Palladium-Catalyzed Aminocarbonylation of Aliphatic Alkenes with N,N-Dimethylformamide as an in Situ Source of CO

Article abstract of DOI:10.1002/cctc.201500824

The palladium-catalyzed aminocarbonylation of aliphatic alkenes is presented for the first time without the need for external CO pressure. N,N-dimethylformamide (DMF) is used as an in situ source of both the required carbon monoxide and the amine substrate. The applied palladium catalytic system is well-known for a number of carbonylation reactions, including those with CO surrogates and tandem isomerizing carbonylations. The reaction pathway was investigated and proved to proceed by an acid-catalyzed DMF decomposition to CO and dimethyl amine with subsequent aminocarbonylation of the alkene. Pressure-versus-time curves gave more insight into the correlation between acid concentration and aminocarbonylation activity. Aliphatic alkenes (terminal and internal) are transformed, also in commercial glassware, into the corresponding linear N,N-dimethylamides with excellent selectivities. Hence, amide synthesis by aminocarbonylation moves closer to application in standard organic laboratories. Do-it-yourself CO production: The aminocarbonylation of alkenes for aliphatic amide synthesis is presented for the first time using N,N-dimethylamine as an in situ source of both, the required CO and dimethylamine. Excellent selectivities to the linear product are ensured by isomerizing carbonylation applying a [Pd]/1,2-DTBPMB system. 1,2-DTBPMB=1,2-bis((di-tert-butylphos- phino)methyl)benzene.

Full text of DOI:10.1002/cctc.201500824

DOI: 10.1002/cctc.201500824
Full Papers
Palladium-Catalyzed Aminocarbonylation of Aliphatic
Alkenes with N,N-Dimethylformamide as an In Situ Source
of CO
Thomas Seidensticker,[a] Marc R. L. Furst,[b] Robin Frauenlob,[b] Johanna Vondran,[a]
Eckhard Paetzold,[b] Udo Kragl,[c] and Andreas J. Vorholt*[a]
The palladium-catalyzed aminocarbonylation of aliphatic al-
kenes is presented for the first time without the need for exter-
nal CO pressure. N,N-dimethylformamide (DMF) is used as an
in situ source of both the required carbon monoxide and the
amine substrate. The applied palladium catalytic system is
well-known for a number of carbonylation reactions, including
those with CO surrogates and tandem isomerizing carbonyla-
tions. The reaction pathway was investigated and proved to
proceed by an acid-catalyzed DMF decomposition to CO and
dimethyl amine with subsequent aminocarbonylation of the
alkene. Pressure-versus-time curves gave more insight into the
correlation between acid concentration and aminocarbonyla-
tion activity. Aliphatic alkenes (terminal and internal) are trans-
formed, also in commercial glassware, into the corresponding
linear N,N-dimethylamides with excellent selectivities. Hence,
amide synthesis by aminocarbonylation moves closer to appli-
cation in standard organic laboratories.
Introduction
Numerous methods exist for the preparation of amides, al-
though their synthesis without the generation of waste and
the use of toxic reagents can be challenging. Usually, amides
are derived from the corresponding carboxylic derivatives
(esters, anhydrides, acyl chlorides) with the respective amines,
and the use of coupling reagents is often necessary.[1] Hence,
the development of more atom-economic and environmentally
benign strategies for amide synthesis is one of the major goals
of synthetic organic chemistry.[2] Catalytic systems offer the po-
tential to apply less activated substrates for amide synthesis,
resulting in less waste production. Therefore, catalytic amide
synthesis has attracted many researchers in recent years and
different systems have been developed.[3] Milstein and co-
workers, for instance, have developed a ruthenium catalyst
yielding an amide by the coupling of an amine and an alco-
hol.[4] Another elegant way for the generation of amides from
readily available substrates is by aminocarbonylation of olefins.
This carbonylative reaction has initially been described by
Reppe with nickel catalysts,[5] and among others, different pal-
ladium catalytic systems have been developed for aminocar-
bonylation of alkenes[6–11] and alkynes[12–23] since then. The ap-
plication of CO as an active, versatile and low-cost C1 building
block for the functionalization of alkenes is nowadays an indis-
pensable technique in the chemical industry. However, its in-
herent toxicity and the need for special equipment to econom-
ically and safely use this gas results in a significant inconven-
ience to handle it, especially in common organic laboratories.
