Palladium-catalyzed carbonylation of allylamines via C-N bond activation leading to β,γ-unsaturated amides

Article abstract of DOI:10.1039/c4ra13939a

Pd(Xantphos)Cl₂ has been identified as an efficient catalyst for the direct carbonylation of allylamines via C-N bond activation. The reaction proceeds smoothly and provides β,γ-unsaturated amides in good to excellent yields under relatively mi

Full text of DOI:10.1039/c4ra13939a

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Palladium-catalyzed carbonylation of allylamines
via C–N bond activation leading to b,g-unsaturated
amides†
Cite this: RSC Adv., 2014, 4, 64235
a
b
a
ab
Received 14th October 2014
Accepted 19th November 2014
*
*
Hui Yu, Guoying Zhang, Zong-Jian Liu and Hanmin Huang
DOI: 10.1039/c4ra13939a
www.rsc.org/advances
Pd(Xantphos)Cl2 has been identified as an efficient catalyst for the the direct carbonylation of allylamines with CO under relatively
direct carbonylation of allylamines via C–N bond activation. The mild condition is still urgent. Inspired by the results and in
reaction proceeds smoothly and provides b,g-unsaturated amides in connection with our interests in the carbonylation and C–N
good to excellent yields under relatively mild conditions.
bonds activation.10 Herein, we present an efficient palladium
catalytic system for the carbonylation of allylamines, which
provides a highly atom economical protocol for the synthesis of
b,g-unsaturated amides under mild condition.
The amide functional group is one of the most important motifs
and exists in many natural products, pharmaceutical molecules
as well as functional materials. As a result, method develop-
ment for the efficient synthesis of amides continues to attract
much interest from both academia and industry.1 Many
synthetic routes, including many named reactions (Beckmann,
Wolff, Schmidt, Ritter, and Ugi reaction, etc.),2 amino-
carbonylation,3 carbonylation of aryl halides with formamides
and their derivatives,4 transamidation reactions,5 and oxidative
coupling reactions with amines,6 have been developed to access
such kinds of molecules.
As an important class of amides, b,g-unsaturated amides
have gained considerable attention because of their unique
synthetic utility.7 Among the many types of synthesis methods
access to b,g-unsaturated amides documented, transition-
metal-catalyzed carbonylation of allyl halides or pseudoha-
lides with amines and CO has provided a rapid and straight-
forward access to such kind of amide skeletons.8 However, the
use of organic halides or pseudohalides produced large
amounts of wasteful by-products which leads to low atom-
economy. To circumvent this problem, the direct carbonyla-
tion of allylamines via C–N bond cleavage has been rstly
developed by Murahashi and co-workers,9 revealing one of the
most atom and step economical process. Despite the signi-
cance of the reaction, the harsh reaction conditions were still
needed. Therefore, a practical and efficient catalytic protocol for
Our initial investigation was conducted in the presence of 10
atm of CO by using N,N-dibenzyl-3-phenylprop-2-en-1-amine
(1a) as model substrate for optimizing the reaction condi-
tions. On the basis of our experience with carbonylation reac-
tions,10c,10e a series of Pd complexes were rstly investigated. To
our delight, the desired product 2a was obtained in 43% yield
with PdCl2 as the catalyst and NMP/THF (1 : 1) as the solvent
(Table 1, entry 1). Several other palladium species, such as
Pd(PPh3)2Cl2, Pd(DPPP)Cl2, Pd(Xantphos)Cl2, Pd(BINAP)Cl2 and
Pd(DPEPhos)Cl2 were examined, but most of them furnished
poor results except Pd(Xantphos)Cl2 (Table 1, entries 2–6). Once
a suitable catalyst was identied, optimizations of solvent, CO
pressure were conducted. Screening of solvents revealed that
the reaction performed in toluene and xylene could afford the
desired product with more than 90% yields (Table 1, entries 7–
12). The best yield of 2a was obtained when the reaction con-
ducted under 10 atm of CO whereas no appreciable increase in
yield was obtained under decreasing pressure of CO. It was
noteworthy that the reaction still worked well even at 6 atm of
CO and 2a was obtained in 90% yield (Table 1, entries 13 and
14). The catalyst loading was lowered from 5 to 0.1 mol%, giving
the corresponding product 2a in 16% yield (TON ¼ 160) (Table
1, entry 15). In the absence of the Pd catalyst, however, no
carbonylation reaction occurred under otherwise identical
conditions (Table 1, entry 16).
With the optimized conditions in hand, we next investigated
the substrate scope of allylamines. As summarized in Table 2,
many cinnamyl amines derived from dialkyl amines were well-
tolerated in this carbonylation process, furnishing the corre-
sponding products 2a–2f in good to excellent yields. It appeared
that the steric hindrance of the substituents on the amine
aCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou
310024, China. E-mail: zjliu@zjut.edu.cn
