of 12
Palladium-Catalyzed Decarbonylative Dehydration of Fatty Acids
for the Production of Linear Alpha Olefins
Yiyang Liu
,
Kelly E. Kim
,
Myles B. Herbert
,
Alexey Fedorov
,
Robert H. Grubbs
*
, and
Brian
M. Stoltz
*
The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering,
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E.
California Blvd, MC 101-20, Pasadena, CA 91125, USA
Abstract
A highly efficient palladium-catalyzed decarbonylative dehydration reaction of carboxylic acids is
reported. This method transforms abundant and renewable even-numbered natural fatty acids into
valuable and expensive odd-numbered alpha olefins. Additionally, the chemistry displays a high
functional group tolerance. The process employs low loading of palladium catalyst and proceeds
under solvent-free and relatively mild conditions.
Keywords
fatty acids; decarbonylative dehydration; linear alpha olefins; renewable feedstocks; palladium;
large scale process
Linear alpha olefins represent an important class of industrial chemicals with a wide range
of applications. They are used as co-monomers for ethylene polymerization
[1]
as well as
precursors to plasticizers, lubricants, and surfactants.
[2]
Currently, these olefins are mainly
produced by oligomerization of ethylene,
[3]
which, in turn, is derived from petroleum. As
the world's oil reserves continue to diminish, development of renewable feedstocks for the
production of alpha olefins becomes increasingly important. One obvious choice is ethylene
from biomass-derived ethanol.
[4]
A potentially more direct method is the decarbonylative
dehydration of long chain fatty acids. The latter route is particularly attractive because fatty
acids are inexpensive and readily available starting materials derived from many natural
sources. Since natural fatty acids contain an even number of carbon atoms, their
corresponding alpha olefins will be odd-numbered after decarbonylative dehydration.
Moreover, conventional ethylene oligomerization processes deliver only even-numbered
alpha olefins,
[3]
and odd-numbered olefins are largely inaccessible and prohibitively
expensive.
[5]
These odd-numbered olefins are valuable building blocks in the synthesis of
various fine chemicals such as lepidopteran insect pheromones, but are currently far too
*
Fax: (+1)-626-395-8436, stoltz@caltech.edu, rhg@caltech.edu.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201######
. ((Please delete if
not appropriate))
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Published in final edited form as:
Adv Synth Catal
. 2014 January 1; 356(1): 130–136. doi:10.1002/adsc.201301109.
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costly to be practical.
[6]
Therefore, the development of an efficient and economic process for
fatty acid decarbonylative dehydration is highly desirable.
Many strategies to convert fatty acids to alpha olefins have been pursued. Lead tetraacetate-
mediated oxidative decarboxylation is a classical method.
[7]
Alternative protocols that avoid
stoichiometric toxic reagents have also been developed, such as Kolbe electrolysis
[8]
and
silver-catalyzed oxidative decarboxylation.
[9]
However, these reactions proceed through
highly reactive radical intermediates, and thus suffer from low yields due to many side
reactions. A more recent approach entails the transition metal-catalyzed decarbonylative
dehydration of fatty acids. A variety of transition metals including rhodium,
[10]
iridium,
[11]
palladium,
[12]
and iron
[13]
have been shown to catalyze decarbonylative dehydration
reactions. To date, palladium has demonstrated the highest activity, and catalyst loadings as
low as 0.01 mol% have been reported independently by Miller
[12a]
and Kraus
[12b]
(Scheme
1A). Unfortunately, their methods require very high temperatures (230–250 °C). In addition,
it is necessary to distill the olefin product from the reaction mixture as soon as it is formed
in order to prevent double bond isomerization, and therefore only volatile olefins can be
produced this way. Decarbonylation processes under milder conditions have been developed
independently by Gooßen
[12c]
and Scott
[12d]
(Scheme 1B). Although their reactions proceed
at 110 °C, much higher palladium catalyst loading (3 mol%) and an expensive, high-boiling-
point solvent (DMPU) are required. We envisioned that by judicious choice of ligand set for
palladium and other parameters, the most advantageous aspects of these two systems could
be combined. Herein we report a palladium-catalyzed decarbonylative dehydration using
low catalyst loading under relatively mild and solvent-free conditions to produce alpha
olefins in good yield and high selectivity (Scheme 1C).
