Synthesis of pyrroles via copper-catalyzed coupling of amines with bromoenones

Article abstract of DOI:10.1055/s-2007-965980

The CuI/N,N-dimethylglycine hydrochloride catalyzed reactions of amines with γ-bromo-substituted γ,δ-unsaturated ketones in the presence of K₃PO₄ and NH₄OAc led to the formation of the corresponding polysubstituted pyrrole

Full text of DOI:10.1055/s-2007-965980

1242
SPECIAL TOPIC
Synthesis of Pyrroles via Copper-Catalyzed Coupling of Amines with
Bromoenones
S
ynthesisof Pyrro
u
les anjia Pan,b Hongjian Lu,a Yewen Fang,a Xinqiang Fang,a Liqun Chen,a Junlu Qian,b Junhua Wang,a
Chaozhong Li*a,b
a
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. of China
Fax +86(21)54925099; E-mail: clig@mail.sioc.ac.cn
Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai 200092, P. R. of China
b
Received 7 February 2007
cal experimental conditions: CuI (20 mol%) as the
Abstract: The CuI/N,N-dimethylglycine hydrochloride catalyzed
catalyst, N,N¢-dimethylethylenediamine (A, 40 mol%) as
reactions of amines with g-bromo-substituted g,d-unsaturated ke-
the ligand, K2CO3 (2 equiv) as the base, MeCN as the sol-
tones in the presence of K3PO4 and NH4OAc led to the formation of
vent, and the mixture was refluxed for 20 hours.7 To our
the corresponding polysubstituted pyrroles in good to excellent
yields.
disappointment, little if any of the expected product 2a
could be observed while most of the starting materials re-
mained unchanged. Changing the ligand to other com-
monly used ligands such as trans-N,N¢-dimethyl-1,2-
cyclohexyldiamine (B), Ph3P (C), 2-aminoethanol (D),
1,10-phenanthroline (E), L-proline (F) and N,N-dimeth-
ylglycine hydrochloride (G) yielded no improvement
(Table 1, entry 1). Assuming that the reaction mixture
might be too basic in the presence of K2CO3, we added
ammonium acetate (2 equiv) to lower the basicity of the
solution. It turned out that the expected pyrrole product 2a
was achieved in 68% isolated yield (Table 1, entry 2).
Moreover, switching the base from K2CO3 to K3PO4 in-
creased the product yield to 91% (Table 1, entry 3). Won-
dering whether the role of NH4OAc was to convert CuI
into CuOAc or to convert the base into (NH4)3PO4, we
tested (NH4)3PO4 and CuOAc, respectively. However, lit-
tle or no reaction was observed (Table 1, entries 4 and 5).
With the use of NH4OAc as the additive, we further
screened the ligands (Table 1, entries 6–11). Among
ligands A to G, the N,N-dimethylglycine hydrochloride G
gave the best result. The product 2a could be obtained in
almost quantitative yield when 10 mol% of CuI and 20
mol% of G were employed (Table 1, entry 12). Further
lowering the amount of CuI to 5 mol% resulted in a de-
crease of product yield (Table 1, entry 13). We then con-
cluded that the optimized conditions were to use 10 mol%
of CuI, 20 mol% of ligand G, 200 mol% of K3PO4 and 200
mol% of NH4OAc. Again, without any one of the above
four elements, the yield of 2a was decreased (Table 1, en-
tries 14–17). It should be noted that the reaction also pro-
ceeded without the ligand G, albeit in a lower efficiency
(Table 1, entry 15). This strongly implied that NH4OAc
might function as the NH3 source, which served as the co-
ligand to improve the efficiency of the copper catalyst.
This was further evidenced by the ineffectiveness of CuI
in the absence of ligand G and NH4OAc (Table 1, entry
18).