As a result, the substitution of CO in carbonylation reactions
by less toxic and easier-to-handle synthetic equivalents is of
considerable academic interest.[24,25] For amide formation from
olefins, formamides represent ideal CO surrogates.
[a] T. Seidensticker, J. Vondran, Dr. A. J. Vorholt
Lehrstuhl Technische Chemie, Fakultät Bio- und Chemieingenieurwesen
Technische Universität Dortmund
The reaction of olefins with formamide to amides under
nickel catalysis and CO pressure was already conducted by
Reppe in his initial studies on catalytic carbonylations.[5] How-
ever, first reports on other metals than nickel for this transfor-
mation have not been published until the report of Kondo and
Watanabe et al. on a ruthenium-catalyzed system.[26] Later on,
the drawback of external CO pressure for maintaining catalytic
activity was addressed by Kondo and co-workers, and the first
CO free aminocarbonylation of olefins with formamides was
developed by ruthenium catalysis.[27] Since then, different cata-
lytic systems for either inter- or intramolecular additions of
formamides to olefins have been developed. Notably, a blurred
taxonomy exists for this transformation (Scheme 1): The amide
formation from an alkene with CO and an amine is designated
aminocarbonylation, but the corresponding addition of form-
Emil-Figge-Straße 66, 44227 Dortmund (Germany)
Fax: (+49)231-7552311
E-mail: andreas.vorholt@bci.tu-dortmund.de
Homepage: http://www.tc.bci.tu-dortmund.de
[b] M. R. L. Furst,+ R. Frauenlob, E. Paetzold
Leibniz Institut für Katalyse (LIKAT)
Albert Einstein Str. 29A, 18059 Rostock (Germany)
[c] U. Kragl
Institut für Chemie
Universität Rostock
Albert Einstein Str. 3A, 18059 Rostock (Germany)
[+] Present Address:
University of Cape Town
Department of Chemical Engineering, Centre for Catalysis Research
South Lane, Rondebosch 7701 (South Africa)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500824.
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composition of those in their investigations on microwave-as-
sisted Pd-catalyzed aminocarbonylation of aryl bromides under
basic conditions.[40,41] Notably, all other reports on carbonyla-
tions with DMF did not mention decomposition, and DMF de-
composition under acidic conditions at 808C is also not report-
ed.
Thus, to effectively keep carbon monoxide and dimethyl-
amine in the condensed phase, thereby expectantly promoting
aminocarbonylation, we changed the reaction vessel to
a custom-made pressure-resistant autoclave. Taking inspiration
from the results of Hallberg, we first raised the temperature to
1208C. In Hallberg’s investigations, imidazole was used as a co-
catalyst in a ratio of 1:1 of substrate/imidazole to promote ami-
nocarbonylation, thus we decided to add imidazole to our re-
action setup. We tested different MSA/imidazole ratios on our
system (Table 1) to find out whether imidazole acts as a co-cat-
alyst in our aminocarbonylation to conclude a catalytic mecha-
nism.
Scheme 1. Reactions of (form)amides with linear 1-alkenes.
amides to olefins is denoted as hydrocarbamoylation[28–33] and
sometimes also as hydroamidation.[34–36] Some reports also use
the term hydroamidation as a synonym for aminocarbonyla-
tion.[37,38] In contrast, hydroamidation is more often referred to
as the addition of an amide to an olefin under the formation
of a higher substituted amide (i.e., CÀN-bond formation).[39]
Low-molecular aliphatic formamides such as N,N-dimethyl-
formamide (DMF) are especially interesting, as they are cheap
and readily available, and hence, their application as an amide
building block is an interesting alternative to the synthesis
with CO, particularly in standard organic laboratories. Such
a way has been reported for aryl halides,[40–44] alkynes,[28,45] and
alkenes.[29] However, usually either high catalyst loadings (up
to 10 mol%) are required or the system is limited to expensive
aryl iodides and bromides as substrates.
