Efficient iron-catalyzed Tsuji-trost coupling reaction of aromatic allylic amides through a sp3-carbon-nitrogen breaking

Article abstract of DOI:10.1055/s-0029-1219809

The catalytic activation of sp³-carbon-nitrogen of allylic amides is generally difficult because of the inefficient leaving-group ability of the amide group. In this article, we have discovered for the first time that FeCl³-catalyzed Tsuji-Trost coupling reaction of aromatic allylic amides with active methylene compounds, cyclohexanone, and allytrimethylsilane work efficiently under mild conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1219809

LETTER
1251
Efficient Iron-Catalyzed Tsuji–Trost Coupling Reaction of Aromatic Allylic
Amides through a sp3-Carbon–Nitrogen Breaking
Iron-Catalyzed
h
T
suji–Trost
e
C
oupling R
n
eaction of
A
-
r
omatic
AY
llylic Amides u Jiang,a Cai-Hua Zhang,a Feng-Lei Gu,a Ke-Fang Yang,a Guo-Qiao Lai,*a Li-Wen Xu,*a,b Chun-Gu Xiab
a
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University,
Hangzhou, 310012, P. R. of China
Fax +86(571)28865135; E-mail: liwenxu@hznu.edu.cn
State Key Laboratory of Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou, 730000, P. R. of China
b
Received 11 January 2010
availability of these metals as well as their high price and
significant toxicity make it desirable to search for more
economical and environmentally friendly alternatives. In
recent years, iron has been recognized as a possible solu-
Abstract: The catalytic activation of sp3-carbon–nitrogen of allylic
amides is generally difficult because of the inefficient leaving-
group ability of the amide group. In this article, we have discovered
for the first time that FeCl3-catalyzed Tsuji–Trost coupling reaction
of aromatic allylic amides with active methylene compounds, cy- tion to this problem.6 Iron is the second most abundant
clohexanone, and allytrimethylsilane work efficiently under mild
conditions.
metal in the earth crust (4.7%), and iron compounds are
relatively nontoxic. Among iron salts, iron(III) chloride is
Key words: iron catalysis, Lewis acid, Brønsted acid, Tsuji–Trost
reaction
a very cheap and efficient Lewis acid catalyst, and has at-
tracted much attention due to its uses in various useful or-
ganic transformations including allylic alkylations.7
Herein, we wish to report the iron-catalyzed Tsuji–Trost
The Tsuji–Trost reaction is the palladium-catalyzed ally- coupling reaction of allylic amide, which represents a rare
lation of nucleophiles such as active methylenes, enolates, example of a synthetically useful iron-catalyzed carbon–
amines, and phenols with allylic compounds such as allyl carbon bond formation through a sp3-carbon–nitrogen
acetates and allyl bromides, which is one of the most com- breaking.
mon methodologies for the carbon–carbon bond construc-
As a starting point for the development of the catalytic
tion.1 In particular, the coupling reaction between allylic
Tsuji–Trost reaction of allylic amides, we studied the
acetates or allylic halides with a carbanion derived from
FeCl3-catalyzed reaction of different aromatic allylic
active methylenes has been intensively studied recently
amides with acetyl acetone (acac), and the results are pre-
using palladium and iridium complex in the presence of
sented in Table 1. Of the allylic amides screened (entries
1–3), (E)-N-(1,3-diphenylallyl)benzamide (1c) as the sub-
strate proved to be the most effective for this Tsuji–Trost
base.2 However, the use of above allylic reagents in the al-
lylation reaction results in the formation of hydrogen ha-
lides, or acetic acid, which may lead to undesired side
coupling in nitromethane (entry 3). Additionally, dramat-
reactions in the absence of a base. Direct use of allylic al-
ic differences in yield were observed in reactions using
cohols for the Tsuji–Trost reactions3 are noteworthy since
MeNO2, THF, MeCN, CH2Cl2, and toluene as solvents
considerable progress has been made in this context with
(entries 5–9). Its major function may be get and keep
catalytic palladium, copper, indium, and other Lewis acid
FeCl3 in solution. A variety of general and cheap Lewis
catalysts.4 Allylic amide is also an attractive allylic re-
acids and Brønsted acids were also examined in this mod-
agent since only neutralized amide would be generated as
el reaction. However, these catalysts did not promote this
a stable side product. Nevertheless, it is a very stable com-
reaction at all.
pound in comparison to allylic alcohols or allylic acetates.
Having established the utilization of 10 mol% FeCl3 in ni-
tromethane at room temperature as the optimized condi-
tions to perform the reaction, we next extended Tsuji–
Trost coupling to different 1,3-dicarbonyl compounds and
(E)-N-(1,3-diarylallyl)benzamides. As can be seen, the
process can tolerate a variety of common functional 1,3-
dicarbonyl compounds (2a–d) and (E)-N-(1,3-diaryl-
allyl)benzamides (1c–f, Table 2). The Tsuji–Trost cross-
coupling of benzamide-activated allylic amines, bearing
either electron-donating or electron-withdrawing groups
on their aromatic rings, with 1,3-dicarbonyl compounds
proceeded smoothly in good to excellent yields. In in-
stances where reactions with allylic amides containing
two different substituents on aromatic rings, normally a
Therefore the catalytic activation of sp3-carbon–nitrogen
of allylic amides is generally difficult because of the inef-
ficient leaving-group ability of the amide group. To the
best of our knowledge, there are no reports on the applica-
tion of allylic amides as alkylated reagents in Tsuji–Trost
reaction or other allylation.5 Furthermore, transition-met-
al catalysts used in the Tsuji–Trost reaction, especially
based on precious metals such as Pd, Ir, and Au, have been
proven to be efficient for a large number of allylic re-
agents and asymmetric version. However, the limited
SYNLETT 2010, No. 8, pp 1251–1254
x
x.
x
x.
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0
1
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Advanced online publication: 07.04.2010
DOI: 10.1055/s-0029-1219809; Art ID: W00410ST
© Georg Thieme Verlag Stuttgart · New York