Key words: Ullmann-type reaction, amine, pyrrole, ammonium
acetate
Pyrroles are an important class of heterocyclic com-
pounds. The pyrrole subunit occurs in a number of phar-
macologically active natural products and synthetic
drugs.1 They have also found application in the field of
material science.2 Although many methods have been re-
ported for the synthesis of pyrroles,3 the pursuit for the
more general, convenient and efficient generation contin-
ues to be an area of intensive research.4 Herein we report
that the copper-catalyzed coupling of amines with g-bro-
mo-substituted g,d-unsaturated ketones led to the efficient
synthesis of polysubstituted pyrroles.
The formation of aryl C–X bonds (X = O, S, N, etc.) via
copper-catalyzed Ullmann coupling between aryl halides
and heteroatom-centered nucleophiles has received con-
siderable attention in the past few years.5 The high stabil-
ity and low cost of the copper catalysts enable these
transformations to be a useful complement to the more ex-
tensively investigated palladium-catalyzed processes.
This methodology was successfully extended to vinylic
C–X bond formation and found important application in
natural product synthesis.6 Owing to our interest7 in the
copper-catalyzed intramolecular N- or O-vinylation, we
wondered if this methodology could be applied to the syn-
thesis of pyrroles by the coupling of amines with carbon-
yl-containing vinyl bromides such as 2-(2-bromo-
allyl)cyclohexanone (1a). Tanyeli et al. reported the acid-
catalyzed condensation of bromoenone 1a with aliphatic
amines in refluxing toluene.8 However, the expected pyr-
role products were obtained only in low yields.
Thus, we chose enone 1a and benzylamine as the model
substrates to explore this possibility. The results are sum-
marized in Table 1. Initially we tested the following typi-
With the optimized conditions in hand, we then examined
the scope and limitation of this methodology (Tables 2
and 3). The reactions of substrate 1a with a number of
amines were performed (Table 2). The primary amines
SYNTHESIS 2007, No. 8, pp 1242–1246
Advanced online publication: 12.03.2007
DOI: 10.1055/s-2007-965980; Art ID: C00307SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
7

SPECIAL TOPIC
Synthesis of Pyrroles
1243
Table 1 Optimization of Reaction Conditions for 2a
Table 2 The Reactions of Enone 1a with Amines
O
O
Bn
R
CuI/G
K3PO4/NH4OAc
N
N
+
+
BnNH2
RNH2
Br
Br
1a
2a
1a
2a–g
Entrya CuI
(mol%)
Base
Ligand
Additive
Yield
(%)b
Entry
RNH2
Time (h)
10a
Product
2a
Yield (%)
1
2
3
4
5
6
BnNH2
99
99
99
78
1
2
20
K2CO3
K2CO3
K3PO4
(NH4)3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
–
A–G
A
A
A
A
B
–
<5
68
91
8
allylamine
15a
2b
20
20
20
20c
20
20
20
20
20
20
10
5
NH4OAc
NH4OAc
–
n-C5H11NH2
c-C6H11NH2
t-BuNH2
15a
2c
3
22b
2d
4
20c
2e
–
d
5
–
0
4-MeOC6H4NH2
12b
2f
92
6
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
–
97
<5
95
<5
95
99
99
87
7
a In refluxing MeCN.
b In refluxing toluene.
7
C
D
E
c Sealed tube, MeCN, ~90 °C.
d Pyrrole 2g (R = H) was isolated in 87% yield.
8
9
10
11
12
13
14
15
16
17
18
F
Table 3 Synthesis of Pyrroles 2
O
O
G
G
G
G
–
O
R
H
Br
Br
Br
1c: R = H
1b
1e
2h
1d: R = Bn
10
10
10
0
O
Bn
O
C5H11
NH4OAc
NH4OAc
NH4OAc
–
65
23
15
0
N
C4H9
G
G
–
Cl
Br
1f
1g
K3PO4
K3PO4
R3
N
Bn
10
R1
Me
R2
Me
R3
Bn
R2
N
j
k
l
a Reaction conditions: 1a (0.5 mmol), Cu(I)/ligand = 1:2, base (2
equiv), additive (2 equiv), MeCN (5 mL), reflux, 20 h.
b Isolated yield based on 1a.
