Pd-catalyzed hydroaminocarbonylation of alkynes with aliphatic amines and its mechanism study

Article abstract of DOI:10.1039/c8cy02337a

This work describes the hydroaminocarbonylation of alkynes with aliphatic amines without the addition of any acid additive. Excellent conversion and regioselectivity toward the formation of branched amides were obtained over a dppp-based Pd-catalytic syst

Full text of DOI:10.1039/c8cy02337a

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ISSN 2044-4753
PAPER
Qingzhu Zhang et al.
Catalytic mechanism of C–F bond cleavage: insights from QM/MM
analysis of fluoroacetate dehalogenase
rsc.li/catalysis

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DOI: 10.1039/C8CY02337A
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Pd-catalyzed hydroaminocarbonylation of alkynes with aliphatic
amines and its mechanism study
Received 00th January 20xx,
Accepted 00th January 20xx
Dong-Liang Wang, Wen-Di Guo, Lei Liu, Qing Zhou, Wen-Yu Liang, Yong Lu and Ye Liu*
DOI: 10.1039/x0xx00000x
www.rsc.org/
This work described the hydroaminocarbonylation of alkynes with strategy by using amine hydrochlorides instead of basic
aliphatic amines without the addition of any acid additive. The amines. With the involvement of an elaborate
excellent conversion and regioselectivity toward the formation of monophosphine,
the
palladium-catalyzed
branched amide were obtained over dppp-based Pd-catalytic hydroaminocarbonylation of olefins proceeded smoothly
3
1
system. The catalytic mechanism was studied and disclosed that affording the branched amides in good yields. But so far, the
the carbamoylpalladium complex intermediate instead of the limited strategies have been achieved towards the
widely accepted palladium-hydride (Pd-H) species was the active hydroaminocarbonylation of alkynes with aliphatic amines for
catalytic species for this reaction.
the synthesis of α,β-unsaturated amides. In 2006, Yu and his
co-workers reported the hydroaminocarbonylation of alkynes
with aliphatic amines in the ionic liquid of [bmim][NTf
2
]
Introduction
32
without the addition of acid additive. In 2009, El Ali and co-
workers reported an Pd-catalyzed hydroaminocarbonylation of
terminal alkynes using p-TsOH as acidic additive to promote
Carbonylation of alkenes or alkynes in the presence of the
nucleophile such as amines or alcohols has been wildly utilized
for the construction of high value-added carbonyl
3
3
the generation of Pd-H species.
1
–14
Herein, we found that even with the presence of aliphatic
amines, the palladium-catalyzed hydroaminocarbonylation of
alkynes could proceed smoothly without the addition of any
acid additive while the diphosphine of dppp was applied as a
chelating ligand, which suggested that the catalytic mechanism
of hydroaminocarbonylation focusing on the generation of Pd-
H species be still open to debate. Based on such fact, the
mechanism of hydroaminocarbonylation of alkynes under
basic condition was investigated carefully through the activity
evaluation of the as-synthesized carbamoylpalladium
intermediate complex as well as FT-IR characterization.
compounds.
Many studies revealed that the use of
Brönsted acid, 1
5–21
22
23,24
H
2
O, or H
2
as additive was usually
required to produce palladium-hydride (Pd-H) species
responsible for the catalytic transformations.
2
5–27
However,
unlike applied alcohols for hydroalkoxycarbonylation in which
Pd-H catalytic species can authentically survive under non-
alkali conditions, organic amines especially aliphatic amines
with strong basicity greatly inhibit the generation of the active
Pd-H species through rapidly quenching proton in
hydroaminocarbonylation. In order to solve this problem,
various methods have been developed to fulfil
hydroaminocarbonylation of alkenes/alkynes. For example, in
2
8
2
015, Huang and his co-workers have reported a novel
Results and Discussion
palladium-catalyzed hydroaminocarbonylation of alkenes with
aminals instead of aliphatic amines to grantee the generation The hydroaminocarbonylation of phenylacetylene with
of Pd-H species.29 In the same year, they also applied the weak propylamine was investigated as a model reaction without
acid (NH OH∙HCl) as a basicity-mask to overcome the basicity addition of the auxiliary additive. The various bidentate
2
barrier.30 Later on, Beller and co-workers developed an elegant phosphines with different bite angles were firstly examined for
this reaction (Table 1, entries 1-7). It was found that in the
presence of a catalytic amount of Pd(OAc)
2
(1 mol%) under 1
o
a.
b.
c.
MPa of CO in CH
3
CN at 120 C, the excellent conversion of
Address here.
Address here.
