Reevaluation of the Palladium/Carbon-Catalyzed Decarbonylation of Aliphatic Aldehydes

Article abstract of DOI:10.1055/s-0037-1610433

An improved method for the decarbonylation of aliphatic aldehydes by using a commercially available Pd/C catalyst is described. The reaction conditions are suitable for linear, cyclic, or sterically demanding substrates, as they afford the corresponding alkanes in yields of up to 99%. In addition, this Pd/C-catalyzed method exhibits good functional-group tolerance. A comparison of previously reported methods with the present one showed that the reaction conditions play a crucial role in the outcome of the reaction. The method can also be applied in a two-step reaction sequence for the synthesis of industrially important compounds.

Full text of DOI:10.1055/s-0037-1610433

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Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
letter
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Synlett
V. Ajdačić et al.
Letter
Reevaluation of the Palladium/Carbon-Catalyzed Decarbonylation
of Aliphatic Aldehydes
Vladimir Ajdačića
Andrea Nikolića
Michael Kernerb
O
Pd/C (5 mol% Pd)
cyclohexane, MS
H
130 °C, 24 h
H
+
CO
Peter Wipfb
Igor M. Opsenica*a
17 examples
50–99% yield
0
0
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0
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0
0
3
4-
9
4
2
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2
a
7
Faculty of Chemistry, University of Belgrade, PO Box 51, Studentski trg 16,
1158 Belgrade, Serbia
1
igorop@chem.bg.ac.rs
Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue,
Pittsburgh, PA 15260, USA
Cl
b
Received: 15.05.2018
Accepted after revision: 22.05.2018
Published online: 28.06.2018
as pesticides, dyes, and surfactants that are key ingredients
9,10
11
of detergents (Figure 1).
Palladium and rhodium are
DOI: 10.1055/s-0037-1610433; Art ID: st-2018-r0310-l
the most frequently used metals in the transition-metal-
catalyzed decarbonylation of aldehydes.12 Several methods
Abstract An improved method for the decarbonylation of aliphatic
aldehydes by using a commercially available Pd/C catalyst is described.
The reaction conditions are suitable for linear, cyclic, or sterically de-
manding substrates, as they afford the corresponding alkanes in yields
of up to 99%. In addition, this Pd/C-catalyzed method exhibits good
functional-group tolerance. A comparison of previously reported meth-
ods with the present one showed that the reaction conditions play a
crucial role in the outcome of the reaction. The method can also be
applied in a two-step reaction sequence for the synthesis of industrially
important compounds.
for the removal of aldehyde functional group employ a solid-
supported palladium catalyst.2
,13
The palladium/carbon-
catalyzed decarbonylation of aromatic aldehydes has been
known since the1960s,1 but the Pd/C catalyzed decarbon-
ylation of aliphatic aldehydes had not been investigated in
2a
14
detail not even when it was reported for the first time by
Hawthorne and Wilt who used palladium/carbon at elevat-
ed temperatures.1 Also, Tsuji and co-workers reported the
2a
palladium-catalyzed decarbonylation of aliphatic aldehydes
Key words decarbonylation, aldehydes, palladium catalysis, adaman-
tine, alkylated aromatic compounds, natural products
12b,12c
in the gas phase by using palladium/carbon.
Despite
their importance, these procedures had several drawbacks:
high temperatures were required (>180 °C), and complex
reaction mixtures were obtained that included products of
dehydrogenation, isomerization, and decarbonylation.
Recently, Monguchi and Sajiki and their co-workers accom-
plished a Pd/C-catalyzed decarbonylation of dihydrocin-
namaldehydes in isopropanol at 120 °C under an oxygen at-
The removal of functional groups from densely func-
tionalized molecules represents a valuable transformation
in synthetic organic chemistry and process research.1
Whereas carbonyl groups are often essential to the efficient
and convergent assembly of target structures, many final
products lack carbonyl groups, and consequently there is a
need for the development of decarbonylation processes. In
particular, the decarbonylation of aldehydes has been
shown to be an important step in syntheses of industrial
mosphere.15 The addition of Na CO3 promoted the retro-
2
hydroformylation reaction, and the corresponding styrene
derivatives were obtained in good yields.
2
3
chemicals from biomass or of complex intermediates; it
4
can also provide an in situ source of carbon monoxide. The
HO
Cl
decarbonylation of aliphatic aldehydes is a step in the bio-
synthesis of linear carbohydrates, which are important for
Monochasiol A
OH
5
6
the survival and reproduction of microorganisms, plants,
7
and animals.