R1
Me CH2Bn Bn
Me CH2Bn C5H11
2i
2j–n
m C6H13 C4H9
Bn
c CuOAc was used as the copper source.
n
C6H13 C4H9 C5H11
Entry
Enone
1ba
1ca
Amine
BnNH2
BnNH2
BnNH2
Product
2h
Yield (%)
such as allylamine or amylamine gave the expected pyr-
roles in almost quantitative yield (Table 2, entries 1–3).
With secondary amines such as cyclohexylamine, the re-
action was slow and the product 2d was isolated in only
38% yield after 22 hours of reflux in acetonitrile. Howev-
er, when the reaction was carried out in toluene at reflux,
2d was obtained in 78% yield (Table 2, entry 4). The re-
action of tert-butylamine with 1a did not give the expect-
ed product 2e presumably because of the low boiling point
and the steric hindrance of the amine. When the reaction
was conducted in a sealed tube, pyrrole 2g (R = H) rather
than 2f (R = t-Bu) was isolated in 87% yield (Table 2, en-
try 5). Apparently NH3 generated from NH4OAc was in-
volved in the coupling. A typical arylamine, p-anisidine,
was also tested and the expected product 2f was obtained
in 92% yield (Table 2, entry 6).
1
2
3
4
5
6
7
8
95
90
85
68
83
93
80
86
2j
1da
1da
1ea
2k
n-C5H11NH2
BnNH2
2l
2i
1fa
BnNH2
2m
2n
1fa
n-C5H11NH2
BnNH2
1gb
2a
a In refluxing MeCN.
b In refluxing toluene.
Synthesis 2007, No. 8, 1242–1246 © Thieme Stuttgart · New York

1244
Y. Pan et al.
SPECIAL TOPIC
IR (film): 3029, 1716, 1631, 1604, 1497, 1454, 890, 750, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.66–2.79 (m, 6 H), 2.91 (t,
Various bromoenones were then prepared and their reac-
tions with amines were carried out (Table 3). In all the
cases the expected pyrroles were achieved in high yields. J = 7.2 Hz, 2 H), 5.39 (d, J = 1.8 Hz, 1 H), 5.59 (s, 1 H), 7.16–7.31
(m, 5 H).
Aldehydes such as 1e also underwent the condensation
13C NMR (100 MHz, CDCl3): d = 29.7, 35.4, 41.2, 44.5, 117.6,
126.2, 128.3, 128.5, 132.8, 140.8, 207.8.
MS: m/z (%) = 187 (28, [M – Br]+), 169 (9), 133 (9), 129 (15), 105
(33), 91 (100), 77 (12), 65 (11).
HRMS (EI): m/z [M+ – Br] calcd for C13H15O: 187.1123; found:
187.1128
with amines in good yield (entry 5, Table 3). The method-
ology could be further extended to the use of chloro-
enones. As an example, the reaction of 2-(2-chloro-
allyl)cyclohexanone with benzylamine under the catalysis
of CuI/G/NH4OAc in refluxing toluene afforded the pyr-
role product 2a in 86% yield.
On the basis of the above results, a plausible mechanism
could be drawn for the copper-catalyzed coupling reac-
tions as follows. The amines undergo condensation with
the carbonyls first to give the corresponding imines,
which rearrange to the enamine structures. The enamines
then undergo intramolecular N-vinylation with the cataly-
sis of Cu(I) to give 2-methylene-2,3-dihydropyrroles,
which then isomerized to the pyrroles as the final prod-
ucts. In fact, we isolated the imine intermediate by reac-
tion of 1a with benzylamine under TsOH-catalyzed
dehydration conditions (in benzene) and then subjected it
to the treatment of CuI under the optimized conditions.
The pyrrole 2a was thus obtained in about 80% yield.
Moreover, the reaction of benzylamine with 2-bromohex-
1-ene under the optimized conditions did not give the N-
vinylation product at all. These provided strong evidence
for the proposed mechanism.