At the outset of our study, we examined the palladium-catalyzed decarbonylative
dehydration of stearic acid
1a
in neat acetic anhydride as the dehydrating agent (Table 1). A
preliminary survey of phosphine ligands revealed Xantphos to be an optimal and unique
ligand for the transformation (entries 1–4). It is believed that acetic anhydride converts the
stearic acid into stearic anhydride in situ, which then undergoes oxidative addition by Pd(0)
to initiate the catalytic cycle.
[12]
Considering that acetic anhydride itself could compete with
stearic anhydride for oxidative addition at the metal center, we sought to simplify the system
by using pre-formed stearic anhydride
1a’
alone. To our surprise, the decarbonylation of
neat stearic anhydride with the same catalyst was exceedingly slow (only 12% yield, 120
TON, in 2 h; entry 5). Comparing the two systems, we found that the former had one
equivalent of acid in it, while the latter was acid-free. Thus, we posited that acid might play
a role in promoting reactivity. Consequently we added 1 mol% isophthalic acid to the
system, and the yield rose to 22% (entry 6). When the ligand-to-metal ratio was reduced
from 4:1 to 1.2:1, the yield dramatically increased to 92%, but the selectivity dropped to
31% (entry 7). Since it has been shown previously that triphenylphosphine can inhibit olefin
isomerization,
[12a]
we used PdCl
2
(PPh
3
)
2
instead of PdCl
2
(nbd) (nbd = norbornadiene), and
we were delighted to observe an increase in selectivity to 54% with negligible erosion in
yield (90%; entry 8). Finally, we examined a number of protic additives (entries 9–12), and
found that (
t
-Bu)
4
biphenol gave the optimal overall performance to furnish the highest yield
of alpha olefin (entry 12).
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One major limitation of using pre-formed stearic anhydride as the substrate is that only half
of the molecule can be converted to the olefin while the other half is wasted as stearic acid,
so the maximum theoretical yield based on the acid is 50%. Control experiments also
revealed that the buildup of acid in the reaction mixture was responsible for olefin
isomerization and erosion of alpha selectivity. We envisioned that portionwise addition of
acetic anhydride to the reaction mixture and distillation of acetic acid in situ could transform
stearic acid back into its anhydride, thereby reducing acid concentration and increasing the
yield and selectivity (Table 2). When two portions of acetic anhydride were added to the
reaction mixture with immediate distillation of acetic acid, once every 1.5 hours, the olefin
product was obtained in 69% yield based on stearic acid and 62% selectivity (entry 1).
Furthermore, when three portions of acetic anhydride were added, once every hour, the
olefin product was obtained in 67% yield and 86% alpha selectivity (entry 2). Finally, when
six portions of acetic anhydride were added, once every half hour, the olefin product was
obtained in 67% isolated yield and 89% alpha selectivity (entry 3). The selectivity trend
clearly shows that the more frequently acetic anhydride is added to dehydrate stearic acid,
the higher the alpha selectivity. This is a remarkable result in that it is possible to maintain
high selectivity without having to distill the olefin product out of the reaction mixture as it
forms.
With the optimized conditions in hand, we explored the decarbonylative dehydration of a
variety of fatty acid substrates, as shown in Table 3. Common saturated fatty acids with
carbon numbers from 12 to 18 all provided the corresponding olefin in good yield and high
alpha selectivity (entries 1–4). In particular, volatile olefins were formed with exceptionally
high selectivities (entries 3 and 4). Terminally functionalized fatty acids were also
competent substrates, and functional groups such as esters, chlorides, imides, silyl ethers,
ketones, terminal olefins, and substituted aromatics were all well tolerated (entries 5–13).
Notably, allylbenzene derivative
2k
was formed with 91% alpha selectivity (entry 11),
which is impressive considering the significant thermodynamic driving force for
isomerization into conjugation with the aromatic ring. Carboxylic acids with
α
- or
β
-
substituents were considerably less reactive (entries 14–16). Nevertheless, catalyst turnovers
up to 400 could be achieved for these challenging substrates. Compared to previous reports
by Miller
[12a]
and Kraus,
[12b]
our reaction exhibits a much broader scope, does not require
distillation of the olefin products to maintain high selectivity, and is compatible with various
heteroatom-containing functional groups.
