Microwave-assisted ring-closing metathesis of diallylamines: a rapid synthesis of pyrrole and pyrroline derivatives

Article abstract of DOI:10.1016/j.tetlet.2006.03.164

The ring-closing metathesis (RCM) reactions of diallylamines occurred under controlled microwave irradiation. In addition to the high reaction rate, the key features of the reaction are that it can be carried out without deactivation of the substrates and

Full text of DOI:10.1016/j.tetlet.2006.03.164

Tetrahedron Letters 47 (2006) 3893–3896
Microwave-assisted ring-closing metathesis of diallylamines:
a rapid synthesis of pyrrole and pyrroline derivatives
Qian Yang, Xin-Yong Li, Hong Wu and Wen-Jing Xiao*
The Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China
Received 30 December 2005; revised 27 March 2006; accepted 28 March 2006
Available online 27 April 2006
Abstract—The ring-closing metathesis (RCM) reactions of diallylamines occurred under controlled microwave irradiation. In addi-
tion to the high reaction rate, the key features of the reaction are that it can be carried out without deactivation of the substrates and
without the use of Lewis acids.
Ó 2006 Elsevier Ltd. All rights reserved.
Ring-closing metathesis (RCM) has been established as
a powerful and effective method for the construction of
many functionalized carbocycles and heterocycles from
acyclic diene precursors.1 Many useful transformations
have been reported for industrial applications as well
as for the synthesis of complex molecules because of
major advances in catalyst design.2 However, RCM
reaction of free amines is rather difficult. They have to
be deactivated by conversion to amides, carbamates,
or sulfonamides or by protonation to perform the
RCM reactions, in order to get reasonable yields.3
Recently, we have reported that such substrates, without
deactivation, can participate in RCM reactions with the
use of the second generation Grubbs ruthenium catalyst
in the presence of catalytic amount of Ti(OiPr)4.4
of carboxymethyl substituted dihydropyrroles or pyr-
roles.5c As part of our ongoing project aimed at investi-
gating the MW effects in organic synthesis under green
chemistry conditions5a and based on the pioneering
work of Wilson and co-workers,5c we report herein
our study on microwave-assisted ruthenium-catalyzed
RCM of diallylamines. This process leads to a straight-
forward procedure for the preparation of pyrrole and/or
pyrroline derivatives.
Initial optimization reactions of microwave-assisted
RCM reactions with catalyst 1 or 2 were conducted with
methyl 2-(diallylamino)-3-phenylpropanoate 3 as the
model substrate (Scheme 1). A variety of microwave
irradiation conditions including time, temperature, and
solvents were investigated. All reactions were performed
in a Smith synthesizer producing controlled irradiation
at 2450 MHz with a power of 0–300 W in closed vessels.
It was found that the highest conversion was obtained
by exposing substrate 3 (0.1 M) in CH2Cl2 to sealed-ves-
sel under microwave irradiation at 150 °C for 10 min
with 5 mol % catalyst 2. With optimal conditions,
Microwave (MW) irradiation as a nonconventional
energy source has emerged as a very useful technique
to promote various reactions and has become increas-
ingly popular within the pharmaceutical and academic
arenas.5 By taking advantage of this efficient source of
energy, a few studies on microwave-assisted metathesis
have been reported,6 but few involve RCM reactions
of diallylamines possessing basic or nucleophilic nitro-
gen atoms. Recently, Wilson and co-workers reported
an example of MW-accelerated RCM of diolefin sub-
strates containing an external carboxymethyl substitu-
ent, which, in certain cases, resulted in the formation
O
PCy3
Ru
Mes
Cl
Cl
N
N Mes
Ph
Ru
Ph
Ph
OCH3
Cl
Cl
N
PCy3
PCy3
Keywords: Microwave; Ring-closing metathesis; Pyrrole; Pyrroline.
1
2
3
*
Corresponding author. Tel./fax: +86 27 67862041; e-mail: wxiao@
mail.ccnu.edu.cn
Scheme 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.164