Table 1. Influence of imidazole addition on the aminocarbonylation.[a]
[b]
Entry
Imidazole
(eq./1a)[c]
MSA
(eq./1a)[c]
S2a+3a
(2a:3a)
Y2a+3a
In our ongoing interest in palladium-catalyzed carbonylation
reactions, especially with the high-performance ligand involved
in the methoxycarbonylation of aliphatic alkenes for the pro-
duction of linear esters, 1,2-bis((di-
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.0
1.0
1.0
0.75
0.5
0.25
0
0.7
0.5
0.2
0.7
0.7
0.7
0.7
0
0
0
0
0
0
0
0
tert-butylphosphino)methyl)ben-
zene (1,2-DTBPMB, Figure 1),[46–56]
94Æ1 (21:1)
91Æ1 (22:1)
0
36Æ5
47Æ5
0
we developed the idea of amino-
carbonylation of linear aliphatic 1-
[a] Conditions: 7 mL stainless steel autoclave, 1a (1 mL, 6.33 mmol),
Pd(acac)2 (19.3 mg, 0.063 mmol), 1,2-DTBPMB (4 equiv./Pd: 100 mg,
0.25 mmol), DMF (5 mL), 1208C, 20 h. [b] Entries 5, 6: all reactions were
repeated 2–4 times. Yield (Y) is given as sum of both amide isomers
(2a+3a) and reported in% based on GC–FID analysis [c] eq.: equivalent
to 1a.
alkenes with formamides using this
Figure 1. Ligand used in the
present study (1,2-bis((di-tert-
butylphosphino)methyl)ben-
zene; 1,2-DTBPMB).
catalytic system. Based on the re-
ports on the alkoxycarbonylation
of alkenes with formates[57] and
our latest investigations in amino-
carbonylation with CO applying
this catalyst system,[10] we herein report the palladium-cata-
lyzed aminocarbonylation of aliphatic alkenes with DMF as an
in situ source of carbon monoxide and dimethylamine.
As imidazole acts as a base and captures all protons, no
active palladium hydride species is formed in this nonacidic
environment. Hence, no activity was observed in entries 1.1 to
1.4 (Table 1). We therefore assume a palladium hydride mecha-
nism, in accordance with preliminary carbonylations applying
this catalytic system. The amount of MSA has thus to be
higher than the amount of imidazole in oncoming optimiza-
tion. However, as soon as the imidazole amount dropped
below the one from MSA, aminocarbonylation of 1a with DMF
was successful and the chosen catalytic system selectively
yielded the desired amide 2a with very high linear-to-
branched ratios exceeding 20:1 (entry 1.5 and 1.6). In the ab-
sence of imidazole as a promoter, no activity was observed
(entry 1.7). Thus, based on our work in methoxy- and amino-
carbonylation and Hallberg’s proposed mechanism, we suggest
the full catalytic cycle of the reaction in Scheme 2, in which
Results and Discussion
We first attempted the transformation of 1-octene (1a) with
DMF at 808C in a glass vial sealed with a Teflon cap. Pd(acac)2,
methanesulfonic acid (MSA), and 1,2-DTBPMB were applied to
form the catalytic system. Unfortunately, no N,N-dimethylnon-
anamide (2a) was formed under the chosen conditions, and
only octene isomers were detected by GC analysis. However,
after the reaction, an increase in pressure and a release of gas
and a weight loss was noticed upon carefully opening the vial.
We assumed a decomposition of DMF to CO and dimethyl-
amine and noticed that for carbonylation reactions employing
formamides, only Hallberg and co-workers reported on the de-
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tion reaction providing such high n:iso ratios. Usually four, five
equivalents or more are used.[46–56]
With the optimized conditions in hand, we decided to apply
the developed catalytic system to a range of alkenes 1a–j with
varying the chain length from 3 to 16 carbon atoms, to prove
the general usability of our system for the synthesis of linear
amides.
First of all, the substrate scope proves that the chemo- as
well as regioselectivities of the developed catalytic system are
independent from the applied substrate at high to very high
values of 92–96% and 21–32:1, respectively (Table 2). Indeed,
Scheme 2. Proposed catalytic cycle.
Table 2. Substrate scope of the developed protocol.[a]
imidazole acts as co-catalyst for the formation of aliphatic
amides by transamidation of the corresponding aromatic imi-
dazoylamide intermediate.