Since this process requires no solvent and low catalyst loading, it can be readily scaled up
(Scheme 2). In a laboratory setting, a 100 mmol scale (28.4 g stearic acid or 23.0 g 10-
acetoxydecanoic acid) decarbonylative dehydration was easily carried out in a 100 mL
round-bottom flask. Compared with small-scale reactions, the large-scale ones afforded
products in similar yields and slightly higher alpha selectivity. When the olefin is
sufficiently volatile, it is distilled out together with the acetic acid (Table 3, entries 3–6, 11,
and 13). Although distillation of olefin is not necessary in order to maintain high selectivity
(e.g. Scheme 2A), it is convenient to do so for volatile olefins (Scheme 2B).
The olefin products thus obtained are important building blocks in chemical synthesis. For
example, 8-nonenyl acetate (
2f
) is a precursor to insect pheromones
4a
(Oriental fruit moth
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pheromone)
[14]
and
4b
(Figure-of-Eight moth pheromone).
[15]
Aided by
Z
-selective cross
metathesis catalyst
5
, olefin
2f
reacts with 1-pentene or 1-hexene to afford pheromones
4a
or
4b
in 58% and 48% yield, respectively, and >98%
Z-
selectivity (Table 4).
[6b]
In summary, we have developed a highly efficient palladium-catalyzed decarbonylative
dehydration process that converts carboxylic acids (e.g. fatty acids) to linear alpha olefins in
good yield and with high selectivity. The reaction requires low palladium catalyst loading
and proceeds under solvent-free and relatively mild conditions. In situ distillation of the
olefin product is not necessary, and a wide range of functionalized and unfunctionalized
carboxylic acids can be transformed into their corresponding olefins. Process development
for large-scale production is underway and will be reported in due course.
Experimental Section
A 15 mL round-bottom flask was charged with PdCl
2
(PPh
3
)
2
(0.01 mmol, 0.05 mol%),
Xantphos (0.012 mmol, 0.06 mol%), (
t
-Bu)
4
biphenol (0.1 mmol, 0.5 mol%), and fatty acid
substrate (20 mmol, 1 equiv). The flask was equipped with a distillation head and a 25 mL
round-bottom receiving flask. The closed system was connected to a vacuum manifold,
equipped with a needle valve and a digital vacuum gauge. The system was evacuated and
refilled with N
2
(x 3), and the first portion of acetic anhydride (20 mmol, 1 equiv) was added
via syringe through the septum that seals the top of the distillation head. The flask was
lowered into a 20 °C oil bath and gradually heated to 132 °C in 23 min. When oil bath
temperature rose to 122 °C, the needle valve was closed, switched to vacuum, and the needle
valve carefully and slowly opened to allow distillation of acetic acid into a receiving flask,
which was cooled to –78 °C. When the oil bath temperature reached 130 °C, time was
recorded as t = 0. After distillation ceased (about t = 3 min), the needle valve was opened
fully and a vacuum of 1–5 mmHg was drawn. At t = 30 min, the system was refilled with
N
2
, and the second portion of acetic anhydride (2.8 mmol, 0.14 equiv) was added via
syringe. The system was then gradually (t = 35 min) resubjected to a vacuum of 1–5 mmHg.
Acetic anhydride was added as follows (0.12, 0.10, 0.09. 0.08 equiv) in the same manner
every 30 min. The reaction was stopped at t = 3 h and allowed to cool to ambient
temperature. The residual reaction mixture was purified by flash chromatography. If it
contained solids, it was suction-filtered first and the solids washed with hexanes, and the
filtrate was concentrated and purified by chromatography. In cases where the product was
distilled together with acetic acid, the distillate was added dropwise to a saturated NaHCO
3
solution, stirred for 30 min, and the resulting mixture was extracted with dichloromethane
(30 mL x 3). The combined extracts were dried over Na
2
SO
4
, filtered and concentrated. The
crude product was then subjected to flash chromatography or distillation to afford the olefin
in pure form.
Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
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Acknowledgments
The authors wish to thank the Resnick Sustainability Institute at Caltech (graduate fellowship to Y.L.), BP
(postdoctoral fellowship to A.F. under the XC2 program), NIH-NIGMS (R01GM080269, B.M.S.), NIH (NIH
5R01GM031332-27, R.H.G.), the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and
Chemical Synthesis, and Caltech for financial support. Materia, Inc. is thanked for the generous donation of
ruthenium catalysts. Dr. David VanderVelde is acknowledged for NMR spectroscopy assistance. Dr. Mona
Shahgholi and Naseem Torian are acknowledged for high-resolution mass spectrometry assistance. Dr. Scott Virgil
is acknowledged for helpful discussions.