(E)-8-Bromotetradec-8-en-5-one (1f)
Light yellow oil; Rf = 0.5 (hexane–EtOAc, 10:1).
IR (film): 2960, 2931, 1718, 1466, 1261 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.82 (t, J = 6.6 Hz, 3 H), 0.84 (t,
J = 7.2 Hz, 3 H), 1.18–1.32 (m, 8 H), 1.45–1.56 (m, 2 H), 1.99 (q,
J = 7.2 Hz, 2 H), 2.36 (t, J = 7.5 Hz, 2 H), 2.60 (br, 1 H), 5.79 (t,
J = 7.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.8, 14.0, 22.3, 22.5, 25.9, 28.8,
29.5, 29.6, 31.3, 40.9, 42.9, 123.9, 133.7, 209.6.
MS: m/z (%) = 291 (0.3, [M (81Br) + 1]+), 289 (0.3, [M (79Br) + 1]+),
209 (43), 109 (16), 85 (76), 81 (11), 67 (31), 57 (100).
HRMS (EI): m/z [M+ – Br] calcd for C14H25O: 209.1905; found:
209.1913.
Copper-Catalyzed Synthesis of Pyrroles 2; 1-Benzyl-2-methyl-
4,5,6,7-tetrahydro-1H-indole (2a);10 Typical Procedure
A mixture of 2-(2-bromoallyl)cyclohexanone (1a; 108.6 mg, 0.5
mmol), CuI (9.5 mg, 0.05 mmol), N,N-dimethylglycine hydrochlo-
ride (15.4 mg, 0.1 mmol), BnNH2 (58.9 mg, 0.55 mmol), NH4OAc
(77.1 mg, 1 mmol), and K3PO4 (212.3 mg, 1 mmol) in MeCN (5
mL) was refluxed for 20 h under N2. The resulting mixture was
cooled down to r.t. and then diluted with brine (25 mL). The aque-
ous solution was extracted with Et2O (3 × 25 mL). The combined
organic phase was then washed with brine (25 mL) and dried
(Na2SO4). After removal of the solvent under reduced pressure, the
crude product was purified by flash chromatography on silica gel
(hexane–EtOAc, 10:1) to afford the pure product 2a as a light yel-
low oil; yield: 111.5 mg (99%); light yellow oil; Rf = 0.7 (hexane–
EtOAc, 10:1).
In conclusion, the chemistry detailed above has clearly
demonstrated that the copper-catalyzed intermolecular
coupling between various amines and bromoenones can
be significantly promoted by the addition of NH4OAc,
leading to the convenient and efficient synthesis of the
corresponding polysubstituted pyrroles.
1H NMR spectra were measured with a Bruker AM-300 spectrom-
eter in CDCl3. 13C NMR spectra were taken with a Varian Unity-
INOVA 400 spectrometer in CDCl3. TMS served as the internal
standard. IR spectra were recorded on a Bio-Rad FTS-185. EIMS
and HRMS were measured on a HP-5989 instrument. All solvents
used were purified according to standard procedures. The substrates
1 were prepared by the conventional procedures according to the lit-
erature methods.9 The analytical and spectral data for some new
substrates 1 are given below.
1H NMR (300 MHz, CDCl3): d = 1.67–1.82 (m, 4 H), 2.14 (s, 3 H),
2.41 (t, J = 5.4 Hz, 2 H), 2.51 (t, J = 5.4 Hz, 2 H), 4.95 (s, 2 H), 5.75
(s, 1 H), 6.91–6.94 (m, 2 H), 7.22–7.32 (m, 3 H).
1-Allyl-2-methyl-4,5,6,7-tetrahydro-1H-indole (2b)
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 1.60–1.77 (m, 4 H), 2.09 (s, 3 H),
2.39 (t, J = 6.3 Hz, 4 H), 4.23 (br, 2 H), 4.75 (dd, J = 16.8, 1.5 Hz,
1 H), 5.01 (dd, J = 10.2, 1.5 Hz, 1 H), 5.61 (s, 1 H), 5.72–5.84 (m,
1 H).
13C NMR (100 MHz, CDCl3): d = 11.8, 21.9, 23.0, 23.5, 23.9, 45.3,
104.9, 115.6, 116.0, 126.7, 134.4.