Encouraged by the promising results and findings from our
initial screening, we were further interested in the decomposi-
tion reaction of DMF under the chosen conditions. To gain
more insight into this important part of the reaction, we first
optimized the decomposition temperature. As a compromise
between the tolerated temperature of the applied palladium
catalyst and the decomposition reaction, we found 1408C to
be purposeful. In time-dependent pressure curves, the individ-
ual components’ influence on the decomposition of DMF was
investigated in detail and the nature of the gaseous products
was characterized (see the Supporting Information). It was re-
vealed that the palladium precursor and imidazole only negli-
gibly cause decarbonylation, and MSA is responsible for the
formation of CO and dimethylamine. The amount of MSA is re-
duced by the application of imidazole, resulting in lower decar-
bonylation activity. CO and dimethylamine are the predomi-
nant species in the gas phase, proving aminocarbonylation
with CO and dimethylamine occurs. Additionally, we assume
that the pressure increase is limited, which might be caused
by the loss of acidity owing to the liberation of dimethylamine.
With the aim to further increase the yield and to gain more
insight into the reaction system, we screened different reaction
temperatures under the conditions of Table 1, entry 1.6 (see
the Supporting Information). As anticipated, after the reaction
at 1608C, we noticed the presence of black particles in suspen-
sion, suggesting a decomposition of the catalytic species. For-
tunately, the optimum temperature was found to be 1408C,
yielding up to 57Æ5% at high selectivity of 95Æ1%. The
screening of different amounts of MSA, imidazole, DMF, and
concentrations and ratios of the catalyst system can be found
in the Supporting Information. Highest yields of 2a of 73%
were achieved at 1408C for 24 h reaction time, using
0.35 equivalents of MSA, 0.15 equivalents of imidazole, a pre-
cursor concentration of 1.5 mol% at a palladium-to-ligand
ratio [Pd]:L of 3 in 1 mL DMF. The selectivity to the linear
amide was high with 94%, although already a [Pd]:L ratio of 2
provided selectivities to the linear amide of approximately
90%. To the best of our knowledge, it is the first time only two
equivalents of the 1,2-DTBPMB ligand are used in a carbonyla-
[b]
Entry
Substrate
S2+3
(2:3)
Y2+3
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
2.10
propene 1b, R=methyl
96 (30:1)
93 (25:1)
92 (22:1)
94 (21:1)
93 (23:1)
92 (21:1)
93 (21:1)
94 (23:1)
96 (32:1)
94 (21:1)
96
85
81
73
43
31
24
12
77
62
1-pentene 1c, R=n-propyl
1-hexene 1d, R=n-ethyl
1-octene 1a, R=n-hexyl
1-decene 1e, R=n-octyl
1-dodecene 1 f, R=n-decyl
1-tetradecene 1g, R=n-dodecyl
1-hexadecene 1h, R=n-tetradecyl
4,4-dimethyl-1-pentene 1i, R=tert-butyl
4-octene 1j
[a] Conditions: 7 mL stainless steel autoclave, 1a–j (2.21 mmol), Pd(acac)2
(1.5 mol%: 10.1 mg, 0.033 mmol), 1,2-DTBPMB (4.5 mol%: 26.2 mg,
0.07 mmol), MSA (0.35 equiv.: 0.05 mL, 0.78 mmol), imidazole (0.15 equiv.:
22.6 mg, 0.33 mmol), 1 mL DMF, 1408C, 24 h. [b] Yield (Y) is given as sum
of both amide isomers and reported in % based on GC–FID analysis.
the catalytic system used is well-known for its ability to isomer-
ize the double bond all over the chain but selectively operat-
ing the carbonylation at the very end of the chain. In all exam-
ples in Table 2 (except entries 2.1 and 2.9), only isomers of the
starting alkene were found in the GC–FID trace, indicating that
isomerization is much faster than carbonylation, but only 1-al-
kenes react regioselectively. This was proven in the reaction of
4-octene 1j under the optimized conditions. Besides the lower
yield of the amides of 62% than for 1-octene 1a, the selectivi-
ty is evenly high (entry 2.10). Whereas selectivity is untouched
by the chain length of the starting alkene, the yield for the
amide significantly decreases with increasing chain length
from propene 1b (96%) to 1-hexadecene 1h (12%, en-
tries 2.1–2.8) The sterically more demanding 4,4-dimethyl-1-
pentene 1i achieves a yield of 77%, although highest selectivi-
ties were observed, presumably caused by the sterically de-
manding tert-butyl group, which protects the internal position
from carbonylation (entry 2.9).