References
1. Ittel SD, Johnson LK, Brookhart M. Chem. Rev. 2000; 100:1169–1203. [PubMed: 11749263]
2. a Marquis DM, Sharman SH, House R, Sweeney WA. J. Am. Oil Chem. Soc. 1966; 43:607–614.b
Franke R, Selent D, Börner A. Chem. Rev. 2012; 112:5675–5732. [PubMed: 22937803]
3. a Al-Jarallah AM, Anabtawi JA, Siddiqui MAB, Aitani AM, Al-Sa'doun AW. Catal. Today. 1992;
14:1–121.b Small BL, Brookhart M. J. Am. Chem. Soc. 1998; 120:7143–7144.
4. Ouyang J, Kong F, Su G, Hu Y, Song Q. Catal. Lett. 2009; 132:64–74.
5. Prices of acids and olefins (Sigma-Aldrich, 10/5/2013):
Acid
$/kg
Olefin
$/kg
Decanoic (C
10
)
16.28
1-Nonene (C
9
)
12,080.00
1-Decene (C
10
)
55.87
Laurie (C
12
)
14.20
1-Undecene (C
11
)
7,240.00
1-Dodecene (C
12
)
187.60
Myristic (C
14
)
11.76
1-Tridecene (C
13
)
23,800.00
1-Tetradecene (C
14
)
47.74
Palmitic (C
16
)
7.68
1-Pentadecene (C
15
)
24,722.58
1-Hexadecene (C
16
)
2,758.62
Stearic (C
18
)
13.20
1-Heptadecene (C
17
)
69,500.00
6. a Herbert MB, Marx VM, Pederson RL, Grubbs RH. Angew. Chem. 2013; 125:328–332.Angew.
Chem. Int. Ed. 2013; 52:310–314.b Rosebrugh LE, Herbert MB, Marx VM, Keitz BK, Grubbs RH.
J. Am. Chem. Soc. 2013; 135:1276–1279. [PubMed: 23317178]
7. Bacha JD, Kochi JK. Tetrahedron. 1968; 24:2215–2226.
8. Kolbe H. Justus Liebigs Ann. Chem. 1849; 69:257–294.
9. a Anderson JM, Kochi JK. J. Org. Chem. 1969; 35:986–989.b van der Klis F, van den Hoorn MH,
Blaauw R, van Haveren J, van Es DS. Eur. J. Lipid Sci. Technol. 2011; 113:562–571.
10. Foglia TA, Barr PA, Am J. Oil Chem. Soc. 1976; 53:737–741.
11. Maetani S, Fukuyama T, Suzuki N, Ishihara D, Ryu I. Organometallics. 2011; 30:1389–1394.
12. a Miller JA, Nelson JA, Byrne MP. J. Org. Chem. 1993; 58:18–20.b Kraus GA, Riley S. Synthesis.
2012; 44:3003–3005.c Gooßen LJ, Rodríguez N. Chem. Commun. 2004:724–725.d Le Nôtre J,
Scott EL, Franssen MCR, Sanders JPM. Tetrahedron Lett. 2010; 51:3712–3715.e Miranda MO,
Pietrangelo A, Hillmyer MA, Tolman WB. Green Chem. 2012; 14:490–494.
13. Maetani S, Fukuyama T, Suzuki N, Ishihara D, Ryu I. Chem. Commun. 2012; 48:2552–2554.
14. Baker TC, Cardé RT, Miller JR. J. Chem. Ecol. 1980; 6:749–758.
15. Subchev M, Toth M, Wu D, Stanimirova L, Toshova T, Karpati Z. J. Appl. Ent. 2000; 124:197–
199.
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Scheme 1.
Palladium-catalyzed decarbonylative dehydration. (
A
) High temperature processes (Miller, Kraus). (
B
) Low temperature
processes (Gooßen, Scott). (
C
) This research.
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Scheme 2.
Large-scale decarbonylative dehydration of stearic acid and 10-acetoxydecanoic acid.
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Table 1
Effects of catalyst, ligand, and additive.
[a]
Entry
Rxn
Pd cat.