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Q. Yang et al. / Tetrahedron Letters 47 (2006) 3893–3896
several chiral diallylamine substrates, which were gener-
ated from L-amino acids, were subjected to RCM reac-
tions and the results are summarized in Table 1.
The data in Table 1 indicate that under microwave
irradiation, all substrates cyclized smoothly in substan-
tially less time than using conventional conditions.4
Table 1. Microwave-assisted RCM reactions of diallylamines7
O
O
O
R
R
R
OCH3
OCH3
OCH3
Ru cat., MW
N
+
N
N
CH2Cl2 (0.1M)
a
b
3 - 8
Entry
Substrate
Producta
Conditions
Yieldb
a (%)
b (%)
O
O
O
Ph
0.1 M in 3
OCH3
Ph
N
Ph
OCH3
OCH3
5 mol % of 2
150 °C, 10 min
N
1
40
57
N
3a
3b
3
O
O
O
OCH3
OCH3
OCH3
N
HN
N
N
HN
HN
2
3
4
0.1 M in 4
39
28
35
54
61
53
5 mol % of 2
150 °C, 10 min
4a
4b
4
O
O
O
OCH3
OCH3
OCH3
N
N
N
0.1 M in 5
O
O
O
5 mol % of 2
150 °C, 10 min
5
5a
5b
O
O
O
H3CO
H3CO
H3CO
N
N
0.1 M in 6
N
5 mol % of 2
150 °C, 10 min
6a
6b
6
O
O
O
OCH3
OCH3
OCH3
H3CO
H3CO
H3CO
N
O
N
O
5
0.1 M in 7
75
16
N
O
5 mol % of 2
100 °C, 10 min
7a
7b
7
O
O
O
OCH3
OCH3
OCH3
N
N
N
6
0.1 M in 8
10
75
5 mol % of 2
150 °C, 10 min
8a
8b
8
a All compounds were characterized by 1H NMR and 13C NMR data.
b Isolated yields.

Q. Yang et al. / Tetrahedron Letters 47 (2006) 3893–3896
Table 2. Microwave-assisted RCM reactions of less basic diallylamines
3895
Ru cat., MW
R
N
R
N
CH2Cl2(0.1M)
9 - 12
13 - 14
Entry
7
Substrate
Producta
Conditions
Yieldb (%)
0.1 M in 9
5 mol % of 1
100 °C, 10 min
N
N
94
89
13
9
MeO
N
MeO
N
8
0.1 M in 10
5 mol % of 1
100 °C, 10 min
14
10
Cl
N
Cl
N
9
0.1 M in 11
98
98
2 mol % of 1
100 °C, 10 min
15
11
O2N
N
O2N
N
10
0.1 M in 12
2 mol % of 1
100 °C, 10 min
16
12
a Compounds were characterized by 1H NMR and 13C NMR.
b Isolated yields.
The reactions gave pyrrole derivatives as the main prod-
product in most cases. The key features of this process
are that it can be carried out without deactivation of
the substrates and without the use of Lewis acids.
ucts,8 except in the case of 7 (entry 5).
We then examined how the basicity of the nitrogen atom
affected the RCM reactions under microwave irradia-
tion. Some substituted aromatic amines 9–11 were syn-
thesized and subjected to the optimal microwave
irradiation conditions. The reactions gave pyrrole deriv-
atives in excellent yields. Among these substrates, Evans
et al. have used compound 10 in the RCM reaction with
CH2Cl2 as the solvent in the presence of catalyst 1.9
Thus, we chose 1 as the catalyst and reduced catalyst
loadings from 5 to 2 mol %. The excellent yields were
obtained under these conditions (Table 2).
Acknowledgements
We are grateful to the Natural Science Foundation of
China (20472021), the National Key Project for Basic
Research of China (2004CCA00100), and the Hubei
Province Science Fund for Distinguished Young Scholar
(2004ABB011), for funding. We thank Materia, Inc.,
Pasadena, CA, for the generous gift of catalysts.
As illustrated in Tables 1 and 2, the basicity of diallyl-
amines had obvious effect on the microwave-accelerated
RCM reactions. When the substrate was more basic, the
more active catalyst 2 had to be used to make the reac-
tion complete (Table 1). In the case of less basic sub-
strates, for example, N,N-diallylaniline, comparable
results could be obtained in the presence of less active
catalyst 1 and with catalyst loadings reduced to
2 mol % (Table 2). Pyrroles were isolated as the sole
products instead of the expected corresponding 3-pyrrol-
ines (Table 2, entries 7–10), which suggested that not
only RCM took place but also isomerization and dehy-
drogenation occurred under microwave irradiation.
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