1252
Z.-Y. Jiang et al.
LETTER
Table 1 Tsuji–Trost Coupling of Different Allylic Amides with Acetylacetone under Different Conditions
O
O
R
HN
O
O
cat. (10 mol%)
solvent, r.t.
+
2a
1a–c
3a
Entrya
R
Catalyst
Solvent
MeNO2
MeNO2
MeNO2
THF
Time (h)
Yield (%)b
1
2
1a Ac
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
TsOH
InCl3
10
10
10
9
<10
58
75
22
10
0
1b COCHCH2
1c Bz
3
4
1c Bz
5
1c Bz
MeCN
toluene
CH2Cl2
MeNO2
MeNO2
MeNO2
MeNO2
9
6
1c Bz
9
7
1c Bz
9
<5
0
8
1c Bz
12
12
12
12
9
1c Bz
<5
0
10
11
1c Bz
CuCl2
Mg(ClO4)2
1c Bz
0
a The reaction was performed with 0.5 mmol of allylic amide 1a, 0.75 mmol of acetyl acetone 2a, and 10 mol% of catalyst.
b Isolated yield.
Table 2 Tsuji–Trost Coupling of Different Activated Methylene Compounds with Allylic Benzamide8
O
O
R3
R4
HN
O
O
O
+
FeCl3 (10 mol%)
MeNO2, r.t.
R1
R2
R3
R4
R1
R2
2a–d
3a–k
1c–f
Entrya
R1
R2
R3
R4
Temp (°C)
Time (h)
24
Yield(%)b
3a 97
1
2
H
H
Me
Ph
Me
Ph
r.t.
r.t.
50
50
50
r.t.
r.t.
r.t.
50
r.t.
H
H
24
3b 74
3c 83
3
H
H
Ph
Ph
12
4
H
H
Me
Me
Me
Me
OEt
OEt
Me
Me
OMe
OMe
Ph
24
3d 90
3g 78
5
H
H
12
6
4-Br
4-Me
H
H
24
3f65c
7
H
24
3g 100d
3h 61
3i 96
8
H
OMe
OMe
Ph
24
9
4-Br
4-Br
4-OMe
4-OMe
24
10
24
3k 55e
a All reaction were performed at r.t. with 0.5 mmol of allylic amide 1, 0.75 mmol of ketone 2, 1.5 mL of MeNO2, and 10 mol% of FeCl3.
b Isolated yields.
c Isolated as an inseparable mixture of regioisomers in a ratio of 1:2.
d Isolated as an inseparable mixture of regioisomers in a ratio of 1:1.
e Isolated as an inseparable mixture of regioisomers in a ratio of 1:6.
Synlett 2010, No. 8, 1251–1254 © Thieme Stuttgart · New York