Ligand (mol%)
Additive
Yield (%)
[b]
Alpha (%)
[b]
Y × A (%)
[c]
1
A
PdCl
2
(nbd)
PPh
3
(0.8)
--
0
--
0
2
A
PdCl
2
(nbd)
dppp (04)
--
0
--
0
3
A
PdCl
2
(nbd)
DPEphos (0.4)
--
43
59
25
4
A
PdCl
2
(nbd)
Xantphos (0.4)
--
60
55
33
5
B
PdCl
2
(nbd)
Xantphos (0.4)
--
12
100
12
6
B
PdCl
2
(nbd)
Xantphos (0.4)
isophthalic acid
22
96
21
7
B
PdCl
2
(nbd)
Xantphos (0.12)
isophthalic acid
92
31
29
8
B
PdCl
2
(PPh
3
)
2
Xantphos (0.12)
isophthalic acid
90
54
49
9
B
PdCl
2
(PPh
3
)
2
Xantphos (0.12)
p
-TsOH·H
2
O
86
5
4
10
B
PdCl
2
(PPh
3
)
2
Xantphos (0.12)
salicylamide
60
90
54
11
B
PdCl
2
(PPh
3
)
2
Xantphos (0.12)
2,2
-biphenol
59
91
54
12
B
PdCl
2
(PPh
3
)
2
Xantphos (0.12)
(
t
-Bu)
4
biphenol
84
70
59
[a]
Conditions
: A) 1 equiv
1a
(5 mmol), 2 equiv Ac
2
O; B) 1 equiv
1a
(5 mmol).
[b]
Determined by
1
H NMR with methyl benzoate as internal standard. Alpha =
2a/(2a+3a)
.
[c]
Y × A = Yield × Alpha.
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Table 2
Portionwise addition of acetic anhydride.
[a]
Entry
Equiv of Ac
2
O
Yield (%)
[b]
Alpha (%)
[b]
1
1+0.5 (once every 1.5 hours)
69
62
2
1+0.5+0.25 (once every hour)
67
86
3
1+0.14+0.12+0.1+0.09+0.08 (once every half hour)
68 (67)
8
[a]
20 mmol
1a
.
[b]
Determined by
1
H NMR (isolated yield in parentheses).
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Table 3
Substrate scope study.
[
b
]
Entry
Substrate
Product
Yield (%)
[
b
]
TON
Alpha (%)
[
c
]
1
67
1340
89
2
41
820
97
3
65
1300
99
4
73
1460
99
5
[
d
,
e
]
63
1260
98
6
[
d
]
67
1340
96
7
[
d
]
60
1200
89
8
75
1500
86
9
76
1520
83
10
64
1280
80
11
80
1600
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Entry
Substrate
Product
Yield (%)
[
b
]
TON
Alpha (%)
[
c
]
12
49
980
88
13
59
1180
87
14
[
f
]
20
80
[
h
]
400
320
[
h
]
--
[
g
]
--
[
h
]
15
19
380
--
[
g
]
16
[
i
]
71
71
--
[
i
]
a
Conditions
: 20 mmol
1
, 6 portions of Ac
2
O, 1+0.14+0.12+0.10+0.09+0.08 equiv, added every 30 min.
b
Isolated yield (column chromatography).
c
Determined by
1
H NMR.
d
Purified by distillation.
e
18.5 mmol
1e
.
f
PdCl
2
(nbd) (0.05 mol%), PPh
3
(0.05 mol%), Xantphos (0.06 mol%), 1.5 h, 3 portions of Ac
2
O (1+0.15+0.10 equiv).
g
Single isomer observed.
h
PdCl
2
(PPh
3
)
2
(0.25 mol%), Xantphos (0.30 mol%), (
t
-Bu)
4
biphenol (1 mol%),
2n
:
3n
= 49:51.
i
2-methyldecanoic anhydride (10 mmol), no Ac
2
O, PdCl
2
(nbd) (1 mol%), Xantphos (1.1 mol%), salicylamide (2 mol%), 160 °C, 10 mmHg
distillation, 10 h,
3p
:
2p
= 73:27.
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Table 4
Synthesis of pheromones
4a
and
4b
from olefin
2f
.
Product
R
Yield (%)
[a]
Z
(%)
[b]
4a
C
3
H
7
58
>98
4b
C
4
H
9
48
>98
[a]
4.8 mmol
2f
.
[b]
Determined by
1
H NMR.
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