The decarbonylation of aromatic compounds leads to
alkylated benzenes, which are a common substructure in
8
natural products (Figure 1). In addition, alkylated aromatic
Diphenylmethane
Dodecylbenzene
compounds are valuable intermediates that are widely used
in the synthesis of industrially important compounds, such
Figure 1 Representative alkylated aromatic compounds
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Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Synlett
V. Ajdačić et al.
Letter
We recently developed a method for decarbonylation of
aromatic aldehydes by using a maghemite-supported palla-
dium catalyst. As a continuation of this research, we
examined the use of a Pd/C catalyst for the decarbonylation
of aliphatic aldehydes and the formation of the correspond-
ing alkanes.
As presented in Table 1, we found that palladium/carbon
afforded good to excellent yields of the corresponding de-
carbonylated products in cyclohexane at 130 °C. The decar-
bonylation of hydrocinnamaldehyde (1a) and phenylacetal-
dehyde (1d) resulted in good yields of the desired products,
ethylbenzene (2a) and toluene (2d), respectively (Table 1).
Table 1 (continued)
Aldehyde
Product
16
O
H
2
k (54%)c,e,f
1
1
k
l
O
7
H
8
2l (72%)a
Cl
CHO
Cl
Table 1 Scope of Pd/C-Catalyzed Decarbonylation of Aliphatic
Aldehydes
2m (51%)b
1
m
a
Yields by GC/MS with naphthalene as an internal standard.
Yield by NMR spectroscopy. (The reaction was performed in C
methyl benzoate was used as an internal standard.)
b
6
D
6
6
, and
, and
Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
c
O
Isolated yield.
d
Yield by NMR spectroscopy. (The reaction was performed in C
naphthalene was used as an internal standard.)
10 mol% Pd/C.
The reaction time was 48 h.
6
D
R
R
H
e
1
2
f
Aldehyde
Product
O
O
Furthermore, 3,3-diphenylpropanal (1b) gave 1,1-
diphenylethane (2b) as the major product, along with 1,1-
diphenylethylene (3b) as the minor product (Table 1 and
Scheme 1).
Ph
a
Ph
H
H
2a (67%)
78%)
b
(
1
a
Ph
Ph
Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
Ph
Ph
2b (78%)c
1
b
Ph
78%
O
This work
Ph
Ph
Ph
H
O
2a
Ph
2
2
c (69%)c
Ph
H
1
c
Pd/C (10 mol%)
Na2CO3 (2 equiv)
i-PrOH, O2,
1a
O
120 °C, 24 h
H
Ph
Previous work
reference 15
68%
d (82%)a
1
d
3a
O
Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
n
n
H
Ph
8%
Ph
e, n = 5 (64%)a
Ph
O
2
2
2
2
1
1
1
1
e, n = 5
f, n = 6
g, n = 7
h, n = 8
f, n = 6 (50%)a
Ph
7
+
Ph
a
Ph
H
g, n = 7 (54%)
6%
3b
h, n = 8 (99%)a
1b
2b
O
Scheme 1 Comparative study of the decarbonylation of hydro-
cinnamaldehyde and 3,3-diphenylpropanal
H
2
2
i (74%)d
A comparison of these experimental results with those
obtained by Monguchi, Sajiki, and co-workers15 suggested
that the outcome of the decarbonylation reaction is strong-
ly dependent on the reaction conditions (Scheme 1). The
1
1
i
j
O
H
j (78%)c,e,f
presence of Na CO and an oxygen atmosphere promote the
2 3
retro-hydroformylation reaction and the formation of the
corresponding styrene.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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V. Ajdačić et al.
Letter
The decarbonylation was also applicable to long-chain
aliphatic aldehydes (Table 1). Nonanal (1f) was completely
consumed to give octane (2f) in 50% yield. Notably, oct-1-
ene was not detected by GC-MS. The lower yield is presum-
ably due to co-evaporation of the desired product during
the reaction. In addition, undecanal (1h) was converted
completely into decane (2h). For octanal (1e) and decanal
compounds 1n and 1o were successfully decarbonylated to
give the corresponding products 2n and 2o in good to ex-
cellent yields (Scheme 2).