LETTER
Iron-Catalyzed Tsuji–Trost Coupling Reaction of Aromatic Allylic Amides
1253
mixture of regioisomeric products was formed (entries 6, The Tsuji–Trost coupling reaction of optically active (R)-
7, and 10).
4-phenyloxazolidin-2-one or (R)-4-benzyloxazolidin-2-
one derived allylic amides (1h–i) with cyclohexanone was
carried out to afford product 5 in nearly racemic
(Scheme 3). This result suggested that a reaction mecha-
nism may involve the formation of a carbenium interme-
diate,9 and the impact of oxazolidin-2-ones-based chiral
auxiliaries on the stereoselectivity in this Tsuji–Trost
reaction is very poor.
The present procedure also worked well for the cross-cou-
pling of cyclic 1,3-diketone with (E)-N-(1,3-diphenylal-
lyl)benzamide (1c), giving corresponding product in good
yield. However, the allylic amide did not react with cyclo-
hexanone in the presence of FeCl3 catalyst. It remains to
be formidable challenge for the coupling of nonactivated
ketones with allylic amides, and hence further explora-
tions in this context are highly desired. We thus investi-
gated the use of other allylic amides to this Tsuji–Trost
coupling. As is evident from the results in Scheme 1 (eq.
3), the use of (E)-3-(1,3-diphenylallyl)oxazolidine-2-one
(1g) under similar conditions mentioned above provided
an efficient Tsuji–Trost coupling of cyclohexanone
through the cleavage of sp3-carbon–nitrogen bonds.
O
O
O
N
R
O
FeCl3 (10 mol%)
MeNO2, r.t., 12 h
+
1h–i R = Ph, Bn
5 racemic
Scheme 3
O
(1.5 equiv)
Based on these findings, we wished to expand the applica-
tion of iron-catalyzed allylation of allylic amide. Hence,
when aromatic allylic amide 1c was reacted with allyltri-
methylsilane in the presence of FeCl3, no allylation prod-
uct could be isolated. However, the addition of catalytic
amount of acac gave the product in excellent yield
(Table 3).
O
O
HN
Ph
FeCl3 (10 mol%)
O
O
(1)
MeNO2, 50 °C, 24 h
Ph
Ph
O
Ph
Ph
1c
4 81% yield
O
(1.5 equiv)
FeCl3 (10 mol%)
MeNO2, r.t., 24 h
HN
Ph
(2)
Table 3 FeCl3-acac Promoted Allylic Alkylation of Allylic Amide
with Allyl Silane
no product
Ph
Ph
1c
Ph
HN
O
O
(1.5 equiv)
TMS
O
cat.
O
O
FeCl3 (10 mol%)
MeNO2, r.t., 12 h
N
(3)
Ph
Ph
Ph
Ph
Entrya Cat.
Additive
Temp (°C) Time (h) Yield (%)b
5 76% yield
dr = 1:1
1g
1
2
3
4
5
6
7
8
9
FeCl3
–
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
48
48
48
48
48
48
48
48
24
<10
<10
<10
<10
0
Scheme 1 FeCl3-catalyzed Tsuji–Trost coupling of aromatic allylic
amides with cyclic ketones
FeCl3
InCl3
InCl3
LiClO4
FeCl2
CuBr
FeCl3
FeCl3
TMSCl
–
The inertness of (E)-N-(1,3-diphenylallyl)benzamide (1c)
was further exemplified by taking an equimolar mixture
of 1c and 1g under similar reaction conditions. As expect-
ed, compound 1c was recovered after the reaction
(Scheme 2). This clearly suggested that such a selectivity
could be useful in synthetic applications.
TMSCl
–
–
0
–
0
Acac
Acac
30
O
O
HN
Ph
HN
Ph
>99
Ph
Ph
Ph
Ph
a Reactions conditions: 10 mol% of transition metal salt, 10 mol% of
additive, allylic amide/allytrimethylsilane = 0.5 mmol:0.75 mmol,
1.5mL of MeNO2.
O
(150 mol%)
FeCl3 (10 mol%)
MeNO2, r.t., 12 h
1c 50% yield
1c 49% yield
O
b GC yield.
O
N
O
Ph
Ph
Ph
5 40% yield
Ph
In summary, we have discovered a FeCl3-catalyzed Tsuji–
Trost coupling reaction of allylic amides with active me-
thylene compounds, allyltrimethylsilane, and cyclohex-
anone under mild conditions. Another important finding
1g 50% yield
Scheme 2
Synlett 2010, No. 8, 1251–1254 © Thieme Stuttgart · New York

1254
Z.-Y. Jiang et al.
LETTER
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Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (No. 20572114, 20973051) and Zhejiang Provincial
Natural Science Foundation of China (Y4090139).
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(8) General Procedure for Tsuji–Trost Coupling Reaction of
Allylic Amides with Activated Methylene Compound or
Cyclohexanone
A catalytic amount of FeCl3 (10 mol%) was added to the
mixture of allylic amide (0.5 mmol) and activated methylene
compound or cyclohexanone (0.75 mmol) in MeNO2 (2
mL). After vigorous stirring at r.t. for the times showed in
the Tables and Schemes, the reaction mixtures were poured
into an extraction funnel containing brine, diluted with
distilled H2O and EtOAc. The aqueous phase was extracted
with EtOAc. The combined organic phases were dried with
Na2SO4, and the solvent was removed under reduced
pressure. The crude product was purified by silica gel
column chromatography to furnish the desired products. All
the products are known compounds and confirmed by GC-
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