Bearing in mind that isomerization is much faster than car-
bonylation, the explanation to the trend in yield might be that
back-isomerization of linear alkenes to the terminal position
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takes longer the further the double bond is buried in the
chain. However, no significant increase in yield was observed if
the reaction of 1-dodcene 1 f was conducted for 96 h. Thus,
we anticipated that another, not yet considered, parallel reac-
tion takes place, which is responsible for the reaction to “fall
asleep”. It was proven that the decomposition of DMF depends
on the amount of MSA (Scheme 3). Hence, if the concentration
MSA, the decomposition of DMF can be performed over
a longer period of time, thereby enabling higher yields for the
desired linear amide 2 f than for the one-step reaction setup in
Table 2, entry 2.6. In contrast, with no MSA refreshment, the
decomposition activity, and hence the pressure increase,
should be less after each pressure release, resulting in no addi-
tional yield for the linear amide 2 f. As seen in Figure 2, after
releasing the pressure from the autoclave without MSA refresh-
ment, the pressure increase flattens significantly after already
four reactions. No increase in yield for the linear amide was de-
tected in the absence of additional MSA. If MSA was refreshed
after 19 h reaction time, the pressure increased to approxi-
mately 6 bar within 72 h, a value higher than that under stan-
dard conditions. It seems as if MSA was not fully consumed
after 19 h and the addition of another 0.35 equivalents of MSA
caused a higher overall concentration of MSA leading to an in-
creased pressure. The following runs with MSA refreshment
after 91 and 115 h showed a parallel pressure curve to the
standard reaction. As a consequence of the successive refresh-
ment of MSA, the yield for the desired amide product 2 f was
expectedly increased to 45% in the second, 54% in the third
and 58% in the fourth run, respectively. Hence, the limited
yield in the aminocarbonylation of longer chained alkenes can
be attributed to two effects:
Scheme 3. Reaction of dimethylamine with MSA in the acid-catalyzed
decomposition of DMF.
of MSA decreases in situ by the liberation of dimethylamine,
the decomposition will stop at one point and no further car-
bonylation will occur. This happens earlier the slower the car-
bonylation is, and thus, the longer the applied alkene.
The pH of the reaction mixture after the aminocarbonylation
was tested with a pH test strip to be approximately 5 whereas
in the reaction setup it was approximately 1. A test decompo-
sition of DMF at a pH adjusted to 5 before the reaction
showed no significant increase in pressure, demonstrating that
an acidic environment is crucial for decomposition.
1) The slower overall carbonylation activity owing to isomeri-
zation of the starting 1-alkene. The longer the applied 1-
alkene is, the more possible internal alkenes result, which
leads to a lower probability of linear palladium–alkyl spe-
cies. As it was already proven for other carbonylations ap-
plying our catalytic system, only the linear palladium–alkyl
species readily react to form the carbonylation product,[50,52]
resulting in high n:branched ratios as also found here.
2) The loss of acidity owing to the in situ neutralization of
MSA by the release of dimethylamine during DMF decom-
position leads to a loss of decomposition activity and lower
concentration of palladium hydride species and thus to
lower carbonylation activity.
We then performed two standard reactions (according to
the conditions in Table 2, entry 2.6) in which 1-dodecene 1 f
was converted over a longer reaction period. In the first reac-
tion, we vented the autoclave, withdrew aliquots for GC analy-
sis, and added additional portions of MSA after certain periods
of time (light gray graphs, Figure 2). In the second reaction,
the reactor was opened, the pressure released, and only ali-
quots were withdrawn from the reactor (gray graphs, Figure 2).
We assumed, based on the hypothesis of the in situ loss of
acidity in our reaction setup, that with regularly refreshing
We demonstrated the general usability of our hitherto devel-
oped protocol for the conversion of short- to medium-chained
alkenes to linear amides with good yields and excellent selec-
tivities. However, long-chained alkenes only lead to poor yields
in our one-step protocol. With successive MSA refreshment,
the yield for linear amides from longer chained 1-alkenes can
be increased. Nonetheless, this approach suffers from long re-
action times, the necessity of high MSA amounts, inconvenient
handling, and still seems to be limited in yield. To develop
a one-step protocol that allows for the useful, preparative iso-
lation with higher yield of the respective linear amides also
from longer chained alkenes, we increased the scale of the re-
action by the factor four. This allowed for a further increase in
concentration, (25% more concentrated than in Table 2) by
using only a 3 mL volume of DMF.