α-Arylation/decarbonylation
Pd(OAc), L
Br
Cs2CO3
dioxane, 80 °C
O
R
(
1g), the corresponding alkanes 2e and 2g were obtained as
+
( )6
H
the major products, along with mixtures of alkenes in 14%
and 13% yield, respectively. The decarbonylation of the ster-
ically demanding adamantanes 1-adamantylacetaldehyde
CHO
R
for 1n L = XantPhos
for 1o L = rac-BINAP
1n, R = OCH3, 65%
1o, R = COCH3, 34%
(
1j) and adamantane-1-carbaldehyde (1k) gave the desired
products 1-methyladamantane (2j) and adamantane (2k)
in 78% and 54% isolated yield, respectively. For the adaman-
tane aldehydes, we observed that the reaction was not
completed with 5 mol% of Pd/C; instead the use of a 10
mol% loading of Pd/C and an extension of the reaction time
to 48 hours were required to attain full conversion of the
starting materials. Moreover, alkenyl aldehyde 1l gave the
desired decarbonylated product 2l in good yield. Notably,
the decarbonylation could also be extended to aryl chlo-
rides. The decarbonylation of 3-(3-chlorophenyl)propanal
Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
R
2
2
n, R = OCH3, 95%
o, R = COCH3, 76%
Scheme 2 The scope of the method
(
1m) afforded 1-chloro-3-ethylbenzene (2m) in 51% yield,
along with a 15% yield of 1-chloro-3-ethenylbenzene.
To gain a better insight into the outcome of the decarbo-
nylation reaction, we performed the decarbonylation of
hydrocinnamaldehyde (1a) and cyclohexanecarbaldehyde
We further demonstrated, in one example, that the de-
carbonylation reaction can be employed on the densely
functionalized inexpensive natural product 4 (Scheme 3).
Unfortunately, besides the desired alkane 5, significant
amounts of alkene products were also obtained (al-
kane/alkene ratio ≤55:45). This drawback was overcome by
(
1i) in C D , at 130 °C for 24 hours, and analyzed the spectra
6 6
of the reaction mixtures (Table 1 and Supporting Informa-
tion). As expected, the starting material was consumed and
the corresponding decarbonylated products, ethylbenzene
adding H gas, and after hydrogenation, the corresponding
2
saturated decarbonylated derivative was obtained in a good
yield. Despite the low selectivity, with this substrate we
demonstrated that the corresponding saturated product
could be obtained in good yield by a two-step procedure.
When (±)-citronellal (6) was subjected to the decarbon-
ylation reaction, the decarbonylated product 7 and p-cy-
mene (9) were obtained in 36% and 23% yield, respectively,
along with 2,6-dimethylheptane (8) and a mixture of
dienes and other compounds (Scheme 4). The formation of
p-cymene might occur through an intramolecular alkene
hydroacylation reaction (Scheme 4).
(
2a) and cyclohexane (2i) were obtained in good yields as
the only products. Notably, the formation of styrene and
cyclohexene was not detected.
The use of the aldehyde functional group as a protective
group17 or as a transient directing group makes the decar-
bonylation reaction very appealing for the synthesis of di-
verse organic compounds, including several natural prod-
18
19
ucts. The utility of the decarbonylation reaction was fur-
ther demonstrated in the syntheses of alkylated aromatic
compounds (Scheme 2). The α-aryl carbonyl compounds 1n
and 1o were synthesized by a previously reported meth-
To gain a better insight into the mechanism of the de-
carbonylation reaction, we performed a deuterium-labeling
20,21
od,
involving the Pd-catalyzed α-arylation of octanal
with the corresponding bromoarenes. The α-aryl carbonyl
experiment. (Scheme 5). The decarbonylation of [α-D ]-1-
1
adamantylacetaldehyde (d-1j) gave [1D ]-1-methylada-
1
O
OAc
1) Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
OAc
H
2) H2, Pd/C, EtOH, r.t.
85%
AcO
OAc
AcO
OAc
H
H
4
5
Scheme 3 Decarbonylation of natural product 4
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Synlett
V. Ajdačić et al.
Letter
Pd/C (5 mol%)
cyclohexane, MS
argon, 130 °C, 24 h
ditions that we report are milder than those previously re-
12a–c
ported, and there are few or no byproducts.
The conver-
sion of all substrates resulted in good to excellent yields of
the desired products. The reaction conditions could also be
applied to sterically demanding substrates. In addition, a
variety of functional groups, including alkenyl, ketone,
ether, and ester, were well tolerated in this process. The
level of functional-group compatibility extends even to re-
active aryl halides. The method is also applicable in a two-
step procedure for the synthesis of alkylated aromatic com-
pounds that have a variety of uses in industry.
+
+
O
6
7
, 36%
8, 8%
9, 23%
Pd0
Pd0
O
PdII
H
O
O
PdII
O
PdII
H
Scheme 4 Decarbonylation of (±)-citronellal (6). The GC-MS yield,
with naphthalene as an internal standard, is reported.
