, 128.1, 127.7,
4-(4-Methylbenzenesulfonyloxy)benzaldehyde. Rf
0.29
127.6, 72.1, 71.8, 45.2, 27.8. MS m/z 254 [M]+. HRMS: m/z calcd (Et2O–pentane 1 : 3). 1H NMR (400 MHz, CDCl3): δ 9.97 (s, 1H),
for C17H18O2 277.1204 [M + Na]+, found 277.1204.
7.86–7.80 (m, 2H), 7.77–7.68 (m, 2H), 7.33 (dd, J = 8.6, 0.6 Hz,
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2H), 7.20–7.13 (m, 2H), 2.46 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 190.8, 154.0, 146.0, 135.0, 132.2, 131.4, 130.1, 128.6,
123.2, 21.9. MS m/z 276 [M]+. Rf 0.29 (Et2O–pentane 1 : 3). NMR
data are in accordance with literature values.7
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7 S. Korsager, R. H. Taaning, A. T. Lindhardt and
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4-Formylphenyl acetate. Rf 0.25 (Et2O–pentane 1 : 5). 1H
NMR (400 MHz, CDCl3): δ 9.91 (s, 1H), 7.86–7.82 (m, 2H),
7.23–7.18 (m, 2H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ 191.0, 168.8, 155.4, 134.1, 131.3, 122.5, 21.2. MS m/z 164 [M]+.
NMR data are in accordance with literature values.25
4-Formylphenyl benzoate. Rf 0.30 (Et2O–pentane 1 : 6). 1H
NMR (400 MHz, CDCl3): δ 9.90 (s, 1H), 8.13–8.06 (m, 2H),
7.89–7.81 (m, 2H), 7.59–7.51 (m, 1H), 7.46–7.38 (m, 2H),
7.34–7.27 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 191.0, 164.5,
155.7, 134.10, 134.07, 131.3, 130.3, 128.9, 128.8, 122.6. MS m/z
226 [M]+. NMR data are in accordance with literature values.26
4-((tert-Butyldiphenylsilyl)oxy)benzaldehyde. Rf 0.28 (Et2O–
pentane 1 : 20). 1H NMR (400 MHz, CDCl3): δ 9.82 (s, 1H),
9 J. J. Verendel, M. Nordlund and P. G. Andersson, Chem-
SusChem, 2013, 6, 426–429.
7.77–7.60 (m, 6H), 7.52–7.33 (m, 6H), 6.93–6.81 (m, 2H), 1.12 10 C. K. Brown and G. Wilkinson, J. Chem. Soc. A, 1970, 2753–2764.
(s, 9H). 13C NMR (100 MHz, CDCl3): δ 191.0, 161.3, 135.5, 11 P. Fristrup, M. Kreis, A. Palmelund, P.-O. Norrby and
132.1, 131.8, 130.39, 130.36, 128.1, 120.4, 26.5, 19.6. MS m/z
360 [M]+. NMR data are in accordance with literature values.27
4-(Benzyloxy)benzaldehyde. Rf 0.22 (Et2O–pentane 1 : 10). 1H
R. Madsen, J. Am. Chem. Soc., 2008, 130, 5206–5215.
12 A. Brennführer, H. Neumann, S. Klaus, T. Riermeier,
J. Almena and M. Beller, Tetrahedron, 2007, 63, 6252–6258.
NMR (400 MHz, CDCl3): δ 9.88 (s, 1H), 7.88–7.80 (m, 2H), 13 R. N. Monrad and R. Madsen, J. Org. Chem., 2007, 72,
7.49–7.33 (m, 5H), 7.12–7.04 (m, 2H), 5.14 (s, 2H). 13C NMR
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(100 MHz, CDCl3): δ 190.8, 163.7, 136.0, 132.0, 130.1, 128.8, 14 A. G. Sergeev, A. Spannenberg and M. Beller, J. Am. Chem.
128.4, 127.5, 115.2, 70.3. MS m/z 212 [M]+. NMR data are in
Soc., 2008, 130, 15549–15563.
accordance with literature values.28
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Acknowledgements
We thank The Danish Council for Strategic Research and 17 H. Li, L. C. M. Castro, J. Zheng, T. Roisnel, V. Dorcet,
Nordic Energy Research (N-INNER II) for financial support.
J.-B. Sortais and C. Darcel, Angew. Chem., Int. Ed., 2013, 52,
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