Figure 2. Pressure curves of the aminocarbonylation of 1-dodecene 1 f with
(light gray) and without (gray) refreshment of MSA. Conditions: 7 mL stain-
less steel autoclave, 1 f (0.49 mL, 2.21 mmol), Pd(acac)2 (1.5 mol%: 10.1 mg,
0.033 mmol), 1,2-DTBPMB (4.5 mol%: 26.2 mg, 0.07 mmol), MSA (0.35 equiv.:
0.05 mL, 0.78 mmol), imidazole (0.15 equiv.: 22.6 mg, 0.33 mmol), 1408C.
Refreshment of MSA equals the initial amount (0.35 equiv.).
With the scale-up, the yield for the respective amides from
the C3–C6 alkenes remained almost constant (Table 3). Howev-
er, for the longer chained alkenes 1e and 1 f, the yield in-
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tions, are linked to the chain length of the alkene: the longer
the alkene, the lower the yield. It was shown that the in situ
loss of acidity by the liberation of dimethylamine is almost cer-
tainly responsible for the limited yields if long-chained alkenes
are employed. With successive acid refreshments, the yield for
long-chain amides was significantly improved. Moreover, the
well-known regioselectivity of the applied catalytic system as
well as its ability to convert internal alkenes to linear products
by preliminary isomerization were confirmed and transferred
to our system. Indeed, a maximum selectivity of 96% was ob-
tained, and an average selectivity of 90% to the linear amides
was usually observed. On a preparative scale, isolated yields of
the respective linear amides were fair to very high up to 85%.
Additionally, up-scaling of the reaction and the operation in
commercial glassware was also successful. Therefore we hope
that this work encourages other researchers to apply, extend,
and improve carbonylations with DMF as a convenient CO sub-
stitute.
Table 3. Upscaling of aminocarbonylation for preparative isolation.[a]
[b]
[c]
Entry
Substrate
S2+3
(2:3)
Y2+3
(GC)
Y2
(isolated)
3.1
3.2
3.3
3.4
3.5
3.6
3.7[d]
3.8[e]
propene 1b, R=methyl
1-pentene 1c, R=n-propyl
1-hexene 1d, R=n-ethyl
1-octene 1a, R=n-hexyl
1-decene 1e, R=n-octyl
1-dodecene 1 f, R=n-decyl
1-octene 1a, R=n-hexyl
1-octene 1a, R=n-hexyl
95 (29:1)
90 (22:1)
92 (21:1)
90 (21:1)
91 (22:1)
92 (22:1)
91 (20:1)
92 (23:1)
94
85
80
72
68
67
63
55
85
82
78
69
61
58
60
50
[a] Conditions: 7 mL stainless steel autoclave, 1a–f (8.8 mmol), Pd(acac)2
(1.5 mol%: 40 mg, 0.133 mmol), 1,2-DTBPMB (4.5 mol%: 105 mg,
0.27 mmol), MSA (0.35 equiv.: 0.2 mL, 3.1 mmol), imidazole (0.15 equiv.:
90 mg, 1.33 mmol), 3 mL DMF, 1408C, 24 h. [b] Yield (Y) is given as sum
of both amide isomers (2+3) and reported in% based on GC-FID analy-
sis. [c] isolated yield after chromatographic workup [d] 300 mL stainless
steel autoclave, 1a (14 mL, 88.6 mmol), Pd(acac)2 (1.5 mol%: 405.8 mg,
1.33 mmol), 1,2-DTBPMB (1048.5 mg, 2.66 mmol), MSA (2 mL, 31 mmol),
imidazole (904.5 mg, 13.29 mmol), DMF (40 mL 1408C, 24 h. [e] 8 mL pres-
sure tube, 1a (8.8 mmol), Pd(acac)2 (1.5 mol%: 40 mg, 0.133 mmol), 1,2-
DTBPMB (4.5 mol%: 105 mg, 0.27 mmol), MSA (0.35 equiv.: 0.2 mL,
3.1 mmol), imidazole (0.15 equiv.: 90 mg, 1.33 mmol), 3 mL DMF, 1408C,
24 h.