Funding Information
This research was financially supported by the Ministry of Education,
Science and Technological Development of Serbia (Grant No. 172008).
The authors acknowledge the support of the FP7 RegPot project FCUB
ERA GA No. 256716. The EC does not share responsibility for the con-
mantane (d-2j; Scheme 5). The partial loss of the deuteri-
um label suggested that the decarbonylation of d-1j is slow-
er than that of 1-adamantylacetaldehyde (1j).
12h
tent of the article.
)(
Pd/C (10 mol%)
cyclohexane, MS
argon, 130 °C, 48 h
O
Supporting Information
D(56%)
D(85%)
Supporting information for this article is available online at
61%
d-1j
d-2j
https://doi.org/10.1055/s-0037-1610433.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
Scheme 5 Deuterium labeling experiment
References and Notes
On the basis of the above observed results and previous
reports, we propose the plausible mechanism for the de-
carbonylation of aliphatic aldehydes shown in Scheme 6.
12h
(1) Modak, A.; Maiti, D. Org. Biomol. Chem. 2016, 14, 21.
(
2) (a) Huang, Y.-B.; Yang, Z.; Chen, M.-Y.; Dai, J.-J.; Guo, Q.-X.; Fu, Y.
ChemSusChem 2013, 6, 1348. (b) Ishida, T.; Kume, K.; Kinjo, K.;
Honma, T.; Nakada, K.; Ohashi, H.; Yokoyama, T.; Hamasaki, A.;
Murayama, H.; Izawa, Y.; Utsunomiya, M.; Tokunaga, M. Chem-
SusChem 2016, 9, 3441.
H2
CO
CO
desorption
(
3) (a) Hu, P.; Snyder, S. A. J. Am. Chem. Soc. 2017, 139, 5007.
L
OC PdII
H
(b) Biswas, P.; Paul, S.; Guin, J. Synlett 2017, 28, 1244. (c) Hu, J.;
OC Pd0
L
H
L
Pd0
O
reductive
elimination
Yu, X.; Xie, W. Synlett 2017, 28, 2517.
(4) Hattori, T.; Ueda, S.; Takakura, R.; Sawama, Y.; Monguchi, Y.;
Sajiki, H. Chem. Eur. J. 2017, 23, 8196.
R
H
R
R
(5) Schirmer, A.; Rude, M. A.; Li, X. Z.; Popova, E.; del Cardayre, S. B.
Science 2010, 329, 559.
oxidative
addition
R
L
(6) (a) Bernard, A.; Joubès, J. Prog. Lipid Res. 2013, 52, 110. (b) Wolf,
F. R. Appl. Biochem. Biotechnol. 1983, 8, 249.
OC PdII
H
L
PdII
H
OC PdII
H
H
(
7) (a) Cheesebrough, T. M.; Kolattukudy, P. E. J. Biol. Chem. 1988,
63, 2738. (b) Yoder, J. A.; Denlinger, D. L.; Dennis, M. W.;
Kolattukudy, P. E. Insect Biochem. Mol. Biol. 1992, 22, 237.
H
R
O
2
R
β−Η elimination
migratory
extrusion
(8) Kikuchi, H.; Ito, I.; Takahashi, K.; Ishigaki, H.; Iizumi, K.;
Kubohara, Y.; Oshima, Y. J. Nat. Prod. 2017, 80, 2716.
Scheme 6 Proposed mechanism for the decarbonylation of aliphatic
aldehydes
(
9) Khadilkar, B. M.; Borkar, S. D. J. Chem. Technol. Biotechnol. 1998,
1, 209.
10) Wang, J.-J.; Chuang, Y.-Y.; Hsu, H.-Y.; Tsai, T.-C. Catal. Today
017, 298, 109.
7
(
(
2
Oxidative addition of the C(O)–H bond of the aldehyde
to palladium provides an acylpalladium hydride complex.
Subsequent migratory extrusion of carbon monoxide and
reductive elimination gives the alkane product, while de-
sorption of CO regenerates the catalyst.
11) (a) Tsuji, J.; Ohno, K. Tetrahedron Lett. 1965, 6, 3969. (b) Ohno,
K.; Tsuji, J. J. Am. Chem. Soc. 1968, 90, 99. (c) Walborsky, H. M.;
Allen, L. E. J. Am. Chem. Soc. 1971, 93, 5465. (d) Doughty, D. H.;
Pignolet, L. H. J. Am. Chem. Soc. 1978, 100, 7083. (e) Fristrup, P.;
Kreis, M.; Palmelund, A.; Norrby, P.-O.; Madsen, R. J. Am. Chem.