MS: m/z (%) = 175 (85, [M]+), 160 (11), 147 (100), 132 (64), 117
(20), 106 (15), 91 (25), 77 (21).
HRMS (EI): m/z [M+ + H] calcd for C12H18N: 176.1433; found:
176.1433.
2-(2-Bromoallyl)cyclopentanone (1b)
Colorless oil; Rf = 0.5 (hexane–EtOAc, 10:1).
IR (film): 3101, 2965, 2879, 1740, 1631, 1452, 1430, 1405, 1156,
892 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.48–2.47 (m, 8 H), 2.96 (dd,
J = 15, 2.4 Hz, 1 H), 5.45 (br, 1 H), 5.63 (br, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.4, 29.0, 37.9, 41.5, 47.8,
118.1, 132.2, 219.0.
MS: m/z (%) = 123 (100, [M – Br]+), 105 (7), 95 (29), 93 (7), 83 (4),
77 (7), 79 (26), 67 (25).
HRMS (EI): m/z [M+ – Br] calcd for C8H11O: 123.0810; found:
123.0810.
2-Methyl-1-pentyl-4,5,6,7-tetrahydro-1H-indole (2c)
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 0.90 (t, J = 6.9 Hz, 3 H), 1.28–
1.35 (m, 4 H), 1.58–1.62 (m, 2 H), 1.69–1.74 (m, 2 H), 1.78–1.83
6-Bromo-1-phenylhept-6-en-3-one (1d)
Light yellow oil; Rf = 0.5 (hexane–EtOAc, 10:1).
Synthesis 2007, No. 8, 1242–1246 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Pyrroles
1245
(m, 2 H), 2.20 (s, 3 H), 2.45–2.53 (m, 4 H), 3.64 (t, J = 7.8 Hz, 2 H),
5.65 (s, 1 H).
1-Benzyl-2,5-dimethyl-1H-pyrrole (2j)14
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
13C NMR (100 MHz, CDCl3): d = 12.0, 13.9, 22.2, 22.4, 23.0, 23.6,
23.9, 29.1, 30.9, 43.3, 104.7, 115.8, 126.5.
1H NMR (300 MHz, CDCl3): d = 2.13 (s, 6 H), 5.00 (s, 2 H), 5.85
(s, 2 H), 6.87–6.89 (m, 2 H), 7.26–7.29 (m, 3 H).
MS: m/z (%) = 205 (100, [M]+), 190 (38), 177 (31), 162 (30), 149
(87), 134 (25), 121 (36), 108 (67).
1-Benzyl-2-methyl-5-phenethyl-1H-pyrrole (2k)
Light yellow oil; Rf = 0.2 (hexane–EtOAc, 50:1).
Anal. Calcd for C14H23N: C, 81.89; H, 11.29; N, 6.82. Found: C,
81.64, H; 11.22; N, 6.86.
IR (film): 3028, 2931, 1604, 1496, 1454, 1418, 1301, 1077, 1029,
751, 730, 697 cm–1.
1-Cyclohexyl-2-methyl-4,5,6,7-tetrahydro-1H-indole (2d)11
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 1.11–1.94 (m, 14 H), 2.27 (s, 3 H),
2.48 (t, J = 5.4 Hz, 2 H), 2.65 (t, J = 5.4 Hz, 2 H), 3.79–3.89 (m, 1
H), 5.65 (s, 1 H).
1H NMR (300 MHz, CDCl3): d = 2.06 (s, 3 H), 2.64–2.70 (m, 2 H),
2.74–2.82 (m, 2 H), 4.91 (s, 2 H), 5.83–5.89 (m, 2 H), 6.77 (d,
J = 7.2 Hz, 2 H), 7.02–7.23 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 12.4, 28.8, 35.4, 46.6, 104.6,
105.7, 125.6, 126.0, 127.1, 128.2, 128.4, 128.8, 132.3, 138.6, 141.9.