Experimental Section
General procedure for aminocarbonylation with DMF
In a 7 mL stainless steel autoclave equipped with a magnetic stir-
ring bar, Pd(acac)2 (10.0 mg, 0.033 mmol), imidazole (22.4 mg,
0.33 mmol), and 1,2-DTBPMB (26.0 mg, 0.07 mmol) were intro-
duced. The autoclave was sealed and purged three times with
argon. Degassed DMF (1 mL), alkene (2.19 mmol), and methanesul-
fonic acid (0.05 mL, 0.77 mmol) were introduced in the autoclave
by a cannula. The autoclave was placed in a preheated oil bath
and magnetically stirred at 1408C for 24 h. After the desired reac-
tion time, the autoclave was cooled down to RT in a water/ice
bath, carefully opened, and an aliquot was taken for GC analysis,
by using dibutyl ether as an internal standard and dichlorome-
thane as a diluter.
creased significantly from 43% and 31% (Table 2, entries 2.5
and 2.6) to 68% and 67%, respectively (Table 3, entries 3.5 and
3.6). Despite the observation of a general a loss of selectivity
of 1 to 2%, the up-scaled protocol allowed for the preparative
isolation of the respective linear amides from a range of linear
1-alkenes with fair to very good isolated yields. Additionally,
a factor 10 upscale with 1-octene 1a (entry 3.7) gives 60% iso-
lated yield of the desired linear amide 2a. Finally, to further
move our developed protocol towards potential application in
common organic laboratories, we tested the reaction of 1a in
a commercially available pressure-resistant glass tube (“pres-
sure tube”, entry 3.8). Besides the high selectivity, the yield was
slightly lower than in the autoclave, presumably caused by the
higher internal volume of the pressure tube. Nevertheless,
50% of the respective linear amide 2a were isolated.
General procedure for the isolation of the products
The reaction mixture from the up-scaled reaction under the condi-
tions of Table 3 was extracted with dichloromethane and filtered
through a plug of celite on a Büchner funnel. The celite was
washed with dichloromethane. The filtrate was concentrated under
reduced pressure on a rotary evaporator. Hexane and water were
added to the flask, and the biphasic system was decanted in a de-
cantation funnel. The organic phase was dried with magnesium
sulfate and filtered on a Büchner funnel and concentrated under
reduced pressure on a rotary evaporator. The residues were puri-
fied by flash chromatography by using ethyl acetate and cyclohex-
ane (EtOAc/cyclohexane, 2:3).
Conclusions
We have developed a new method for the synthesis of N,N-di-
methyl-substituted amides from aliphatic alkenes by aminocar- Acknowledgements
bonylation, involving the [Pd]/H+/1,2-DTBPMB (DTBPMB=1,2-
bis((di-tert-butylphosphino)methyl)benzene) system in an envi-
ronment free from initial pressure of carbon monoxide. N,N-di-
methylformamide (DMF) was used as an in situ source of both
carbon monoxide and dimethylamine. The reaction path was
investigated, and evidence was found for the reaction to pro-
ceed through DMF decomposition with subsequent aminocar-
bonylation. Obtained yields, up to 96% in the optimized condi-
We gratefully acknowledge Graham R. Eastham (Lucite Interna-
tional, UK) and Digital Specialty Chemicals Limited (Toronto,
Canada) for a generous gift of the 1,2-bis(di-tert-butylphosphino-
methyl)benzene ligand. The authors are also very grateful to the
“Fonds der Chemischen Industrie” for financial support and
granting a PhD scholarship to T.S. Additionally, we also thank
Umicore AG&Co. KG for the donation of precious metal catalysts.
ChemCatChem 2015, 7, 4085 – 4090
www.chemcatchem.org
4089
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Papers
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ChemCatChem 2015, 7, 836–845.
Keywords: alkenes · amides · carbonylation · homogeneous
catalysis · palladium
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Published online on October 14, 2015
ChemCatChem 2015, 7, 4085 – 4090
www.chemcatchem.org
4090
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim