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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
4089
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