MS: m/z (%) = 217 (32, [M]+), 202 (8), 189 (12), 174 (3), 162 (3),
MS: m/z (%) = 275 (7, [M]+), 192 (1), 184 (77), 167 (2), 91 (100),
148 (3), 135 (20), 107 (100).
77 (2), 70 (4), 65 (14).
HRMS (EI): m/z [M+] calcd for C20H21N: 275.1674; found:
275.1671.
1-(4-Methoxyphenyl)-2-methyl-4,5,6,7-tetrahydro-1H-indole
(2f)
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
2-Methyl-1-pentyl-5-phenethyl-1H-pyrrole (2l)
Light yellow oil; Rf = 0.2 (hexane–EtOAc, 50:1).
IR (film): 3101, 2939, 2862, 1712, 1631, 1516, 1448, 1427, 1365,
1276, 1192, 1130, 888, 839, 816, 763 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.62–1.67 (m, 4 H), 1.95 (s, 3 H),
2.20 (br, 2 H), 2.43 (br, 2 H), 3.72 (s, 3 H), 5.70 (s, 1 H), 6.82–6.85
(m, 2 H), 7.02–7.05 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 12.4, 22.7, 23.0, 23.5, 23.8, 55.2,
105.4, 114.0, 116.3, 127.9, 128.0, 128.7, 131.5, 158.5.
IR (film): 2959, 2931, 1454, 1419, 1300, 1261, 1026, 804, 747, 698
cm–1.
1H NMR (300 MHz, CDCl3): d = 0.82 (t, J = 6.6 Hz, 3 H), 1.18–
1.26 (m, 4 H), 1.42–1.59 (m, 2 H), 2.16 (s, 3 H), 2.71–2.93 (m, 4 H),
3.62 (t, J = 7.5 Hz, 2 H), 5.75 (d, J = 3.3 Hz, 1 H), 5.80 (d, J = 3.3
Hz, 1 H), 7.14–7.27 (m, 5 H).
MS: m/z (%) = 241 (80, [M]+), 226 (9), 213 (100), 198 (16), 182
(11), 168 (7), 154 (5), 120 (5).
13C NMR (100 MHz, CDCl3): d = 12.4, 14.0, 22.4, 29.0, 29.1, 30.9,
35.3, 43.6, 103.8, 105.2, 126.0, 127.5, 127.7, 128.4, 131.6, 142.1.
HRMS (EI): m/z [M+ + H] calcd for C16H20NO: 242.1535; found:
MS: m/z (%) = 255 (5, [M]+), 234 (1), 164 (100), 134 (3), 120 (4),
242.1539.
108 (43), 94 (38), 77 (6).
HRMS (EI): m/z [M+] calcd for C18H25N: 255.1987; found:
255.1983.
2-Methyl-4,5,6,7-tetrahydro-1H-indole (2g)12
Dark oil; Rf = 0.4 (hexane–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 1.70–1.81 (m, 4 H), 2.23 (s, 3 H),
2.45 (br t, J = 5.7 Hz, 2 H), 2.53 (br t, J = 5.1 Hz, 2 H), 5.64 (s, 1
H), 7.47 (br, 1 H, NH).
1-Benzyl-2-butyl-5-hexyl-1H-pyrrole (2m)
Light yellow oil; Rf = 0.5 (hexane–EtOAc, 50:1).
IR (film): 2957, 2930, 1455, 1425, 1299, 1029, 728, 695 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.75–0.81 (m, 6 H), 1.12–1.32 (m,
8 H), 1.41–1.53 (m, 4 H), 2.31–2.38 (m, 4 H), 4.95 (s, 2 H), 5.83 (s,
2 H), 6.77 (d, J = 6.9 Hz, 2 H), 7.13–7.24 (m, 3 H).
1-Benzyl-2-methyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole
(2h)10
Light yellow oil; Rf = 0.7 (hexane–EtOAc, 10:1).