Address here.
phenylacetylene and 100% selectivity to the branched amide
were obtained in 2 h with the involvement of dppp at P/Pd
†
Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any molar ratio of 2 (Entry 3). The other bidentate phosphines like
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
dppe and dppb with the similar natural bite angle of ca. 90 o
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1

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just corresponded to the moderate yields to the target amide group toward Pd-center. The internal alkyne like
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DOI: 10.1039/C8CY02337A
(
Entries 2 and 4). In contrast, the uses of phosphines with the diphenylacetylene showed the poor reactivity even when the
o
bite angle much larger or less than 90 corresponded to the reaction time was prolonged (1o).
completely inhibited transformation (Entries 1 and 5-7). Upon
The successful hydroaminocarbonylation of alkynes with
further screening the reaction parameters such as CO pressure aliphatic amines or aryl amines (i.e. under the strong basic
and the reaction time (Entries 8-10), the highest yield of the condition) without the addition of acid additive suggested that
product (99%) was obtained under 0.5 MPa of CO in 1 h (Entry Pd-H species not be the active catalytic intermediate for this
o
1
0 @ 120 C, Pd(OAc)
2
1 mol%, P/Pd=2:1). It was found that transformation. Instead, the carbamoylpalladium intermediate
the decrease of CO pressure dow to 0.1 MPa compleltely (B) upon reacting palladium(Ⅱ)-precursor with amine and CO
stopped the reaction (Entry 9).
Pd(OAc)2 (1 mol%)
R2
H
N
Table 1 Pd-catalyzed hydroaminocarbonylation of phenylethyne with n-propylaminea
dppp (1 mol%)
N
R
+
+
CO
R
R1
R2
R1
CH3CN
O
O
1
Pd/Ligand
+
NH2
+
HN
CO
Table 2 Pd-catalyzed hydroaminocarbonylation of alkyne with aminea
2
-phenyl-N-propylacrylamide
H
H
N
Entry
Ligand
Natural
bite angle( )
Conv.
(%)c
0
Sel. B-amide
(%)c
N
N
o
b
O
O
O
1
2
dppm
dppe
73
86
--
1a 90%
1b 88%
1c 86%
H
H
H
75
100
N
N
N
O
3
dppp
91
99
100
O
O
1
d 88%
1
1
e 90%
1f 80%
4
5
6
7
dppb
dppf
94
99
40
trace
0
100
H
N
H
H
N
N
--
O
O
O
Xantphos
108
114
91
--
O
1
g 75%
1i 88%
Nixantphos
dppp
0
--
100
h 85%
8d
99
H
N
H
N
9e
O
N
H
dppp
91
trace
99
--
O
O
F
O2N
1
0f
dppp
91
100 (90g)
1k 90%
1
j 70%
1l trace
a
O
Reaction conditions: phenylacetylene (2.0 mmol), Pd(OAc)
2
(1 mol%), P/Pd=2:1
H
NH
◦
b
H
N
(molar ratio), n-propylamine (2.5 mmol), CH
3
CN (2 ml), CO (1 MPa), 2 h, 120 C;
2
O N
N
c
O
Nature bite angles are taken from ref 34; Determined by GC. Sel.B-amide
represents the selectivity to the branched product of 2-phenyl-N-
propylacrylamide; CO (0.5 MPa); CO (0.1 MPa); CO (0.5 MPa), 1h; The
isolated yield of the branched product.
O
NC
1n trace
1
m trace
d
e
f
g
1o No reaction
(1mol%), dppp (1 mol%),
CN (2 ml), 120 C, 2 h; The isolated yield to
a
Reaction conditions: alkyne (2.0 mmol), Pd(OAc)
2
◦
amine (2.5 mmol), CO (0.5 MPa), CH
the branched product was indicated.
3
With the optimized reaction conditions in hand, we
examined the substrate scope for the synthesis of the
branched amides over dppp-based Pd-system. The results
were summarized in Table 2. A variety of amines were initially
surveyed. Both aliphatic amines and aryl amines were
compatible with this transformation (1a-1e). In addition, a
series of phenylacetylene derivatives with the electron-
donating substituents like methyl, tert-butyl, and methoxy in
phenyl ring were efficiently transformed, giving the
corresponding branched amides in good yields (1f-1i, 75~88%).
It was noted, 1-ethynyl-4-fluorobenzene with the strong
electron-withdrawing substituent of –F also gave a good
product yield (1g, 70%), which implied that the reactivity of
the corresponding alkynes showed no obvious discrimination
to the electronic effect of the substituent. Aliphatic alkynes 1-
octyne was also suitable for this reaction to give the
corresponding branched amides in 90% isolated yield (1k).