bState Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China. E-mail:
hmhuang@licp.cas.cn
† Electronic supplementary information (ESI) available. DOI: 10.1039/c4ra13939a
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Table 1 Optimize of the reaction conditionsa
reaction (Table 3). The carbonylation of cinnamyl amines
bearing an electron-withdrawing or electron-donating group at
the meta or para position of the phenyl ring proceeded
smoothly to provide corresponding adducts 2k–2r in 73–86%
yields. It is noteworthy that the tolerance of halide substitu-
ents in this transformation offers an opportunity for subse-
quent cross-coupling reactions, which facilitates expedient
synthesis of functional amides. N,N-dibenzyl-3-(naphthalen-2-
yl)prop-2-en-1-amine 1s was a suitable substrate, giving the
desired amide 2s in 84% yield under the optimized conditions.
Besides cinnamyl amines, the simple alkyl group substituted
allylamine 1t was subjected to the reaction and transformed
into the corresponding product 2t in 67% yields, but with
lower stereoselectivity.
On the basis of our experimental results and previous work, a
plausible reaction pathway was outlined in Fig. 1. Initially, Pd(0)
species A derived from the reduction of Pd(II) serve as an
effective catalytic species to react with allylamine 1a to give rise
to the intermediate B through oxidative addition. Then, the
intermediate C would be generated via CO insertion. Finally,
reductive elimination of C afforded the desired product 2a and
Entry
[Pd] (5 mol%)
CO (atm)
Solvent
Yield (%)
1
2
3
4
5
6
7
8
PdCl2
Pd(PPh3)2Cl2
Pd(DPPP)Cl2
Pd(Xantphos)Cl2
Pd(BINAP)Cl2
Pd(DPEPhos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
Pd(Xantphos)Cl2
10
10
10
10
10
10
10
10
10
10
10
10
6
NMP/THF (1/1)
NMP/THF (1/1)
NMP/THF (1/1)
NMP/THF (1/1)
NMP/THF (1/1)
NMP/THF (1/1)
NMP
THF
CH3CN
Toluene
Xylene
Mesitylene
Toluene
Toluene
Toluene
Toluene
43
38
0
82
0
29
77
87(81)b
0
9
10
11
12
13
14
15
16
99(91)b
99
22
90
2
10
10
44
16b,c
0
—
a
Reaction conditions: 1a (0.5 mmol), CO (10 atm), [Pd] (0.025 mmol)
solvent (2.0 mL), 120 ꢀC, 15 h, yields determined by GC using
b
n-hexadecane as an internal standard.
Isolated yields.
Table 3 Substrate scope of allylaminesa
c
Pd(Xantphos)Cl2 (0.1 mol%), 48 h.
Table 2 Effect of amine moiety of allylaminea
Entry
R
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
4-CH3C6H4
3-CH3C6H4
4-t-BuC6H4
4-MeOC6H4
4-EtOC6H4
4-FC6H4
2k, 75 (7 : 1)c
2l, 73 (>20 : 1)c
2m, 76 (6 : 1)c
2n, 74 (6 : 1)c
2o, 74 (14 : 1)c
2p, 86 (8 : 1)c
2q, 77 (7 : 1)c
2r, 83 (9 : 1)c
2s, 84 (13 : 1)c
2t, 67 (3 : 1)c
Entry
R1
R2
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
Bn
Et
n-Pr
i-Pr
n-Bu
1-Octane
–(CH2)4–
–(CH2)5–
Bn
Et
n-Pr
i-Pr
n-Bu
1-Octane
2a, 91 (9 : 1)c
2b, 93 (9 : 1)c
2c, 82 (13 : 1)c
2d, 78 (>20 : 1)c
2e, 75 (11 : 1)c
2f, 72 (7 : 1)c
2g, 51 (12 : 1)c
2h, 66 (13 : 1)c
2i, 83 (19 : 1)c
2j, 63 (7 : 1)c
4-ClC6H4
4-AcOC6H4
Naphthyl-2-yl
CH3
a
Reaction conditions: allylamine 1 (0.5 mmol), Pd(Xantphos)Cl2 (0.025
mmol) in toluene (2.0 mL) under CO (10 atm) at 120 ꢀC for 15 h.
–(CH2CH2OCH2CH2)–
Bn
b
c
Isolated yields. Ratios of Z/E determined by 1H NMR are given
n-Pr
within parentheses. Major isomers are shown.
a
Reaction conditions: allylamine 1 (0.5 mmol), Pd(Xantphos)Cl2 (0.025
mmol) in toluene (2.0 mL) under CO (10 atm) at 120 ꢀC for 15 h.
b
c
Isolated yields. Ratios of Z/E determined by 1H NMR are given
within parentheses. Major isomers are shown.
moiety of the allylamines has no remarkable inuence on the
reactivity (Table 2, entries 2–6). Moreover, cinnamyl amines
derived from cyclic amines could also be used as carbonylation
partners, giving the corresponding b,g-unsaturated amides 2g–
2i in 51%, 66% and 83% yields, respectively. Besides, N-benzyl-
3-phenyl-N-propylprop-2-en-1-amine 1j was transformed into
the corresponding amide 2j in 63% yield.
Allylamines with different substituents attached in
aromatic rings were also investigated in this carbonylation Fig. 1 Proposed mechanism of allylic carbonylation.
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along with regeneration of the active catalyst species A for the
next catalytic cycle.
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In summary, we have identied Pd(Xantphos)Cl2 can act as
an efficient catalyst for the direct carbonylation of simple
allylamines via C–N activation under mild reaction conditions.
With 5 mol% of Pd(Xantphos)Cl2 as the catalyst, the carbonyl-
ation reaction can proceed smoothly to afford the desired b,g-
unsaturated amides in good to excellent yields. Further studies
on exploring new reactions via C–N activation are ongoing in
our group.
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Acknowledgements
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M. Zhang, S. Imm, S. Bahn, L. Neubert, H. Neumann and
This research was supported by the Chinese Academy of
Sciences and the National Natural Science Foundation of China
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