Soc. 2008, 130, 5206.
In conclusion, we have reassessed the reaction condi-
tions for the decarbonylation of aliphatic aldehydes and the
22
formation of the corresponding alkanes. The reaction con-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

E
Synlett
V. Ajdačić et al.
Letter
(
12) (a) Hawthorne, J. O.; Wilt, M. H. J. Org. Chem. 1960, 25, 2215.
b) Tsuji, J.; Ohno, K.; Kajimoto, T. Tetrahedron Lett. 1965, 6,
565. (c) Tsuji, J.; Ohno, K. J. Am. Chem. Soc. 1968, 90, 94.
d) Wilt, J. W.; Pawlikowski, W. W. Jr. J. Org. Chem. 1975, 40,
(22) Pd/C-Catalyzed Decarbonylation of Aliphatic Aldehydes:
Decarbonylation of 3-phenylpropanal to ethylbenzene (2a);
Typical Procedure
(
4
(
[CAS Reg. No. 100-41-4]
3
641. (e) Matsubara, S.; Yokota, Y.; Oshima, K. Org. Lett. 2004, 6,
A dry glass reaction tube, purged with argon and equipped with
a magnetic stirrer bar, was charged with 3–4 Å MS (100 mg),
aldehyde 1a (50 μL, 0.38 mmol), Pd/C (20 mg, 5 mol% Pd), and
cyclohexane (1 mL). The tube was sealed and heated at 130 °C
for 24 h. The mixture was then cooled to r.t., filtered through a
pad of Celite, and washed with CH Cl (15–20 mL), to give PhEt
2071. (f) Modak, A.; Deb, A.; Patra, T.; Rana, S.; Maity, S.; Maiti,
D. Chem. Commun. 2012, 48, 4253. (g) Modak, A.; Naveen, T.;
Maiti, D. Chem. Commun. 2013, 49, 252. (h) Modak, A.; Rana, S.;
Phukan, A. K.; Maiti, D. Eur. J. Org. Chem. 2017, 4168.
(
13) Kundu, P. K.; Dhiman, M.; Modak, A.; Chowdhury, A.;
Polshettiwar, V.; Maiti, D. ChemPlusChem 2016, 81, 1142.
14) Tsuji, J.; Ohno, K. Synthesis 1969, 157.
2
2
(2a) in 67% GC-MS yield (naphthalene as standard); GC-MS:
+
(
(
m/z = 106.1 [M] .
15) Hattori, T.; Takakura, R.; Ichikawa, T.; Sawama, Y.; Monguchi, Y.;
Sajiki, H. J. Org. Chem. 2016, 81, 2737.
NMR Spectroscopic Analysis: A dry glass reaction tube, purged
with argon and equipped with a magnetic stirrer bar, was
charged with 3–4 Å MS (100 mg), aldehyde 1a (40 μL, 0.30
mmol), Pd/C (16 mg, 5 mol% Pd), and C D (1 mL). The tube was
sealed and heated at 130 °C for 24 h. The mixture was then
cooled to r.t. and filtered through a short pad of silica gel to
(
16) Ajdačić, V.; Nikolić, A.; Simić, S.; Manojlović, D.; Stojanović, Z.;
Nikodinovic-Runic, J.; Opsenica, I. M. Synthesis 2018, 50, 119.
17) Smari, I.; Youssef, C.; Yuan, K.; Beladhria, A.; Ben Ammar, H.;
Ben Hassine, B.; Doucet, H. Eur. J. Org. Chem. 2014, 1778.
18) Taarning, E.; Madsen, R. Chem. Eur. J. 2008, 14, 5638.
19) Akanksha, ???.; Maiti, D. Green Chem. 2012, 14, 2314.
20) Martín, R.; Buchwald, S. L. Org. Lett. 2008, 10, 4561.
21) Martín, R.; Buchwald, S. L. Angew. Chem. Int. Ed. 2007, 46, 7236.
6
6
(
(
(
(
(
remove the catalyst. The silica gel was then washed with C D6
6
(2 × 0.5 mL) to give PhEt (2a) in 78% NMR yield (BzOMe as stan-
1
dard). H NMR (500 MHz, C D ): δ = 7.10–7.00 (m, 5 H), 2.43 (q,
6
6
13
J = 7.5 Hz, 2 H), 1.06 (t, J = 7.5 Hz, 3 H). C NMR (125 MHz,
C D ): δ = 144.3, 128.6, 128.1, 125.9, 29.2, 15.8..
6
6
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E