Pd(OAc)2
dppp NHR1R2
NR1R2
R
NR1R2
OAc
+
O
P
CO
OAc-
91
o
Pd
Aminolysis
NHR1R2
P
A
+
+
O
C
P
NR1R2
R
OAc-
R1=H
OAc- (- O=C=N-R2)
O
NR1R2
H
P
P
P
P
Pd
Base
Pd0
Pd
Pd
P
H
OAc
OAc
E (favored)
B
+
O
C
+
R
P
P
NR1R2
NR1R2
R
O
P
P
OAc-
Pd
OAc-
Pd
H
However, when the aromatic alkyne with –NO
2
or -CN was
R
D (unfavored)
C
applied, only trace amounts of the desired products were
detected (1l-n), which was mainly attributed to the
competitive coordination of such substituent with the alkynyl
2
| J. Name., 2012, 00, 1-3
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Scheme 1 The alternative mechanism for hydroaminocarbonylation of alkynes
with organic amines.
proposed in Scheme 1, which was compatible withViethe al line
organic amines. Subsequently, the coordinate and insertion of
leka
DOI: 10.1039/C8CY02337A
w Artic Online
was believed to be crucial active species for the reaction with the alkyne into B generates the corresponding (-vinyl)
an amine to yield the corresponding amide. As proposed in carbamoylpalladium intermediate (E), which is aminolyzed by
Scheme 1, the carbamoylpalladium intermediate (B) was another amine to give the target branched amide along with
readily formed upon complexation of Pd(OAc)
2
with organic the regeneration of B followed by CO insertion. Reasonably,
amine in CO atmosphere. The subsequent insertion of - the intermediate B also can evolve into Pd-H species which
0
coordinated CC bond in Pd-C bond (C) led to the favored unavoidably converts to inactive Pd with the presence of a
formation of (-vinyl) carbamoylpalladium intermediate base, leading to the deactivation of Pd(II)-catalyst as shown in
complex (E) due to steric effect. The later (E) irreversibly Scheme 1.
proceeded aminolysis to afford the branched ,-unsaturated
amide
accompanied
by
the
regeneration
of
O
C
S1 at R.T.
S1 at 100℃ for 30min
Propyl isocyanate (authentic sample)
PPh3
Cl
NHnPr
oC
PPh3
Cl
nPr
carbamoylpalladium intermediate (B).
In order to verify the above mechanism, the
120
H
Pd
Pd
+
O C N
PPh3
PPh3
S1
carbamoylpalladium complex (S1) as a kind of intermediate B
was synthesized purposely by reacting PdCl
2
(PPh
3 2
) with
n
35
PrNH
2
in CO atmosphere and then applied as the active
intermediate complex to react with phenylacetylene
stoichiometryically and free of CO (Scheme 2, see ESI provided
with the detailed reaction procedures). When the as-
synthesized S1 (0.1 mmol) reacted with phenylacetylene (0.1
o
mmol) at 120 C in CH
3
CN (eq. 2), only styrene (Yield 90%) but
not the desired amide was formed unexpectedly, along with
the unreacted phenylacetylene. However, when Et N was
introduced to provide an alkaline environment, styrene was
3
1
560
1500
2
000
1750
1250
1000
750
500
not formed anymore under the same conditions (eq. 3). The
-1
o
Wavenumber (cm )
FT-IR spectra upon treating at 120 C for 30 min (Fig. 1)
-1
showed that an intensive vibration at 1560 cm appeared
obviously which was attributed to isocyanate group. These
results indicated that, via β-H migration and propyl isocyanate
elimination, S1 was evolved to propyl isocyanate along with
the release of the active Pd-H species (eq. 4). Herein, since CO
was not introduced in the controlling experiment in eq. 2, the
Fig. 1 FT-IR spectra of S1 and its derivative upon treating at 120 oC
O
PPh3
Cl
n
R.T.