13C NMR (100 MHz, CDCl3): d = 14.0, 14.1, 22.6, 26.3, 26.6, 28.7,
29.2, 30.9, 31.7, 46.4, 104.2, 125.6, 126.9, 128.7, 132.9, 133.0,
138.9.
MS: m/z (%) = 297 (9, [M]+), 254 (21), 226 (25), 182 (2), 163 (4),
91 (100), 83 (10), 65 (10).
HRMS (EI): m/z [M+] calcd for C21H31N: 297.2457; found:
297.2450.
1H NMR (300 MHz, CDCl3): d = 2.14 (s, 3 H), 2.33–2.37 (m, 2 H),
2.53–2.65 (m, 4 H), 4.95 (s, 2 H), 5.74 (s, 1 H), 7.01 (d, J = 7.5 Hz,
2 H), 7.23–7.30 (m, 3 H).
1-Benzyl-4-ethyl-2-methyl-1H-pyrrole (2i)13
Dark oil; Rf = 0.7 (hexane–EtOAc, 10:1).
IR (film): 3088, 3065, 3030, 2963, 2931, 1728, 1631, 1516, 1496,
1454, 1417, 1355, 1313, 1184, 1141, 1075, 1030, 895, 797, 731,
698 cm–1.
2-Butyl-5-hexyl-1-pentyl-1H-pyrrole (2n)
1H NMR (300 MHz, CDCl3): d = 1.18 (t, J = 7.5 Hz, 3 H), 2.11 (s,
3 H), 2.46 (q, J = 7.5 Hz, 2 H), 4.96 (s, 2 H), 5.82 (s, 1 H), 6.40 (s,
1 H), 7.01 (d, J = 6.6 Hz, 2 H), 7.24–7.35 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 12.0, 15.4, 20.1, 50.2, 107.1,
117.4, 125.3, 126.5, 127.2, 128.6, 128.7, 138.7.
MS: m/z (%) = 199 (43, [M]+), 184 (36), 170 (4), 155 (1), 141 (1),
129 (1), 108 (2), 91 (100).
HRMS (EI): m/z [M+] calcd for C14H17N: 199.1364; found:
199.1361.
Light yellow oil; Rf = 0.5 (hexane–EtOAc, 50:1).
IR (film): 2958, 2930, 1467, 1426, 1378, 1297, 746 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.87–0.98 (m, 9 H), 1.27–1.47 (m,
12 H), 1.55–1.69 (m, 6 H), 2.47–2.54 (m, 4 H), 3.70 (t, J = 7.5 Hz,
2 H), 5.80 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.0, 14.1, 14.2, 22.4, 22.7, 22.8,
26.3, 26.7, 28.8, 29.2, 29.5, 31.0, 31.8, 43.4, 103.6, 132.2, 132.3.
MS: m/z (%) = 277 (29, [M]+), 248 (3), 234 (97), 220 (10), 206
(100), 164 (13), 150 (18), 94 (31).
HRMS (EI): m/z [M+] calcd for C19H35N: 277.2770; found:
277.2769.
Synthesis 2007, No. 8, 1242–1246 © Thieme Stuttgart · New York

1246
Y. Pan et al.
SPECIAL TOPIC
(5) For reviews, see: (a) Kunz, K.; Scholz, U.; Ganzer, D.
Acknowledgment
Synlett 2003, 2428. (b) Ley, S. V.; Thomas, A. W. Angew.
Chem. Int. Ed. 2003, 42, 5400. (c) Beletskaya, I. P.;
Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337.
(d) Deng, W.; Liu, L.; Guo, Q. X. Chin. J. Org. Chem. 2004,
24, 150; Chem. Abstr. 2004, 140, 406327. (e) Dehli, J. R.;
Legros, J.; Bolm, C. Chem. Commun. 2005, 973. (f)Corbet,
J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
This project was supported by the National Natural Science Foun-
dation of China (Nos. 20325207 and 20472109).
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Synthesis 2007, No. 8, 1242–1246 © Thieme Stuttgart · New York