C
NH Pr
PdCl2(PPh3)2 + nPrNH2 + CO
Pd
eq. 1
CH3CN
PPh3
available Pd-H species derived from S1 under non-alkaline
S1 51%
o
O
condition ((heating at 120 C in CH
3
CN) just reacted with
PPh3
Cl
n
C
NH Pr
20 o
1
C
phenylacetylene to afford the hydrogenated product (styrene:
yield 90%) instead of the desired amide. Whereas under the
+
+
Pd
eq. 2
eq. 3
eq. 4
PPh3
S1
CH3CN
(free of CO)
9
0%
alkaline condition by adding Et
3
N, the Pd-H species derived
O
C
0
from S1 susceptibly transformed to the inactive Pd upon the
PPh3
n
NH Pr
1
20 o
C
+
+
Et3N
capture of H by the base as a driving force, leading to the
Pd
3
CH CN
Cl
PPh3
S1
(free of CO)
termination of hydrogenation of phenylacetylene as observed
in eq. 3. Accordingly, Pd-H species can be generated from S1
as shown in eq. 4, which was absolutely unavailable under
alkaline condition. Hence, it was believed that the successful
hydroaminocarbonylation of alkynes with alkaline organic
amines in this work was not driven by Pd-H species.
Interestingly, when S1 reacted with phenylacetylene in the
presence of propylamine or aniline, the target amide was
formed in good yields (eqs. 5 and 6). It was noted that upon
completion of each control experiment (eq. 2, 5 or 6), only the
unreacted phenylacetylene and the target product were
obtained. The other by-product or S1 was not found. Without
the presence of CO in eqs. 5 and 6, S1 was not able to be
regenerated after reacting with phenylacetylene and the
amine in stoichiometry as the active agent. These results
confirmatively supported that the carbamoylpalladium
complex (B, similar to S1) was the real catalytic species as
0
%
O
C
PPh3
Cl
n
PPh3
Cl
nPr
NH Pr
20 o
H
1
C
Pd
Pd
+
O C N
PPh3
PPh3
S1
PdII
H
+
Base
Pd0
+ H Base
+
O
HN
O
PPh3
n
C
NH Pr
nPrNH2
eq. 5
Pd
+
CH3CN (free of CO)
120 oC, 2 h
Cl
PPh3
S1
9
0%
O
O
C
PPh3
Cl
n
NH Pr
aniline
HN
Pd
+
eq. 6
CH3CN (free of CO)
120 oC, 2 h
PPh3
S1
80%
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Scheme 2 Synthesis of carbamoylpalladium complex (S1) and its stoichiometric
1
4 I. Ryu, T. Fukuyama, M. Tojino, Y. Uenoyama, VYie.wYAortnicalemOinnlinee,
control reaction with phenylacetylene under different conditions free of CO
N. Terasoma and H. Matsubara, Org. Biomol. Chem., 2011, 9,
DOI: 10.1039/C8CY02337A
3
780.
1
1
5 S. M. Shakil Hussain, R. Suleiman and B. E. Ali, Tetrahedron
Lett., 2012, 53, 6535–6539.
6 B. E. Ali, J. Tijani and A. M. El-Ghanam, Appl. Organomet.
Chem., 2002, 16, 369–376.
Conclusions
The palladium-catalyzed aminocarbonylation of alkynes with
aliphatic amines proceeds efficiently without any acid additive, 17 X. Fang, R. Jackstell and M. Beller, Angew. Chem. Int. Ed.,
2
013, 52, 14089–14093.
yields the corresponding branch amides in excellent
regioselectivity and good yields. In the presence of dppp with
the natural bite angle of 91 , the excellent conversion of
phenylacetylene and 100% selectivity to the branched amide
were obtained over Pd(OAc)
also exhibited wide generality to aminocarbonylation of
alkynes with organic amines including the weak alkaline aryl
amines and the strong alkaline aliphatic ones. The mechanism
1
1
8 T. Xu, F. Sha and H. Alper, J. Am. Chem. Soc., 2016, 138,
6
629–6635.
o
9 D. Yang, H. Liu, D.-L. Wang, Z. Luo, Y. Lu, F. Xia and Y. Liu,
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. Dppp-based Pd(OAc)
2
2
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2 H. Liu, N. Yan and P. J. Dyson, Chem Commun, 2014, 50,
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2
2
7
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under strong alkaline condition.
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Conflicts of interest
There are no conflicts to declare.
2
2
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1
Acknowledgements
5
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21673077 and 21473058),
and the Science and Technology Commission of Shanghai
Municipality (18JC1412100).
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3
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| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C8CY02337A
Table of contents graphic:
Pd(OAc) (1 mol%)
2
R2
N
H
dppp (1 mol%)
R
+
N
+
CO
R
R1
R2
R1
Free of auxiliary additive
O
O
PPh3
Cl
n
C NH Pr
R.T.
n
Pd
PdCl (PPh ) + PrNH + CO
2
3 2
2
CH CN
PPh3
3
S1
O
O
PPh3
Cl
n
C NH Pr
nPrNH
2
HN
Pd
S1
+
CH CN
PPh3
3
o
120 C, 2 h
9
0%
CO
1